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Nidagest
Allylestrenol
Nidagest
Allylestrenol
Indications
Threatened abortion
Indication detailsView
Allylestrenol is indicated in:
- Intra Uterine Growth Retardation (IUGR)
- Threatened abortion
- Habitual abortion
- Threatened premature delivery
Therapeutic classView
Female Sex hormones
PharmacologyView
Allylestrenol has been found to have a relatively weak progestational effect on the human endometrium. To obtain a full secretory endometrium in oestrogen-primed castrated women or to postpone menstruation (with an oestrogen added) in normal ovulating women, doses of allylestrenol were required which were higher than those recommended for the treatment/prevention of abortion.
In vitro studies have shown that allylestrenol stimulates the synthesis of progesterone in the human placenta. It also brought about a significant (p/. 0,01) increase in the production of some specific placental enzymes (cystine aminopeptidase and heat-stable alkaline phosphatase).
Histological and histochemical changes indicating an increased activity have been found in the placenta, particularly in the syncytiotrophoblast of women with a normal and threatened pregnancy, treated with allylestrenol. The stimulatory effect of allylestrenol on placental function was also suggested by the increased level of placental hormones (pregnanediol, oestriol, HCG and HPL) and enzymes (oxytocinase, CAP) in the maternal urine and plasma, which followed the administration of the drug e.g. in the early weeks as well as in the last trimester of pregnancy.
A study in full-term pregnant women revealed that allylestrenol in high doses (up to 100 mg daily) did suppress the intensity of spontaneous uterine contractions, but had no effect on the sensitivity of the uterine muscle to oxytocin, and no adverse effect on the progress of normal delivery.
Studies in non-pregnant women with and without endocrinological disorders have shown that allylestrenol has no oestrogenic or androgenic properties and no adverse effects on the adrenal function.
No abnormal liver function tests or water and salt retention were observed in healthy female volunteers (non pregnant) who were given allylestrenol.
In vitro studies have shown that allylestrenol stimulates the synthesis of progesterone in the human placenta. It also brought about a significant (p/. 0,01) increase in the production of some specific placental enzymes (cystine aminopeptidase and heat-stable alkaline phosphatase).
Histological and histochemical changes indicating an increased activity have been found in the placenta, particularly in the syncytiotrophoblast of women with a normal and threatened pregnancy, treated with allylestrenol. The stimulatory effect of allylestrenol on placental function was also suggested by the increased level of placental hormones (pregnanediol, oestriol, HCG and HPL) and enzymes (oxytocinase, CAP) in the maternal urine and plasma, which followed the administration of the drug e.g. in the early weeks as well as in the last trimester of pregnancy.
A study in full-term pregnant women revealed that allylestrenol in high doses (up to 100 mg daily) did suppress the intensity of spontaneous uterine contractions, but had no effect on the sensitivity of the uterine muscle to oxytocin, and no adverse effect on the progress of normal delivery.
Studies in non-pregnant women with and without endocrinological disorders have shown that allylestrenol has no oestrogenic or androgenic properties and no adverse effects on the adrenal function.
No abnormal liver function tests or water and salt retention were observed in healthy female volunteers (non pregnant) who were given allylestrenol.
DosageView
Intra Uterine Growth Retardation: 1 tablet three times a day at least two months. Dose to be reduced if symptoms improve.
Threatened abortion: 1 tablet three times daily until symptoms disappear.
Habitual abortion: 1-2 tablets daily as soon as pregnancy is diagnosed. The administration should be continued for at least one month after the end of the critical period.
Threatened premature delivery: Dosage must be determined individually. High dosages (up to 40 mg daily) have been used.
In case of a missed dose, it should be taken as soon as the patient remembers & she should continue the regular dosing schedule. A double dose is not recommended.
Threatened abortion: 1 tablet three times daily until symptoms disappear.
Habitual abortion: 1-2 tablets daily as soon as pregnancy is diagnosed. The administration should be continued for at least one month after the end of the critical period.
Threatened premature delivery: Dosage must be determined individually. High dosages (up to 40 mg daily) have been used.
In case of a missed dose, it should be taken as soon as the patient remembers & she should continue the regular dosing schedule. A double dose is not recommended.
Side effectsView
Treatment with Allylestrenol (especially a long term treatment) is known to cause some gastrointestinal complaints such as vomiting, nausea, and sometimes epigastric discomfort.
ContraindicationsView
- Breast Cancer or history of problem with the breasts like- Nodules,an abnormal Mammogram, or Fibrocystic Diseases.
- Severe liver disease such as Cholestatic Jaundice or Hepatitis, Hepatic Cell Tumours, Rotor Syndrome and Dubin Jhonson Syndrome.
- Undiagnosed vaginal bleeding
- Toxaemia of Pregnancy
- Crisis Seizures, Migraines
PrecautionsView
Patients with the following conditions should be cautious: Heart disease, congestive heart failure, sick sinus syndrome, coronary artery disease, seizures, epilepsy, renal dysfunction, migraine headaches, or breathing diseases including asthma, emphysema, chronic bronchitis, or COPD, breast-feeding.
Pregnancy & lactationView
Allylestrenol is specifically designed to be taken during pregnancy. It should be discontinued after delivery as it may affect a nursing infant to a small but noticeable degree.
Pediatric usageView
It should not be used for children younger than 16 years old.
Overdose effectsView
Symptoms of overdose may include unusual drowsiness; rapid pulse; fainting; unusual muscle movement or rigidity of the face, neck, or limbs; seizures; and loss of consciousness.
StorageView
Keep below 30°C temperature, away from light & moisture. Keep out of the reach of children.
Nidazyl
Metronidazole
Nidazyl
Metronidazole
Indications
Vaginal trichomoniasis
Indication detailsView
Metronidazole is indicated in the treatment of following diseases:
- The prevention of post-operative infections due to anaerobic bacteria (particularly species of bacteroides and anaerobic streptococci).
- The treatment of septicaemia, bacteraemia, peritonitis, brain abscess, pelvic abscess, pelvic cellulitis and post-operative wound infections caused by anaerobes.
- In the treatment of urogenital trichomoniasis.
- Bacterial vaginosis (also known as non-specific vaginitis).
- All forms of amoebiasis (intestinal, extra-intestinal disease and that of symptomless cyst passers).
- Giardiasis.
- Acute ulcerative gingivitis.
- Anaerobically infected leg ulcers and pressure sores.
- Acute dental infections due to anaerobic organisms.
- Antibiotic associated pseudomembranus colitis.
Therapeutic classView
Amoebicides, Anti-diarrhoeal Antiprotozoal
PharmacologyView
Metronidazole is a member of the imidazole class of antibacterial drug and is classified therapeutically as an antiprotozoal agent. The 5-nitro group of Metronidazole is reduced by anaerobes metabolically. Studies have demonstrated that the reduced form of this drug interacts with DNA and gives bactericidal action of Metronidazole.
DosageView
Tablet and Suspension:
Trichomoniasis (Adults & Children over 10 yrs)-- 200 mg tid or 400 mg bid for 7 days
- 800 mg in the morning and 1-2 gm at night for 2 days
- 2 gm as a single dose for 1 days
- Children 7-10 yrs: 100 mg tid
- Children 3-7 yrs: 100 mg bid
- Children 1-3 yrs: 50 mg tid
- 800 mg tid for 5 days
- Children 7-10 yrs: 400 mg tid
- Children 3-7 yrs: 200 mg qid
- Children 1-3 yrs: 200 mg tid
- 400-800 mg tid for 5-10 days
- Children 7-10 yrs: 200-400 mg tid
- Children 3-7 yrs: 100-200 mg qid
- Children 1-3 yrs: 100-200 mg tid
- 2 gm once daily for 3 days
- Children 7-10 yrs: 1 gm once daily
- Children 3-7 yrs: 600-800 mg once daily
- Children 1-3 yrs: 500 mg once daily
- 200 mg tid for 3 days
- Children 7-10 yrs: 100 mg tid
- Children 3-7 yrs: 100 mg bid
- Children 1-3 yrs: 50 mg tid
- 200 mg tid for 3-7 days
- 400 mg bid for 7 days
- 2 gm as a single dose for 1 days
- 400 mg tid for 7 days
- 800 mg initially and then 400 mg tid for 7 days
- Children 1-10 yrs: 7.5 mg/kg tid
- 400 mg tid started 24 hours before surgery for 1 days
- Children 1-10 yrs: 7.5 mg/kg tid
Vaginal Gel:
The recommended dose is one applicator full of Metronidazole gel (approximately 5 grams containing approximately 37.5 mg of Metronidazole) intravaginally once or twice a day for 5 days. For once a day dosing, Metronidazole gel should be administered at bedtime.
Suppository:
Anaerobic Infections-- Adults: 1 g every 8 hours for 3 days, then 1 g every 12 hours.
- Children: 5-10 years: 500 mg every 8 hours for 3 days, then every 12 hours, Over 10 years adult dose.
- Adults: 1 g 2 hours before surgery; up to 3 further doses of 1 g may be given every 8 hours for high risk procedures.
- Children: 5-10 years: 500 mg 2 hours before surgery; up to 3 further doses of 500 mg may be given every 8 hours for high risk procedures.
IV Infusion:
Metronidazole intravenous infusion requires no dilution and should not be mixed with any other drugs prior to administration.- Adults and children over 12 years: Infuse 500 mg 8 hourly at a rate of 5 ml/minute and a maximum of 4 g should not be exceeded during a 24-hour period. Treatment for 7 days is sufficient for most patients, but treatment can be extended, especially for cases where reinfection is likely. For surgical prophylaxis, administration shortly before surgery should be followed by 8-hourly doses for the next 24 hours.
- Children under 12 years: 7.5 mg/kg body weight/day every 8 hours at a rate of 5 ml/minute.
Side effectsView
Metallic taste, nausea, vomiting, diarrhoea, drowsiness, rashes may be observed during treatment.
ContraindicationsView
Metronidazole is contraindicated in patients with a history of hypersensitivity to Metronidazole or other Nitroimidazole derivatives.
PrecautionsView
- If for compelling reasons, metronidazole must be administered longer than the usually recommended duration, it is recommended that hematological tests, especially leucocyte count should be carried out regularly and that patients should be monitored for adverse reactions such as peripheral or central neuropathy (such as paresthesia, ataxia, dizziness, convulsive seizures).
- Metronidazole should be administered with caution to patients with hepatic encephalopathy.
- Patients should be warned that metronidazole may darken urine.
InteractionsView
- Disulfiram: Psychotic reactions have been reported in patients who were using metronidazole and disulfiram concurrently.
- Alcohol: Alcoholic beverages and drugs containing alcohol should not be consumed during therapy and for at least one day afterwards because of the possibility of a disulfiram-like (antabuse effect) reaction (flushing, vomiting, tachycardia). Oral anticoagulant therapy (warfarin type): Potentiation of the anticoagulant effect and increased hemorrhagic risk caused by decreased hepatic catabolism. In case of co-administration, prothrombin time should be more frequently monitored and anticoagulant therapy adjusted during treatment with metronidazole.
- Lithium: Plasma levels of lithium may be increased by metronidazole.
- Cyclosporin: Serum cyclosporin and serum creatinine should be closely monitored when co-administration is necessary.
- Phenytoin or phenobarbital: increased elimination of metronidazole resulting in reduced plasma levels.
- 5-Fluorouracil: Reduced clearance of 5-fluorouracil resulting in increased toxicity of 5-fluorouracil.
- Busulfan: Plasma levels of busulfan may be increased by metronidazole, which may lead to severe busulfan toxicity.
Pregnancy & lactationView
US FDA Pregnancy Category of Metronidazole is B. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed. Metronidazole have been shown to be excreted in human milk. So, caution should be exercised when Metronidazole is administered to a nursing woman.
Pediatric usageView
Hepatic impairment: Metronidazole is mainly metabolised by hepatic oxidation. Substantial impairment of metronidazole clearance may occur in the presence of advanced hepatic insufficiency. Significant cumulation may occur in patients with hepatic encephalopathy and the resulting high plasma concentrations of metronidazole may contribute to the symptoms of the encephalopathy. Metronidazole should therefore, be administered with caution to patients with hepatic encephalopathy. The daily dosage should be reduced to one third and may be administered once daily. Patients should be warned that metronidazole may darken urine.
Renal impairment: The elimination half-life of metronidazole remains unchanged in the presence of renal failure. The dosage of metronidazole therefore needs no reduction. Such patients however retain the metabolites of metronidazole. The clinical significance of this is not known at present. In patients undergoing haemodialysis metronidazole and metabolites are efficiently removed during an eight hour period of dialysis. Metronidazole should therefore be re-administered immediately after haemodialysis. No routine adjustment in the dosage of Metronidazole need be made in patients with renal failure undergoing intermittent peritoneal dialysis (IDP) or continuous ambulatory peritoneal dialysis (CAPD).
Renal impairment: The elimination half-life of metronidazole remains unchanged in the presence of renal failure. The dosage of metronidazole therefore needs no reduction. Such patients however retain the metabolites of metronidazole. The clinical significance of this is not known at present. In patients undergoing haemodialysis metronidazole and metabolites are efficiently removed during an eight hour period of dialysis. Metronidazole should therefore be re-administered immediately after haemodialysis. No routine adjustment in the dosage of Metronidazole need be made in patients with renal failure undergoing intermittent peritoneal dialysis (IDP) or continuous ambulatory peritoneal dialysis (CAPD).
Overdose effectsView
Single oral doses of metronidazole, up to 12 g have been reported in suicide attempts and accidental overdoses. Symptoms were limited to vomiting, ataxia and slight disorientation. There is no specific antidote for metronidazole overdosages. In case of suspected massive overdosages, a symptomatic and supportive treatment should be instituted.
StorageView
Store below 30°C. Keep protected from light. Keep medicines out of the reach of children. Do not use later than the date of expiry.
Nidazyl
Metronidazole
Nidazyl
Metronidazole
Indications
Vaginal trichomoniasis
Indication detailsView
Metronidazole is indicated in the treatment of following diseases:
- The prevention of post-operative infections due to anaerobic bacteria (particularly species of bacteroides and anaerobic streptococci).
- The treatment of septicaemia, bacteraemia, peritonitis, brain abscess, pelvic abscess, pelvic cellulitis and post-operative wound infections caused by anaerobes.
- In the treatment of urogenital trichomoniasis.
- Bacterial vaginosis (also known as non-specific vaginitis).
- All forms of amoebiasis (intestinal, extra-intestinal disease and that of symptomless cyst passers).
- Giardiasis.
- Acute ulcerative gingivitis.
- Anaerobically infected leg ulcers and pressure sores.
- Acute dental infections due to anaerobic organisms.
- Antibiotic associated pseudomembranus colitis.
Therapeutic classView
Amoebicides, Anti-diarrhoeal Antiprotozoal
PharmacologyView
Metronidazole is a member of the imidazole class of antibacterial drug and is classified therapeutically as an antiprotozoal agent. The 5-nitro group of Metronidazole is reduced by anaerobes metabolically. Studies have demonstrated that the reduced form of this drug interacts with DNA and gives bactericidal action of Metronidazole.
DosageView
Tablet and Suspension:
Trichomoniasis (Adults & Children over 10 yrs)-- 200 mg tid or 400 mg bid for 7 days
- 800 mg in the morning and 1-2 gm at night for 2 days
- 2 gm as a single dose for 1 days
- Children 7-10 yrs: 100 mg tid
- Children 3-7 yrs: 100 mg bid
- Children 1-3 yrs: 50 mg tid
- 800 mg tid for 5 days
- Children 7-10 yrs: 400 mg tid
- Children 3-7 yrs: 200 mg qid
- Children 1-3 yrs: 200 mg tid
- 400-800 mg tid for 5-10 days
- Children 7-10 yrs: 200-400 mg tid
- Children 3-7 yrs: 100-200 mg qid
- Children 1-3 yrs: 100-200 mg tid
- 2 gm once daily for 3 days
- Children 7-10 yrs: 1 gm once daily
- Children 3-7 yrs: 600-800 mg once daily
- Children 1-3 yrs: 500 mg once daily
- 200 mg tid for 3 days
- Children 7-10 yrs: 100 mg tid
- Children 3-7 yrs: 100 mg bid
- Children 1-3 yrs: 50 mg tid
- 200 mg tid for 3-7 days
- 400 mg bid for 7 days
- 2 gm as a single dose for 1 days
- 400 mg tid for 7 days
- 800 mg initially and then 400 mg tid for 7 days
- Children 1-10 yrs: 7.5 mg/kg tid
- 400 mg tid started 24 hours before surgery for 1 days
- Children 1-10 yrs: 7.5 mg/kg tid
Vaginal Gel:
The recommended dose is one applicator full of Metronidazole gel (approximately 5 grams containing approximately 37.5 mg of Metronidazole) intravaginally once or twice a day for 5 days. For once a day dosing, Metronidazole gel should be administered at bedtime.
Suppository:
Anaerobic Infections-- Adults: 1 g every 8 hours for 3 days, then 1 g every 12 hours.
- Children: 5-10 years: 500 mg every 8 hours for 3 days, then every 12 hours, Over 10 years adult dose.
- Adults: 1 g 2 hours before surgery; up to 3 further doses of 1 g may be given every 8 hours for high risk procedures.
- Children: 5-10 years: 500 mg 2 hours before surgery; up to 3 further doses of 500 mg may be given every 8 hours for high risk procedures.
IV Infusion:
Metronidazole intravenous infusion requires no dilution and should not be mixed with any other drugs prior to administration.- Adults and children over 12 years: Infuse 500 mg 8 hourly at a rate of 5 ml/minute and a maximum of 4 g should not be exceeded during a 24-hour period. Treatment for 7 days is sufficient for most patients, but treatment can be extended, especially for cases where reinfection is likely. For surgical prophylaxis, administration shortly before surgery should be followed by 8-hourly doses for the next 24 hours.
- Children under 12 years: 7.5 mg/kg body weight/day every 8 hours at a rate of 5 ml/minute.
Side effectsView
Metallic taste, nausea, vomiting, diarrhoea, drowsiness, rashes may be observed during treatment.
ContraindicationsView
Metronidazole is contraindicated in patients with a history of hypersensitivity to Metronidazole or other Nitroimidazole derivatives.
PrecautionsView
- If for compelling reasons, metronidazole must be administered longer than the usually recommended duration, it is recommended that hematological tests, especially leucocyte count should be carried out regularly and that patients should be monitored for adverse reactions such as peripheral or central neuropathy (such as paresthesia, ataxia, dizziness, convulsive seizures).
- Metronidazole should be administered with caution to patients with hepatic encephalopathy.
- Patients should be warned that metronidazole may darken urine.
InteractionsView
- Disulfiram: Psychotic reactions have been reported in patients who were using metronidazole and disulfiram concurrently.
- Alcohol: Alcoholic beverages and drugs containing alcohol should not be consumed during therapy and for at least one day afterwards because of the possibility of a disulfiram-like (antabuse effect) reaction (flushing, vomiting, tachycardia). Oral anticoagulant therapy (warfarin type): Potentiation of the anticoagulant effect and increased hemorrhagic risk caused by decreased hepatic catabolism. In case of co-administration, prothrombin time should be more frequently monitored and anticoagulant therapy adjusted during treatment with metronidazole.
- Lithium: Plasma levels of lithium may be increased by metronidazole.
- Cyclosporin: Serum cyclosporin and serum creatinine should be closely monitored when co-administration is necessary.
- Phenytoin or phenobarbital: increased elimination of metronidazole resulting in reduced plasma levels.
- 5-Fluorouracil: Reduced clearance of 5-fluorouracil resulting in increased toxicity of 5-fluorouracil.
- Busulfan: Plasma levels of busulfan may be increased by metronidazole, which may lead to severe busulfan toxicity.
Pregnancy & lactationView
US FDA Pregnancy Category of Metronidazole is B. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed. Metronidazole have been shown to be excreted in human milk. So, caution should be exercised when Metronidazole is administered to a nursing woman.
Pediatric usageView
Hepatic impairment: Metronidazole is mainly metabolised by hepatic oxidation. Substantial impairment of metronidazole clearance may occur in the presence of advanced hepatic insufficiency. Significant cumulation may occur in patients with hepatic encephalopathy and the resulting high plasma concentrations of metronidazole may contribute to the symptoms of the encephalopathy. Metronidazole should therefore, be administered with caution to patients with hepatic encephalopathy. The daily dosage should be reduced to one third and may be administered once daily. Patients should be warned that metronidazole may darken urine.
Renal impairment: The elimination half-life of metronidazole remains unchanged in the presence of renal failure. The dosage of metronidazole therefore needs no reduction. Such patients however retain the metabolites of metronidazole. The clinical significance of this is not known at present. In patients undergoing haemodialysis metronidazole and metabolites are efficiently removed during an eight hour period of dialysis. Metronidazole should therefore be re-administered immediately after haemodialysis. No routine adjustment in the dosage of Metronidazole need be made in patients with renal failure undergoing intermittent peritoneal dialysis (IDP) or continuous ambulatory peritoneal dialysis (CAPD).
Renal impairment: The elimination half-life of metronidazole remains unchanged in the presence of renal failure. The dosage of metronidazole therefore needs no reduction. Such patients however retain the metabolites of metronidazole. The clinical significance of this is not known at present. In patients undergoing haemodialysis metronidazole and metabolites are efficiently removed during an eight hour period of dialysis. Metronidazole should therefore be re-administered immediately after haemodialysis. No routine adjustment in the dosage of Metronidazole need be made in patients with renal failure undergoing intermittent peritoneal dialysis (IDP) or continuous ambulatory peritoneal dialysis (CAPD).
Overdose effectsView
Single oral doses of metronidazole, up to 12 g have been reported in suicide attempts and accidental overdoses. Symptoms were limited to vomiting, ataxia and slight disorientation. There is no specific antidote for metronidazole overdosages. In case of suspected massive overdosages, a symptomatic and supportive treatment should be instituted.
StorageView
Store below 30°C. Keep protected from light. Keep medicines out of the reach of children. Do not use later than the date of expiry.
Nidazyl
Metronidazole
Nidazyl
Metronidazole
Indications
Vaginal trichomoniasis
Indication detailsView
Metronidazole is indicated in the treatment of following diseases:
- The prevention of post-operative infections due to anaerobic bacteria (particularly species of bacteroides and anaerobic streptococci).
- The treatment of septicaemia, bacteraemia, peritonitis, brain abscess, pelvic abscess, pelvic cellulitis and post-operative wound infections caused by anaerobes.
- In the treatment of urogenital trichomoniasis.
- Bacterial vaginosis (also known as non-specific vaginitis).
- All forms of amoebiasis (intestinal, extra-intestinal disease and that of symptomless cyst passers).
- Giardiasis.
- Acute ulcerative gingivitis.
- Anaerobically infected leg ulcers and pressure sores.
- Acute dental infections due to anaerobic organisms.
- Antibiotic associated pseudomembranus colitis.
Therapeutic classView
Amoebicides, Anti-diarrhoeal Antiprotozoal
PharmacologyView
Metronidazole is a member of the imidazole class of antibacterial drug and is classified therapeutically as an antiprotozoal agent. The 5-nitro group of Metronidazole is reduced by anaerobes metabolically. Studies have demonstrated that the reduced form of this drug interacts with DNA and gives bactericidal action of Metronidazole.
DosageView
Tablet and Suspension:
Trichomoniasis (Adults & Children over 10 yrs)-- 200 mg tid or 400 mg bid for 7 days
- 800 mg in the morning and 1-2 gm at night for 2 days
- 2 gm as a single dose for 1 days
- Children 7-10 yrs: 100 mg tid
- Children 3-7 yrs: 100 mg bid
- Children 1-3 yrs: 50 mg tid
- 800 mg tid for 5 days
- Children 7-10 yrs: 400 mg tid
- Children 3-7 yrs: 200 mg qid
- Children 1-3 yrs: 200 mg tid
- 400-800 mg tid for 5-10 days
- Children 7-10 yrs: 200-400 mg tid
- Children 3-7 yrs: 100-200 mg qid
- Children 1-3 yrs: 100-200 mg tid
- 2 gm once daily for 3 days
- Children 7-10 yrs: 1 gm once daily
- Children 3-7 yrs: 600-800 mg once daily
- Children 1-3 yrs: 500 mg once daily
- 200 mg tid for 3 days
- Children 7-10 yrs: 100 mg tid
- Children 3-7 yrs: 100 mg bid
- Children 1-3 yrs: 50 mg tid
- 200 mg tid for 3-7 days
- 400 mg bid for 7 days
- 2 gm as a single dose for 1 days
- 400 mg tid for 7 days
- 800 mg initially and then 400 mg tid for 7 days
- Children 1-10 yrs: 7.5 mg/kg tid
- 400 mg tid started 24 hours before surgery for 1 days
- Children 1-10 yrs: 7.5 mg/kg tid
Vaginal Gel:
The recommended dose is one applicator full of Metronidazole gel (approximately 5 grams containing approximately 37.5 mg of Metronidazole) intravaginally once or twice a day for 5 days. For once a day dosing, Metronidazole gel should be administered at bedtime.
Suppository:
Anaerobic Infections-- Adults: 1 g every 8 hours for 3 days, then 1 g every 12 hours.
- Children: 5-10 years: 500 mg every 8 hours for 3 days, then every 12 hours, Over 10 years adult dose.
- Adults: 1 g 2 hours before surgery; up to 3 further doses of 1 g may be given every 8 hours for high risk procedures.
- Children: 5-10 years: 500 mg 2 hours before surgery; up to 3 further doses of 500 mg may be given every 8 hours for high risk procedures.
IV Infusion:
Metronidazole intravenous infusion requires no dilution and should not be mixed with any other drugs prior to administration.- Adults and children over 12 years: Infuse 500 mg 8 hourly at a rate of 5 ml/minute and a maximum of 4 g should not be exceeded during a 24-hour period. Treatment for 7 days is sufficient for most patients, but treatment can be extended, especially for cases where reinfection is likely. For surgical prophylaxis, administration shortly before surgery should be followed by 8-hourly doses for the next 24 hours.
- Children under 12 years: 7.5 mg/kg body weight/day every 8 hours at a rate of 5 ml/minute.
Side effectsView
Metallic taste, nausea, vomiting, diarrhoea, drowsiness, rashes may be observed during treatment.
ContraindicationsView
Metronidazole is contraindicated in patients with a history of hypersensitivity to Metronidazole or other Nitroimidazole derivatives.
PrecautionsView
- If for compelling reasons, metronidazole must be administered longer than the usually recommended duration, it is recommended that hematological tests, especially leucocyte count should be carried out regularly and that patients should be monitored for adverse reactions such as peripheral or central neuropathy (such as paresthesia, ataxia, dizziness, convulsive seizures).
- Metronidazole should be administered with caution to patients with hepatic encephalopathy.
- Patients should be warned that metronidazole may darken urine.
InteractionsView
- Disulfiram: Psychotic reactions have been reported in patients who were using metronidazole and disulfiram concurrently.
- Alcohol: Alcoholic beverages and drugs containing alcohol should not be consumed during therapy and for at least one day afterwards because of the possibility of a disulfiram-like (antabuse effect) reaction (flushing, vomiting, tachycardia). Oral anticoagulant therapy (warfarin type): Potentiation of the anticoagulant effect and increased hemorrhagic risk caused by decreased hepatic catabolism. In case of co-administration, prothrombin time should be more frequently monitored and anticoagulant therapy adjusted during treatment with metronidazole.
- Lithium: Plasma levels of lithium may be increased by metronidazole.
- Cyclosporin: Serum cyclosporin and serum creatinine should be closely monitored when co-administration is necessary.
- Phenytoin or phenobarbital: increased elimination of metronidazole resulting in reduced plasma levels.
- 5-Fluorouracil: Reduced clearance of 5-fluorouracil resulting in increased toxicity of 5-fluorouracil.
- Busulfan: Plasma levels of busulfan may be increased by metronidazole, which may lead to severe busulfan toxicity.
Pregnancy & lactationView
US FDA Pregnancy Category of Metronidazole is B. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed. Metronidazole have been shown to be excreted in human milk. So, caution should be exercised when Metronidazole is administered to a nursing woman.
Pediatric usageView
Hepatic impairment: Metronidazole is mainly metabolised by hepatic oxidation. Substantial impairment of metronidazole clearance may occur in the presence of advanced hepatic insufficiency. Significant cumulation may occur in patients with hepatic encephalopathy and the resulting high plasma concentrations of metronidazole may contribute to the symptoms of the encephalopathy. Metronidazole should therefore, be administered with caution to patients with hepatic encephalopathy. The daily dosage should be reduced to one third and may be administered once daily. Patients should be warned that metronidazole may darken urine.
Renal impairment: The elimination half-life of metronidazole remains unchanged in the presence of renal failure. The dosage of metronidazole therefore needs no reduction. Such patients however retain the metabolites of metronidazole. The clinical significance of this is not known at present. In patients undergoing haemodialysis metronidazole and metabolites are efficiently removed during an eight hour period of dialysis. Metronidazole should therefore be re-administered immediately after haemodialysis. No routine adjustment in the dosage of Metronidazole need be made in patients with renal failure undergoing intermittent peritoneal dialysis (IDP) or continuous ambulatory peritoneal dialysis (CAPD).
Renal impairment: The elimination half-life of metronidazole remains unchanged in the presence of renal failure. The dosage of metronidazole therefore needs no reduction. Such patients however retain the metabolites of metronidazole. The clinical significance of this is not known at present. In patients undergoing haemodialysis metronidazole and metabolites are efficiently removed during an eight hour period of dialysis. Metronidazole should therefore be re-administered immediately after haemodialysis. No routine adjustment in the dosage of Metronidazole need be made in patients with renal failure undergoing intermittent peritoneal dialysis (IDP) or continuous ambulatory peritoneal dialysis (CAPD).
Overdose effectsView
Single oral doses of metronidazole, up to 12 g have been reported in suicide attempts and accidental overdoses. Symptoms were limited to vomiting, ataxia and slight disorientation. There is no specific antidote for metronidazole overdosages. In case of suspected massive overdosages, a symptomatic and supportive treatment should be instituted.
StorageView
Store below 30°C. Keep protected from light. Keep medicines out of the reach of children. Do not use later than the date of expiry.
Nidependiol
Chloramphenicol (Ophthalmic)
Nidependiol
Chloramphenicol (Ophthalmic)
Indications
Whipple’s disease
Indication detailsView
Chloramphenicol is indicated for the treatment of ocular infections involving the conjunctiva and/or cornea caused by chloramphenicol-susceptible organisms. Such as Staphylococcus aureus, Streptococcus pneumoniae, E.coli, H. influenzae, Klebsiella/Enterobacter spp, Moraxella lacunata, and Neisseria species.
Therapeutic classView
Ear Anti-Infectives & Antiseptics, Eye Anti-Infectives & Antiseptics, Macrolides
PharmacologyView
Chloramphenicol is a broad-spectrum bacteriostatic antibiotic which acts through the inhibition of bacterial protein synthesis by interfering with the transfer of activated amino acids from soluble RNA to ribosomes.
DosageView
Adult and Children: Instill 1 or 2 drops in the conjunctival sac 4-6 times per day for the first 72 hours and then every 4 hours thereafter. Treatment should be continued for approximately 7 days, but should not be continued for more than 3 weeks without re-evaluation by the physician.
Side effectsView
The systemic adverse reaction has not been observed within short-term topical use of Chloramphenicol. The most frequently reported adverse reactions have been burning, stinging, conjunctival hyperemia, blood dyscrasia, allergic or inflammatory reactions, vesicular and maculopapular dermatitis.
ContraindicationsView
It is contraindicated in individuals with a history of hypersensitivity to Chloramphenicol or any ingredients of the preparation.
PrecautionsView
Chloramphenicol ophthalmic solution should never be given for minor infections or for prophylaxis. Repeated course and prolonged treatment should be avoided. Blood dyscrasias (granulocytopenia, thrombocytopenia and moderate anaemia) may occur after prolonged ophthalmic use.
InteractionsView
Chymotrypsin may be inhibited if given simultaneously with Chloramphenicol.
Pregnancy & lactationView
Safety for use in pregnancy and lactation has not been established. Therefore, use only when considered essential by the physicians.
Overdose effectsView
Accidental ingestion of the medicine is unlikely to cause any toxicity due to low content of antibiotic.
StorageView
Store in a cool (between 2°C-8°C) and dry place, protect from light, keep out of reach of children. Do not touch the dropper tip to the surface since this may contaminate the solution. Do not use after 30 days of the first opening.
Nidependiol D
Dexamethasone + Chloramphenicol
Nidependiol D
Dexamethasone + Chloramphenicol
Indications
Post-herpetic keratitis
Indication detailsView
Eye: This combination is indicated in acute purulent conjunctivitis, fresh inflammation of the superficial and deeper corneal layers and corneal ulceration. It is also used in keratitis disciformis and the more deep-seated forms of post-herpetic keratitis, allergic conjunctivitis, allergic blepharitis, acute and chronic iritis, chronic anterior uveitis and corneal injury from chemical radiation or thermal burns, or penetration of foreign bodies. The combination is used in steroid-responsive inflammatory ocular conditions for which a corticosteroid is indicated and where bacterial infection or arisk of bacterial ocular infection exists. The combination can also be used for post-operative inflammation and any other ocular inflammation associated with infection.
Ear: This combination is indicated in otitis externa, otitis media and chronic suppurative otitis media.
Ear: This combination is indicated in otitis externa, otitis media and chronic suppurative otitis media.
Therapeutic classView
Ophthalmic steroid - antibiotic combined preparations
PharmacologyView
Dexamethasone is a glucocorticoid. It has an anti-inflammatory and anti-allergic action. It is used topically in the treatment of inflammatory conditions of the anterior segment of the eye. Dexamethasone is absorbed rapidly after oral administration with a half-life of about 190 minutes. Sufficient absorption may occur after topical application to the skin and eye to produce systemic effects.
Chloramphenicol is a broad spectrum bacteriostatic antibiotic active against a wide variety of gram-negative and gram-positive organisms. Chloramphenicol exerts its antibacterial effect by binding to bacterial ribosomes and inhibiting bacterial protein synthesis at an early stage
Chloramphenicol is a broad spectrum bacteriostatic antibiotic active against a wide variety of gram-negative and gram-positive organisms. Chloramphenicol exerts its antibacterial effect by binding to bacterial ribosomes and inhibiting bacterial protein synthesis at an early stage
DosageView
Eye:
- Bacterial Conjunctivitis: The recommended dosage regimen for the treatment of bacterial conjunctivitis is 1 to 2 drops instilled into the conjunctival sac (s) every 2 hours for 2 days and 1 or 2 drops every 4 hours for the next 5(five days) while awake.
- Corneal Ulcers: The recommended dosage regimen for the treatment of comeal ulcer is 2 drops in the affected eye (s) every 15 minutes for the first 6 hours then 2 drops into the affected eye(s) every 30 minutes for the remainder of first day. On the second day, instill 2 drops in the affected eye (s) hourly. On the 3 to 14 days, place 2 drops in the affected eye (s) every 4 hours. Treatment may be continued after 14 days if corneal re-epithelialization has not occurred.
Side effectsView
Adverse reactions seen with Chloramphenicol are transient ocular burning or discomfort and other reported reactions include stinging, redness, itching, conjunctivitis, foreign body sensation, photophobia, blurred vision, dryness and eye pain. Allergic sensitization may occur with the local use of Chloramphenicol. Elevation of intraocular pressure with possible development of glaucoma, infrequent optic nerve damage and posterior subcapsular cataract formation.
ContraindicationsView
The combination is contraindicated in epithelial herpes simplex cornealis, fungal, viral, tuberculous and other infections of the eye and in glaucoma. Myelosuppression during previous exposure to Chloramphenicol. Hypersensitivity to Chloramphenicol & Dexamethasone Phosphate or to any other ingredients of the preparations.
PrecautionsView
The possibility of persistent fungal infections of the cornea should be considered after prolonged corticosteroid dosing. Prolonged use of steroids containing products may result in posterior subcapsular cataract formation and glaucoma with optic nerve damage. Intraocular pressure monitoring is needed. Prolonged use of antibiotics may result in the overgrowth of non-susceptible organisms, including fungi. If new infections appear during treatment, the drug should be discontinued and alternative therapy should be instituted.
InteractionsView
If Chloramphenicol is absorbed from eye when taking anticoagulants e.g. warfarin, there may be an increase in the effect of this medicine. Action of Chloramphenicol will be inhibited if given simultaneously with Phenobarbital. The therapeutic efficacy of Dexamethasone may be reduced with the concomitant administration of phenytoin, phenobarbitone, ephedrine and rifampicin.
Pregnancy & lactationView
There are no adequate and well-controlled studies in pregnant women. This drug should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Caution should be exercised when Chloramphenicol and Dexamethasone ophthalmic solution is administered to a nursing mother.
StorageView
Keep in a cool and dry place, away from light & keep out of the reach of children. Do not use after 30 days of first opening.
Nidipine SR
Nifedipine
Nidipine SR
Nifedipine
Indications
Stroke
Indication detailsView
Nifedipine is indicated in the management of all types of essential & renal hypertension. Also indicated in the management of hypertension during pregnancy & during coronary by pass surgery.
Nifedipine is also used for prophylaxis and the treatment of unstable & variant angina, myocardial infarction, and silent myocardial ischaemia. Moreover Nifedipine is also used in Raynaud's phenomenon & heart failure.
Nifedipine is also used for prophylaxis and the treatment of unstable & variant angina, myocardial infarction, and silent myocardial ischaemia. Moreover Nifedipine is also used in Raynaud's phenomenon & heart failure.
Therapeutic classView
Calcium-channel blockers
PharmacologyView
Nifedipine is an inhibitor of Calcium Channel Blocker that blocks the transmembrane influx of Calcium ions into muscle cells. Nifedipine has selective effects as a dilator of arterial vessels. Nifedipine dilates main coronary and systemic arteries. As a result blood pressure falls and this elicits a sympathetic reflex response causing tachycardia and an increased cardiac output. Pulmonary arterial pressure also falls. Nifedipine has direct negative inotropic effects on cardiac muscles and these effects are seen at higher doses than dose which causes arterial vasodilatation.
DosageView
Nifedipine 10 mg:
Patients with liver dysfunction should commence therapy with 10 mg twice daily with careful monitoring.
Patients with renal impairment do not require adjustment of dosage.
- Angina: Initially 10 mg 3 times daily with food increased to 20 mg 3 times daily if necessary, in elderly patients, initially 5 mg 3 times daily.
- Raynaud's Phenomenon: 10 mg 3 times daily; maximum 60 mg daily. In urgent cases, the tablet should be dissolved under the tongue like a sublingual tablet. The effect occurs within some minutes.
Patients with liver dysfunction should commence therapy with 10 mg twice daily with careful monitoring.
Patients with renal impairment do not require adjustment of dosage.
Side effectsView
Headache, flushing, lethargy, gravitational oedema rash, nausea, increased frequency of micturation, eye pain, gum hyperplasia, depression, tremor, photosensitivity and few cases of jaundice have been reported. These reactions may regress on discontinuation of therapy. Its introduction may induce attacks of ischaemic pain in some patients with angina pectoris.
ContraindicationsView
Cardiogenic shock, advanced aortic stenosis, nursing mothers, GI obstruction, inflammatory bowel disease, hypotension.
PrecautionsView
Tablets should be swallowed whole and should not be bitten, chewed or broken up. It should be used with caution in patient whose cardiac reserve is poor. Should be withdrawn if ischaemic pain occurs or existing pain worsens shortly after initiating treatment. Use in diabetic patients requires adjustment of their control. Since the absorption of the drug could be modified by renal disease, caution should be exercised in treating such patients.
InteractionsView
- ACE inhibitors: Enhanced hypotensive effect.
- Anti-arrythmics: Plasma concentration of quinidine is reduced.
- Anti-bacterials: Rifampicin possibly increases metabolism of Nifedipine.
- Anti-epileptics: Plasma concentration of phenytoin increases.
- Antipsychotics: Enhanced hypotensive effect.
- β-blockers: Occasionally severe hypotension and heart failure may occur.
- Cyclosporin: Plasma concentration of Nifedipine possibly increases.
- Muscle relaxants: Effect of muscle relaxants e.g. tubocurarine increases.
- Ulcer healing drugs: Metabolism of Nifedipine increases.
Pregnancy & lactationView
There are no adequate and well controlled studies in pregnant women. It should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
StorageView
Protect from strong light, store in a cool place in the original pack
Nidocard
Nitroglycerin (IV Infusion)
Nidocard
Nitroglycerin (IV Infusion)
Indications
Angina pectoris
Indication detailsView
Nitroglycerin Injection is indicated for the treatment of peri-operative hypertension; for controlling of congestive heart failure in the setting of acute myocardial infarction; for treatment of angina pectoris in patients who have not responded to sublingual nitroglycerin and beta blockers and for induction of Intraoperative hypotension.
Therapeutic classView
Nitrates: Coronary vasodilators
PharmacologyView
The principal pharmacological action of nitroglycerin is relaxation of vascular smooth muscle and consequent dilatation of peripheral arteries and veins. Dilatation of the veins promotes peripheral pooling of blood and decreases venous return to the heart, thereby reducing left ventricular end-diastolic pressure and pulmonary capillary wedge pressure (preload). Arteriolar relaxation reduces systemic vascular resistance,systolic arterial pressure, and mean arterial pressure (after load). Dilatation of the coronary arteries also occurs.
DosageView
Not for direct intravenous injection. Nitroglycerin injection is a concentrated, potent drug which must be diluted in dextrose (5%) injection or sodium chloride (0.9%) injection prior to its infusion. Nitroglycerin injection should not be mixed with other drugs.
Initial Dilution: Aseptically transfer the contents of one nitroglycerin ampoule (containing 50 mg of nitroglycerin) into a 500 ml glass bottle of either Dextrose (5%) Injection or Sodium Chloride Injection (0.9%).This yields a final concentration of 100 mcg/ml.
Maintenance Dilution: It is important to consider the fluid requirements of the patient as well as the expected duration of infusion in selecting the appropriate dilution of Nitroglycerin Injection. After the initial dosage titration, the concentration of the solution may be increased, if necessary, to limit fluids given to the patient. The nitroglycerin concentration should not exceed 400 mcg/ml.
Initial Dilution: Aseptically transfer the contents of one nitroglycerin ampoule (containing 50 mg of nitroglycerin) into a 500 ml glass bottle of either Dextrose (5%) Injection or Sodium Chloride Injection (0.9%).This yields a final concentration of 100 mcg/ml.
Maintenance Dilution: It is important to consider the fluid requirements of the patient as well as the expected duration of infusion in selecting the appropriate dilution of Nitroglycerin Injection. After the initial dosage titration, the concentration of the solution may be increased, if necessary, to limit fluids given to the patient. The nitroglycerin concentration should not exceed 400 mcg/ml.
Side effectsView
Adverse reactions to nitroglycerin are generally dose-related and almost all of these reactions are the result of nitroglycerin's activity as a vasodilator. Headache, which may be severe, is the most commonly reported side effect. Headache may be recurrent with each daily dose, especially at higher doses. Transient episodes of lightheadedness, occasionally related to blood pressure changes, may also occur. Hypotension occurs infrequently, but in some patients it may be severe enough to warrant discontinuation of therapy. Syncope, crescendo angina, and rebound hypertension have been reported but are uncommon. Extremely rarely, ordinary doses of organic nitrates have caused methemoglobinemia in normal-seeming patients. Methemoglobinemia is so infrequent at these doses that further discussion of its diagnosis and treatment is deferred.
ContraindicationsView
Allergic reactionsto organic nitrates are extremely rare,but they do occur. Nitroglycerin Injection is contraindicated in patients who are allergic to it. In patients with pericardial tamponade, restrictive cardiomyopathy, or constrictive pericarditis, cardiac output is dependent upon venousreturn. Intravenous nitroglycerin is contraindicated in patients with these conditions.
PrecautionsView
Severe hypotension and shock may occur with even small doses of nitroglycerin. This drug should therefore be used with caution in patients who may be volume depleted or who, for whatever reason, are already hypotensive. Hypotension induced by nitroglycerin may be accompanied by paradoxical bradycardia and increased angina pectoris. Nitrate therapy may aggravate the angina caused by hypertrophic cardiomyopathy. As tolerance to other forms of nitroglycerin develops,the effect of sublingual nitroglycerin on exercise tolerance, although still observable, is somewhat blunted. In industrial workers who have had long-term exposure to unknown (presumably high) doses of organic nitrates, tolerance clearly occurs. Chest pain, acute myocardial infarction, and even sudden death have occurred during temporary withdrawal of nitratesfrom these workers, demonstrating the existence of true physical dependence.
InteractionsView
The vasodilating effects of nitroglycerin may be additive with those of other vasodilators. Administration of nitroglycerin infusions through the same infusion set as blood can result in pseudoagglutination and hemolysis. More generally, nitroglycerin in 5% dextrose or sodium chloride 0.9% should not be mixed with any other medication of any kind. Intravenous nitroglycerin interferes, at least in some patients, with the anticoagulant effect of heparin. In patients receiving intravenous nitroglycerin, concomitant heparin therapy should be guided by frequent measurement of the activated partial thromboplastin time.
Pregnancy & lactationView
Pregnancy category C. It is not known whether nitroglycerin is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when nitroglycerin injection is administered to a nursing mother.
Pediatric usageView
Safety and effectiveness in children have not been established.
Overdose effectsView
Homodynamic Effects: The ill effects of nitroglycerin overdose are generally the results of nitroglycerin's capacity to induce vasodilatation, venous pooling, reduced cardiac output, and hypotension. These hemodynamic changes may have protean manifestations, including increased intracranial pressure, with any or all of persistent throbbing headache, confusion, and moderate fever; vertigo; palpitation; visual disturbances; nausea and vomiting (possibly with colic and even bloody diarrhea); syncope (especially in the upright posture); air hunger and dyspnea, later followed by reduced ventilatory effort; diaphoresis, with the skin either flushed or cold and clammy; heart block and bradycardia; paralysis; coma; seizures; and death.
StorageView
Keep below 30°C temperature, away from light & moisture. Keep out of the reach of children.
Nidocard
Nitroglycerin (Sublingual Spray)
Nidocard
Nitroglycerin (Sublingual Spray)
Indications
Angina pectoris
Indication detailsView
Nitroglycerin sublingual spray is indicated for acute relief of an attack or prophylaxis of angina pectoris due to coronary artery disease.
Therapeutic classView
Nitrates: Coronary vasodilators
PharmacologyView
The principal pharmacological action of nitroglycerin is relaxation of vascular smooth muscle, producing a vasodilator effect on both peripheral arteries and veins with more prominent effects on the latter. Dilation of the post-capillary vessels, including large veins, promotes peripheral pooling of blood and decreases venous return to the heart, thereby reducing left ventricular enddiastolic pressure (pre-load). Arteriolar relaxation reduces systemic vascular resistance and arterial pressure (after-load).
DosageView
At the onset of an attack, 1 or 2 metered sprays should be administered under the tongue. No more than 3 metered sprays are recommended within a 15 minute period. If the chest pain persists, prompt medical attention is recommended. Nitroglycerin spray may be used prophylactically 5 to 10 minutes prior to engaging in activities which might precipitate an acute attack.
Side effectsView
A number of nitrate related adverse effects may occur including headache, facial flushing, dizziness, nausea, vomiting, feelings of weakness, postural hypotension and reflex tachycardia .
ContraindicationsView
Hypersensitivity to nitrates or any constituents of the formulation. Hypotension, hypovolaemia, severe anaemia, cerebral haemorrhage and brain trauma, mitral stenosis and angina caused by hypertrophic obstructive cardiomyopathy. Concomitant administration of phosphodiesterase inhibitors used for the treatment of erectile dysfunction.
PrecautionsView
The use of Nitroglycerin during the early days of acute myocardial infarction requires particular attention to monitoring hemodynamics and clinical status. Nitroglycerin should be used with caution in patients with severely impaired renal or hepatic function, hypothyroidism, malnutrition or hypothermia.
InteractionsView
Use of alcohol with Nitroglycerin may produce severe hypotension and collapse. Oral Nitroglycerin may enhance the bioavailability of dihydroergotamine. Orthostatic hypotension may occur with the combined use of calcium channel blocker, phenothiazines and tricyclic antidepressants.
Pregnancy & lactationView
Pregnancy Category C. There are no adequate and well controlled studies in pregnant women. Nitroglycerin should be given to pregnant women only if clearly needed. It is not known whether nitroglycerin is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Nitroglycerin spray is administered to a nursing woman.
Pediatric usageView
Safety and effectiveness of nitroglycerin in pediatric patients have not been established.
Overdose effectsView
Nitrate overdosage may result in: severe hypotension, persistent throbbing headache, vertigo, palpitation, visual disturbance, flushing and perspiring skin (later becoming cold and cyanotic), nausea and vomiting (possibly with colic and even bloody diarrhea), syncope (especially in the upright posture), methemoglobinemia with cyanosis and anorexia, initial hyperpnea, dyspnea and slow breathing, slow pulse, heart block, increased intracranial pressure with cerebral symptoms of confusion and moderate fever, paralysis and coma followed by clonic convulsions and possibly death due to circulatory collapse.
Methemoglobinemia: Case reports of clinically significant methemoglobinemia are rare at conventional doses of organic nitrates. The formation of methemoglobin is dose-related and in the case of genetic abnormalities of hemoglobin that favor methemoglobin formation, even conventional doses of organic nitrates could produce harmful concentrations of methemoglobin.
Treatment of Overdosage: Keep the patient recumbent in a shock position and comfortably warm. Passive movement of the extremities may aid venous return. Administer oxygen and artificial ventilation, if necessary. If methemoglobinemia is present, administration of methylene blue (1% solution), 1-2 mg per kilogram of body weight intravenously, may be required. If an excessive quantity of Nitroglycerin spray has been recently swallowed, gastric lavage may be of use.
Methemoglobinemia: Case reports of clinically significant methemoglobinemia are rare at conventional doses of organic nitrates. The formation of methemoglobin is dose-related and in the case of genetic abnormalities of hemoglobin that favor methemoglobin formation, even conventional doses of organic nitrates could produce harmful concentrations of methemoglobin.
Treatment of Overdosage: Keep the patient recumbent in a shock position and comfortably warm. Passive movement of the extremities may aid venous return. Administer oxygen and artificial ventilation, if necessary. If methemoglobinemia is present, administration of methylene blue (1% solution), 1-2 mg per kilogram of body weight intravenously, may be required. If an excessive quantity of Nitroglycerin spray has been recently swallowed, gastric lavage may be of use.
StorageView
Store in a cool and dry place away from light and heat. Keep all medicines out of the reach of children.
Nidocard Retard
Nitroglycerin (Oral preparation)
Nidocard Retard
Nitroglycerin (Oral preparation)
Indications
Severe hypertension
Indication detailsView
Nitroglycerin is indicated for the prophylaxis of angina pectoris. The onset of action is not sufficiently rapid for this form to be useful in aborting an acute anginal episode.
Therapeutic classView
Nitrates: Coronary vasodilators
PharmacologyView
Nitroglycerin causes relaxation of vascular smooth muscle, producing a vasodilator effect on both peripheral arteries and veins. Dilation of veins promote peripheral pooling of blood and decreases venous return to the heart, thereby reducing left ventricular end-diastolic pressure (preload) and relaxation of arteries reduce systemic vascular resistance and arterial pressure (afterload).
DosageView
Dosage should always to be adjusted according to the requirement and response obtained by the individual patient and the severity of the anginal pain. For adults, one Nitroglycerin 2.6 mg sustained released tablet or capsule in morning and evening. This should be taken empty stomach.
Side effectsView
Headache may occur at the onset of treatment but will usually subside after a few days. If the headache persists dosage should be decreased. Other side effects include tachycardia, postural hypotension and syncope, cyanosis and methaemoglobinaemia.
ContraindicationsView
Nitroglycerin is contraindicated in patients with a known hypersensitivity to nitroglycerin, other organic nitrates, or nitrites or to the excipients of the medicine. It is also contraindicated in patients with acute myocardial infarction, marked anaemia, head trauma, cerebral haemorrhage, or closed angle glaucoma.
PrecautionsView
Nitroglycerin should be used with caution in patients who are predisposed to closed-angle glaucoma. As with other drugs for the treatment of angina pectoris, abrupt discontinuation of therapy may lead to exacerbation of symptoms. When discontinuing long term treatment, the dosage should be reduced gradually over several days, and the patient carefully monitored. The use of nitroglycerin during the early days of acute myocardial infarction requires particular attention to hemodynamic monitoring and clinical status to avoid the hazards of hypotension and tachycardia.
InteractionsView
Nitroglycerin dilates peripheral blood vessels and may increase the antihypertensive properties of vasodilators, calcium antagonists, beta-adrenergic blockers. Concomitant use of nitrates with tricyclic antidepressants and alcohol may cause high blood pressure. Concomitant use of nitrates with phosphodiesterase type 5 (PDE5) inhibitors, such as sildenafil, vardenafil and tadalafil cause fall in blood pressure. Aspirin decreases the clearance and enhances the hemodynamic effects of nitroglycerin. Nitroglycerin may reduce the pharmacologic effects of heparin when used concomitantly. Nitrates increase the bioavailability of dihydroergotamine.
Pregnancy & lactationView
Nitroglycerin should not be used during pregnancy or lactation unless considered essential by the physician.
StorageView
Store in a cool and dry place away from light and heat. Keep all medicines out of the reach of children.
Nidocard Retard
Nitroglycerin (Oral preparation)
Nidocard Retard
Nitroglycerin (Oral preparation)
Indications
Severe hypertension
Indication detailsView
Nitroglycerin is indicated for the prophylaxis of angina pectoris. The onset of action is not sufficiently rapid for this form to be useful in aborting an acute anginal episode.
Therapeutic classView
Nitrates: Coronary vasodilators
PharmacologyView
Nitroglycerin causes relaxation of vascular smooth muscle, producing a vasodilator effect on both peripheral arteries and veins. Dilation of veins promote peripheral pooling of blood and decreases venous return to the heart, thereby reducing left ventricular end-diastolic pressure (preload) and relaxation of arteries reduce systemic vascular resistance and arterial pressure (afterload).
DosageView
Dosage should always to be adjusted according to the requirement and response obtained by the individual patient and the severity of the anginal pain. For adults, one Nitroglycerin 2.6 mg sustained released tablet or capsule in morning and evening. This should be taken empty stomach.
Side effectsView
Headache may occur at the onset of treatment but will usually subside after a few days. If the headache persists dosage should be decreased. Other side effects include tachycardia, postural hypotension and syncope, cyanosis and methaemoglobinaemia.
ContraindicationsView
Nitroglycerin is contraindicated in patients with a known hypersensitivity to nitroglycerin, other organic nitrates, or nitrites or to the excipients of the medicine. It is also contraindicated in patients with acute myocardial infarction, marked anaemia, head trauma, cerebral haemorrhage, or closed angle glaucoma.
PrecautionsView
Nitroglycerin should be used with caution in patients who are predisposed to closed-angle glaucoma. As with other drugs for the treatment of angina pectoris, abrupt discontinuation of therapy may lead to exacerbation of symptoms. When discontinuing long term treatment, the dosage should be reduced gradually over several days, and the patient carefully monitored. The use of nitroglycerin during the early days of acute myocardial infarction requires particular attention to hemodynamic monitoring and clinical status to avoid the hazards of hypotension and tachycardia.
InteractionsView
Nitroglycerin dilates peripheral blood vessels and may increase the antihypertensive properties of vasodilators, calcium antagonists, beta-adrenergic blockers. Concomitant use of nitrates with tricyclic antidepressants and alcohol may cause high blood pressure. Concomitant use of nitrates with phosphodiesterase type 5 (PDE5) inhibitors, such as sildenafil, vardenafil and tadalafil cause fall in blood pressure. Aspirin decreases the clearance and enhances the hemodynamic effects of nitroglycerin. Nitroglycerin may reduce the pharmacologic effects of heparin when used concomitantly. Nitrates increase the bioavailability of dihydroergotamine.
Pregnancy & lactationView
Nitroglycerin should not be used during pregnancy or lactation unless considered essential by the physician.
StorageView
Store in a cool and dry place away from light and heat. Keep all medicines out of the reach of children.
Nidor
Nitazoxanide
Nidor
Nitazoxanide
Indications
Giardiasis
Indication detailsView
Nitazoxanide is indicated for the treatment of diarrhea caused by Cryptosporidium parvum, Giardia lamblia and Entamoeba histolytica.
Therapeutic classView
Anti-diarrhoeal Antiprotozoal
PharmacologyView
Nitazoxanide is a synthetic antiprotozoal agent for oral administration. The antiprotozoal activity of Nitazoxanide is believed to be interference with the Pyruvate Ferredoxin Oxido Reductase (PFOR) enzyme-dependant electron transfer reaction. This reaction is essential for anaerobic energy metabolism of the protozoa. Nitazoxanide and its metabolites, tizoxanid are active in vitro in inhibiting the growth of sporozoites and oocyst of Cryptosporidium parvum and trophozoites of Giardia lamblia.
DosageView
Age 1-3 years: 1 tea-spoonfull or 5 ml suspension every 12 hours for 3 days.
Age 4-11 years: 2 tea-spoonfulls or 10 ml suspension every 12 hours for 3 days.
Age 12 years or above: 5 tea-spoonfulls (25 ml) suspension or 1 tablet every 12 hours for 3 days.
It is recommended to be administered with food.
Age 4-11 years: 2 tea-spoonfulls or 10 ml suspension every 12 hours for 3 days.
Age 12 years or above: 5 tea-spoonfulls (25 ml) suspension or 1 tablet every 12 hours for 3 days.
It is recommended to be administered with food.
Side effectsView
The most frequent side effects, reported by Nitazoxanide are abdominal pain, vomiting and headache. These side effects are typically mild and transient in nature. Very rare side effects include- nausea, anorexia, flatulence, increased appetite, enlarged salivary glands, increased creatinine & SGPT level, pruritus, rhinitis, sweating, dizziness, discolored urine etc.
ContraindicationsView
It is contraindicated in patients with known hypersensitivity to Nitazoxanide or any components of the preparation.
PrecautionsView
Nitazoxanide must be administered with caution to patients with hepatic & biliary disease and to patients with renal disease.
InteractionsView
It is highly bound to plasma protein. Therefore, caution should be exercised when administering Nitazoxanide concurrently with other highly plasma protein-bound drugs with narrow therapeutic index.
Pregnancy & lactationView
US FDA pregnancy category of Nitazoxanide is B. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed. Nitazoxanide have been shown to be excreted in human milk. So, caution should be exercised when Nitazoxanide is administered during lactation.
StorageView
Keep in a dry place away from light and heat. Keep out of the reach of children.
Nidor
Nitazoxanide
Nidor
Nitazoxanide
Indications
Giardiasis
Indication detailsView
Nitazoxanide is indicated for the treatment of diarrhea caused by Cryptosporidium parvum, Giardia lamblia and Entamoeba histolytica.
Therapeutic classView
Anti-diarrhoeal Antiprotozoal
PharmacologyView
Nitazoxanide is a synthetic antiprotozoal agent for oral administration. The antiprotozoal activity of Nitazoxanide is believed to be interference with the Pyruvate Ferredoxin Oxido Reductase (PFOR) enzyme-dependant electron transfer reaction. This reaction is essential for anaerobic energy metabolism of the protozoa. Nitazoxanide and its metabolites, tizoxanid are active in vitro in inhibiting the growth of sporozoites and oocyst of Cryptosporidium parvum and trophozoites of Giardia lamblia.
DosageView
Age 1-3 years: 1 tea-spoonfull or 5 ml suspension every 12 hours for 3 days.
Age 4-11 years: 2 tea-spoonfulls or 10 ml suspension every 12 hours for 3 days.
Age 12 years or above: 5 tea-spoonfulls (25 ml) suspension or 1 tablet every 12 hours for 3 days.
It is recommended to be administered with food.
Age 4-11 years: 2 tea-spoonfulls or 10 ml suspension every 12 hours for 3 days.
Age 12 years or above: 5 tea-spoonfulls (25 ml) suspension or 1 tablet every 12 hours for 3 days.
It is recommended to be administered with food.
Side effectsView
The most frequent side effects, reported by Nitazoxanide are abdominal pain, vomiting and headache. These side effects are typically mild and transient in nature. Very rare side effects include- nausea, anorexia, flatulence, increased appetite, enlarged salivary glands, increased creatinine & SGPT level, pruritus, rhinitis, sweating, dizziness, discolored urine etc.
ContraindicationsView
It is contraindicated in patients with known hypersensitivity to Nitazoxanide or any components of the preparation.
PrecautionsView
Nitazoxanide must be administered with caution to patients with hepatic & biliary disease and to patients with renal disease.
InteractionsView
It is highly bound to plasma protein. Therefore, caution should be exercised when administering Nitazoxanide concurrently with other highly plasma protein-bound drugs with narrow therapeutic index.
Pregnancy & lactationView
US FDA pregnancy category of Nitazoxanide is B. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed. Nitazoxanide have been shown to be excreted in human milk. So, caution should be exercised when Nitazoxanide is administered during lactation.
StorageView
Keep in a dry place away from light and heat. Keep out of the reach of children.
Nidozox
Nitazoxanide
Nidozox
Nitazoxanide
Indications
Giardiasis
Indication detailsView
Nitazoxanide is indicated for the treatment of diarrhea caused by Cryptosporidium parvum, Giardia lamblia and Entamoeba histolytica.
Therapeutic classView
Anti-diarrhoeal Antiprotozoal
PharmacologyView
Nitazoxanide is a synthetic antiprotozoal agent for oral administration. The antiprotozoal activity of Nitazoxanide is believed to be interference with the Pyruvate Ferredoxin Oxido Reductase (PFOR) enzyme-dependant electron transfer reaction. This reaction is essential for anaerobic energy metabolism of the protozoa. Nitazoxanide and its metabolites, tizoxanid are active in vitro in inhibiting the growth of sporozoites and oocyst of Cryptosporidium parvum and trophozoites of Giardia lamblia.
DosageView
Age 1-3 years: 1 tea-spoonfull or 5 ml suspension every 12 hours for 3 days.
Age 4-11 years: 2 tea-spoonfulls or 10 ml suspension every 12 hours for 3 days.
Age 12 years or above: 5 tea-spoonfulls (25 ml) suspension or 1 tablet every 12 hours for 3 days.
It is recommended to be administered with food.
Age 4-11 years: 2 tea-spoonfulls or 10 ml suspension every 12 hours for 3 days.
Age 12 years or above: 5 tea-spoonfulls (25 ml) suspension or 1 tablet every 12 hours for 3 days.
It is recommended to be administered with food.
Side effectsView
The most frequent side effects, reported by Nitazoxanide are abdominal pain, vomiting and headache. These side effects are typically mild and transient in nature. Very rare side effects include- nausea, anorexia, flatulence, increased appetite, enlarged salivary glands, increased creatinine & SGPT level, pruritus, rhinitis, sweating, dizziness, discolored urine etc.
ContraindicationsView
It is contraindicated in patients with known hypersensitivity to Nitazoxanide or any components of the preparation.
PrecautionsView
Nitazoxanide must be administered with caution to patients with hepatic & biliary disease and to patients with renal disease.
InteractionsView
It is highly bound to plasma protein. Therefore, caution should be exercised when administering Nitazoxanide concurrently with other highly plasma protein-bound drugs with narrow therapeutic index.
Pregnancy & lactationView
US FDA pregnancy category of Nitazoxanide is B. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed. Nitazoxanide have been shown to be excreted in human milk. So, caution should be exercised when Nitazoxanide is administered during lactation.
StorageView
Keep in a dry place away from light and heat. Keep out of the reach of children.
Nidozox
Nitazoxanide
Nidozox
Nitazoxanide
Indications
Giardiasis
Indication detailsView
Nitazoxanide is indicated for the treatment of diarrhea caused by Cryptosporidium parvum, Giardia lamblia and Entamoeba histolytica.
Therapeutic classView
Anti-diarrhoeal Antiprotozoal
PharmacologyView
Nitazoxanide is a synthetic antiprotozoal agent for oral administration. The antiprotozoal activity of Nitazoxanide is believed to be interference with the Pyruvate Ferredoxin Oxido Reductase (PFOR) enzyme-dependant electron transfer reaction. This reaction is essential for anaerobic energy metabolism of the protozoa. Nitazoxanide and its metabolites, tizoxanid are active in vitro in inhibiting the growth of sporozoites and oocyst of Cryptosporidium parvum and trophozoites of Giardia lamblia.
DosageView
Age 1-3 years: 1 tea-spoonfull or 5 ml suspension every 12 hours for 3 days.
Age 4-11 years: 2 tea-spoonfulls or 10 ml suspension every 12 hours for 3 days.
Age 12 years or above: 5 tea-spoonfulls (25 ml) suspension or 1 tablet every 12 hours for 3 days.
It is recommended to be administered with food.
Age 4-11 years: 2 tea-spoonfulls or 10 ml suspension every 12 hours for 3 days.
Age 12 years or above: 5 tea-spoonfulls (25 ml) suspension or 1 tablet every 12 hours for 3 days.
It is recommended to be administered with food.
Side effectsView
The most frequent side effects, reported by Nitazoxanide are abdominal pain, vomiting and headache. These side effects are typically mild and transient in nature. Very rare side effects include- nausea, anorexia, flatulence, increased appetite, enlarged salivary glands, increased creatinine & SGPT level, pruritus, rhinitis, sweating, dizziness, discolored urine etc.
ContraindicationsView
It is contraindicated in patients with known hypersensitivity to Nitazoxanide or any components of the preparation.
PrecautionsView
Nitazoxanide must be administered with caution to patients with hepatic & biliary disease and to patients with renal disease.
InteractionsView
It is highly bound to plasma protein. Therefore, caution should be exercised when administering Nitazoxanide concurrently with other highly plasma protein-bound drugs with narrow therapeutic index.
Pregnancy & lactationView
US FDA pregnancy category of Nitazoxanide is B. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed. Nitazoxanide have been shown to be excreted in human milk. So, caution should be exercised when Nitazoxanide is administered during lactation.
StorageView
Keep in a dry place away from light and heat. Keep out of the reach of children.
Nifecap
Nifedipine
Nifecap
Nifedipine
Indications
Stroke
Indication detailsView
Nifedipine is indicated in the management of all types of essential & renal hypertension. Also indicated in the management of hypertension during pregnancy & during coronary by pass surgery.
Nifedipine is also used for prophylaxis and the treatment of unstable & variant angina, myocardial infarction, and silent myocardial ischaemia. Moreover Nifedipine is also used in Raynaud's phenomenon & heart failure.
Nifedipine is also used for prophylaxis and the treatment of unstable & variant angina, myocardial infarction, and silent myocardial ischaemia. Moreover Nifedipine is also used in Raynaud's phenomenon & heart failure.
Therapeutic classView
Calcium-channel blockers
PharmacologyView
Nifedipine is an inhibitor of Calcium Channel Blocker that blocks the transmembrane influx of Calcium ions into muscle cells. Nifedipine has selective effects as a dilator of arterial vessels. Nifedipine dilates main coronary and systemic arteries. As a result blood pressure falls and this elicits a sympathetic reflex response causing tachycardia and an increased cardiac output. Pulmonary arterial pressure also falls. Nifedipine has direct negative inotropic effects on cardiac muscles and these effects are seen at higher doses than dose which causes arterial vasodilatation.
DosageView
Nifedipine 10 mg:
Patients with liver dysfunction should commence therapy with 10 mg twice daily with careful monitoring.
Patients with renal impairment do not require adjustment of dosage.
- Angina: Initially 10 mg 3 times daily with food increased to 20 mg 3 times daily if necessary, in elderly patients, initially 5 mg 3 times daily.
- Raynaud's Phenomenon: 10 mg 3 times daily; maximum 60 mg daily. In urgent cases, the tablet should be dissolved under the tongue like a sublingual tablet. The effect occurs within some minutes.
Patients with liver dysfunction should commence therapy with 10 mg twice daily with careful monitoring.
Patients with renal impairment do not require adjustment of dosage.
Side effectsView
Headache, flushing, lethargy, gravitational oedema rash, nausea, increased frequency of micturation, eye pain, gum hyperplasia, depression, tremor, photosensitivity and few cases of jaundice have been reported. These reactions may regress on discontinuation of therapy. Its introduction may induce attacks of ischaemic pain in some patients with angina pectoris.
ContraindicationsView
Cardiogenic shock, advanced aortic stenosis, nursing mothers, GI obstruction, inflammatory bowel disease, hypotension.
PrecautionsView
Tablets should be swallowed whole and should not be bitten, chewed or broken up. It should be used with caution in patient whose cardiac reserve is poor. Should be withdrawn if ischaemic pain occurs or existing pain worsens shortly after initiating treatment. Use in diabetic patients requires adjustment of their control. Since the absorption of the drug could be modified by renal disease, caution should be exercised in treating such patients.
InteractionsView
- ACE inhibitors: Enhanced hypotensive effect.
- Anti-arrythmics: Plasma concentration of quinidine is reduced.
- Anti-bacterials: Rifampicin possibly increases metabolism of Nifedipine.
- Anti-epileptics: Plasma concentration of phenytoin increases.
- Antipsychotics: Enhanced hypotensive effect.
- β-blockers: Occasionally severe hypotension and heart failure may occur.
- Cyclosporin: Plasma concentration of Nifedipine possibly increases.
- Muscle relaxants: Effect of muscle relaxants e.g. tubocurarine increases.
- Ulcer healing drugs: Metabolism of Nifedipine increases.
Pregnancy & lactationView
There are no adequate and well controlled studies in pregnant women. It should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
StorageView
Protect from strong light, store in a cool place in the original pack
Nifev
Nintedanib
Nifev
Nintedanib
Indications
Idiopathic Pulmonary Fibrosis
Indication detailsView
- Nintedanib is indicated in adults for the treatment of Idiopathic Pulmonary Fibrosis (IPF).
- Nintedanib is indicated in adults for the treatment of chronic fibrosing interstitial lung diseases (ILDs) with a progressive phenotype.
- Nintedanib is indicated in adults for the treatment of systemic sclerosis-associated interstitial lung disease (SSc-ILD).
- Nintedanib is indicated in combination with docetaxel for the treatment of adult patients with locally advanced, metastatic or locally recurrent non-small cell lung cancer (NSCLC) of adenocarcinoma tumor histology after first-line chemotherapy.
Therapeutic classView
Tyrosine Kinase Inhibitor
PharmacologyView
Nintedanib is a small molecule, competitive, triple angiokinase inhibitor that targets multiple receptor tyrosine kinases (RTKs) and non-receptor tyrosine kinases (nRTKs). Many of these RTKs are implicated in lung fibrosis and tumour angiogenesis, so nintedanib is therefore used in the treatment of proliferative diseases such as idiopathic pulmonary fibrosis, non-small cell lung cancer, and systemic sclerosis-associated interstitial lung disease. The specific RTKs that nintedanib inhibits are platelet-derived growth factor (PDGFR) α and β, fibroblast growth factor receptor (FGFR) 1-3, vascular endothelial growth factor receptor (VEGFR), and Fns-Like tyrosine kinase-3 (FLT3). Nintedanib binds to the ATP-binding pocket of these receptors and inhibits their activity, thereby blocking signalling cascades that result in the proliferation and migration of lung fibroblasts. Nintedanib also inhibits kinase signalling pathways in various cells within tumour tissues, including endothelial cells, pericytes, smooth muscle cells, and cells contributing to angiogenesis, culminating in an inhibition of cell proliferation and apoptosis of affected tumour cells.
In addition to RTK inhibition, nintedanib also prevents the actions of the nRTKs Lck, Lyn, and Src. The contribution of the inhibition of Lck and Lyn towards the therapeutic efficacy of nintedanib is unclear, but inhibition of the Src pathway by nintedanib has been shown to reduce lung fibrosis.
In addition to RTK inhibition, nintedanib also prevents the actions of the nRTKs Lck, Lyn, and Src. The contribution of the inhibition of Lck and Lyn towards the therapeutic efficacy of nintedanib is unclear, but inhibition of the Src pathway by nintedanib has been shown to reduce lung fibrosis.
DosageView
Treatment with Nintedanib should be initiated by physicians experienced in the diagnosis and treatment of IPF.
Posology: The recommended dose is 150 mg Nintedanib twice daily administered approximately 12 hours apart. The 100 mg twice daily dose is only recommended to be used in patients who do not tolerate the 150 mg twice daily dose. If a dose is missed, administration should resume at the next scheduled time at the recommended dose. If a dose is missed the patient should not take an additional dose. The recommended maximum daily dose of 300 mg should not be exceeded.
For NSCLC:
Posology: The recommended dose is 150 mg Nintedanib twice daily administered approximately 12 hours apart. The 100 mg twice daily dose is only recommended to be used in patients who do not tolerate the 150 mg twice daily dose. If a dose is missed, administration should resume at the next scheduled time at the recommended dose. If a dose is missed the patient should not take an additional dose. The recommended maximum daily dose of 300 mg should not be exceeded.
For NSCLC:
- The recommended dose of nintedanib is 200 mg twice daily administered approximately 12 hours apart, on days 2 to 21 of a standard 21 day docetaxel treatment cycle.
- Nintedanib must not be taken on the same day of docetaxel chemotherapy administration (= day 1). If a dose of nintedanib is missed, administration should resume at the next scheduled time at the recommended dose. The individual daily doses of nintedanib should not be increased beyond the recommended dose to make up for missed doses. The recommended maximum daily dose of 400 mg should not be exceeded.
- Patients may continue therapy with nintedanib after discontinuation of docetaxel for as long as clinical benefit is observed or until unacceptable toxicity occurs.
- Dose adjustments: In addition to symptomatic treatment if applicable, the management of adverse reactions to Nintedanib could include dose reduction and temporary interruption until the specific adverse reaction has resolved to levels that allow continuation of therapy. Nintedanib treatment may be resumed at the full dose (150 mg twice daily) or a reduced dose (100 mg twice daily). If a patient does not tolerate 100 mg twice daily, treatment with Nintedanib should be discontinued.
- In case of interruptions due to aspartate aminotransferase (AST) or alanine aminotransferase (ALT) elevations > 3x upper limit of normal (ULN), once transaminases have returned to baseline values, treatment with Nintedanib may be reintroduced at a reduced dose (100 mg twice daily) which subsequently may be increased to the full dose (150 mg twice daily).
AdministrationView
Nintedanib is for oral use. The capsules should be taken with food, swallowed whole with water, and should not be chewed or crushed.
Side effectsView
Summary of the safety profile: Nintedanib has been studied in clinical trials of 1,529 patients suffering from IPF. The safety data provided in the following are based on the two Phase III, randomized, double-blind, placebo-controlled studies in 1,061 patients comparing treatment with Nintedanib 150 mg twice daily to placebo for 52 weeks (INPULSIS-1 and INPULSIS-2) and based on data observed during the post-marketing period.
The most frequently reported adverse reactions associated with the use of Nintedanib included diarrhea, nausea and vomiting, abdominal pain, decreased appetite, weight decreased and hepatic enzyme increased.
Tabulated list of adverse reactions: The below table provides a summary of the adverse reactions by MedDRA System Organ Class (SOC) and frequency category.
Below table summarizes the frequencies of adverse drug reactions (ADRs) that were reported in the Nintedanib group (638 patients) pooled from the two placebo-controlled Phase III clinical trials of 52 weeks duration or from the post-marketing period.
Frequency categories are defined using the following convention: Very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to < 1/100), rare (≥ 1/10,000 to < 1/1,000), very rare (< 1/10,000), not known (cannot be estimated from the available data).
The most frequently reported adverse reactions associated with the use of Nintedanib included diarrhea, nausea and vomiting, abdominal pain, decreased appetite, weight decreased and hepatic enzyme increased.
Tabulated list of adverse reactions: The below table provides a summary of the adverse reactions by MedDRA System Organ Class (SOC) and frequency category.
Below table summarizes the frequencies of adverse drug reactions (ADRs) that were reported in the Nintedanib group (638 patients) pooled from the two placebo-controlled Phase III clinical trials of 52 weeks duration or from the post-marketing period.
Frequency categories are defined using the following convention: Very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to < 1/100), rare (≥ 1/10,000 to < 1/1,000), very rare (< 1/10,000), not known (cannot be estimated from the available data).
ContraindicationsView
Hypersensitivity to Nintedanib, to peanut or soya, or to any of the excipients.
PrecautionsView
Diarrhoea: In the INPULSIS trials, diarrhoea was the most frequent gastro-intestinal adverse reaction reported in 62.4% versus 18.4% of patients treated with Nintedanib and placebo, respectively. In most patients the adverse reaction was of mild to moderate intensity and occurred within the first 3 months of treatment. Diarrhoea led to dose reduction in 10.7% of the patients and to discontinuation of Nintedanib in 4.4% of the patients in clinical trials. Serious cases of diarrhoea leading to dehydration and electrolyte disturbances have been reported in the post-marketing. Patients should be treated at first signs with adequate hydration and anti-diarrhoeal medicinal products, e.g. loperamide, and may require treatment interruption. Nintedanib treatment may be resumed at a reduced dose (100 mg twice daily) or at the full dose (150 mg twice daily). In case of persisting severe diarrhoea despite symptomatic treatment, therapy with Nintedanib should be discontinued.
Nausea and vomiting: Nausea and vomiting were frequently reported gastrointestinal adverse reactions. In most patients with nausea and vomiting, the event was of mild to moderate intensity. Nausea led to discontinuation of Nintedanib in 2.0% of patients. Vomiting led to discontinuation in 0.8% of the patients. If symptoms persist despite appropriate supportive care (including anti-emetic therapy), dose reduction or treatment interruption may be required. The treatment may be resumed at a reduced dose (100 mg twice daily) or at the full dose (150 mg twice daily). In case of persisting severe symptoms therapy with Nintedanib should be discontinued.
Hepatic function: The safety and efficacy of Nintedanib has not been studied in patients with moderate (Child Pugh B) or severe (Child Pugh C) hepatic impairment. Therefore, treatment with Nintedanib is not recommended in such patients. Based on increased exposure, the risk for adverse events may be increased in patients with mild hepatic impairment (Child Pugh A). Patients with mild hepatic impairment (Child Pugh A) should be treated with a reduced dose of Nintedanib. Cases of drug-induced liver injury have been observed with Nintedanib treatment, including severe liver injury with fatal outcome. The majority of hepatic events occur within the first three months of treatment. Therefore, hepatic transaminase and bilirubin levels should be investigated before treatment initiation and during the first month of treatment with Nintedanib. Patients should then be monitored at regular intervals during the subsequent two months of treatment and periodically thereafter, e.g. at each patient visit or as clinically indicated. Elevations of liver enzymes (ALT, AST, ALKP, gamma-glutamyl-transferase (GGT) and bilirubin were reversible upon dose reduction or interruption in the majority of cases. If transaminase (AST or ALT) elevations > 3x ULN are measured, dose reduction or interruption of the therapy with Nintedanib is recommended and the patient should be monitored closely. Once transaminases have returned to baseline values, treatment with Nintedanib may be resumed at the full dose (150 mg twice daily) or reintroduced at a reduced dose (100 mg twice daily) which subsequently may be increased to the full dose. If any liver test elevations are associated with clinical signs or symptoms of liver injury, e.g. jaundice, treatment with Nintedanib should be permanently discontinued. Alternative causes of the liver enzyme elevations should be investigated.
Patients with low body weight (<65 kg), Asian and female patients have a higher risk of elevations of liver enzymes. Nintedanib exposure increased linearly with patient age, which may also result in a higher risk of developing liver enzyme elevations. Close monitoring is recommended in patients with these risk factors.
Renal Function: Cases of renal impairment/failure, in some cases with fatal outcome, have been reported with Nintedanib use. Patients should be monitored during Nintedanib therapy, with particular attention to those patients exhibiting risk factors for renal impairment/failure. In case of renal impairment/failure, therapy adjustment should be considered.
Haemorrhage: Vascular endothelial growth factor receptor (VEGFR) inhibition might be associated with an increased risk of bleeding. In the INPULSIS trials with Nintedanib, the frequency of patients who experienced bleeding AEs was slightly higher in the Nintedanib arm (10.3%) than in the placebo arm (7.8%). Non-serious epistaxis was the most frequent bleeding event. Serious bleeding events occurred with low and similar frequencies in the 2 treatment groups (placebo: 1.4%; Nintedanib: 1.3%). Patients at known risk for bleeding including patients with inherited predisposition to bleeding or patients receiving a full dose of anti-coagulative treatment were not included in the INPULSIS studies. Non-serious and serious bleeding events, some of which were fatal, have been reported in the post-marketing period (including patients with or without anticoagulant therapy or other drugs that could cause bleeding). Therefore, these patients should only be treated with Nintedanib if the anticipated benefit outweighs the potential risk. Post-marketing bleeding events include but are not limited to gastrointestinal, respiratory and central nervous organ systems, with the most frequent being gastrointestinal.
Arterial thromboembolic events: Patients with a recent history of myocardial infarction or stroke were excluded from the INPULSIS trials. Arterial thromboembolic events were infrequently reported: in 0.7% of patients in the placebo and 2.5% in the Nintedanib treated group. While adverse events reflecting ischemic heart disease were balanced between the Nintedanib and placebo groups, a higher percentage of patients experienced myocardial infarctions in the Nintedanib group (1.6%) compared to the placebo group (0.5%). Caution should be used when treating patients at higher cardiovascular risk including known coronary artery disease. Treatment interruption should be considered in patients who develop signs or symptoms of acute myocardial ischemia.
Venous thromboembolism: In the INPULSIS trials no increased risk of venous thromboembolism was observed in Nintedanib treated patients. Due to the mechanism of action of Nintedanib patients might have an increased risk of thromboembolic events.
Gastrointestinal perforations: In the INPULSIS trials, the frequency of patients with perforation was very low in both treatment groups: 0% placebo, 0.3% Nintedanib (involving two patients). Due to the mechanism of action of Nintedanib patients might have an increased risk of gastrointestinal perforation. Cases of gastrointestinal perforations, some of which were fatal, have been reported in the post-marketing period. Particular caution should be exercised when treating patients with previous abdominal surgery, previous history of peptic ulceration, diverticular disease or receiving concomitant corticosteroids or NSAIDs. Nintedanib should only be initiated at least 4 weeks after abdominal surgery. Therapy with Nintedanib should be permanently discontinued in patients who develop gastrointestinal perforation.
Hypertension: Administration of Nintedanib may increase blood pressure. Systemic blood pressure should be measured periodically and as clinically indicated.
Wound healing complication: No increased frequency of impaired wound healing was observed in the INPULSIS trials. Based on the mechanism of action Nintedanib may impair wound healing. No dedicated studies investigating the effect of Nintedanib on wound healing were performed. Treatment with Nintedanib should therefore only be initiated or – in case of perioperative interruption – resumed based on clinical judgement of adequate wound healing.
Co-administration with Pirfenidone: In a dedicated pharmacokinetic study, concomitant treatment of Nintedanib with Pirfenidone was investigated in patients with IPF. Based on these results, there is no evidence of a relevant pharmacokinetic drug-drug interaction between Nintedanib and Pirfenidone when administered in combination. In view of the limited number of patients, this study detected only the most frequent adverse events and showed an increase in gastrointestinal adverse events and a trend toward increased hepatic adverse events. Given the similarity in safety profiles for both medicinal products, additive adverse events, including gastrointestinal and hepatic adverse events, may be expected. The benefit-risk balance of concomitant treatment with Pirfenidone has not been established.
Effect on QT interval: No evidence of QT prolongation was observed for Nintedanib in the clinical trial programme. As some other tyrosine kinase inhibitors are known to exert an effect on QT, caution should be exercised when administered Nintedanib in patients who may develop QTc prolongation.
Allergic reaction: Dietary soya products are known to cause allergic reactions including severe anaphylaxis in persons with soya allergy. Patients with known allergy to peanut protein carry an enhanced risk for severe reactions to soya preparations.
Nausea and vomiting: Nausea and vomiting were frequently reported gastrointestinal adverse reactions. In most patients with nausea and vomiting, the event was of mild to moderate intensity. Nausea led to discontinuation of Nintedanib in 2.0% of patients. Vomiting led to discontinuation in 0.8% of the patients. If symptoms persist despite appropriate supportive care (including anti-emetic therapy), dose reduction or treatment interruption may be required. The treatment may be resumed at a reduced dose (100 mg twice daily) or at the full dose (150 mg twice daily). In case of persisting severe symptoms therapy with Nintedanib should be discontinued.
Hepatic function: The safety and efficacy of Nintedanib has not been studied in patients with moderate (Child Pugh B) or severe (Child Pugh C) hepatic impairment. Therefore, treatment with Nintedanib is not recommended in such patients. Based on increased exposure, the risk for adverse events may be increased in patients with mild hepatic impairment (Child Pugh A). Patients with mild hepatic impairment (Child Pugh A) should be treated with a reduced dose of Nintedanib. Cases of drug-induced liver injury have been observed with Nintedanib treatment, including severe liver injury with fatal outcome. The majority of hepatic events occur within the first three months of treatment. Therefore, hepatic transaminase and bilirubin levels should be investigated before treatment initiation and during the first month of treatment with Nintedanib. Patients should then be monitored at regular intervals during the subsequent two months of treatment and periodically thereafter, e.g. at each patient visit or as clinically indicated. Elevations of liver enzymes (ALT, AST, ALKP, gamma-glutamyl-transferase (GGT) and bilirubin were reversible upon dose reduction or interruption in the majority of cases. If transaminase (AST or ALT) elevations > 3x ULN are measured, dose reduction or interruption of the therapy with Nintedanib is recommended and the patient should be monitored closely. Once transaminases have returned to baseline values, treatment with Nintedanib may be resumed at the full dose (150 mg twice daily) or reintroduced at a reduced dose (100 mg twice daily) which subsequently may be increased to the full dose. If any liver test elevations are associated with clinical signs or symptoms of liver injury, e.g. jaundice, treatment with Nintedanib should be permanently discontinued. Alternative causes of the liver enzyme elevations should be investigated.
Patients with low body weight (<65 kg), Asian and female patients have a higher risk of elevations of liver enzymes. Nintedanib exposure increased linearly with patient age, which may also result in a higher risk of developing liver enzyme elevations. Close monitoring is recommended in patients with these risk factors.
Renal Function: Cases of renal impairment/failure, in some cases with fatal outcome, have been reported with Nintedanib use. Patients should be monitored during Nintedanib therapy, with particular attention to those patients exhibiting risk factors for renal impairment/failure. In case of renal impairment/failure, therapy adjustment should be considered.
Haemorrhage: Vascular endothelial growth factor receptor (VEGFR) inhibition might be associated with an increased risk of bleeding. In the INPULSIS trials with Nintedanib, the frequency of patients who experienced bleeding AEs was slightly higher in the Nintedanib arm (10.3%) than in the placebo arm (7.8%). Non-serious epistaxis was the most frequent bleeding event. Serious bleeding events occurred with low and similar frequencies in the 2 treatment groups (placebo: 1.4%; Nintedanib: 1.3%). Patients at known risk for bleeding including patients with inherited predisposition to bleeding or patients receiving a full dose of anti-coagulative treatment were not included in the INPULSIS studies. Non-serious and serious bleeding events, some of which were fatal, have been reported in the post-marketing period (including patients with or without anticoagulant therapy or other drugs that could cause bleeding). Therefore, these patients should only be treated with Nintedanib if the anticipated benefit outweighs the potential risk. Post-marketing bleeding events include but are not limited to gastrointestinal, respiratory and central nervous organ systems, with the most frequent being gastrointestinal.
Arterial thromboembolic events: Patients with a recent history of myocardial infarction or stroke were excluded from the INPULSIS trials. Arterial thromboembolic events were infrequently reported: in 0.7% of patients in the placebo and 2.5% in the Nintedanib treated group. While adverse events reflecting ischemic heart disease were balanced between the Nintedanib and placebo groups, a higher percentage of patients experienced myocardial infarctions in the Nintedanib group (1.6%) compared to the placebo group (0.5%). Caution should be used when treating patients at higher cardiovascular risk including known coronary artery disease. Treatment interruption should be considered in patients who develop signs or symptoms of acute myocardial ischemia.
Venous thromboembolism: In the INPULSIS trials no increased risk of venous thromboembolism was observed in Nintedanib treated patients. Due to the mechanism of action of Nintedanib patients might have an increased risk of thromboembolic events.
Gastrointestinal perforations: In the INPULSIS trials, the frequency of patients with perforation was very low in both treatment groups: 0% placebo, 0.3% Nintedanib (involving two patients). Due to the mechanism of action of Nintedanib patients might have an increased risk of gastrointestinal perforation. Cases of gastrointestinal perforations, some of which were fatal, have been reported in the post-marketing period. Particular caution should be exercised when treating patients with previous abdominal surgery, previous history of peptic ulceration, diverticular disease or receiving concomitant corticosteroids or NSAIDs. Nintedanib should only be initiated at least 4 weeks after abdominal surgery. Therapy with Nintedanib should be permanently discontinued in patients who develop gastrointestinal perforation.
Hypertension: Administration of Nintedanib may increase blood pressure. Systemic blood pressure should be measured periodically and as clinically indicated.
Wound healing complication: No increased frequency of impaired wound healing was observed in the INPULSIS trials. Based on the mechanism of action Nintedanib may impair wound healing. No dedicated studies investigating the effect of Nintedanib on wound healing were performed. Treatment with Nintedanib should therefore only be initiated or – in case of perioperative interruption – resumed based on clinical judgement of adequate wound healing.
Co-administration with Pirfenidone: In a dedicated pharmacokinetic study, concomitant treatment of Nintedanib with Pirfenidone was investigated in patients with IPF. Based on these results, there is no evidence of a relevant pharmacokinetic drug-drug interaction between Nintedanib and Pirfenidone when administered in combination. In view of the limited number of patients, this study detected only the most frequent adverse events and showed an increase in gastrointestinal adverse events and a trend toward increased hepatic adverse events. Given the similarity in safety profiles for both medicinal products, additive adverse events, including gastrointestinal and hepatic adverse events, may be expected. The benefit-risk balance of concomitant treatment with Pirfenidone has not been established.
Effect on QT interval: No evidence of QT prolongation was observed for Nintedanib in the clinical trial programme. As some other tyrosine kinase inhibitors are known to exert an effect on QT, caution should be exercised when administered Nintedanib in patients who may develop QTc prolongation.
Allergic reaction: Dietary soya products are known to cause allergic reactions including severe anaphylaxis in persons with soya allergy. Patients with known allergy to peanut protein carry an enhanced risk for severe reactions to soya preparations.
InteractionsView
P-glycoprotein (P-gp): Nintedanib is a substrate of P-gp. Co-administration with the potent P-gp inhibitor ketoconazole increased exposure to Nintedanib 1.61-fold based on AUC and 1.83-fold based on Cmax in a dedicated drug-drug interaction study. In a drug-drug interaction study with the potent P-gp inducer rifampicin, exposure to Nintedanib decreased to 50.3% based on AUC and to 60.3% based on Cmax upon co-administration with rifampicin compared to administration of Nintedanib alone. If co-administered with Nintedanib, potent P-gp inhibitors (e.g. ketoconazole, erythromycin or cyclosporine) may increase exposure to Nintedanib. In such cases, patients should be monitored closely for tolerability of Nintedanib. Management of side effects may require interruption, dose reduction, or discontinuation of therapy with Nintedanib. Potent P-gp inducers (e.g. rifampicin, carbamazepine, phenytoin, and St. John’s Wort) may decrease exposure to Nintedanib. Selection of an alternate concomitant medicinal product with no or minimal P-gp induction potential should be considered.
Cytochrome (CYP)-enzymes: Only a minor extent of the biotransformation of Nintedanib consisted of CYP pathways. Nintedanib and its metabolites, the free acid moiety BIBF 1202 and its glucuronide BIBF 1202 glucuronide, did not inhibit or induce CYP enzymes in preclinical studies. The likelihood of drug-drug interactions with Nintedanib based on CYP metabolism is therefore considered to be low.
Co-administration with other medicinal products: The potential for interactions of Nintedanib with hormonal contraceptives was not explored.
Cytochrome (CYP)-enzymes: Only a minor extent of the biotransformation of Nintedanib consisted of CYP pathways. Nintedanib and its metabolites, the free acid moiety BIBF 1202 and its glucuronide BIBF 1202 glucuronide, did not inhibit or induce CYP enzymes in preclinical studies. The likelihood of drug-drug interactions with Nintedanib based on CYP metabolism is therefore considered to be low.
Co-administration with other medicinal products: The potential for interactions of Nintedanib with hormonal contraceptives was not explored.
Pregnancy & lactationView
Women of childbearing potential/Contraception: Nintedanib may cause foetalharm in humans. Women of childbearing potential should be advised to avoid becoming pregnant while receiving treatment with Nintedanib. They should be advised to use adequate contraception during and at least 3 months after the last dose of Nintedanib. Since the effect of Nintedanib on the metabolism and efficacy of hormonal contraceptives has not been investigated, barrier methods should be applied as a second form of contraception, to avoid pregnancy.
Pregnancy: There is no information on the use of Nintedanib in pregnant women, but pre-clinical studies in animals have shown reproductive toxicity of this active substance. As Nintedanib may cause foetal harm also in humans, it must not be used during pregnancy. Female patients should be advised to notify their doctor or pharmacist if they become pregnant during therapy with Nintedanib. If the patient becomes pregnant while receiving Nintedanib, she should be apprised of the potential hazard to the foetus. Termination of the treatment with Nintedanib should be considered.
Lactation: There is no information on the excretion of Nintedanib and its metabolites in human milk. Pre-clinical studies showed that small amounts of Nintedanib and its metabolites (≤ 0.5% of the administered dose) were secreted into milk of lactating rats. A risk to the newborns/infants cannot be excluded. Breast-feeding should be discontinued during treatment with Nintedanib.
Fertility: Based on preclinical investigations there is no evidence for impairment of male fertility. From subchronic and chronic toxicity studies, there is no evidence that female fertility in rats is impaired at a systemic exposure level comparable with that at the maximum recommended human dose (MRHD) of 150 mg twice daily.
Pregnancy: There is no information on the use of Nintedanib in pregnant women, but pre-clinical studies in animals have shown reproductive toxicity of this active substance. As Nintedanib may cause foetal harm also in humans, it must not be used during pregnancy. Female patients should be advised to notify their doctor or pharmacist if they become pregnant during therapy with Nintedanib. If the patient becomes pregnant while receiving Nintedanib, she should be apprised of the potential hazard to the foetus. Termination of the treatment with Nintedanib should be considered.
Lactation: There is no information on the excretion of Nintedanib and its metabolites in human milk. Pre-clinical studies showed that small amounts of Nintedanib and its metabolites (≤ 0.5% of the administered dose) were secreted into milk of lactating rats. A risk to the newborns/infants cannot be excluded. Breast-feeding should be discontinued during treatment with Nintedanib.
Fertility: Based on preclinical investigations there is no evidence for impairment of male fertility. From subchronic and chronic toxicity studies, there is no evidence that female fertility in rats is impaired at a systemic exposure level comparable with that at the maximum recommended human dose (MRHD) of 150 mg twice daily.
Pediatric usageView
Elderly patients (≥65 years): No overall differences in safety and efficacy were observed for elderly patients. No a-priori dose adjustment is required on the basis of a patient’s age. Patients ≥75 years may be more likely to require dose reduction to manage adverse effects.
Renal impairment: Less than 1% of a single dose of Nintedanib is excreted via the kidney. Adjustment of the starting dose in patients with mild to moderate renal impairment is not required. The safety, efficacy, and pharmacokinetics of Nintedanib have not been studied in patients with severe renal impairment (<30 ml/min creatinine clearance).
Hepatic impairment: Nintedanib is predominantly eliminated via biliary/faecal excretion (> 90%). Exposure increased in patients with hepatic impairment (Child Pugh A, Child Pugh B). In patients with mild hepatic impairment (Child Pugh A), the recommended dose of Nintedanib is 100 mg twice daily approximately 12 hours apart. In patients with mild hepatic impairment (Child Pugh A), treatment interruption or discontinuation for management of adverse reactions should be considered. The safety and efficacy of Nintedanib have not been investigated in patients with hepatic impairment classified as Child Pugh B and C. Treatment of patients with moderate (Child Pugh B) and severe (Child Pugh C) hepatic impairment with Nintedanib is not recommended.
Paediatric population: The safety and efficacy of Nintedanib in children aged 0-18 years have not been established. No data are available.
Renal impairment: Less than 1% of a single dose of Nintedanib is excreted via the kidney. Adjustment of the starting dose in patients with mild to moderate renal impairment is not required. The safety, efficacy, and pharmacokinetics of Nintedanib have not been studied in patients with severe renal impairment (<30 ml/min creatinine clearance).
Hepatic impairment: Nintedanib is predominantly eliminated via biliary/faecal excretion (> 90%). Exposure increased in patients with hepatic impairment (Child Pugh A, Child Pugh B). In patients with mild hepatic impairment (Child Pugh A), the recommended dose of Nintedanib is 100 mg twice daily approximately 12 hours apart. In patients with mild hepatic impairment (Child Pugh A), treatment interruption or discontinuation for management of adverse reactions should be considered. The safety and efficacy of Nintedanib have not been investigated in patients with hepatic impairment classified as Child Pugh B and C. Treatment of patients with moderate (Child Pugh B) and severe (Child Pugh C) hepatic impairment with Nintedanib is not recommended.
Paediatric population: The safety and efficacy of Nintedanib in children aged 0-18 years have not been established. No data are available.
StorageView
Store in a cool and dry place, protected from light. Do not store above 25°C.
Nifev
Nintedanib
Nifev
Nintedanib
Indications
Idiopathic Pulmonary Fibrosis
Indication detailsView
- Nintedanib is indicated in adults for the treatment of Idiopathic Pulmonary Fibrosis (IPF).
- Nintedanib is indicated in adults for the treatment of chronic fibrosing interstitial lung diseases (ILDs) with a progressive phenotype.
- Nintedanib is indicated in adults for the treatment of systemic sclerosis-associated interstitial lung disease (SSc-ILD).
- Nintedanib is indicated in combination with docetaxel for the treatment of adult patients with locally advanced, metastatic or locally recurrent non-small cell lung cancer (NSCLC) of adenocarcinoma tumor histology after first-line chemotherapy.
Therapeutic classView
Tyrosine Kinase Inhibitor
PharmacologyView
Nintedanib is a small molecule, competitive, triple angiokinase inhibitor that targets multiple receptor tyrosine kinases (RTKs) and non-receptor tyrosine kinases (nRTKs). Many of these RTKs are implicated in lung fibrosis and tumour angiogenesis, so nintedanib is therefore used in the treatment of proliferative diseases such as idiopathic pulmonary fibrosis, non-small cell lung cancer, and systemic sclerosis-associated interstitial lung disease. The specific RTKs that nintedanib inhibits are platelet-derived growth factor (PDGFR) α and β, fibroblast growth factor receptor (FGFR) 1-3, vascular endothelial growth factor receptor (VEGFR), and Fns-Like tyrosine kinase-3 (FLT3). Nintedanib binds to the ATP-binding pocket of these receptors and inhibits their activity, thereby blocking signalling cascades that result in the proliferation and migration of lung fibroblasts. Nintedanib also inhibits kinase signalling pathways in various cells within tumour tissues, including endothelial cells, pericytes, smooth muscle cells, and cells contributing to angiogenesis, culminating in an inhibition of cell proliferation and apoptosis of affected tumour cells.
In addition to RTK inhibition, nintedanib also prevents the actions of the nRTKs Lck, Lyn, and Src. The contribution of the inhibition of Lck and Lyn towards the therapeutic efficacy of nintedanib is unclear, but inhibition of the Src pathway by nintedanib has been shown to reduce lung fibrosis.
In addition to RTK inhibition, nintedanib also prevents the actions of the nRTKs Lck, Lyn, and Src. The contribution of the inhibition of Lck and Lyn towards the therapeutic efficacy of nintedanib is unclear, but inhibition of the Src pathway by nintedanib has been shown to reduce lung fibrosis.
DosageView
Treatment with Nintedanib should be initiated by physicians experienced in the diagnosis and treatment of IPF.
Posology: The recommended dose is 150 mg Nintedanib twice daily administered approximately 12 hours apart. The 100 mg twice daily dose is only recommended to be used in patients who do not tolerate the 150 mg twice daily dose. If a dose is missed, administration should resume at the next scheduled time at the recommended dose. If a dose is missed the patient should not take an additional dose. The recommended maximum daily dose of 300 mg should not be exceeded.
For NSCLC:
Posology: The recommended dose is 150 mg Nintedanib twice daily administered approximately 12 hours apart. The 100 mg twice daily dose is only recommended to be used in patients who do not tolerate the 150 mg twice daily dose. If a dose is missed, administration should resume at the next scheduled time at the recommended dose. If a dose is missed the patient should not take an additional dose. The recommended maximum daily dose of 300 mg should not be exceeded.
For NSCLC:
- The recommended dose of nintedanib is 200 mg twice daily administered approximately 12 hours apart, on days 2 to 21 of a standard 21 day docetaxel treatment cycle.
- Nintedanib must not be taken on the same day of docetaxel chemotherapy administration (= day 1). If a dose of nintedanib is missed, administration should resume at the next scheduled time at the recommended dose. The individual daily doses of nintedanib should not be increased beyond the recommended dose to make up for missed doses. The recommended maximum daily dose of 400 mg should not be exceeded.
- Patients may continue therapy with nintedanib after discontinuation of docetaxel for as long as clinical benefit is observed or until unacceptable toxicity occurs.
- Dose adjustments: In addition to symptomatic treatment if applicable, the management of adverse reactions to Nintedanib could include dose reduction and temporary interruption until the specific adverse reaction has resolved to levels that allow continuation of therapy. Nintedanib treatment may be resumed at the full dose (150 mg twice daily) or a reduced dose (100 mg twice daily). If a patient does not tolerate 100 mg twice daily, treatment with Nintedanib should be discontinued.
- In case of interruptions due to aspartate aminotransferase (AST) or alanine aminotransferase (ALT) elevations > 3x upper limit of normal (ULN), once transaminases have returned to baseline values, treatment with Nintedanib may be reintroduced at a reduced dose (100 mg twice daily) which subsequently may be increased to the full dose (150 mg twice daily).
AdministrationView
Nintedanib is for oral use. The capsules should be taken with food, swallowed whole with water, and should not be chewed or crushed.
Side effectsView
Summary of the safety profile: Nintedanib has been studied in clinical trials of 1,529 patients suffering from IPF. The safety data provided in the following are based on the two Phase III, randomized, double-blind, placebo-controlled studies in 1,061 patients comparing treatment with Nintedanib 150 mg twice daily to placebo for 52 weeks (INPULSIS-1 and INPULSIS-2) and based on data observed during the post-marketing period.
The most frequently reported adverse reactions associated with the use of Nintedanib included diarrhea, nausea and vomiting, abdominal pain, decreased appetite, weight decreased and hepatic enzyme increased.
Tabulated list of adverse reactions: The below table provides a summary of the adverse reactions by MedDRA System Organ Class (SOC) and frequency category.
Below table summarizes the frequencies of adverse drug reactions (ADRs) that were reported in the Nintedanib group (638 patients) pooled from the two placebo-controlled Phase III clinical trials of 52 weeks duration or from the post-marketing period.
Frequency categories are defined using the following convention: Very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to < 1/100), rare (≥ 1/10,000 to < 1/1,000), very rare (< 1/10,000), not known (cannot be estimated from the available data).
The most frequently reported adverse reactions associated with the use of Nintedanib included diarrhea, nausea and vomiting, abdominal pain, decreased appetite, weight decreased and hepatic enzyme increased.
Tabulated list of adverse reactions: The below table provides a summary of the adverse reactions by MedDRA System Organ Class (SOC) and frequency category.
Below table summarizes the frequencies of adverse drug reactions (ADRs) that were reported in the Nintedanib group (638 patients) pooled from the two placebo-controlled Phase III clinical trials of 52 weeks duration or from the post-marketing period.
Frequency categories are defined using the following convention: Very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to < 1/100), rare (≥ 1/10,000 to < 1/1,000), very rare (< 1/10,000), not known (cannot be estimated from the available data).
ContraindicationsView
Hypersensitivity to Nintedanib, to peanut or soya, or to any of the excipients.
PrecautionsView
Diarrhoea: In the INPULSIS trials, diarrhoea was the most frequent gastro-intestinal adverse reaction reported in 62.4% versus 18.4% of patients treated with Nintedanib and placebo, respectively. In most patients the adverse reaction was of mild to moderate intensity and occurred within the first 3 months of treatment. Diarrhoea led to dose reduction in 10.7% of the patients and to discontinuation of Nintedanib in 4.4% of the patients in clinical trials. Serious cases of diarrhoea leading to dehydration and electrolyte disturbances have been reported in the post-marketing. Patients should be treated at first signs with adequate hydration and anti-diarrhoeal medicinal products, e.g. loperamide, and may require treatment interruption. Nintedanib treatment may be resumed at a reduced dose (100 mg twice daily) or at the full dose (150 mg twice daily). In case of persisting severe diarrhoea despite symptomatic treatment, therapy with Nintedanib should be discontinued.
Nausea and vomiting: Nausea and vomiting were frequently reported gastrointestinal adverse reactions. In most patients with nausea and vomiting, the event was of mild to moderate intensity. Nausea led to discontinuation of Nintedanib in 2.0% of patients. Vomiting led to discontinuation in 0.8% of the patients. If symptoms persist despite appropriate supportive care (including anti-emetic therapy), dose reduction or treatment interruption may be required. The treatment may be resumed at a reduced dose (100 mg twice daily) or at the full dose (150 mg twice daily). In case of persisting severe symptoms therapy with Nintedanib should be discontinued.
Hepatic function: The safety and efficacy of Nintedanib has not been studied in patients with moderate (Child Pugh B) or severe (Child Pugh C) hepatic impairment. Therefore, treatment with Nintedanib is not recommended in such patients. Based on increased exposure, the risk for adverse events may be increased in patients with mild hepatic impairment (Child Pugh A). Patients with mild hepatic impairment (Child Pugh A) should be treated with a reduced dose of Nintedanib. Cases of drug-induced liver injury have been observed with Nintedanib treatment, including severe liver injury with fatal outcome. The majority of hepatic events occur within the first three months of treatment. Therefore, hepatic transaminase and bilirubin levels should be investigated before treatment initiation and during the first month of treatment with Nintedanib. Patients should then be monitored at regular intervals during the subsequent two months of treatment and periodically thereafter, e.g. at each patient visit or as clinically indicated. Elevations of liver enzymes (ALT, AST, ALKP, gamma-glutamyl-transferase (GGT) and bilirubin were reversible upon dose reduction or interruption in the majority of cases. If transaminase (AST or ALT) elevations > 3x ULN are measured, dose reduction or interruption of the therapy with Nintedanib is recommended and the patient should be monitored closely. Once transaminases have returned to baseline values, treatment with Nintedanib may be resumed at the full dose (150 mg twice daily) or reintroduced at a reduced dose (100 mg twice daily) which subsequently may be increased to the full dose. If any liver test elevations are associated with clinical signs or symptoms of liver injury, e.g. jaundice, treatment with Nintedanib should be permanently discontinued. Alternative causes of the liver enzyme elevations should be investigated.
Patients with low body weight (<65 kg), Asian and female patients have a higher risk of elevations of liver enzymes. Nintedanib exposure increased linearly with patient age, which may also result in a higher risk of developing liver enzyme elevations. Close monitoring is recommended in patients with these risk factors.
Renal Function: Cases of renal impairment/failure, in some cases with fatal outcome, have been reported with Nintedanib use. Patients should be monitored during Nintedanib therapy, with particular attention to those patients exhibiting risk factors for renal impairment/failure. In case of renal impairment/failure, therapy adjustment should be considered.
Haemorrhage: Vascular endothelial growth factor receptor (VEGFR) inhibition might be associated with an increased risk of bleeding. In the INPULSIS trials with Nintedanib, the frequency of patients who experienced bleeding AEs was slightly higher in the Nintedanib arm (10.3%) than in the placebo arm (7.8%). Non-serious epistaxis was the most frequent bleeding event. Serious bleeding events occurred with low and similar frequencies in the 2 treatment groups (placebo: 1.4%; Nintedanib: 1.3%). Patients at known risk for bleeding including patients with inherited predisposition to bleeding or patients receiving a full dose of anti-coagulative treatment were not included in the INPULSIS studies. Non-serious and serious bleeding events, some of which were fatal, have been reported in the post-marketing period (including patients with or without anticoagulant therapy or other drugs that could cause bleeding). Therefore, these patients should only be treated with Nintedanib if the anticipated benefit outweighs the potential risk. Post-marketing bleeding events include but are not limited to gastrointestinal, respiratory and central nervous organ systems, with the most frequent being gastrointestinal.
Arterial thromboembolic events: Patients with a recent history of myocardial infarction or stroke were excluded from the INPULSIS trials. Arterial thromboembolic events were infrequently reported: in 0.7% of patients in the placebo and 2.5% in the Nintedanib treated group. While adverse events reflecting ischemic heart disease were balanced between the Nintedanib and placebo groups, a higher percentage of patients experienced myocardial infarctions in the Nintedanib group (1.6%) compared to the placebo group (0.5%). Caution should be used when treating patients at higher cardiovascular risk including known coronary artery disease. Treatment interruption should be considered in patients who develop signs or symptoms of acute myocardial ischemia.
Venous thromboembolism: In the INPULSIS trials no increased risk of venous thromboembolism was observed in Nintedanib treated patients. Due to the mechanism of action of Nintedanib patients might have an increased risk of thromboembolic events.
Gastrointestinal perforations: In the INPULSIS trials, the frequency of patients with perforation was very low in both treatment groups: 0% placebo, 0.3% Nintedanib (involving two patients). Due to the mechanism of action of Nintedanib patients might have an increased risk of gastrointestinal perforation. Cases of gastrointestinal perforations, some of which were fatal, have been reported in the post-marketing period. Particular caution should be exercised when treating patients with previous abdominal surgery, previous history of peptic ulceration, diverticular disease or receiving concomitant corticosteroids or NSAIDs. Nintedanib should only be initiated at least 4 weeks after abdominal surgery. Therapy with Nintedanib should be permanently discontinued in patients who develop gastrointestinal perforation.
Hypertension: Administration of Nintedanib may increase blood pressure. Systemic blood pressure should be measured periodically and as clinically indicated.
Wound healing complication: No increased frequency of impaired wound healing was observed in the INPULSIS trials. Based on the mechanism of action Nintedanib may impair wound healing. No dedicated studies investigating the effect of Nintedanib on wound healing were performed. Treatment with Nintedanib should therefore only be initiated or – in case of perioperative interruption – resumed based on clinical judgement of adequate wound healing.
Co-administration with Pirfenidone: In a dedicated pharmacokinetic study, concomitant treatment of Nintedanib with Pirfenidone was investigated in patients with IPF. Based on these results, there is no evidence of a relevant pharmacokinetic drug-drug interaction between Nintedanib and Pirfenidone when administered in combination. In view of the limited number of patients, this study detected only the most frequent adverse events and showed an increase in gastrointestinal adverse events and a trend toward increased hepatic adverse events. Given the similarity in safety profiles for both medicinal products, additive adverse events, including gastrointestinal and hepatic adverse events, may be expected. The benefit-risk balance of concomitant treatment with Pirfenidone has not been established.
Effect on QT interval: No evidence of QT prolongation was observed for Nintedanib in the clinical trial programme. As some other tyrosine kinase inhibitors are known to exert an effect on QT, caution should be exercised when administered Nintedanib in patients who may develop QTc prolongation.
Allergic reaction: Dietary soya products are known to cause allergic reactions including severe anaphylaxis in persons with soya allergy. Patients with known allergy to peanut protein carry an enhanced risk for severe reactions to soya preparations.
Nausea and vomiting: Nausea and vomiting were frequently reported gastrointestinal adverse reactions. In most patients with nausea and vomiting, the event was of mild to moderate intensity. Nausea led to discontinuation of Nintedanib in 2.0% of patients. Vomiting led to discontinuation in 0.8% of the patients. If symptoms persist despite appropriate supportive care (including anti-emetic therapy), dose reduction or treatment interruption may be required. The treatment may be resumed at a reduced dose (100 mg twice daily) or at the full dose (150 mg twice daily). In case of persisting severe symptoms therapy with Nintedanib should be discontinued.
Hepatic function: The safety and efficacy of Nintedanib has not been studied in patients with moderate (Child Pugh B) or severe (Child Pugh C) hepatic impairment. Therefore, treatment with Nintedanib is not recommended in such patients. Based on increased exposure, the risk for adverse events may be increased in patients with mild hepatic impairment (Child Pugh A). Patients with mild hepatic impairment (Child Pugh A) should be treated with a reduced dose of Nintedanib. Cases of drug-induced liver injury have been observed with Nintedanib treatment, including severe liver injury with fatal outcome. The majority of hepatic events occur within the first three months of treatment. Therefore, hepatic transaminase and bilirubin levels should be investigated before treatment initiation and during the first month of treatment with Nintedanib. Patients should then be monitored at regular intervals during the subsequent two months of treatment and periodically thereafter, e.g. at each patient visit or as clinically indicated. Elevations of liver enzymes (ALT, AST, ALKP, gamma-glutamyl-transferase (GGT) and bilirubin were reversible upon dose reduction or interruption in the majority of cases. If transaminase (AST or ALT) elevations > 3x ULN are measured, dose reduction or interruption of the therapy with Nintedanib is recommended and the patient should be monitored closely. Once transaminases have returned to baseline values, treatment with Nintedanib may be resumed at the full dose (150 mg twice daily) or reintroduced at a reduced dose (100 mg twice daily) which subsequently may be increased to the full dose. If any liver test elevations are associated with clinical signs or symptoms of liver injury, e.g. jaundice, treatment with Nintedanib should be permanently discontinued. Alternative causes of the liver enzyme elevations should be investigated.
Patients with low body weight (<65 kg), Asian and female patients have a higher risk of elevations of liver enzymes. Nintedanib exposure increased linearly with patient age, which may also result in a higher risk of developing liver enzyme elevations. Close monitoring is recommended in patients with these risk factors.
Renal Function: Cases of renal impairment/failure, in some cases with fatal outcome, have been reported with Nintedanib use. Patients should be monitored during Nintedanib therapy, with particular attention to those patients exhibiting risk factors for renal impairment/failure. In case of renal impairment/failure, therapy adjustment should be considered.
Haemorrhage: Vascular endothelial growth factor receptor (VEGFR) inhibition might be associated with an increased risk of bleeding. In the INPULSIS trials with Nintedanib, the frequency of patients who experienced bleeding AEs was slightly higher in the Nintedanib arm (10.3%) than in the placebo arm (7.8%). Non-serious epistaxis was the most frequent bleeding event. Serious bleeding events occurred with low and similar frequencies in the 2 treatment groups (placebo: 1.4%; Nintedanib: 1.3%). Patients at known risk for bleeding including patients with inherited predisposition to bleeding or patients receiving a full dose of anti-coagulative treatment were not included in the INPULSIS studies. Non-serious and serious bleeding events, some of which were fatal, have been reported in the post-marketing period (including patients with or without anticoagulant therapy or other drugs that could cause bleeding). Therefore, these patients should only be treated with Nintedanib if the anticipated benefit outweighs the potential risk. Post-marketing bleeding events include but are not limited to gastrointestinal, respiratory and central nervous organ systems, with the most frequent being gastrointestinal.
Arterial thromboembolic events: Patients with a recent history of myocardial infarction or stroke were excluded from the INPULSIS trials. Arterial thromboembolic events were infrequently reported: in 0.7% of patients in the placebo and 2.5% in the Nintedanib treated group. While adverse events reflecting ischemic heart disease were balanced between the Nintedanib and placebo groups, a higher percentage of patients experienced myocardial infarctions in the Nintedanib group (1.6%) compared to the placebo group (0.5%). Caution should be used when treating patients at higher cardiovascular risk including known coronary artery disease. Treatment interruption should be considered in patients who develop signs or symptoms of acute myocardial ischemia.
Venous thromboembolism: In the INPULSIS trials no increased risk of venous thromboembolism was observed in Nintedanib treated patients. Due to the mechanism of action of Nintedanib patients might have an increased risk of thromboembolic events.
Gastrointestinal perforations: In the INPULSIS trials, the frequency of patients with perforation was very low in both treatment groups: 0% placebo, 0.3% Nintedanib (involving two patients). Due to the mechanism of action of Nintedanib patients might have an increased risk of gastrointestinal perforation. Cases of gastrointestinal perforations, some of which were fatal, have been reported in the post-marketing period. Particular caution should be exercised when treating patients with previous abdominal surgery, previous history of peptic ulceration, diverticular disease or receiving concomitant corticosteroids or NSAIDs. Nintedanib should only be initiated at least 4 weeks after abdominal surgery. Therapy with Nintedanib should be permanently discontinued in patients who develop gastrointestinal perforation.
Hypertension: Administration of Nintedanib may increase blood pressure. Systemic blood pressure should be measured periodically and as clinically indicated.
Wound healing complication: No increased frequency of impaired wound healing was observed in the INPULSIS trials. Based on the mechanism of action Nintedanib may impair wound healing. No dedicated studies investigating the effect of Nintedanib on wound healing were performed. Treatment with Nintedanib should therefore only be initiated or – in case of perioperative interruption – resumed based on clinical judgement of adequate wound healing.
Co-administration with Pirfenidone: In a dedicated pharmacokinetic study, concomitant treatment of Nintedanib with Pirfenidone was investigated in patients with IPF. Based on these results, there is no evidence of a relevant pharmacokinetic drug-drug interaction between Nintedanib and Pirfenidone when administered in combination. In view of the limited number of patients, this study detected only the most frequent adverse events and showed an increase in gastrointestinal adverse events and a trend toward increased hepatic adverse events. Given the similarity in safety profiles for both medicinal products, additive adverse events, including gastrointestinal and hepatic adverse events, may be expected. The benefit-risk balance of concomitant treatment with Pirfenidone has not been established.
Effect on QT interval: No evidence of QT prolongation was observed for Nintedanib in the clinical trial programme. As some other tyrosine kinase inhibitors are known to exert an effect on QT, caution should be exercised when administered Nintedanib in patients who may develop QTc prolongation.
Allergic reaction: Dietary soya products are known to cause allergic reactions including severe anaphylaxis in persons with soya allergy. Patients with known allergy to peanut protein carry an enhanced risk for severe reactions to soya preparations.
InteractionsView
P-glycoprotein (P-gp): Nintedanib is a substrate of P-gp. Co-administration with the potent P-gp inhibitor ketoconazole increased exposure to Nintedanib 1.61-fold based on AUC and 1.83-fold based on Cmax in a dedicated drug-drug interaction study. In a drug-drug interaction study with the potent P-gp inducer rifampicin, exposure to Nintedanib decreased to 50.3% based on AUC and to 60.3% based on Cmax upon co-administration with rifampicin compared to administration of Nintedanib alone. If co-administered with Nintedanib, potent P-gp inhibitors (e.g. ketoconazole, erythromycin or cyclosporine) may increase exposure to Nintedanib. In such cases, patients should be monitored closely for tolerability of Nintedanib. Management of side effects may require interruption, dose reduction, or discontinuation of therapy with Nintedanib. Potent P-gp inducers (e.g. rifampicin, carbamazepine, phenytoin, and St. John’s Wort) may decrease exposure to Nintedanib. Selection of an alternate concomitant medicinal product with no or minimal P-gp induction potential should be considered.
Cytochrome (CYP)-enzymes: Only a minor extent of the biotransformation of Nintedanib consisted of CYP pathways. Nintedanib and its metabolites, the free acid moiety BIBF 1202 and its glucuronide BIBF 1202 glucuronide, did not inhibit or induce CYP enzymes in preclinical studies. The likelihood of drug-drug interactions with Nintedanib based on CYP metabolism is therefore considered to be low.
Co-administration with other medicinal products: The potential for interactions of Nintedanib with hormonal contraceptives was not explored.
Cytochrome (CYP)-enzymes: Only a minor extent of the biotransformation of Nintedanib consisted of CYP pathways. Nintedanib and its metabolites, the free acid moiety BIBF 1202 and its glucuronide BIBF 1202 glucuronide, did not inhibit or induce CYP enzymes in preclinical studies. The likelihood of drug-drug interactions with Nintedanib based on CYP metabolism is therefore considered to be low.
Co-administration with other medicinal products: The potential for interactions of Nintedanib with hormonal contraceptives was not explored.
Pregnancy & lactationView
Women of childbearing potential/Contraception: Nintedanib may cause foetalharm in humans. Women of childbearing potential should be advised to avoid becoming pregnant while receiving treatment with Nintedanib. They should be advised to use adequate contraception during and at least 3 months after the last dose of Nintedanib. Since the effect of Nintedanib on the metabolism and efficacy of hormonal contraceptives has not been investigated, barrier methods should be applied as a second form of contraception, to avoid pregnancy.
Pregnancy: There is no information on the use of Nintedanib in pregnant women, but pre-clinical studies in animals have shown reproductive toxicity of this active substance. As Nintedanib may cause foetal harm also in humans, it must not be used during pregnancy. Female patients should be advised to notify their doctor or pharmacist if they become pregnant during therapy with Nintedanib. If the patient becomes pregnant while receiving Nintedanib, she should be apprised of the potential hazard to the foetus. Termination of the treatment with Nintedanib should be considered.
Lactation: There is no information on the excretion of Nintedanib and its metabolites in human milk. Pre-clinical studies showed that small amounts of Nintedanib and its metabolites (≤ 0.5% of the administered dose) were secreted into milk of lactating rats. A risk to the newborns/infants cannot be excluded. Breast-feeding should be discontinued during treatment with Nintedanib.
Fertility: Based on preclinical investigations there is no evidence for impairment of male fertility. From subchronic and chronic toxicity studies, there is no evidence that female fertility in rats is impaired at a systemic exposure level comparable with that at the maximum recommended human dose (MRHD) of 150 mg twice daily.
Pregnancy: There is no information on the use of Nintedanib in pregnant women, but pre-clinical studies in animals have shown reproductive toxicity of this active substance. As Nintedanib may cause foetal harm also in humans, it must not be used during pregnancy. Female patients should be advised to notify their doctor or pharmacist if they become pregnant during therapy with Nintedanib. If the patient becomes pregnant while receiving Nintedanib, she should be apprised of the potential hazard to the foetus. Termination of the treatment with Nintedanib should be considered.
Lactation: There is no information on the excretion of Nintedanib and its metabolites in human milk. Pre-clinical studies showed that small amounts of Nintedanib and its metabolites (≤ 0.5% of the administered dose) were secreted into milk of lactating rats. A risk to the newborns/infants cannot be excluded. Breast-feeding should be discontinued during treatment with Nintedanib.
Fertility: Based on preclinical investigations there is no evidence for impairment of male fertility. From subchronic and chronic toxicity studies, there is no evidence that female fertility in rats is impaired at a systemic exposure level comparable with that at the maximum recommended human dose (MRHD) of 150 mg twice daily.
Pediatric usageView
Elderly patients (≥65 years): No overall differences in safety and efficacy were observed for elderly patients. No a-priori dose adjustment is required on the basis of a patient’s age. Patients ≥75 years may be more likely to require dose reduction to manage adverse effects.
Renal impairment: Less than 1% of a single dose of Nintedanib is excreted via the kidney. Adjustment of the starting dose in patients with mild to moderate renal impairment is not required. The safety, efficacy, and pharmacokinetics of Nintedanib have not been studied in patients with severe renal impairment (<30 ml/min creatinine clearance).
Hepatic impairment: Nintedanib is predominantly eliminated via biliary/faecal excretion (> 90%). Exposure increased in patients with hepatic impairment (Child Pugh A, Child Pugh B). In patients with mild hepatic impairment (Child Pugh A), the recommended dose of Nintedanib is 100 mg twice daily approximately 12 hours apart. In patients with mild hepatic impairment (Child Pugh A), treatment interruption or discontinuation for management of adverse reactions should be considered. The safety and efficacy of Nintedanib have not been investigated in patients with hepatic impairment classified as Child Pugh B and C. Treatment of patients with moderate (Child Pugh B) and severe (Child Pugh C) hepatic impairment with Nintedanib is not recommended.
Paediatric population: The safety and efficacy of Nintedanib in children aged 0-18 years have not been established. No data are available.
Renal impairment: Less than 1% of a single dose of Nintedanib is excreted via the kidney. Adjustment of the starting dose in patients with mild to moderate renal impairment is not required. The safety, efficacy, and pharmacokinetics of Nintedanib have not been studied in patients with severe renal impairment (<30 ml/min creatinine clearance).
Hepatic impairment: Nintedanib is predominantly eliminated via biliary/faecal excretion (> 90%). Exposure increased in patients with hepatic impairment (Child Pugh A, Child Pugh B). In patients with mild hepatic impairment (Child Pugh A), the recommended dose of Nintedanib is 100 mg twice daily approximately 12 hours apart. In patients with mild hepatic impairment (Child Pugh A), treatment interruption or discontinuation for management of adverse reactions should be considered. The safety and efficacy of Nintedanib have not been investigated in patients with hepatic impairment classified as Child Pugh B and C. Treatment of patients with moderate (Child Pugh B) and severe (Child Pugh C) hepatic impairment with Nintedanib is not recommended.
Paediatric population: The safety and efficacy of Nintedanib in children aged 0-18 years have not been established. No data are available.
StorageView
Store in a cool and dry place, protected from light. Do not store above 25°C.
Nifin
Nifedipine
Nifin
Nifedipine
Indications
Stroke
Indication detailsView
Nifedipine is indicated in the management of all types of essential & renal hypertension. Also indicated in the management of hypertension during pregnancy & during coronary by pass surgery.
Nifedipine is also used for prophylaxis and the treatment of unstable & variant angina, myocardial infarction, and silent myocardial ischaemia. Moreover Nifedipine is also used in Raynaud's phenomenon & heart failure.
Nifedipine is also used for prophylaxis and the treatment of unstable & variant angina, myocardial infarction, and silent myocardial ischaemia. Moreover Nifedipine is also used in Raynaud's phenomenon & heart failure.
Therapeutic classView
Calcium-channel blockers
PharmacologyView
Nifedipine is an inhibitor of Calcium Channel Blocker that blocks the transmembrane influx of Calcium ions into muscle cells. Nifedipine has selective effects as a dilator of arterial vessels. Nifedipine dilates main coronary and systemic arteries. As a result blood pressure falls and this elicits a sympathetic reflex response causing tachycardia and an increased cardiac output. Pulmonary arterial pressure also falls. Nifedipine has direct negative inotropic effects on cardiac muscles and these effects are seen at higher doses than dose which causes arterial vasodilatation.
DosageView
Nifedipine 10 mg:
Patients with liver dysfunction should commence therapy with 10 mg twice daily with careful monitoring.
Patients with renal impairment do not require adjustment of dosage.
- Angina: Initially 10 mg 3 times daily with food increased to 20 mg 3 times daily if necessary, in elderly patients, initially 5 mg 3 times daily.
- Raynaud's Phenomenon: 10 mg 3 times daily; maximum 60 mg daily. In urgent cases, the tablet should be dissolved under the tongue like a sublingual tablet. The effect occurs within some minutes.
Patients with liver dysfunction should commence therapy with 10 mg twice daily with careful monitoring.
Patients with renal impairment do not require adjustment of dosage.
Side effectsView
Headache, flushing, lethargy, gravitational oedema rash, nausea, increased frequency of micturation, eye pain, gum hyperplasia, depression, tremor, photosensitivity and few cases of jaundice have been reported. These reactions may regress on discontinuation of therapy. Its introduction may induce attacks of ischaemic pain in some patients with angina pectoris.
ContraindicationsView
Cardiogenic shock, advanced aortic stenosis, nursing mothers, GI obstruction, inflammatory bowel disease, hypotension.
PrecautionsView
Tablets should be swallowed whole and should not be bitten, chewed or broken up. It should be used with caution in patient whose cardiac reserve is poor. Should be withdrawn if ischaemic pain occurs or existing pain worsens shortly after initiating treatment. Use in diabetic patients requires adjustment of their control. Since the absorption of the drug could be modified by renal disease, caution should be exercised in treating such patients.
InteractionsView
- ACE inhibitors: Enhanced hypotensive effect.
- Anti-arrythmics: Plasma concentration of quinidine is reduced.
- Anti-bacterials: Rifampicin possibly increases metabolism of Nifedipine.
- Anti-epileptics: Plasma concentration of phenytoin increases.
- Antipsychotics: Enhanced hypotensive effect.
- β-blockers: Occasionally severe hypotension and heart failure may occur.
- Cyclosporin: Plasma concentration of Nifedipine possibly increases.
- Muscle relaxants: Effect of muscle relaxants e.g. tubocurarine increases.
- Ulcer healing drugs: Metabolism of Nifedipine increases.
Pregnancy & lactationView
There are no adequate and well controlled studies in pregnant women. It should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
StorageView
Protect from strong light, store in a cool place in the original pack
Nifura
Nitrofurazone
Nifura
Nitrofurazone
Indications
Wounds
Indication detailsView
Nitrofurazone is indicated in the infectious conditions of the skin such as burns, wounds, ulcers, skin infections and skin grafting.
Therapeutic classView
Topical Antibiotic preparations
PharmacologyView
Nitrofurazone is a broad spectrum topical antibacterial agent indicated for the treatment of mixed skin infections of superficial wounds and diseases of the skin.
DosageView
To be applied directly to the lesion or on gauze first; 2-3 times daily or as advised by the physician.
Side effectsView
Sensitization and generalized allergic skin reactions may be produced after few days of initial application. Cross sensitization to other Nitrofurazone derivatives may occur. Intolerance to Nitrofurazone necessitating withdrawal has been encountered.
ContraindicationsView
Nitrofurazone is contraindicated to patients with known sensitivity to Nitrofurazone. It is not advisable to use Nitrofurazone after the infection is cured. It should be used with caution in patients with known or suspected renal impairment.
PrecautionsView
G6PD deficiency, renal impairment.
Pregnancy & lactationView
Pregnancy category- B