Find Medicines

Macrolides

Dosage of Clindamycin Capsule:

• Serious Infections: 150 mg-300 mg every six hours.
• More severe infections: 300 mg-450 mg every six hours.

To avoid the possibility of oesophageal irritation, Clindacin capsules should be taken with a full glass of water.

Several researches has found that Clindamycin 300 mg capsule provides plasma concentration over MIC₉₀ for more than 12 hours. This finding supports the twice-daily dosing of Clindacin 300 mg capsule, particularly in SSTIs & RTIs. However, in case of bone & joint infections, diabetic foot infections dose of Clindamycin should be 300 mg capsule 3-4 times daily.

Dosage of Clindamycin Powder for oral solution:

• Serious infections: 8-12 mg/kg/day divided into 3 or 4 equal doses.
• Severe infections: 13-16 mg/kg/day divided into 3 or 4 equal doses.
• More severe infections: 17-25 mg/kg/day divided into 3 or 4 equal doses.

In pediatric patients weighing 10 kg or less, 1/2 teaspoon (37.5 mg) three times a day should be considered the minimum recommended dose.

Dosage of Clindamycin IV/IM Injection:
Adults-

• Serious infections due to aerobic gram-positive cocci and the more susceptible anaerobes: 600-1200 mg/day in 2- 4 equal doses.
• More severe infections: 1200-2700 mg/day in 2-4 equal doses.
• For more serious infections: these doses may have to be increased. In life-threatening situations due to either aerobes or anaerobes, these doses may be increased.
• Doses of as much as 4800 mg daily have been given intravenously to adults. Single intramuscular injections of greater than 600 mg are not recommended.

Neonates (less than 1 month): 15 to 20 mg/kg/day in 3 to 4 equal doses. The lower effective dosage may be adequate for small prematures.

Pediatric patients (1 month of age to 16 years):

• 20 to 40 mg/kg/day in 3 or 4 equal doses. The higher doses would be used for more severe infections.
• Parenteral therapy may be changed to Capsules (clindamycin hydrochloride) when the condition warrants and at the discretion of the physician.
• In cases of (3-hemolytic streptococcal infections, treatment should be continued for at least 10 days.

The adverse effects have been reported with the use of clindamycin are- abdominal pain, oesophagitis and oesophagial ulcer, nausea, vomiting and diarrhoea, pruritus, skin rashes, urticaria.

Clindamycin is contraindicated in patients previously found to be sensitive to clindamycin or any of the ingredients of this medicine.

Clindamycin should be prescribed with caution in individuals with a history of gastrointestinal disease, particularly colitis.

Clindamycin enhances the action of other neuromuscular blocking agents. Therefore, it should be used with caution in patients receiving such agents. Antagonism has been demonstrated between clindamycin and erythromycin in vitro. Because of possible clinical significance, these two drugs should not be administered concurrently.

Pregnancy Category B. Clindamycin crosses the placenta in humans. After multiple doses, amniotic fluid concentrations were approximately 30% of maternal concentrations. Clindamycin should be used in pregnancy only if clearly needed. Clindamycin has been reported to appear in breast milk. Therefore, it is not recommended for nursing mothers if not clearly needed.

Use in newborns and infants: When Clindamycin is administered to newborns and infants (birth to 16 years), appropriate monitoring of organ system functions is desirable.

Geriatric use: Dose adjustment of Clindamycin is not necessary.

Overdosage with orally administered clindamycin has been rare. Adverse reactions similar to those seen with normal doses can be expected, however, unexpected reactions could occur. Haemodialysis and peritoneal dialysis are not effective in removing clindamycin from the serum. Overdosage should be treated with simple gastric lavage. No specific antidote is known.

Direction for reconstitution (powder for oral solution): Shake the bottle well to loosen the powder. Add 80 ml of boiled and cooled water to the dry mixture in the bottle. For ease of preparation, add water to the bottle in two proportions. Shake well after each addition until all the powder is in solution. Keep the bottle tightly closed. The reconstituted solution should be used within 2 weeks if kept at room temperature.

Dilution of Clindamycin injection for intravenous use: Clindamycin phosphate must be diluted prior to IV administration. The concentration of clindamycin in diluent for infusion should not exceed 18 mg per ml. Infusion rates should not exceed 30 mg per minute.

• Administration of more than 1200 mg in a single 1 hour infusion is not recommended.
• Single IM injections of greater than 600 mg are not recommended. Dilution is not required for intramuscular administration.
• Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

Dilution and Compatibility: Physical and biological compatibility studies monitored for 24 hours at room temperature have demonstrated no inactivation or incompatibility with the use of Clindamycin phosphate Sterile Solution (clindamycin phosphate) in IV solutions containing sodium chloride, glucose, calcium or potassium, and solutions containing vitamin B complex in concentrations usually used clinically. No incompatibility has been demonstrated with the antibiotics cephalothin, kanamycin, gentamicin, penicillin or carbenicillin.

Physico-Chemical Stability of diluted solutions of Clindacin Injection-

• Room temperature: 16 days at 25°C.
• Refrigeration: 32 days at 4°C.

Keep below 30°C temperature, away from light & moisture. Keep out of the reach of children.

Clindamycin and Tretinoin gel is indicated for the topical treatment of Acne vulgaris.

Topical antibiotic & retinoid preparations

This is a combination of lincosamide antibiotic Clindamycin phosphate and retinoid Tretinoin. Clindamycin binds with the 50s ribosomal subunit of susceptible bacteria and prevents elongation of peptide chain by interfering with the peptidyl transfer, thereby suppressing bacterial protein synthesis. Clindamycin inhibits the activity of Propionibacterium acne as reduces the occurrence of acne. Tretinoin decreases the cohesiveness of follicular epithelial cells and increases the turn over thereby brings the comedones out.

Before sleep: Wash the face gently with a mild soap and water, then pat the skin dry. Apply the Gel with finger tips through the face gently.

In the morning: Apply a sunscreen after the application of Gel. Do not wash your face more than 2 or 3 times a day. Apply the sunscreen cream as needed.

Safety and effectiveness in children below 12 years of age have not been established.

Erythema, scaling, nasopharyngitis, dry skin, cough, sinusitis and diarrhea are the common side effects.

Clindamycin and Tretinoin should not be administered to individuals who are hypersensitive to Clindamycin or Tretinoin or any other component of the Gel.

Clindamycin and Tretinoin should not be applied to eyes, nose, ear, lips, cut, burn and other infections. After the application of the Gel, keep away from sunlight.

It is not known whether Clindamycin or Tretinoin is excreted in human milk. Exercise special caution while applying Clindamycin or Tretinoin to a nursing mother.

Keep below 25°C temperature, away from light & moisture. Keep out of the reach of children.

First generation Cephalosporins

Cephradine is a semisynthetic broad spectrum bactericidal antibiotic, it is active against infections caused by both gram-positive and gram-negative microorganisms. Both penicillinase producing and nonproducing staphylococci are sensitive to Cephradine. The main site of action of Cephradine is the cell wall of bacteria. Cell wall of sensitive organism contains peptidoglycan. Cephradine inhibits cross-linking process and as a result cell wall with many pores are formed, thus lysis of bacteria occur due to external osmotic pressure.

For oral administration-
Adults:

• Urinary tract infections: 500mg four times daily or 1g twice daily. Infections which are severe or chronic may necessitate the administration of higher doses. Where complications arise including prostatitis and epididymitis continued intensive treatment is required.
• Respiratory tract infections: 250 to 500mg four times daily or 500mg to 1g twice daily, dependent on the site and severity of the infection.
• Skin and soft tissue infections: 250 to 500mg four times daily or 500mg to 1g twice daily, again dependent on the site and severity of the infection.

Children:

• Total daily dose of 25 to 50mg/kg given in two or four equally divided doses.
• Otitis media: Total daily dose of 75 to 100mg/kg given in divided doses 6 to 12 hourly.
• Maximum daily dosage: 4 gm

Elderly: The normal adult dose is appropriate. Patients with impaired renal or hepatic function should be monitored during treatment.

For injectable administration-

• Adult: The usual dose is 2-4 gm daily in four equally divided doses up to 8 gm daily. For prophylaxis a single preoperative dose of 1-2 gm intramuscularly or intravenously is given.
• Children: The dose is 50-100 mg/kg daily in four equally divided doses, up to 300 mg/kg daily in severe infection.

Limited essentially to gastro-intestinal disturbances and on occasions to hypersensitivity phenomena. The latter are more likely to occur in individuals, who have previously demonstrated hypersensitivity and thos with a history of allergy, asthma, hay fever or urticaria. Skin reactions have occasionally been reported. Rare- Glossitis, heartburn, dizziness, tightness in the chest, nausea, vomiting, diarrhoea, abdominal pain, vaginitis, candida overgrowth. Skin and hypersensitivity reactions include urticaria, skin rashes, joint pains, oedema.

• Blood and lymphatic system disorders- Unknown: blood disorders (including thrombocytopenia, leucopenia, agranulocytosis, aplastic anaemia and haemolytic anaemia)
• Immune system disorders- Unknown: Fever, serum sickness like reactions, anaphylaxis
• Psychiatric disorders- Unknown: Confusion, sleep disturbances
• Nervous system disorders- Unknown: hyperactivity, hypertonia, dizziness, nervousness; Rarely: Headache
• Hepatobiliary disorders- Frequency unknown: Liver, enzyme disturbances, transient hepatitis, cholestatic jaundice
• Renal and urinary disorders- Unknown: Reversible interstitial nephritis
• Investigations- Unknown: Elevation of blood urea nitrogen, serum creatinine, alanine aminotransferase, aspartate aminotransferase, total bilirubin, alkaline phosphatase.

Cephradine should not be used in patients with known or suspected hypersensitivity to cephalosporins.

The concomitant use of nephrotoxic drugs such as aminoglycosides with Cefradine may increase the risk of kidney damage. Diuretics (e.g. frusemide, ethacrynic acid) and probenecid enhanced the possibility of renal toxicity.

Although animal studies have not demonstrated any teratogenicity, safety in pregnancy has not been established. Cephradine is excreted in breast milk and should be used with caution in lactating mothers. Since the medicine may cause dizziness, patients should be cautioned about operating hazardous machinery, including automobiles.

Renal Impairment: The following doses are recommended (based on 500 mg every 6 hours) for patients not on haemodialysis:

• CrCl: >20 ml/min: 500 mg every 6 hours
• CrCl: 5-20 ml/min: 250 mg every 6 hours
• CrCl: <5 ml/min: 250 mg every 50-70 hours.

Recommendations for patients on chronic, intermittent haemodialysis:

• 250 mg at the start of haemodialysis
• 250 mg 6 to 12 hours after the start
• 250 mg 36 to 48 hours after the start
• 250 mg at the start of the next haemodialysis session if more than 30 hours have elapsed since the last dose.

Additional Information for all patients Regardless of patient age or weight, higher doses of up to 1 gm four times daily may be required for infections which are chronic or severe. Treatment should continue for at least 2 to 3 days after symptoms have resolved or bacteria have been eradicated. To reduce the possibility of rheumatic fever or glomerulonephritis resulting from infections with haemolytic streptococci, treatment should be continued for at least 10 days. Throughout treatment of chronic urinary tract infections and for several months thereafter, regular bacteriological and clinical monitoring is required.

Doses below those recommended above should not be prescribed. Paediatric dosages should not exceed those specified for adults, regardless of severity of infection. It may be necessary to continue Cephradine therapy for several weeks in persistent infections. Patients may be transferred from intramuscular/intravenous Cephradine therapy to oral treatment at the same dosage level.

The symptoms of Sefrad overdose are non-specific and are generally nausea, vomiting, diarrhoea and gastric upsets. Treatment is mainly supportive although gastric lavage will be necessary if a large amount has been ingested.

Cephradine Suspension should be freshly prepared. Reconstituted Suspension should be used within 7 days if kept at room temperature or within 14 days, if kept in a refrigerator. Cephradine Injection solutions should be used within 2 hours when kept at room temperature. When stored at 5°C, solutions retain potency for 12 hours. Reconstituted solutions may vary in colour from light to straw yellow; however, this does not affect the potency. Do not use later than the date of expiry. Keep all medicines out of the reach of children. To be dispensed only on the prescription of a registered physician

First generation Cephalosporins

Cephradine is a semisynthetic broad spectrum bactericidal antibiotic, it is active against infections caused by both gram-positive and gram-negative microorganisms. Both penicillinase producing and nonproducing staphylococci are sensitive to Cephradine. The main site of action of Cephradine is the cell wall of bacteria. Cell wall of sensitive organism contains peptidoglycan. Cephradine inhibits cross-linking process and as a result cell wall with many pores are formed, thus lysis of bacteria occur due to external osmotic pressure.

For oral administration-
Adults:

• Urinary tract infections: 500mg four times daily or 1g twice daily. Infections which are severe or chronic may necessitate the administration of higher doses. Where complications arise including prostatitis and epididymitis continued intensive treatment is required.
• Respiratory tract infections: 250 to 500mg four times daily or 500mg to 1g twice daily, dependent on the site and severity of the infection.
• Skin and soft tissue infections: 250 to 500mg four times daily or 500mg to 1g twice daily, again dependent on the site and severity of the infection.

Children:

• Total daily dose of 25 to 50mg/kg given in two or four equally divided doses.
• Otitis media: Total daily dose of 75 to 100mg/kg given in divided doses 6 to 12 hourly.
• Maximum daily dosage: 4 gm

Elderly: The normal adult dose is appropriate. Patients with impaired renal or hepatic function should be monitored during treatment.

For injectable administration-

• Adult: The usual dose is 2-4 gm daily in four equally divided doses up to 8 gm daily. For prophylaxis a single preoperative dose of 1-2 gm intramuscularly or intravenously is given.
• Children: The dose is 50-100 mg/kg daily in four equally divided doses, up to 300 mg/kg daily in severe infection.

Limited essentially to gastro-intestinal disturbances and on occasions to hypersensitivity phenomena. The latter are more likely to occur in individuals, who have previously demonstrated hypersensitivity and thos with a history of allergy, asthma, hay fever or urticaria. Skin reactions have occasionally been reported. Rare- Glossitis, heartburn, dizziness, tightness in the chest, nausea, vomiting, diarrhoea, abdominal pain, vaginitis, candida overgrowth. Skin and hypersensitivity reactions include urticaria, skin rashes, joint pains, oedema.

• Blood and lymphatic system disorders- Unknown: blood disorders (including thrombocytopenia, leucopenia, agranulocytosis, aplastic anaemia and haemolytic anaemia)
• Immune system disorders- Unknown: Fever, serum sickness like reactions, anaphylaxis
• Psychiatric disorders- Unknown: Confusion, sleep disturbances
• Nervous system disorders- Unknown: hyperactivity, hypertonia, dizziness, nervousness; Rarely: Headache
• Hepatobiliary disorders- Frequency unknown: Liver, enzyme disturbances, transient hepatitis, cholestatic jaundice
• Renal and urinary disorders- Unknown: Reversible interstitial nephritis
• Investigations- Unknown: Elevation of blood urea nitrogen, serum creatinine, alanine aminotransferase, aspartate aminotransferase, total bilirubin, alkaline phosphatase.

Cephradine should not be used in patients with known or suspected hypersensitivity to cephalosporins.

The concomitant use of nephrotoxic drugs such as aminoglycosides with Cefradine may increase the risk of kidney damage. Diuretics (e.g. frusemide, ethacrynic acid) and probenecid enhanced the possibility of renal toxicity.

Although animal studies have not demonstrated any teratogenicity, safety in pregnancy has not been established. Cephradine is excreted in breast milk and should be used with caution in lactating mothers. Since the medicine may cause dizziness, patients should be cautioned about operating hazardous machinery, including automobiles.

Renal Impairment: The following doses are recommended (based on 500 mg every 6 hours) for patients not on haemodialysis:

• CrCl: >20 ml/min: 500 mg every 6 hours
• CrCl: 5-20 ml/min: 250 mg every 6 hours
• CrCl: <5 ml/min: 250 mg every 50-70 hours.

Recommendations for patients on chronic, intermittent haemodialysis:

• 250 mg at the start of haemodialysis
• 250 mg 6 to 12 hours after the start
• 250 mg 36 to 48 hours after the start
• 250 mg at the start of the next haemodialysis session if more than 30 hours have elapsed since the last dose.

Additional Information for all patients Regardless of patient age or weight, higher doses of up to 1 gm four times daily may be required for infections which are chronic or severe. Treatment should continue for at least 2 to 3 days after symptoms have resolved or bacteria have been eradicated. To reduce the possibility of rheumatic fever or glomerulonephritis resulting from infections with haemolytic streptococci, treatment should be continued for at least 10 days. Throughout treatment of chronic urinary tract infections and for several months thereafter, regular bacteriological and clinical monitoring is required.

Doses below those recommended above should not be prescribed. Paediatric dosages should not exceed those specified for adults, regardless of severity of infection. It may be necessary to continue Cephradine therapy for several weeks in persistent infections. Patients may be transferred from intramuscular/intravenous Cephradine therapy to oral treatment at the same dosage level.

The symptoms of Sefrad overdose are non-specific and are generally nausea, vomiting, diarrhoea and gastric upsets. Treatment is mainly supportive although gastric lavage will be necessary if a large amount has been ingested.

Cephradine Suspension should be freshly prepared. Reconstituted Suspension should be used within 7 days if kept at room temperature or within 14 days, if kept in a refrigerator. Cephradine Injection solutions should be used within 2 hours when kept at room temperature. When stored at 5°C, solutions retain potency for 12 hours. Reconstituted solutions may vary in colour from light to straw yellow; however, this does not affect the potency. Do not use later than the date of expiry. Keep all medicines out of the reach of children. To be dispensed only on the prescription of a registered physician

First generation Cephalosporins

Cephradine is a semisynthetic broad spectrum bactericidal antibiotic, it is active against infections caused by both gram-positive and gram-negative microorganisms. Both penicillinase producing and nonproducing staphylococci are sensitive to Cephradine. The main site of action of Cephradine is the cell wall of bacteria. Cell wall of sensitive organism contains peptidoglycan. Cephradine inhibits cross-linking process and as a result cell wall with many pores are formed, thus lysis of bacteria occur due to external osmotic pressure.

For oral administration-
Adults:

• Urinary tract infections: 500mg four times daily or 1g twice daily. Infections which are severe or chronic may necessitate the administration of higher doses. Where complications arise including prostatitis and epididymitis continued intensive treatment is required.
• Respiratory tract infections: 250 to 500mg four times daily or 500mg to 1g twice daily, dependent on the site and severity of the infection.
• Skin and soft tissue infections: 250 to 500mg four times daily or 500mg to 1g twice daily, again dependent on the site and severity of the infection.

Children:

• Total daily dose of 25 to 50mg/kg given in two or four equally divided doses.
• Otitis media: Total daily dose of 75 to 100mg/kg given in divided doses 6 to 12 hourly.
• Maximum daily dosage: 4 gm

Elderly: The normal adult dose is appropriate. Patients with impaired renal or hepatic function should be monitored during treatment.

For injectable administration-

• Adult: The usual dose is 2-4 gm daily in four equally divided doses up to 8 gm daily. For prophylaxis a single preoperative dose of 1-2 gm intramuscularly or intravenously is given.
• Children: The dose is 50-100 mg/kg daily in four equally divided doses, up to 300 mg/kg daily in severe infection.

Limited essentially to gastro-intestinal disturbances and on occasions to hypersensitivity phenomena. The latter are more likely to occur in individuals, who have previously demonstrated hypersensitivity and thos with a history of allergy, asthma, hay fever or urticaria. Skin reactions have occasionally been reported. Rare- Glossitis, heartburn, dizziness, tightness in the chest, nausea, vomiting, diarrhoea, abdominal pain, vaginitis, candida overgrowth. Skin and hypersensitivity reactions include urticaria, skin rashes, joint pains, oedema.

• Blood and lymphatic system disorders- Unknown: blood disorders (including thrombocytopenia, leucopenia, agranulocytosis, aplastic anaemia and haemolytic anaemia)
• Immune system disorders- Unknown: Fever, serum sickness like reactions, anaphylaxis
• Psychiatric disorders- Unknown: Confusion, sleep disturbances
• Nervous system disorders- Unknown: hyperactivity, hypertonia, dizziness, nervousness; Rarely: Headache
• Hepatobiliary disorders- Frequency unknown: Liver, enzyme disturbances, transient hepatitis, cholestatic jaundice
• Renal and urinary disorders- Unknown: Reversible interstitial nephritis
• Investigations- Unknown: Elevation of blood urea nitrogen, serum creatinine, alanine aminotransferase, aspartate aminotransferase, total bilirubin, alkaline phosphatase.

Cephradine should not be used in patients with known or suspected hypersensitivity to cephalosporins.

The concomitant use of nephrotoxic drugs such as aminoglycosides with Cefradine may increase the risk of kidney damage. Diuretics (e.g. frusemide, ethacrynic acid) and probenecid enhanced the possibility of renal toxicity.

Although animal studies have not demonstrated any teratogenicity, safety in pregnancy has not been established. Cephradine is excreted in breast milk and should be used with caution in lactating mothers. Since the medicine may cause dizziness, patients should be cautioned about operating hazardous machinery, including automobiles.

Renal Impairment: The following doses are recommended (based on 500 mg every 6 hours) for patients not on haemodialysis:

• CrCl: >20 ml/min: 500 mg every 6 hours
• CrCl: 5-20 ml/min: 250 mg every 6 hours
• CrCl: <5 ml/min: 250 mg every 50-70 hours.

Recommendations for patients on chronic, intermittent haemodialysis:

• 250 mg at the start of haemodialysis
• 250 mg 6 to 12 hours after the start
• 250 mg 36 to 48 hours after the start
• 250 mg at the start of the next haemodialysis session if more than 30 hours have elapsed since the last dose.

Additional Information for all patients Regardless of patient age or weight, higher doses of up to 1 gm four times daily may be required for infections which are chronic or severe. Treatment should continue for at least 2 to 3 days after symptoms have resolved or bacteria have been eradicated. To reduce the possibility of rheumatic fever or glomerulonephritis resulting from infections with haemolytic streptococci, treatment should be continued for at least 10 days. Throughout treatment of chronic urinary tract infections and for several months thereafter, regular bacteriological and clinical monitoring is required.

Doses below those recommended above should not be prescribed. Paediatric dosages should not exceed those specified for adults, regardless of severity of infection. It may be necessary to continue Cephradine therapy for several weeks in persistent infections. Patients may be transferred from intramuscular/intravenous Cephradine therapy to oral treatment at the same dosage level.

The symptoms of Sefrad overdose are non-specific and are generally nausea, vomiting, diarrhoea and gastric upsets. Treatment is mainly supportive although gastric lavage will be necessary if a large amount has been ingested.

Cephradine Suspension should be freshly prepared. Reconstituted Suspension should be used within 7 days if kept at room temperature or within 14 days, if kept in a refrigerator. Cephradine Injection solutions should be used within 2 hours when kept at room temperature. When stored at 5°C, solutions retain potency for 12 hours. Reconstituted solutions may vary in colour from light to straw yellow; however, this does not affect the potency. Do not use later than the date of expiry. Keep all medicines out of the reach of children. To be dispensed only on the prescription of a registered physician

First generation Cephalosporins

Cephradine is a semisynthetic broad spectrum bactericidal antibiotic, it is active against infections caused by both gram-positive and gram-negative microorganisms. Both penicillinase producing and nonproducing staphylococci are sensitive to Cephradine. The main site of action of Cephradine is the cell wall of bacteria. Cell wall of sensitive organism contains peptidoglycan. Cephradine inhibits cross-linking process and as a result cell wall with many pores are formed, thus lysis of bacteria occur due to external osmotic pressure.

For oral administration-
Adults:

• Urinary tract infections: 500mg four times daily or 1g twice daily. Infections which are severe or chronic may necessitate the administration of higher doses. Where complications arise including prostatitis and epididymitis continued intensive treatment is required.
• Respiratory tract infections: 250 to 500mg four times daily or 500mg to 1g twice daily, dependent on the site and severity of the infection.
• Skin and soft tissue infections: 250 to 500mg four times daily or 500mg to 1g twice daily, again dependent on the site and severity of the infection.

Children:

• Total daily dose of 25 to 50mg/kg given in two or four equally divided doses.
• Otitis media: Total daily dose of 75 to 100mg/kg given in divided doses 6 to 12 hourly.
• Maximum daily dosage: 4 gm

Elderly: The normal adult dose is appropriate. Patients with impaired renal or hepatic function should be monitored during treatment.

For injectable administration-

• Adult: The usual dose is 2-4 gm daily in four equally divided doses up to 8 gm daily. For prophylaxis a single preoperative dose of 1-2 gm intramuscularly or intravenously is given.
• Children: The dose is 50-100 mg/kg daily in four equally divided doses, up to 300 mg/kg daily in severe infection.

Limited essentially to gastro-intestinal disturbances and on occasions to hypersensitivity phenomena. The latter are more likely to occur in individuals, who have previously demonstrated hypersensitivity and thos with a history of allergy, asthma, hay fever or urticaria. Skin reactions have occasionally been reported. Rare- Glossitis, heartburn, dizziness, tightness in the chest, nausea, vomiting, diarrhoea, abdominal pain, vaginitis, candida overgrowth. Skin and hypersensitivity reactions include urticaria, skin rashes, joint pains, oedema.

• Blood and lymphatic system disorders- Unknown: blood disorders (including thrombocytopenia, leucopenia, agranulocytosis, aplastic anaemia and haemolytic anaemia)
• Immune system disorders- Unknown: Fever, serum sickness like reactions, anaphylaxis
• Psychiatric disorders- Unknown: Confusion, sleep disturbances
• Nervous system disorders- Unknown: hyperactivity, hypertonia, dizziness, nervousness; Rarely: Headache
• Hepatobiliary disorders- Frequency unknown: Liver, enzyme disturbances, transient hepatitis, cholestatic jaundice
• Renal and urinary disorders- Unknown: Reversible interstitial nephritis
• Investigations- Unknown: Elevation of blood urea nitrogen, serum creatinine, alanine aminotransferase, aspartate aminotransferase, total bilirubin, alkaline phosphatase.

Cephradine should not be used in patients with known or suspected hypersensitivity to cephalosporins.

The concomitant use of nephrotoxic drugs such as aminoglycosides with Cefradine may increase the risk of kidney damage. Diuretics (e.g. frusemide, ethacrynic acid) and probenecid enhanced the possibility of renal toxicity.

Although animal studies have not demonstrated any teratogenicity, safety in pregnancy has not been established. Cephradine is excreted in breast milk and should be used with caution in lactating mothers. Since the medicine may cause dizziness, patients should be cautioned about operating hazardous machinery, including automobiles.

Renal Impairment: The following doses are recommended (based on 500 mg every 6 hours) for patients not on haemodialysis:

• CrCl: >20 ml/min: 500 mg every 6 hours
• CrCl: 5-20 ml/min: 250 mg every 6 hours
• CrCl: <5 ml/min: 250 mg every 50-70 hours.

Recommendations for patients on chronic, intermittent haemodialysis:

• 250 mg at the start of haemodialysis
• 250 mg 6 to 12 hours after the start
• 250 mg 36 to 48 hours after the start
• 250 mg at the start of the next haemodialysis session if more than 30 hours have elapsed since the last dose.

Additional Information for all patients Regardless of patient age or weight, higher doses of up to 1 gm four times daily may be required for infections which are chronic or severe. Treatment should continue for at least 2 to 3 days after symptoms have resolved or bacteria have been eradicated. To reduce the possibility of rheumatic fever or glomerulonephritis resulting from infections with haemolytic streptococci, treatment should be continued for at least 10 days. Throughout treatment of chronic urinary tract infections and for several months thereafter, regular bacteriological and clinical monitoring is required.

Doses below those recommended above should not be prescribed. Paediatric dosages should not exceed those specified for adults, regardless of severity of infection. It may be necessary to continue Cephradine therapy for several weeks in persistent infections. Patients may be transferred from intramuscular/intravenous Cephradine therapy to oral treatment at the same dosage level.

The symptoms of Sefrad overdose are non-specific and are generally nausea, vomiting, diarrhoea and gastric upsets. Treatment is mainly supportive although gastric lavage will be necessary if a large amount has been ingested.

Cephradine Suspension should be freshly prepared. Reconstituted Suspension should be used within 7 days if kept at room temperature or within 14 days, if kept in a refrigerator. Cephradine Injection solutions should be used within 2 hours when kept at room temperature. When stored at 5°C, solutions retain potency for 12 hours. Reconstituted solutions may vary in colour from light to straw yellow; however, this does not affect the potency. Do not use later than the date of expiry. Keep all medicines out of the reach of children. To be dispensed only on the prescription of a registered physician

First generation Cephalosporins

Cephradine is a semisynthetic broad spectrum bactericidal antibiotic, it is active against infections caused by both gram-positive and gram-negative microorganisms. Both penicillinase producing and nonproducing staphylococci are sensitive to Cephradine. The main site of action of Cephradine is the cell wall of bacteria. Cell wall of sensitive organism contains peptidoglycan. Cephradine inhibits cross-linking process and as a result cell wall with many pores are formed, thus lysis of bacteria occur due to external osmotic pressure.

For oral administration-
Adults:

• Urinary tract infections: 500mg four times daily or 1g twice daily. Infections which are severe or chronic may necessitate the administration of higher doses. Where complications arise including prostatitis and epididymitis continued intensive treatment is required.
• Respiratory tract infections: 250 to 500mg four times daily or 500mg to 1g twice daily, dependent on the site and severity of the infection.
• Skin and soft tissue infections: 250 to 500mg four times daily or 500mg to 1g twice daily, again dependent on the site and severity of the infection.

Children:

• Total daily dose of 25 to 50mg/kg given in two or four equally divided doses.
• Otitis media: Total daily dose of 75 to 100mg/kg given in divided doses 6 to 12 hourly.
• Maximum daily dosage: 4 gm

Elderly: The normal adult dose is appropriate. Patients with impaired renal or hepatic function should be monitored during treatment.

For injectable administration-

• Adult: The usual dose is 2-4 gm daily in four equally divided doses up to 8 gm daily. For prophylaxis a single preoperative dose of 1-2 gm intramuscularly or intravenously is given.
• Children: The dose is 50-100 mg/kg daily in four equally divided doses, up to 300 mg/kg daily in severe infection.

Limited essentially to gastro-intestinal disturbances and on occasions to hypersensitivity phenomena. The latter are more likely to occur in individuals, who have previously demonstrated hypersensitivity and thos with a history of allergy, asthma, hay fever or urticaria. Skin reactions have occasionally been reported. Rare- Glossitis, heartburn, dizziness, tightness in the chest, nausea, vomiting, diarrhoea, abdominal pain, vaginitis, candida overgrowth. Skin and hypersensitivity reactions include urticaria, skin rashes, joint pains, oedema.

• Blood and lymphatic system disorders- Unknown: blood disorders (including thrombocytopenia, leucopenia, agranulocytosis, aplastic anaemia and haemolytic anaemia)
• Immune system disorders- Unknown: Fever, serum sickness like reactions, anaphylaxis
• Psychiatric disorders- Unknown: Confusion, sleep disturbances
• Nervous system disorders- Unknown: hyperactivity, hypertonia, dizziness, nervousness; Rarely: Headache
• Hepatobiliary disorders- Frequency unknown: Liver, enzyme disturbances, transient hepatitis, cholestatic jaundice
• Renal and urinary disorders- Unknown: Reversible interstitial nephritis
• Investigations- Unknown: Elevation of blood urea nitrogen, serum creatinine, alanine aminotransferase, aspartate aminotransferase, total bilirubin, alkaline phosphatase.

Cephradine should not be used in patients with known or suspected hypersensitivity to cephalosporins.

The concomitant use of nephrotoxic drugs such as aminoglycosides with Cefradine may increase the risk of kidney damage. Diuretics (e.g. frusemide, ethacrynic acid) and probenecid enhanced the possibility of renal toxicity.

Although animal studies have not demonstrated any teratogenicity, safety in pregnancy has not been established. Cephradine is excreted in breast milk and should be used with caution in lactating mothers. Since the medicine may cause dizziness, patients should be cautioned about operating hazardous machinery, including automobiles.

Renal Impairment: The following doses are recommended (based on 500 mg every 6 hours) for patients not on haemodialysis:

• CrCl: >20 ml/min: 500 mg every 6 hours
• CrCl: 5-20 ml/min: 250 mg every 6 hours
• CrCl: <5 ml/min: 250 mg every 50-70 hours.

Recommendations for patients on chronic, intermittent haemodialysis:

• 250 mg at the start of haemodialysis
• 250 mg 6 to 12 hours after the start
• 250 mg 36 to 48 hours after the start
• 250 mg at the start of the next haemodialysis session if more than 30 hours have elapsed since the last dose.

Additional Information for all patients Regardless of patient age or weight, higher doses of up to 1 gm four times daily may be required for infections which are chronic or severe. Treatment should continue for at least 2 to 3 days after symptoms have resolved or bacteria have been eradicated. To reduce the possibility of rheumatic fever or glomerulonephritis resulting from infections with haemolytic streptococci, treatment should be continued for at least 10 days. Throughout treatment of chronic urinary tract infections and for several months thereafter, regular bacteriological and clinical monitoring is required.

Doses below those recommended above should not be prescribed. Paediatric dosages should not exceed those specified for adults, regardless of severity of infection. It may be necessary to continue Cephradine therapy for several weeks in persistent infections. Patients may be transferred from intramuscular/intravenous Cephradine therapy to oral treatment at the same dosage level.

The symptoms of Sefrad overdose are non-specific and are generally nausea, vomiting, diarrhoea and gastric upsets. Treatment is mainly supportive although gastric lavage will be necessary if a large amount has been ingested.

Cephradine Suspension should be freshly prepared. Reconstituted Suspension should be used within 7 days if kept at room temperature or within 14 days, if kept in a refrigerator. Cephradine Injection solutions should be used within 2 hours when kept at room temperature. When stored at 5°C, solutions retain potency for 12 hours. Reconstituted solutions may vary in colour from light to straw yellow; however, this does not affect the potency. Do not use later than the date of expiry. Keep all medicines out of the reach of children. To be dispensed only on the prescription of a registered physician

First generation Cephalosporins

Cephradine is a semisynthetic broad spectrum bactericidal antibiotic, it is active against infections caused by both gram-positive and gram-negative microorganisms. Both penicillinase producing and nonproducing staphylococci are sensitive to Cephradine. The main site of action of Cephradine is the cell wall of bacteria. Cell wall of sensitive organism contains peptidoglycan. Cephradine inhibits cross-linking process and as a result cell wall with many pores are formed, thus lysis of bacteria occur due to external osmotic pressure.

For oral administration-
Adults:

• Urinary tract infections: 500mg four times daily or 1g twice daily. Infections which are severe or chronic may necessitate the administration of higher doses. Where complications arise including prostatitis and epididymitis continued intensive treatment is required.
• Respiratory tract infections: 250 to 500mg four times daily or 500mg to 1g twice daily, dependent on the site and severity of the infection.
• Skin and soft tissue infections: 250 to 500mg four times daily or 500mg to 1g twice daily, again dependent on the site and severity of the infection.

Children:

• Total daily dose of 25 to 50mg/kg given in two or four equally divided doses.
• Otitis media: Total daily dose of 75 to 100mg/kg given in divided doses 6 to 12 hourly.
• Maximum daily dosage: 4 gm

Elderly: The normal adult dose is appropriate. Patients with impaired renal or hepatic function should be monitored during treatment.

For injectable administration-

• Adult: The usual dose is 2-4 gm daily in four equally divided doses up to 8 gm daily. For prophylaxis a single preoperative dose of 1-2 gm intramuscularly or intravenously is given.
• Children: The dose is 50-100 mg/kg daily in four equally divided doses, up to 300 mg/kg daily in severe infection.

Limited essentially to gastro-intestinal disturbances and on occasions to hypersensitivity phenomena. The latter are more likely to occur in individuals, who have previously demonstrated hypersensitivity and thos with a history of allergy, asthma, hay fever or urticaria. Skin reactions have occasionally been reported. Rare- Glossitis, heartburn, dizziness, tightness in the chest, nausea, vomiting, diarrhoea, abdominal pain, vaginitis, candida overgrowth. Skin and hypersensitivity reactions include urticaria, skin rashes, joint pains, oedema.

• Blood and lymphatic system disorders- Unknown: blood disorders (including thrombocytopenia, leucopenia, agranulocytosis, aplastic anaemia and haemolytic anaemia)
• Immune system disorders- Unknown: Fever, serum sickness like reactions, anaphylaxis
• Psychiatric disorders- Unknown: Confusion, sleep disturbances
• Nervous system disorders- Unknown: hyperactivity, hypertonia, dizziness, nervousness; Rarely: Headache
• Hepatobiliary disorders- Frequency unknown: Liver, enzyme disturbances, transient hepatitis, cholestatic jaundice
• Renal and urinary disorders- Unknown: Reversible interstitial nephritis
• Investigations- Unknown: Elevation of blood urea nitrogen, serum creatinine, alanine aminotransferase, aspartate aminotransferase, total bilirubin, alkaline phosphatase.

Cephradine should not be used in patients with known or suspected hypersensitivity to cephalosporins.

The concomitant use of nephrotoxic drugs such as aminoglycosides with Cefradine may increase the risk of kidney damage. Diuretics (e.g. frusemide, ethacrynic acid) and probenecid enhanced the possibility of renal toxicity.

Although animal studies have not demonstrated any teratogenicity, safety in pregnancy has not been established. Cephradine is excreted in breast milk and should be used with caution in lactating mothers. Since the medicine may cause dizziness, patients should be cautioned about operating hazardous machinery, including automobiles.

Renal Impairment: The following doses are recommended (based on 500 mg every 6 hours) for patients not on haemodialysis:

• CrCl: >20 ml/min: 500 mg every 6 hours
• CrCl: 5-20 ml/min: 250 mg every 6 hours
• CrCl: <5 ml/min: 250 mg every 50-70 hours.

Recommendations for patients on chronic, intermittent haemodialysis:

• 250 mg at the start of haemodialysis
• 250 mg 6 to 12 hours after the start
• 250 mg 36 to 48 hours after the start
• 250 mg at the start of the next haemodialysis session if more than 30 hours have elapsed since the last dose.

Additional Information for all patients Regardless of patient age or weight, higher doses of up to 1 gm four times daily may be required for infections which are chronic or severe. Treatment should continue for at least 2 to 3 days after symptoms have resolved or bacteria have been eradicated. To reduce the possibility of rheumatic fever or glomerulonephritis resulting from infections with haemolytic streptococci, treatment should be continued for at least 10 days. Throughout treatment of chronic urinary tract infections and for several months thereafter, regular bacteriological and clinical monitoring is required.

Doses below those recommended above should not be prescribed. Paediatric dosages should not exceed those specified for adults, regardless of severity of infection. It may be necessary to continue Cephradine therapy for several weeks in persistent infections. Patients may be transferred from intramuscular/intravenous Cephradine therapy to oral treatment at the same dosage level.

The symptoms of Sefrad overdose are non-specific and are generally nausea, vomiting, diarrhoea and gastric upsets. Treatment is mainly supportive although gastric lavage will be necessary if a large amount has been ingested.

Cephradine Suspension should be freshly prepared. Reconstituted Suspension should be used within 7 days if kept at room temperature or within 14 days, if kept in a refrigerator. Cephradine Injection solutions should be used within 2 hours when kept at room temperature. When stored at 5°C, solutions retain potency for 12 hours. Reconstituted solutions may vary in colour from light to straw yellow; however, this does not affect the potency. Do not use later than the date of expiry. Keep all medicines out of the reach of children. To be dispensed only on the prescription of a registered physician

First generation Cephalosporins

Cephradine is a semisynthetic broad spectrum bactericidal antibiotic, it is active against infections caused by both gram-positive and gram-negative microorganisms. Both penicillinase producing and nonproducing staphylococci are sensitive to Cephradine. The main site of action of Cephradine is the cell wall of bacteria. Cell wall of sensitive organism contains peptidoglycan. Cephradine inhibits cross-linking process and as a result cell wall with many pores are formed, thus lysis of bacteria occur due to external osmotic pressure.

For oral administration-
Adults:

• Urinary tract infections: 500mg four times daily or 1g twice daily. Infections which are severe or chronic may necessitate the administration of higher doses. Where complications arise including prostatitis and epididymitis continued intensive treatment is required.
• Respiratory tract infections: 250 to 500mg four times daily or 500mg to 1g twice daily, dependent on the site and severity of the infection.
• Skin and soft tissue infections: 250 to 500mg four times daily or 500mg to 1g twice daily, again dependent on the site and severity of the infection.

Children:

• Total daily dose of 25 to 50mg/kg given in two or four equally divided doses.
• Otitis media: Total daily dose of 75 to 100mg/kg given in divided doses 6 to 12 hourly.
• Maximum daily dosage: 4 gm

Elderly: The normal adult dose is appropriate. Patients with impaired renal or hepatic function should be monitored during treatment.

For injectable administration-

• Adult: The usual dose is 2-4 gm daily in four equally divided doses up to 8 gm daily. For prophylaxis a single preoperative dose of 1-2 gm intramuscularly or intravenously is given.
• Children: The dose is 50-100 mg/kg daily in four equally divided doses, up to 300 mg/kg daily in severe infection.

Limited essentially to gastro-intestinal disturbances and on occasions to hypersensitivity phenomena. The latter are more likely to occur in individuals, who have previously demonstrated hypersensitivity and thos with a history of allergy, asthma, hay fever or urticaria. Skin reactions have occasionally been reported. Rare- Glossitis, heartburn, dizziness, tightness in the chest, nausea, vomiting, diarrhoea, abdominal pain, vaginitis, candida overgrowth. Skin and hypersensitivity reactions include urticaria, skin rashes, joint pains, oedema.

• Blood and lymphatic system disorders- Unknown: blood disorders (including thrombocytopenia, leucopenia, agranulocytosis, aplastic anaemia and haemolytic anaemia)
• Immune system disorders- Unknown: Fever, serum sickness like reactions, anaphylaxis
• Psychiatric disorders- Unknown: Confusion, sleep disturbances
• Nervous system disorders- Unknown: hyperactivity, hypertonia, dizziness, nervousness; Rarely: Headache
• Hepatobiliary disorders- Frequency unknown: Liver, enzyme disturbances, transient hepatitis, cholestatic jaundice
• Renal and urinary disorders- Unknown: Reversible interstitial nephritis
• Investigations- Unknown: Elevation of blood urea nitrogen, serum creatinine, alanine aminotransferase, aspartate aminotransferase, total bilirubin, alkaline phosphatase.

Cephradine should not be used in patients with known or suspected hypersensitivity to cephalosporins.

The concomitant use of nephrotoxic drugs such as aminoglycosides with Cefradine may increase the risk of kidney damage. Diuretics (e.g. frusemide, ethacrynic acid) and probenecid enhanced the possibility of renal toxicity.

Although animal studies have not demonstrated any teratogenicity, safety in pregnancy has not been established. Cephradine is excreted in breast milk and should be used with caution in lactating mothers. Since the medicine may cause dizziness, patients should be cautioned about operating hazardous machinery, including automobiles.

Renal Impairment: The following doses are recommended (based on 500 mg every 6 hours) for patients not on haemodialysis:

• CrCl: >20 ml/min: 500 mg every 6 hours
• CrCl: 5-20 ml/min: 250 mg every 6 hours
• CrCl: <5 ml/min: 250 mg every 50-70 hours.

Recommendations for patients on chronic, intermittent haemodialysis:

• 250 mg at the start of haemodialysis
• 250 mg 6 to 12 hours after the start
• 250 mg 36 to 48 hours after the start
• 250 mg at the start of the next haemodialysis session if more than 30 hours have elapsed since the last dose.

Additional Information for all patients Regardless of patient age or weight, higher doses of up to 1 gm four times daily may be required for infections which are chronic or severe. Treatment should continue for at least 2 to 3 days after symptoms have resolved or bacteria have been eradicated. To reduce the possibility of rheumatic fever or glomerulonephritis resulting from infections with haemolytic streptococci, treatment should be continued for at least 10 days. Throughout treatment of chronic urinary tract infections and for several months thereafter, regular bacteriological and clinical monitoring is required.

Doses below those recommended above should not be prescribed. Paediatric dosages should not exceed those specified for adults, regardless of severity of infection. It may be necessary to continue Cephradine therapy for several weeks in persistent infections. Patients may be transferred from intramuscular/intravenous Cephradine therapy to oral treatment at the same dosage level.

The symptoms of Sefrad overdose are non-specific and are generally nausea, vomiting, diarrhoea and gastric upsets. Treatment is mainly supportive although gastric lavage will be necessary if a large amount has been ingested.

Cephradine Suspension should be freshly prepared. Reconstituted Suspension should be used within 7 days if kept at room temperature or within 14 days, if kept in a refrigerator. Cephradine Injection solutions should be used within 2 hours when kept at room temperature. When stored at 5°C, solutions retain potency for 12 hours. Reconstituted solutions may vary in colour from light to straw yellow; however, this does not affect the potency. Do not use later than the date of expiry. Keep all medicines out of the reach of children. To be dispensed only on the prescription of a registered physician

Dipeptidyl Peptidase-4 (DPP-4) inhibitor

Linagliptin is indicated to improve glycemic control in patients with type 2 diabetes mellitus. Linagliptin is an inhibitor of DPP-4 (dipeptidyl peptidase-4), an enzyme that degrades the incretin hormones GLP-1 (glucagon like peptide-1) and GIP (glucose dependent insulinotropic polypeptide). Thus, Linagliptin increases the concentrations of active incretin hormones, stimulating the release of insulin from pancreatic beta (β) cells in a glucose-dependent manner and decreasing the secretion of glucagon from pancreatic alpha (α) cells in the circulation.

Linagliptin 5 mg once daily. If added to metformin, the dose of metformin should be maintained and linagliptin administered concomitantly. When used in combination with a sulfonylurea, a lower dose of the sulphonylurea may be considered to reduce the risk of hypoglycaemia.

Patients with renal impairment: No dose adjustment required. Linagliptin can be taken with or without a meal at any time of the day.

There may be hypoglycaemia, nasopharyngitis, cough and pancreatitis in combination with metformin and sulfonylurea.

Hypersensitivity to the active substance or to any of the excipients.

Hypersensitivity to the active substance or to any of the excipients.

Linagliptin is a weak competitive and a weak to moderate mechanism-based inhibitor of CYP isozyme CYP3A4, but does not inhibit other CYP isozymes. The risk for clinically meaningful interactions by other medicinal products on linagliptin is low and in clinical studies linagliptin had no clinically relevant effect on the pharmacokinetics of metformin, glyburide, simvastatin, warfarin, digoxin or oral contraceptives.

Pregnancy category B. There are no adequate and well controlled studies in pregnant women. So, Linagliptin tablets should be used during pregnancy only if clearly needed. It is not known whether Linagliptin passes into breast milk or not.

Keep in a dry place away from light and heat. Keep out of the reach of children.

This is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus when treatment with both Linagliptin and Metformin Hydrochloride is appropriate

Combination Oral hypoglycemic preparations

Linagliptin is indicated to improve glycemic control in patients with type 2 diabetes mellitus. Linagliptin is an inhibitor of DPP-4 (dipeptidyl peptidase-4), an enzyme that degrades the incretin hormones GLP-1 (glucagon like peptide-1) and GIP (glucose dependent insulinotropic polypeptide). Thus, Linagliptin increases the concentrations of active incretin hormones, stimulating the release of insulin from pancreatic beta (β) cells in a glucose-dependent manner and decreasing the secretion of glucagon from pancreatic alpha (α) cells in the circulation.

Metformin Hydrochloride is a biguanide type oral antihyperglycemic drug used in the management of type 2 diabetes. It lowers both basal and postprandial plasma glucose. Its mechanism of action is different from those of sulfonylureas and it does not produce hypoglycemia. Metformin Hydrochloride decreases hepatic glucose production, decreases intestinal absorption of glucose and improves insulin sensitivity by an increase in peripheral glucose uptake and utilization.

Linagliptin & Metformin immediate release tablet: The dosage of Linagliptin & Metformin should be individualized on the basis of both effectiveness and tolerability. Maximum recommended dose of 2.5 mg Linagliptin and 1000 mg Metformin Hydrochloride twice daily with meals. Dose escalation should be gradual to reduce the gastrointestinal (GI) side effects associated with Metformin Hydrochloride use.

Recommended starting dose: In patients currently not treated with Metformin Hydrochloride, initiate treatment with 2.5 mg Linagliptin and 500 mg Metformin Hydrochloride twice daily.

In patients already treated with Metformin Hydrochloride, start with 2.5 mg Linagliptin and the current dose of Metformin Hydrochloride twice daily.

Patients already treated with Linagliptin and Metformin Hydrochloride, individual components may be switched to this combination containing the same doses of each component.


Linagliptin & Metformin extend release tablet: The dosage of this combination should be individualized on the basis of both effectiveness and tolerability, while not exceeding the maximum recommended total daily dose of Linagliptin 5 mg and Metformin Hydrochloride 2000 mg. this combination should be given once daily with a meal.

Recommended starting dose: In patients currently not treated with metformin, initiate this combination treatment with 5 mg Linagliptin/1000 mg Metformin Hydrochloride extended-release once daily with a meal.

In patients already treated with Metformin, start this combination with 5 mg of Linagliptin total daily dose and a similar total daily dose of Metformin once daily with a meal.

In patients already treated with Linagliptin & Metformin immediate release tablet, switch to extend release tablet containing 5 mg of Linagliptin total daily dose and a similar total daily dose of Metformin once daily with a meal.

5 mg Linagliptin & 1000 mg Metformin Hydrochloride extended-release tablet should be taken as a single tablet once daily. Patients using 2.5 mg Linagliptin & 1000 mg Metformin extended release tablets should take two tablets together once daily.

Most common side effects are nasopharyngitis and diarrhea. Hypoglycemia is more common in patients treated with this combination and sulfonylureas.

Although Linagliptin undergoes minimal renal excretion, Metformin Hydrochloride is known to be substantially excreted by the kidney. The risk of Metformin Hydrochloride accumulation and lactic acidosis increases with the degree of renal impairment. Therefore, this combination is contraindicated in patients with renal impairment. It is also contraindicated in acute or chronic metabolic acidosis (diabetic ketoacidosis) and in hypersensitivity to Linagliptin or Metformin Hydrochloride.

In a patient with lactic acidosis who is taking Metformin, the drug should be discontinued immediately and supportive therapy promptly instituted. There have been postmarketing reports of acute pancreatitis. If pancreatitis is suspected, promptly discontinue Linagliptin & Metformin. Temporarily discontinue Linagliptin & Metformin in patients undergoing radiologic studies with intravascular administration of iodinated contrast materials or any surgical procedures necessitating restricted intake of food and fluids. Metformin may lower Vitamin B12 levels; so hematologic parameters shoud be monitored annually.

Cationic drugs (amiloride, digoxin, morphine, ranitidine, trimethoprim etc.): May reduce metformin elimination.

P-glycoprotien/CYP3A4 inducer (i.e. rifampin): The efficacy of this medicine may be reduced when administered in combination.

There are no adequate and well-controlled studies in pregnant women with this combination or its individual component; so it should be used during pregnancy only if clearly needed. Caution should also be excercised when it is administered to a lactating mother.

In the event of an overdose with this combination the usual supportive measures (i.e. remove unabsorbed material from the gastrointestinal tract, perform clinical monitoring, and institute supportive treatment) should be employed. Removal of Linagliptin by hemodialysis or peritoneal dialysis is unlikely but Metformin Hydrochloride is dialyzable.

During controlled clinical trials in healthy subjects, with single doses of up to 600 mg of Linagliptin (equivalent to 120 times the recommended daily dose), there were no dose-related clinical adverse drug reactions.

Overdose of Metformin Hydrochloride has occurred in case of ingestion of amounts greater than 50 grams. Hypoglycemia was reported in approximately 10% of cases, but no causal association with Metformin Hydrochloride has been established. Lactic acidosis has been reported in approximately 32% of Metformin Hydrochloride overdose cases.

Keep in a cool & dry place (below 30°C), protected from light & moisture. Keep out of the reach of children.

This is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus when treatment with both Linagliptin and Metformin Hydrochloride is appropriate

Combination Oral hypoglycemic preparations

Linagliptin is indicated to improve glycemic control in patients with type 2 diabetes mellitus. Linagliptin is an inhibitor of DPP-4 (dipeptidyl peptidase-4), an enzyme that degrades the incretin hormones GLP-1 (glucagon like peptide-1) and GIP (glucose dependent insulinotropic polypeptide). Thus, Linagliptin increases the concentrations of active incretin hormones, stimulating the release of insulin from pancreatic beta (β) cells in a glucose-dependent manner and decreasing the secretion of glucagon from pancreatic alpha (α) cells in the circulation.

Metformin Hydrochloride is a biguanide type oral antihyperglycemic drug used in the management of type 2 diabetes. It lowers both basal and postprandial plasma glucose. Its mechanism of action is different from those of sulfonylureas and it does not produce hypoglycemia. Metformin Hydrochloride decreases hepatic glucose production, decreases intestinal absorption of glucose and improves insulin sensitivity by an increase in peripheral glucose uptake and utilization.

Linagliptin & Metformin immediate release tablet: The dosage of Linagliptin & Metformin should be individualized on the basis of both effectiveness and tolerability. Maximum recommended dose of 2.5 mg Linagliptin and 1000 mg Metformin Hydrochloride twice daily with meals. Dose escalation should be gradual to reduce the gastrointestinal (GI) side effects associated with Metformin Hydrochloride use.

Recommended starting dose: In patients currently not treated with Metformin Hydrochloride, initiate treatment with 2.5 mg Linagliptin and 500 mg Metformin Hydrochloride twice daily.

In patients already treated with Metformin Hydrochloride, start with 2.5 mg Linagliptin and the current dose of Metformin Hydrochloride twice daily.

Patients already treated with Linagliptin and Metformin Hydrochloride, individual components may be switched to this combination containing the same doses of each component.


Linagliptin & Metformin extend release tablet: The dosage of this combination should be individualized on the basis of both effectiveness and tolerability, while not exceeding the maximum recommended total daily dose of Linagliptin 5 mg and Metformin Hydrochloride 2000 mg. this combination should be given once daily with a meal.

Recommended starting dose: In patients currently not treated with metformin, initiate this combination treatment with 5 mg Linagliptin/1000 mg Metformin Hydrochloride extended-release once daily with a meal.

In patients already treated with Metformin, start this combination with 5 mg of Linagliptin total daily dose and a similar total daily dose of Metformin once daily with a meal.

In patients already treated with Linagliptin & Metformin immediate release tablet, switch to extend release tablet containing 5 mg of Linagliptin total daily dose and a similar total daily dose of Metformin once daily with a meal.

5 mg Linagliptin & 1000 mg Metformin Hydrochloride extended-release tablet should be taken as a single tablet once daily. Patients using 2.5 mg Linagliptin & 1000 mg Metformin extended release tablets should take two tablets together once daily.

Most common side effects are nasopharyngitis and diarrhea. Hypoglycemia is more common in patients treated with this combination and sulfonylureas.

Although Linagliptin undergoes minimal renal excretion, Metformin Hydrochloride is known to be substantially excreted by the kidney. The risk of Metformin Hydrochloride accumulation and lactic acidosis increases with the degree of renal impairment. Therefore, this combination is contraindicated in patients with renal impairment. It is also contraindicated in acute or chronic metabolic acidosis (diabetic ketoacidosis) and in hypersensitivity to Linagliptin or Metformin Hydrochloride.

In a patient with lactic acidosis who is taking Metformin, the drug should be discontinued immediately and supportive therapy promptly instituted. There have been postmarketing reports of acute pancreatitis. If pancreatitis is suspected, promptly discontinue Linagliptin & Metformin. Temporarily discontinue Linagliptin & Metformin in patients undergoing radiologic studies with intravascular administration of iodinated contrast materials or any surgical procedures necessitating restricted intake of food and fluids. Metformin may lower Vitamin B12 levels; so hematologic parameters shoud be monitored annually.

Cationic drugs (amiloride, digoxin, morphine, ranitidine, trimethoprim etc.): May reduce metformin elimination.

P-glycoprotien/CYP3A4 inducer (i.e. rifampin): The efficacy of this medicine may be reduced when administered in combination.

There are no adequate and well-controlled studies in pregnant women with this combination or its individual component; so it should be used during pregnancy only if clearly needed. Caution should also be excercised when it is administered to a lactating mother.

In the event of an overdose with this combination the usual supportive measures (i.e. remove unabsorbed material from the gastrointestinal tract, perform clinical monitoring, and institute supportive treatment) should be employed. Removal of Linagliptin by hemodialysis or peritoneal dialysis is unlikely but Metformin Hydrochloride is dialyzable.

During controlled clinical trials in healthy subjects, with single doses of up to 600 mg of Linagliptin (equivalent to 120 times the recommended daily dose), there were no dose-related clinical adverse drug reactions.

Overdose of Metformin Hydrochloride has occurred in case of ingestion of amounts greater than 50 grams. Hypoglycemia was reported in approximately 10% of cases, but no causal association with Metformin Hydrochloride has been established. Lactic acidosis has been reported in approximately 32% of Metformin Hydrochloride overdose cases.

Keep in a cool & dry place (below 30°C), protected from light & moisture. Keep out of the reach of children.

This is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus when treatment with both Linagliptin and Metformin Hydrochloride is appropriate

Combination Oral hypoglycemic preparations

Linagliptin is indicated to improve glycemic control in patients with type 2 diabetes mellitus. Linagliptin is an inhibitor of DPP-4 (dipeptidyl peptidase-4), an enzyme that degrades the incretin hormones GLP-1 (glucagon like peptide-1) and GIP (glucose dependent insulinotropic polypeptide). Thus, Linagliptin increases the concentrations of active incretin hormones, stimulating the release of insulin from pancreatic beta (β) cells in a glucose-dependent manner and decreasing the secretion of glucagon from pancreatic alpha (α) cells in the circulation.

Metformin Hydrochloride is a biguanide type oral antihyperglycemic drug used in the management of type 2 diabetes. It lowers both basal and postprandial plasma glucose. Its mechanism of action is different from those of sulfonylureas and it does not produce hypoglycemia. Metformin Hydrochloride decreases hepatic glucose production, decreases intestinal absorption of glucose and improves insulin sensitivity by an increase in peripheral glucose uptake and utilization.

Linagliptin & Metformin immediate release tablet: The dosage of Linagliptin & Metformin should be individualized on the basis of both effectiveness and tolerability. Maximum recommended dose of 2.5 mg Linagliptin and 1000 mg Metformin Hydrochloride twice daily with meals. Dose escalation should be gradual to reduce the gastrointestinal (GI) side effects associated with Metformin Hydrochloride use.

Recommended starting dose: In patients currently not treated with Metformin Hydrochloride, initiate treatment with 2.5 mg Linagliptin and 500 mg Metformin Hydrochloride twice daily.

In patients already treated with Metformin Hydrochloride, start with 2.5 mg Linagliptin and the current dose of Metformin Hydrochloride twice daily.

Patients already treated with Linagliptin and Metformin Hydrochloride, individual components may be switched to this combination containing the same doses of each component.


Linagliptin & Metformin extend release tablet: The dosage of this combination should be individualized on the basis of both effectiveness and tolerability, while not exceeding the maximum recommended total daily dose of Linagliptin 5 mg and Metformin Hydrochloride 2000 mg. this combination should be given once daily with a meal.

Recommended starting dose: In patients currently not treated with metformin, initiate this combination treatment with 5 mg Linagliptin/1000 mg Metformin Hydrochloride extended-release once daily with a meal.

In patients already treated with Metformin, start this combination with 5 mg of Linagliptin total daily dose and a similar total daily dose of Metformin once daily with a meal.

In patients already treated with Linagliptin & Metformin immediate release tablet, switch to extend release tablet containing 5 mg of Linagliptin total daily dose and a similar total daily dose of Metformin once daily with a meal.

5 mg Linagliptin & 1000 mg Metformin Hydrochloride extended-release tablet should be taken as a single tablet once daily. Patients using 2.5 mg Linagliptin & 1000 mg Metformin extended release tablets should take two tablets together once daily.

Most common side effects are nasopharyngitis and diarrhea. Hypoglycemia is more common in patients treated with this combination and sulfonylureas.

Although Linagliptin undergoes minimal renal excretion, Metformin Hydrochloride is known to be substantially excreted by the kidney. The risk of Metformin Hydrochloride accumulation and lactic acidosis increases with the degree of renal impairment. Therefore, this combination is contraindicated in patients with renal impairment. It is also contraindicated in acute or chronic metabolic acidosis (diabetic ketoacidosis) and in hypersensitivity to Linagliptin or Metformin Hydrochloride.

In a patient with lactic acidosis who is taking Metformin, the drug should be discontinued immediately and supportive therapy promptly instituted. There have been postmarketing reports of acute pancreatitis. If pancreatitis is suspected, promptly discontinue Linagliptin & Metformin. Temporarily discontinue Linagliptin & Metformin in patients undergoing radiologic studies with intravascular administration of iodinated contrast materials or any surgical procedures necessitating restricted intake of food and fluids. Metformin may lower Vitamin B12 levels; so hematologic parameters shoud be monitored annually.

Cationic drugs (amiloride, digoxin, morphine, ranitidine, trimethoprim etc.): May reduce metformin elimination.

P-glycoprotien/CYP3A4 inducer (i.e. rifampin): The efficacy of this medicine may be reduced when administered in combination.

There are no adequate and well-controlled studies in pregnant women with this combination or its individual component; so it should be used during pregnancy only if clearly needed. Caution should also be excercised when it is administered to a lactating mother.

In the event of an overdose with this combination the usual supportive measures (i.e. remove unabsorbed material from the gastrointestinal tract, perform clinical monitoring, and institute supportive treatment) should be employed. Removal of Linagliptin by hemodialysis or peritoneal dialysis is unlikely but Metformin Hydrochloride is dialyzable.

During controlled clinical trials in healthy subjects, with single doses of up to 600 mg of Linagliptin (equivalent to 120 times the recommended daily dose), there were no dose-related clinical adverse drug reactions.

Overdose of Metformin Hydrochloride has occurred in case of ingestion of amounts greater than 50 grams. Hypoglycemia was reported in approximately 10% of cases, but no causal association with Metformin Hydrochloride has been established. Lactic acidosis has been reported in approximately 32% of Metformin Hydrochloride overdose cases.

Keep in a cool & dry place (below 30°C), protected from light & moisture. Keep out of the reach of children.

Macrolides

Linezolid is a synthetic, antibacterial agent belonging to a new class of antibiotics, the oxazolidinones, with in vitro activity against Gram positive aerobic bacteria, some Gram positive anaerobic bacteria and certain Gram negative bacteria. It selectively inhibits bacterial protein synthesis via a mechanism of action different from that of other antibacterial agents. Linezolid binds to the 23S ribosomal RNA of the 50S subunit of the bacterial ribosome and prevents the formation of a functional 70S initiation complex which is an essential component of the bacterial translation process. The results of time-kill studies have shown Linezolid to be bacteriostatic against enterococci and staphylococci. For streptococci, Linezolid was found to be bactericidal for the majority of strains.

Patients who commence treatment on the parenteral formulation may be switched to oral presentation when clinically indicated. In such circumstances, no dose adjustment is required as Linezolid has an oral bioavailability of approximately 100%. The injection should be administered over a period of 30 to 120 minutes. The film-coated tablets or oral suspension may be taken with or without food.

Complicated skin and skin structure infections, Community-acquired pneumonia, including concurrent bacteremia-

• Pediatric Patients (Birth through 11 Years of Age): 10 mg/kg IV or oral t.i.d.
• Adults and Adolescents (12 Years and Older): 600 mg IV or oral b.i.d.
• Recommended Duration of Treatment (consecutive days): 10 to 14

Nosocomial pneumonia, Vancomycin-resistant Enterococcus faecium infections including concurrent bacteremia-

• Pediatric Patients (Birth through 11 Years of Age): 10 mg/kg IV or oral t.i.d.
• Adults and Adolescents (12 Years and Older): 600 mg IV or oral b.i.d.
• Recommended Duration of Treatment (consecutive days): 14 to 28

Uncomplicated skin and skin structure infections-

• Pediatric Patients (Birth through 11 Years of Age): <5 yrs: 10 mg/kg oral t.i.d. 5-11 yrs: 10 mg/kg oral b.i.d
• Adults and Adolescents (12 Years and Older): Adults: 400 mg oral b.i.d. Adolescents: 600 mg oral b.i.d
• Recommended Duration of Treatment (consecutive days): 10 to 14

Neonates <7 days: Most pre-term neonates <7 days of age (gestational age <34 weeks) have lower systemic Linezolid clearance values and larger AUC values than many full-term neonates and older infants. These neonates should be initiated with a dosing regimen of 10 mg/kg every 12 hours. Consideration may be given to the use of 10 mg/kg in every eight hours regimen in neonates with a sub-optimal clinical response. All neonatal patients should receive 10 mg/kg t.i.d. by 7 days of life.

Reconstitution of Oral Suspension: Shake the bottle to loosen powder. Add 75 ml (with the help of given cup) of boiled and cooled water to the dry mixture in the bottle. For the ease of preparation, add water to the bottle in two portions. Shake well after each addition until all the powder is in suspension.

Note: Shake the suspension well before each use. Keep the bottle tightly closed. The reconstituted suspension should be stored in a cool and dry place. Use within 21 days after constitution.

Intravenous Administration: Linezolid IV Injection is supplied in single-use, ready-to-use infusion bottles. Linezolid IV Injection should be administered by intravenous infusion over a period of 30 to 120 minutes. The intravenous infusion bottles should not be used in series connections. Additives should not be introduced into this solution. The infusion bottles should be stored at room temperature and protected from freezing. Linezolid IV Injection may exhibit a yellow color that can intensify over time without adversely affecting potency.

Most of the adverse events reported with Linezolid were mild to moderate in intensity. The most common adverse events in patients treated with Linezolid were diarrhea, headache and nausea. Other adverse events includes oral moniliasis, vaginal moniliasis, hypertension, dyspepsia, localized abdominal pain, pruritus, and tongue discoloration.

Linezolid formulations are contraindicated for using in patients who have known hypersensitivity to Linezolid or any of the other product components. Linezolid should not be used in patients taking any medicinal product which inhibits monoamine oxidases A or B (e.g. Phenelzine, Isocarboxazid) or within two weeks of taking any such medicinal product. Linezolid should not be administered to patients with uncontrolled hypertension, pheochromocytoma, thyrotoxicosis, carcinoid syndrome and/or patients taking directly and indirectly acting sympathomimetic agents (e.g. Pseudoephedrine), vasopressive agents (e.g. Epinephrine, Norepinephrine), dopaminergic agents (e.g. Dopamine, Dobutamine), serotonin re-uptake inhibitors, tricyclic antidepressants, serotonin 5-HT1 receptor agonists (triptans), meperidine or buspirone.

Patients who develop recurrent nausea or vomiting, unexplained acidosis or low bicarbonate level while receiving Linezolid should receive immediate medical evaluation. Where administration of Linezolid and concomitant serotonergic agents are clinically appropriate, patients should be closely observed for signs and symptoms of serotonin syndrome such as cognitive dysfunction, hyperpyrexia, hyperreflexia and incoordination. If signs or symptoms occur, physicians should consider discontinuation of either one or both agents. If the concomitant serotonergic agent is withdrawn, discontinuation symptoms can be observed. If patients experience symptoms of visual impairment, such as changes in visual acuity, changes in color vision, blurred vision or visual field defect, prompt ophthalmic evaluation is recommended. Convulsions have been reported in patients when treated with Linezolid. In some of these cases, a history of seizures or risk factors for seizures was reported.

Monoamine Oxidase Inhibition: Linezolid is a reversible and nonselective inhibitor of monoamine oxidase. Therefore, Linezolid has the potential for interaction with adrenergic and serotonergic agents.

Adrenergic Agents: Some individuals receiving Linezolid may experience a reversible enhancement of the pressor response to indirect-acting sympathomimetic agents, vasopressor or dopaminergic agents. Initial doses of adrenergic agents such as dopamine or epinephrine should be reduced and titrated to achieve the desired response.

Serotonergic Agents: Physicians should be alert to the possible signs and symptoms of serotonergic syndrome in patients receiving concomitant Linezolid and serotonergic agents.

Pregnancy Category C. There are no adequate and well-controlled studies in pregnant women. Linezolid should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. It is not known whether Linezolid is excreted in human milk. Because many drugs are excreted in human milk. Caution should be exercised when Linezolid is administered to a nursing woman.

No cases of overdose have been reported. Symptomatic and supportive care is advised together with maintenance of glomerular filtration. Approximately 30% of a Linezolid dose is removed during 3 hours of haemodialysis. No data are available for the removal of Linezolid by peritoneal dialysis or haemoperfusion.

Linezolid formulations should be stored at room temperature (15°C-30°C), away from light and moisture. All medicines should be kept away from children.

Macrolides

Linezolid is a synthetic, antibacterial agent belonging to a new class of antibiotics, the oxazolidinones, with in vitro activity against Gram positive aerobic bacteria, some Gram positive anaerobic bacteria and certain Gram negative bacteria. It selectively inhibits bacterial protein synthesis via a mechanism of action different from that of other antibacterial agents. Linezolid binds to the 23S ribosomal RNA of the 50S subunit of the bacterial ribosome and prevents the formation of a functional 70S initiation complex which is an essential component of the bacterial translation process. The results of time-kill studies have shown Linezolid to be bacteriostatic against enterococci and staphylococci. For streptococci, Linezolid was found to be bactericidal for the majority of strains.

Patients who commence treatment on the parenteral formulation may be switched to oral presentation when clinically indicated. In such circumstances, no dose adjustment is required as Linezolid has an oral bioavailability of approximately 100%. The injection should be administered over a period of 30 to 120 minutes. The film-coated tablets or oral suspension may be taken with or without food.

Complicated skin and skin structure infections, Community-acquired pneumonia, including concurrent bacteremia-

• Pediatric Patients (Birth through 11 Years of Age): 10 mg/kg IV or oral t.i.d.
• Adults and Adolescents (12 Years and Older): 600 mg IV or oral b.i.d.
• Recommended Duration of Treatment (consecutive days): 10 to 14

Nosocomial pneumonia, Vancomycin-resistant Enterococcus faecium infections including concurrent bacteremia-

• Pediatric Patients (Birth through 11 Years of Age): 10 mg/kg IV or oral t.i.d.
• Adults and Adolescents (12 Years and Older): 600 mg IV or oral b.i.d.
• Recommended Duration of Treatment (consecutive days): 14 to 28

Uncomplicated skin and skin structure infections-

• Pediatric Patients (Birth through 11 Years of Age): <5 yrs: 10 mg/kg oral t.i.d. 5-11 yrs: 10 mg/kg oral b.i.d
• Adults and Adolescents (12 Years and Older): Adults: 400 mg oral b.i.d. Adolescents: 600 mg oral b.i.d
• Recommended Duration of Treatment (consecutive days): 10 to 14

Neonates <7 days: Most pre-term neonates <7 days of age (gestational age <34 weeks) have lower systemic Linezolid clearance values and larger AUC values than many full-term neonates and older infants. These neonates should be initiated with a dosing regimen of 10 mg/kg every 12 hours. Consideration may be given to the use of 10 mg/kg in every eight hours regimen in neonates with a sub-optimal clinical response. All neonatal patients should receive 10 mg/kg t.i.d. by 7 days of life.

Reconstitution of Oral Suspension: Shake the bottle to loosen powder. Add 75 ml (with the help of given cup) of boiled and cooled water to the dry mixture in the bottle. For the ease of preparation, add water to the bottle in two portions. Shake well after each addition until all the powder is in suspension.

Note: Shake the suspension well before each use. Keep the bottle tightly closed. The reconstituted suspension should be stored in a cool and dry place. Use within 21 days after constitution.

Intravenous Administration: Linezolid IV Injection is supplied in single-use, ready-to-use infusion bottles. Linezolid IV Injection should be administered by intravenous infusion over a period of 30 to 120 minutes. The intravenous infusion bottles should not be used in series connections. Additives should not be introduced into this solution. The infusion bottles should be stored at room temperature and protected from freezing. Linezolid IV Injection may exhibit a yellow color that can intensify over time without adversely affecting potency.

Most of the adverse events reported with Linezolid were mild to moderate in intensity. The most common adverse events in patients treated with Linezolid were diarrhea, headache and nausea. Other adverse events includes oral moniliasis, vaginal moniliasis, hypertension, dyspepsia, localized abdominal pain, pruritus, and tongue discoloration.

Linezolid formulations are contraindicated for using in patients who have known hypersensitivity to Linezolid or any of the other product components. Linezolid should not be used in patients taking any medicinal product which inhibits monoamine oxidases A or B (e.g. Phenelzine, Isocarboxazid) or within two weeks of taking any such medicinal product. Linezolid should not be administered to patients with uncontrolled hypertension, pheochromocytoma, thyrotoxicosis, carcinoid syndrome and/or patients taking directly and indirectly acting sympathomimetic agents (e.g. Pseudoephedrine), vasopressive agents (e.g. Epinephrine, Norepinephrine), dopaminergic agents (e.g. Dopamine, Dobutamine), serotonin re-uptake inhibitors, tricyclic antidepressants, serotonin 5-HT1 receptor agonists (triptans), meperidine or buspirone.

Patients who develop recurrent nausea or vomiting, unexplained acidosis or low bicarbonate level while receiving Linezolid should receive immediate medical evaluation. Where administration of Linezolid and concomitant serotonergic agents are clinically appropriate, patients should be closely observed for signs and symptoms of serotonin syndrome such as cognitive dysfunction, hyperpyrexia, hyperreflexia and incoordination. If signs or symptoms occur, physicians should consider discontinuation of either one or both agents. If the concomitant serotonergic agent is withdrawn, discontinuation symptoms can be observed. If patients experience symptoms of visual impairment, such as changes in visual acuity, changes in color vision, blurred vision or visual field defect, prompt ophthalmic evaluation is recommended. Convulsions have been reported in patients when treated with Linezolid. In some of these cases, a history of seizures or risk factors for seizures was reported.

Monoamine Oxidase Inhibition: Linezolid is a reversible and nonselective inhibitor of monoamine oxidase. Therefore, Linezolid has the potential for interaction with adrenergic and serotonergic agents.

Adrenergic Agents: Some individuals receiving Linezolid may experience a reversible enhancement of the pressor response to indirect-acting sympathomimetic agents, vasopressor or dopaminergic agents. Initial doses of adrenergic agents such as dopamine or epinephrine should be reduced and titrated to achieve the desired response.

Serotonergic Agents: Physicians should be alert to the possible signs and symptoms of serotonergic syndrome in patients receiving concomitant Linezolid and serotonergic agents.

Pregnancy Category C. There are no adequate and well-controlled studies in pregnant women. Linezolid should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. It is not known whether Linezolid is excreted in human milk. Because many drugs are excreted in human milk. Caution should be exercised when Linezolid is administered to a nursing woman.

No cases of overdose have been reported. Symptomatic and supportive care is advised together with maintenance of glomerular filtration. Approximately 30% of a Linezolid dose is removed during 3 hours of haemodialysis. No data are available for the removal of Linezolid by peritoneal dialysis or haemoperfusion.

Linezolid formulations should be stored at room temperature (15°C-30°C), away from light and moisture. All medicines should be kept away from children.

Macrolides

Linezolid is a synthetic, antibacterial agent belonging to a new class of antibiotics, the oxazolidinones, with in vitro activity against Gram positive aerobic bacteria, some Gram positive anaerobic bacteria and certain Gram negative bacteria. It selectively inhibits bacterial protein synthesis via a mechanism of action different from that of other antibacterial agents. Linezolid binds to the 23S ribosomal RNA of the 50S subunit of the bacterial ribosome and prevents the formation of a functional 70S initiation complex which is an essential component of the bacterial translation process. The results of time-kill studies have shown Linezolid to be bacteriostatic against enterococci and staphylococci. For streptococci, Linezolid was found to be bactericidal for the majority of strains.

Patients who commence treatment on the parenteral formulation may be switched to oral presentation when clinically indicated. In such circumstances, no dose adjustment is required as Linezolid has an oral bioavailability of approximately 100%. The injection should be administered over a period of 30 to 120 minutes. The film-coated tablets or oral suspension may be taken with or without food.

Complicated skin and skin structure infections, Community-acquired pneumonia, including concurrent bacteremia-

• Pediatric Patients (Birth through 11 Years of Age): 10 mg/kg IV or oral t.i.d.
• Adults and Adolescents (12 Years and Older): 600 mg IV or oral b.i.d.
• Recommended Duration of Treatment (consecutive days): 10 to 14

Nosocomial pneumonia, Vancomycin-resistant Enterococcus faecium infections including concurrent bacteremia-

• Pediatric Patients (Birth through 11 Years of Age): 10 mg/kg IV or oral t.i.d.
• Adults and Adolescents (12 Years and Older): 600 mg IV or oral b.i.d.
• Recommended Duration of Treatment (consecutive days): 14 to 28

Uncomplicated skin and skin structure infections-

• Pediatric Patients (Birth through 11 Years of Age): <5 yrs: 10 mg/kg oral t.i.d. 5-11 yrs: 10 mg/kg oral b.i.d
• Adults and Adolescents (12 Years and Older): Adults: 400 mg oral b.i.d. Adolescents: 600 mg oral b.i.d
• Recommended Duration of Treatment (consecutive days): 10 to 14

Neonates <7 days: Most pre-term neonates <7 days of age (gestational age <34 weeks) have lower systemic Linezolid clearance values and larger AUC values than many full-term neonates and older infants. These neonates should be initiated with a dosing regimen of 10 mg/kg every 12 hours. Consideration may be given to the use of 10 mg/kg in every eight hours regimen in neonates with a sub-optimal clinical response. All neonatal patients should receive 10 mg/kg t.i.d. by 7 days of life.

Reconstitution of Oral Suspension: Shake the bottle to loosen powder. Add 75 ml (with the help of given cup) of boiled and cooled water to the dry mixture in the bottle. For the ease of preparation, add water to the bottle in two portions. Shake well after each addition until all the powder is in suspension.

Note: Shake the suspension well before each use. Keep the bottle tightly closed. The reconstituted suspension should be stored in a cool and dry place. Use within 21 days after constitution.

Intravenous Administration: Linezolid IV Injection is supplied in single-use, ready-to-use infusion bottles. Linezolid IV Injection should be administered by intravenous infusion over a period of 30 to 120 minutes. The intravenous infusion bottles should not be used in series connections. Additives should not be introduced into this solution. The infusion bottles should be stored at room temperature and protected from freezing. Linezolid IV Injection may exhibit a yellow color that can intensify over time without adversely affecting potency.

Most of the adverse events reported with Linezolid were mild to moderate in intensity. The most common adverse events in patients treated with Linezolid were diarrhea, headache and nausea. Other adverse events includes oral moniliasis, vaginal moniliasis, hypertension, dyspepsia, localized abdominal pain, pruritus, and tongue discoloration.

Linezolid formulations are contraindicated for using in patients who have known hypersensitivity to Linezolid or any of the other product components. Linezolid should not be used in patients taking any medicinal product which inhibits monoamine oxidases A or B (e.g. Phenelzine, Isocarboxazid) or within two weeks of taking any such medicinal product. Linezolid should not be administered to patients with uncontrolled hypertension, pheochromocytoma, thyrotoxicosis, carcinoid syndrome and/or patients taking directly and indirectly acting sympathomimetic agents (e.g. Pseudoephedrine), vasopressive agents (e.g. Epinephrine, Norepinephrine), dopaminergic agents (e.g. Dopamine, Dobutamine), serotonin re-uptake inhibitors, tricyclic antidepressants, serotonin 5-HT1 receptor agonists (triptans), meperidine or buspirone.

Patients who develop recurrent nausea or vomiting, unexplained acidosis or low bicarbonate level while receiving Linezolid should receive immediate medical evaluation. Where administration of Linezolid and concomitant serotonergic agents are clinically appropriate, patients should be closely observed for signs and symptoms of serotonin syndrome such as cognitive dysfunction, hyperpyrexia, hyperreflexia and incoordination. If signs or symptoms occur, physicians should consider discontinuation of either one or both agents. If the concomitant serotonergic agent is withdrawn, discontinuation symptoms can be observed. If patients experience symptoms of visual impairment, such as changes in visual acuity, changes in color vision, blurred vision or visual field defect, prompt ophthalmic evaluation is recommended. Convulsions have been reported in patients when treated with Linezolid. In some of these cases, a history of seizures or risk factors for seizures was reported.

Monoamine Oxidase Inhibition: Linezolid is a reversible and nonselective inhibitor of monoamine oxidase. Therefore, Linezolid has the potential for interaction with adrenergic and serotonergic agents.

Adrenergic Agents: Some individuals receiving Linezolid may experience a reversible enhancement of the pressor response to indirect-acting sympathomimetic agents, vasopressor or dopaminergic agents. Initial doses of adrenergic agents such as dopamine or epinephrine should be reduced and titrated to achieve the desired response.

Serotonergic Agents: Physicians should be alert to the possible signs and symptoms of serotonergic syndrome in patients receiving concomitant Linezolid and serotonergic agents.

Pregnancy Category C. There are no adequate and well-controlled studies in pregnant women. Linezolid should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. It is not known whether Linezolid is excreted in human milk. Because many drugs are excreted in human milk. Caution should be exercised when Linezolid is administered to a nursing woman.

No cases of overdose have been reported. Symptomatic and supportive care is advised together with maintenance of glomerular filtration. Approximately 30% of a Linezolid dose is removed during 3 hours of haemodialysis. No data are available for the removal of Linezolid by peritoneal dialysis or haemoperfusion.

Linezolid formulations should be stored at room temperature (15°C-30°C), away from light and moisture. All medicines should be kept away from children.

Macrolides

Linezolid is a synthetic, antibacterial agent belonging to a new class of antibiotics, the oxazolidinones, with in vitro activity against Gram positive aerobic bacteria, some Gram positive anaerobic bacteria and certain Gram negative bacteria. It selectively inhibits bacterial protein synthesis via a mechanism of action different from that of other antibacterial agents. Linezolid binds to the 23S ribosomal RNA of the 50S subunit of the bacterial ribosome and prevents the formation of a functional 70S initiation complex which is an essential component of the bacterial translation process. The results of time-kill studies have shown Linezolid to be bacteriostatic against enterococci and staphylococci. For streptococci, Linezolid was found to be bactericidal for the majority of strains.

Patients who commence treatment on the parenteral formulation may be switched to oral presentation when clinically indicated. In such circumstances, no dose adjustment is required as Linezolid has an oral bioavailability of approximately 100%. The injection should be administered over a period of 30 to 120 minutes. The film-coated tablets or oral suspension may be taken with or without food.

Complicated skin and skin structure infections, Community-acquired pneumonia, including concurrent bacteremia-

• Pediatric Patients (Birth through 11 Years of Age): 10 mg/kg IV or oral t.i.d.
• Adults and Adolescents (12 Years and Older): 600 mg IV or oral b.i.d.
• Recommended Duration of Treatment (consecutive days): 10 to 14

Nosocomial pneumonia, Vancomycin-resistant Enterococcus faecium infections including concurrent bacteremia-

• Pediatric Patients (Birth through 11 Years of Age): 10 mg/kg IV or oral t.i.d.
• Adults and Adolescents (12 Years and Older): 600 mg IV or oral b.i.d.
• Recommended Duration of Treatment (consecutive days): 14 to 28

Uncomplicated skin and skin structure infections-

• Pediatric Patients (Birth through 11 Years of Age): <5 yrs: 10 mg/kg oral t.i.d. 5-11 yrs: 10 mg/kg oral b.i.d
• Adults and Adolescents (12 Years and Older): Adults: 400 mg oral b.i.d. Adolescents: 600 mg oral b.i.d
• Recommended Duration of Treatment (consecutive days): 10 to 14

Neonates <7 days: Most pre-term neonates <7 days of age (gestational age <34 weeks) have lower systemic Linezolid clearance values and larger AUC values than many full-term neonates and older infants. These neonates should be initiated with a dosing regimen of 10 mg/kg every 12 hours. Consideration may be given to the use of 10 mg/kg in every eight hours regimen in neonates with a sub-optimal clinical response. All neonatal patients should receive 10 mg/kg t.i.d. by 7 days of life.

Reconstitution of Oral Suspension: Shake the bottle to loosen powder. Add 75 ml (with the help of given cup) of boiled and cooled water to the dry mixture in the bottle. For the ease of preparation, add water to the bottle in two portions. Shake well after each addition until all the powder is in suspension.

Note: Shake the suspension well before each use. Keep the bottle tightly closed. The reconstituted suspension should be stored in a cool and dry place. Use within 21 days after constitution.

Intravenous Administration: Linezolid IV Injection is supplied in single-use, ready-to-use infusion bottles. Linezolid IV Injection should be administered by intravenous infusion over a period of 30 to 120 minutes. The intravenous infusion bottles should not be used in series connections. Additives should not be introduced into this solution. The infusion bottles should be stored at room temperature and protected from freezing. Linezolid IV Injection may exhibit a yellow color that can intensify over time without adversely affecting potency.

Most of the adverse events reported with Linezolid were mild to moderate in intensity. The most common adverse events in patients treated with Linezolid were diarrhea, headache and nausea. Other adverse events includes oral moniliasis, vaginal moniliasis, hypertension, dyspepsia, localized abdominal pain, pruritus, and tongue discoloration.

Linezolid formulations are contraindicated for using in patients who have known hypersensitivity to Linezolid or any of the other product components. Linezolid should not be used in patients taking any medicinal product which inhibits monoamine oxidases A or B (e.g. Phenelzine, Isocarboxazid) or within two weeks of taking any such medicinal product. Linezolid should not be administered to patients with uncontrolled hypertension, pheochromocytoma, thyrotoxicosis, carcinoid syndrome and/or patients taking directly and indirectly acting sympathomimetic agents (e.g. Pseudoephedrine), vasopressive agents (e.g. Epinephrine, Norepinephrine), dopaminergic agents (e.g. Dopamine, Dobutamine), serotonin re-uptake inhibitors, tricyclic antidepressants, serotonin 5-HT1 receptor agonists (triptans), meperidine or buspirone.

Patients who develop recurrent nausea or vomiting, unexplained acidosis or low bicarbonate level while receiving Linezolid should receive immediate medical evaluation. Where administration of Linezolid and concomitant serotonergic agents are clinically appropriate, patients should be closely observed for signs and symptoms of serotonin syndrome such as cognitive dysfunction, hyperpyrexia, hyperreflexia and incoordination. If signs or symptoms occur, physicians should consider discontinuation of either one or both agents. If the concomitant serotonergic agent is withdrawn, discontinuation symptoms can be observed. If patients experience symptoms of visual impairment, such as changes in visual acuity, changes in color vision, blurred vision or visual field defect, prompt ophthalmic evaluation is recommended. Convulsions have been reported in patients when treated with Linezolid. In some of these cases, a history of seizures or risk factors for seizures was reported.

Monoamine Oxidase Inhibition: Linezolid is a reversible and nonselective inhibitor of monoamine oxidase. Therefore, Linezolid has the potential for interaction with adrenergic and serotonergic agents.

Adrenergic Agents: Some individuals receiving Linezolid may experience a reversible enhancement of the pressor response to indirect-acting sympathomimetic agents, vasopressor or dopaminergic agents. Initial doses of adrenergic agents such as dopamine or epinephrine should be reduced and titrated to achieve the desired response.

Serotonergic Agents: Physicians should be alert to the possible signs and symptoms of serotonergic syndrome in patients receiving concomitant Linezolid and serotonergic agents.

Pregnancy Category C. There are no adequate and well-controlled studies in pregnant women. Linezolid should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. It is not known whether Linezolid is excreted in human milk. Because many drugs are excreted in human milk. Caution should be exercised when Linezolid is administered to a nursing woman.

No cases of overdose have been reported. Symptomatic and supportive care is advised together with maintenance of glomerular filtration. Approximately 30% of a Linezolid dose is removed during 3 hours of haemodialysis. No data are available for the removal of Linezolid by peritoneal dialysis or haemoperfusion.

Linezolid formulations should be stored at room temperature (15°C-30°C), away from light and moisture. All medicines should be kept away from children.

Macrolides

Linezolid is a synthetic, antibacterial agent belonging to a new class of antibiotics, the oxazolidinones, with in vitro activity against Gram positive aerobic bacteria, some Gram positive anaerobic bacteria and certain Gram negative bacteria. It selectively inhibits bacterial protein synthesis via a mechanism of action different from that of other antibacterial agents. Linezolid binds to the 23S ribosomal RNA of the 50S subunit of the bacterial ribosome and prevents the formation of a functional 70S initiation complex which is an essential component of the bacterial translation process. The results of time-kill studies have shown Linezolid to be bacteriostatic against enterococci and staphylococci. For streptococci, Linezolid was found to be bactericidal for the majority of strains.

Patients who commence treatment on the parenteral formulation may be switched to oral presentation when clinically indicated. In such circumstances, no dose adjustment is required as Linezolid has an oral bioavailability of approximately 100%. The injection should be administered over a period of 30 to 120 minutes. The film-coated tablets or oral suspension may be taken with or without food.

Complicated skin and skin structure infections, Community-acquired pneumonia, including concurrent bacteremia-

• Pediatric Patients (Birth through 11 Years of Age): 10 mg/kg IV or oral t.i.d.
• Adults and Adolescents (12 Years and Older): 600 mg IV or oral b.i.d.
• Recommended Duration of Treatment (consecutive days): 10 to 14

Nosocomial pneumonia, Vancomycin-resistant Enterococcus faecium infections including concurrent bacteremia-

• Pediatric Patients (Birth through 11 Years of Age): 10 mg/kg IV or oral t.i.d.
• Adults and Adolescents (12 Years and Older): 600 mg IV or oral b.i.d.
• Recommended Duration of Treatment (consecutive days): 14 to 28

Uncomplicated skin and skin structure infections-

• Pediatric Patients (Birth through 11 Years of Age): <5 yrs: 10 mg/kg oral t.i.d. 5-11 yrs: 10 mg/kg oral b.i.d
• Adults and Adolescents (12 Years and Older): Adults: 400 mg oral b.i.d. Adolescents: 600 mg oral b.i.d
• Recommended Duration of Treatment (consecutive days): 10 to 14

Neonates <7 days: Most pre-term neonates <7 days of age (gestational age <34 weeks) have lower systemic Linezolid clearance values and larger AUC values than many full-term neonates and older infants. These neonates should be initiated with a dosing regimen of 10 mg/kg every 12 hours. Consideration may be given to the use of 10 mg/kg in every eight hours regimen in neonates with a sub-optimal clinical response. All neonatal patients should receive 10 mg/kg t.i.d. by 7 days of life.

Reconstitution of Oral Suspension: Shake the bottle to loosen powder. Add 75 ml (with the help of given cup) of boiled and cooled water to the dry mixture in the bottle. For the ease of preparation, add water to the bottle in two portions. Shake well after each addition until all the powder is in suspension.

Note: Shake the suspension well before each use. Keep the bottle tightly closed. The reconstituted suspension should be stored in a cool and dry place. Use within 21 days after constitution.

Intravenous Administration: Linezolid IV Injection is supplied in single-use, ready-to-use infusion bottles. Linezolid IV Injection should be administered by intravenous infusion over a period of 30 to 120 minutes. The intravenous infusion bottles should not be used in series connections. Additives should not be introduced into this solution. The infusion bottles should be stored at room temperature and protected from freezing. Linezolid IV Injection may exhibit a yellow color that can intensify over time without adversely affecting potency.

Most of the adverse events reported with Linezolid were mild to moderate in intensity. The most common adverse events in patients treated with Linezolid were diarrhea, headache and nausea. Other adverse events includes oral moniliasis, vaginal moniliasis, hypertension, dyspepsia, localized abdominal pain, pruritus, and tongue discoloration.

Linezolid formulations are contraindicated for using in patients who have known hypersensitivity to Linezolid or any of the other product components. Linezolid should not be used in patients taking any medicinal product which inhibits monoamine oxidases A or B (e.g. Phenelzine, Isocarboxazid) or within two weeks of taking any such medicinal product. Linezolid should not be administered to patients with uncontrolled hypertension, pheochromocytoma, thyrotoxicosis, carcinoid syndrome and/or patients taking directly and indirectly acting sympathomimetic agents (e.g. Pseudoephedrine), vasopressive agents (e.g. Epinephrine, Norepinephrine), dopaminergic agents (e.g. Dopamine, Dobutamine), serotonin re-uptake inhibitors, tricyclic antidepressants, serotonin 5-HT1 receptor agonists (triptans), meperidine or buspirone.

Patients who develop recurrent nausea or vomiting, unexplained acidosis or low bicarbonate level while receiving Linezolid should receive immediate medical evaluation. Where administration of Linezolid and concomitant serotonergic agents are clinically appropriate, patients should be closely observed for signs and symptoms of serotonin syndrome such as cognitive dysfunction, hyperpyrexia, hyperreflexia and incoordination. If signs or symptoms occur, physicians should consider discontinuation of either one or both agents. If the concomitant serotonergic agent is withdrawn, discontinuation symptoms can be observed. If patients experience symptoms of visual impairment, such as changes in visual acuity, changes in color vision, blurred vision or visual field defect, prompt ophthalmic evaluation is recommended. Convulsions have been reported in patients when treated with Linezolid. In some of these cases, a history of seizures or risk factors for seizures was reported.

Monoamine Oxidase Inhibition: Linezolid is a reversible and nonselective inhibitor of monoamine oxidase. Therefore, Linezolid has the potential for interaction with adrenergic and serotonergic agents.

Adrenergic Agents: Some individuals receiving Linezolid may experience a reversible enhancement of the pressor response to indirect-acting sympathomimetic agents, vasopressor or dopaminergic agents. Initial doses of adrenergic agents such as dopamine or epinephrine should be reduced and titrated to achieve the desired response.

Serotonergic Agents: Physicians should be alert to the possible signs and symptoms of serotonergic syndrome in patients receiving concomitant Linezolid and serotonergic agents.

Pregnancy Category C. There are no adequate and well-controlled studies in pregnant women. Linezolid should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. It is not known whether Linezolid is excreted in human milk. Because many drugs are excreted in human milk. Caution should be exercised when Linezolid is administered to a nursing woman.

No cases of overdose have been reported. Symptomatic and supportive care is advised together with maintenance of glomerular filtration. Approximately 30% of a Linezolid dose is removed during 3 hours of haemodialysis. No data are available for the removal of Linezolid by peritoneal dialysis or haemoperfusion.

Linezolid formulations should be stored at room temperature (15°C-30°C), away from light and moisture. All medicines should be kept away from children.

Macrolides

Linezolid is a synthetic, antibacterial agent belonging to a new class of antibiotics, the oxazolidinones, with in vitro activity against Gram positive aerobic bacteria, some Gram positive anaerobic bacteria and certain Gram negative bacteria. It selectively inhibits bacterial protein synthesis via a mechanism of action different from that of other antibacterial agents. Linezolid binds to the 23S ribosomal RNA of the 50S subunit of the bacterial ribosome and prevents the formation of a functional 70S initiation complex which is an essential component of the bacterial translation process. The results of time-kill studies have shown Linezolid to be bacteriostatic against enterococci and staphylococci. For streptococci, Linezolid was found to be bactericidal for the majority of strains.

Patients who commence treatment on the parenteral formulation may be switched to oral presentation when clinically indicated. In such circumstances, no dose adjustment is required as Linezolid has an oral bioavailability of approximately 100%. The injection should be administered over a period of 30 to 120 minutes. The film-coated tablets or oral suspension may be taken with or without food.

Complicated skin and skin structure infections, Community-acquired pneumonia, including concurrent bacteremia-

• Pediatric Patients (Birth through 11 Years of Age): 10 mg/kg IV or oral t.i.d.
• Adults and Adolescents (12 Years and Older): 600 mg IV or oral b.i.d.
• Recommended Duration of Treatment (consecutive days): 10 to 14

Nosocomial pneumonia, Vancomycin-resistant Enterococcus faecium infections including concurrent bacteremia-

• Pediatric Patients (Birth through 11 Years of Age): 10 mg/kg IV or oral t.i.d.
• Adults and Adolescents (12 Years and Older): 600 mg IV or oral b.i.d.
• Recommended Duration of Treatment (consecutive days): 14 to 28

Uncomplicated skin and skin structure infections-

• Pediatric Patients (Birth through 11 Years of Age): <5 yrs: 10 mg/kg oral t.i.d. 5-11 yrs: 10 mg/kg oral b.i.d
• Adults and Adolescents (12 Years and Older): Adults: 400 mg oral b.i.d. Adolescents: 600 mg oral b.i.d
• Recommended Duration of Treatment (consecutive days): 10 to 14

Neonates <7 days: Most pre-term neonates <7 days of age (gestational age <34 weeks) have lower systemic Linezolid clearance values and larger AUC values than many full-term neonates and older infants. These neonates should be initiated with a dosing regimen of 10 mg/kg every 12 hours. Consideration may be given to the use of 10 mg/kg in every eight hours regimen in neonates with a sub-optimal clinical response. All neonatal patients should receive 10 mg/kg t.i.d. by 7 days of life.

Reconstitution of Oral Suspension: Shake the bottle to loosen powder. Add 75 ml (with the help of given cup) of boiled and cooled water to the dry mixture in the bottle. For the ease of preparation, add water to the bottle in two portions. Shake well after each addition until all the powder is in suspension.

Note: Shake the suspension well before each use. Keep the bottle tightly closed. The reconstituted suspension should be stored in a cool and dry place. Use within 21 days after constitution.

Intravenous Administration: Linezolid IV Injection is supplied in single-use, ready-to-use infusion bottles. Linezolid IV Injection should be administered by intravenous infusion over a period of 30 to 120 minutes. The intravenous infusion bottles should not be used in series connections. Additives should not be introduced into this solution. The infusion bottles should be stored at room temperature and protected from freezing. Linezolid IV Injection may exhibit a yellow color that can intensify over time without adversely affecting potency.

Most of the adverse events reported with Linezolid were mild to moderate in intensity. The most common adverse events in patients treated with Linezolid were diarrhea, headache and nausea. Other adverse events includes oral moniliasis, vaginal moniliasis, hypertension, dyspepsia, localized abdominal pain, pruritus, and tongue discoloration.

Linezolid formulations are contraindicated for using in patients who have known hypersensitivity to Linezolid or any of the other product components. Linezolid should not be used in patients taking any medicinal product which inhibits monoamine oxidases A or B (e.g. Phenelzine, Isocarboxazid) or within two weeks of taking any such medicinal product. Linezolid should not be administered to patients with uncontrolled hypertension, pheochromocytoma, thyrotoxicosis, carcinoid syndrome and/or patients taking directly and indirectly acting sympathomimetic agents (e.g. Pseudoephedrine), vasopressive agents (e.g. Epinephrine, Norepinephrine), dopaminergic agents (e.g. Dopamine, Dobutamine), serotonin re-uptake inhibitors, tricyclic antidepressants, serotonin 5-HT1 receptor agonists (triptans), meperidine or buspirone.

Patients who develop recurrent nausea or vomiting, unexplained acidosis or low bicarbonate level while receiving Linezolid should receive immediate medical evaluation. Where administration of Linezolid and concomitant serotonergic agents are clinically appropriate, patients should be closely observed for signs and symptoms of serotonin syndrome such as cognitive dysfunction, hyperpyrexia, hyperreflexia and incoordination. If signs or symptoms occur, physicians should consider discontinuation of either one or both agents. If the concomitant serotonergic agent is withdrawn, discontinuation symptoms can be observed. If patients experience symptoms of visual impairment, such as changes in visual acuity, changes in color vision, blurred vision or visual field defect, prompt ophthalmic evaluation is recommended. Convulsions have been reported in patients when treated with Linezolid. In some of these cases, a history of seizures or risk factors for seizures was reported.

Monoamine Oxidase Inhibition: Linezolid is a reversible and nonselective inhibitor of monoamine oxidase. Therefore, Linezolid has the potential for interaction with adrenergic and serotonergic agents.

Adrenergic Agents: Some individuals receiving Linezolid may experience a reversible enhancement of the pressor response to indirect-acting sympathomimetic agents, vasopressor or dopaminergic agents. Initial doses of adrenergic agents such as dopamine or epinephrine should be reduced and titrated to achieve the desired response.

Serotonergic Agents: Physicians should be alert to the possible signs and symptoms of serotonergic syndrome in patients receiving concomitant Linezolid and serotonergic agents.

Pregnancy Category C. There are no adequate and well-controlled studies in pregnant women. Linezolid should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. It is not known whether Linezolid is excreted in human milk. Because many drugs are excreted in human milk. Caution should be exercised when Linezolid is administered to a nursing woman.

No cases of overdose have been reported. Symptomatic and supportive care is advised together with maintenance of glomerular filtration. Approximately 30% of a Linezolid dose is removed during 3 hours of haemodialysis. No data are available for the removal of Linezolid by peritoneal dialysis or haemoperfusion.

Linezolid formulations should be stored at room temperature (15°C-30°C), away from light and moisture. All medicines should be kept away from children.

Dipeptidyl Peptidase-4 (DPP-4) inhibitor

Linagliptin is indicated to improve glycemic control in patients with type 2 diabetes mellitus. Linagliptin is an inhibitor of DPP-4 (dipeptidyl peptidase-4), an enzyme that degrades the incretin hormones GLP-1 (glucagon like peptide-1) and GIP (glucose dependent insulinotropic polypeptide). Thus, Linagliptin increases the concentrations of active incretin hormones, stimulating the release of insulin from pancreatic beta (β) cells in a glucose-dependent manner and decreasing the secretion of glucagon from pancreatic alpha (α) cells in the circulation.

Linagliptin 5 mg once daily. If added to metformin, the dose of metformin should be maintained and linagliptin administered concomitantly. When used in combination with a sulfonylurea, a lower dose of the sulphonylurea may be considered to reduce the risk of hypoglycaemia.

Patients with renal impairment: No dose adjustment required. Linagliptin can be taken with or without a meal at any time of the day.

There may be hypoglycaemia, nasopharyngitis, cough and pancreatitis in combination with metformin and sulfonylurea.

Hypersensitivity to the active substance or to any of the excipients.

Hypersensitivity to the active substance or to any of the excipients.

Linagliptin is a weak competitive and a weak to moderate mechanism-based inhibitor of CYP isozyme CYP3A4, but does not inhibit other CYP isozymes. The risk for clinically meaningful interactions by other medicinal products on linagliptin is low and in clinical studies linagliptin had no clinically relevant effect on the pharmacokinetics of metformin, glyburide, simvastatin, warfarin, digoxin or oral contraceptives.

Pregnancy category B. There are no adequate and well controlled studies in pregnant women. So, Linagliptin tablets should be used during pregnancy only if clearly needed. It is not known whether Linagliptin passes into breast milk or not.

Keep in a dry place away from light and heat. Keep out of the reach of children.