Find Medicines

Tapentadol is indicated for the relief of moderate to severe acute pain in patients 18 years of age or older.

Opioid analgesics

Tapentadol is a centrally-acting synthetic analgesic. It is 18 times less potent than morphine in terms of binding to human mu-opioid receptors. It also increases norepinephrine concentrations in the brains of rats via inhibition of norepinephrine reuptake. Selective mu-opioid antagonists like naloxone can block analgesia from tapentadol. It also has not effect on the QT interval.

Tapendadol causes large increases in levels of extracellular norepinephrine (NE) due to a dual mechanism of action involving mu opioid receptor (MOR) agonism as well as noradrenaline reuptake inhibition.

As with many centrally-acting analgesic medications, the dosing regimen should be individualized according to the severity of pain being treated, the previous experience with similar drugs and the ability to monitor the patient.

The dose is 50 mg, 75 mg, or 100 mg every 4 to 6 hours depending upon pain intensity. On the first day of dosing, the second dose may be administered as soon as one hour after the first dose, if adequate pain relief is not attained with the first dose. Subsequent dosing is 50 mg, 75 mg, or 100 mg every 4 to 6 hours and should be adjusted to maintain adequate analgesia with acceptable tolerability.

Daily doses greater than 700 mg on the first day of therapy and 600 mg on subsequent days have not been studied and are not recommended.

The following treatment-emergent adverse events may happen: heart rate increased, heart rate decreased, visual disturbance, abdominal discomfort, impaired gastric emptying, irritability, edema, drug withdrawal syndrome, hypersensitivity, involuntary muscle contractions, sensation of heaviness, hypoesthesia, paresthesia, disturbance in attention, sedation, dysarthria, memory impairment, ataxia, presyncope, syncope, coordination abnormal, seizure, urticaria, blood pressure decreased etc.

This drug is contraindicated in patients with impaired Pulmonary Function, It is also contraindicated in patients with acute or severe bronchial asthma or hypercapnia in unmonitored settings or the absence of resuscitative equipment. This drug is contraindicated in any patient who has or is suspected of having paralytic ileus.

Tapentadol should be administered with caution to patients with conditions accompanied by hypoxia, hypercapnia respiratory problems such as: asthma, chronic obstructive pulmonary disease etc. Besides this in case of patient with sleep apnea syndrome, myxedema, kyphoscoliosis, central nervous system (CNS) depression should have to be cautious prior administration of Tapentadol. Patients receiving other mu-opioid agonist analgesics, general anesthetics, phenothiazines, other tranquilizers, sedatives, hypnotics, or other CNS depressants (including alcohol) concomitantly with Tapentadol may exhibit additive CNS depression.

Increased risk of serotonin syndrome with other drugs that enhance monoaminergic neurotransmission (e.g. TCAs, triptans, SSRIs, serotonin and norepinephrine reuptake inhibitors). Enhanced sedative effect with benzodiazepines, barbiturates, antipsychotics, H1-antihistamines and other opioids. Increased potential for addiction with mixed μ-opioid agonists/antagonists (e.g. nalbuphine, pentazocine) or partial μ-opioid agonists (e.g. buprenorphine). Increased systemic exposure with strong inhibitors of UGT1A6, UGT1A9 and UGT2B7 isoenzymes. Decreased efficacy with strong enzyme inducers (e.g. rifampicin, phenobarbital).

Pregnancy Category C. There are no adequate and well-controlled studies in pregnant women. This preparation should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Neonates whose mothers have been taking Tapentadol should be monitored for respiratory depression.

Pediatric use: The safety and effectiveness of Tapentadol in pediatric patients less than 18 years of age have not been established.

Use in elderly patients: In general, recommended dosing for elderly patients with normal renal and hepatic function is the same as for younger adult patients with normal renal and hepatic function. consideration should be given to starting elderly patients with the lower range of recommended doses.

Use in Renal Disease: In patients with severe renal impairment, the safety and effectiveness of Tapentadol has not been established.

Use in Hepatic Disease: Tapentadol should be used with caution in patients with moderate hepatic impairment. Tapentadol has not been studied in patients with severe hepatic impairment.

Symptoms: Vomiting, miosis, CV collapse, consciousness disorders up to coma, convulsions and resp depression up to resp arrest.

Management: Re-establish a patent airway and institute assisted or controlled ventilation. GI decontamination with activated charcoal or by gastric lavage may be considered within 2 hr after intake. Pure opioid receptor antagonists (e.g. naloxone) may be given as antidote.

Store in a cool and dry place, protected from light and moisture. Keep the medicine out of the reach of children.

Tapentadol is indicated for the relief of moderate to severe acute pain in patients 18 years of age or older.

Opioid analgesics

Tapentadol is a centrally-acting synthetic analgesic. It is 18 times less potent than morphine in terms of binding to human mu-opioid receptors. It also increases norepinephrine concentrations in the brains of rats via inhibition of norepinephrine reuptake. Selective mu-opioid antagonists like naloxone can block analgesia from tapentadol. It also has not effect on the QT interval.

Tapendadol causes large increases in levels of extracellular norepinephrine (NE) due to a dual mechanism of action involving mu opioid receptor (MOR) agonism as well as noradrenaline reuptake inhibition.

As with many centrally-acting analgesic medications, the dosing regimen should be individualized according to the severity of pain being treated, the previous experience with similar drugs and the ability to monitor the patient.

The dose is 50 mg, 75 mg, or 100 mg every 4 to 6 hours depending upon pain intensity. On the first day of dosing, the second dose may be administered as soon as one hour after the first dose, if adequate pain relief is not attained with the first dose. Subsequent dosing is 50 mg, 75 mg, or 100 mg every 4 to 6 hours and should be adjusted to maintain adequate analgesia with acceptable tolerability.

Daily doses greater than 700 mg on the first day of therapy and 600 mg on subsequent days have not been studied and are not recommended.

The following treatment-emergent adverse events may happen: heart rate increased, heart rate decreased, visual disturbance, abdominal discomfort, impaired gastric emptying, irritability, edema, drug withdrawal syndrome, hypersensitivity, involuntary muscle contractions, sensation of heaviness, hypoesthesia, paresthesia, disturbance in attention, sedation, dysarthria, memory impairment, ataxia, presyncope, syncope, coordination abnormal, seizure, urticaria, blood pressure decreased etc.

This drug is contraindicated in patients with impaired Pulmonary Function, It is also contraindicated in patients with acute or severe bronchial asthma or hypercapnia in unmonitored settings or the absence of resuscitative equipment. This drug is contraindicated in any patient who has or is suspected of having paralytic ileus.

Tapentadol should be administered with caution to patients with conditions accompanied by hypoxia, hypercapnia respiratory problems such as: asthma, chronic obstructive pulmonary disease etc. Besides this in case of patient with sleep apnea syndrome, myxedema, kyphoscoliosis, central nervous system (CNS) depression should have to be cautious prior administration of Tapentadol. Patients receiving other mu-opioid agonist analgesics, general anesthetics, phenothiazines, other tranquilizers, sedatives, hypnotics, or other CNS depressants (including alcohol) concomitantly with Tapentadol may exhibit additive CNS depression.

Increased risk of serotonin syndrome with other drugs that enhance monoaminergic neurotransmission (e.g. TCAs, triptans, SSRIs, serotonin and norepinephrine reuptake inhibitors). Enhanced sedative effect with benzodiazepines, barbiturates, antipsychotics, H1-antihistamines and other opioids. Increased potential for addiction with mixed μ-opioid agonists/antagonists (e.g. nalbuphine, pentazocine) or partial μ-opioid agonists (e.g. buprenorphine). Increased systemic exposure with strong inhibitors of UGT1A6, UGT1A9 and UGT2B7 isoenzymes. Decreased efficacy with strong enzyme inducers (e.g. rifampicin, phenobarbital).

Pregnancy Category C. There are no adequate and well-controlled studies in pregnant women. This preparation should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Neonates whose mothers have been taking Tapentadol should be monitored for respiratory depression.

Pediatric use: The safety and effectiveness of Tapentadol in pediatric patients less than 18 years of age have not been established.

Use in elderly patients: In general, recommended dosing for elderly patients with normal renal and hepatic function is the same as for younger adult patients with normal renal and hepatic function. consideration should be given to starting elderly patients with the lower range of recommended doses.

Use in Renal Disease: In patients with severe renal impairment, the safety and effectiveness of Tapentadol has not been established.

Use in Hepatic Disease: Tapentadol should be used with caution in patients with moderate hepatic impairment. Tapentadol has not been studied in patients with severe hepatic impairment.

Symptoms: Vomiting, miosis, CV collapse, consciousness disorders up to coma, convulsions and resp depression up to resp arrest.

Management: Re-establish a patent airway and institute assisted or controlled ventilation. GI decontamination with activated charcoal or by gastric lavage may be considered within 2 hr after intake. Pure opioid receptor antagonists (e.g. naloxone) may be given as antidote.

Store in a cool and dry place, protected from light and moisture. Keep the medicine out of the reach of children.

Tapentadol is indicated for the relief of moderate to severe acute pain in patients 18 years of age or older.

Opioid analgesics

Tapentadol is a centrally-acting synthetic analgesic. It is 18 times less potent than morphine in terms of binding to human mu-opioid receptors. It also increases norepinephrine concentrations in the brains of rats via inhibition of norepinephrine reuptake. Selective mu-opioid antagonists like naloxone can block analgesia from tapentadol. It also has not effect on the QT interval.

Tapendadol causes large increases in levels of extracellular norepinephrine (NE) due to a dual mechanism of action involving mu opioid receptor (MOR) agonism as well as noradrenaline reuptake inhibition.

As with many centrally-acting analgesic medications, the dosing regimen should be individualized according to the severity of pain being treated, the previous experience with similar drugs and the ability to monitor the patient.

The dose is 50 mg, 75 mg, or 100 mg every 4 to 6 hours depending upon pain intensity. On the first day of dosing, the second dose may be administered as soon as one hour after the first dose, if adequate pain relief is not attained with the first dose. Subsequent dosing is 50 mg, 75 mg, or 100 mg every 4 to 6 hours and should be adjusted to maintain adequate analgesia with acceptable tolerability.

Daily doses greater than 700 mg on the first day of therapy and 600 mg on subsequent days have not been studied and are not recommended.

The following treatment-emergent adverse events may happen: heart rate increased, heart rate decreased, visual disturbance, abdominal discomfort, impaired gastric emptying, irritability, edema, drug withdrawal syndrome, hypersensitivity, involuntary muscle contractions, sensation of heaviness, hypoesthesia, paresthesia, disturbance in attention, sedation, dysarthria, memory impairment, ataxia, presyncope, syncope, coordination abnormal, seizure, urticaria, blood pressure decreased etc.

This drug is contraindicated in patients with impaired Pulmonary Function, It is also contraindicated in patients with acute or severe bronchial asthma or hypercapnia in unmonitored settings or the absence of resuscitative equipment. This drug is contraindicated in any patient who has or is suspected of having paralytic ileus.

Tapentadol should be administered with caution to patients with conditions accompanied by hypoxia, hypercapnia respiratory problems such as: asthma, chronic obstructive pulmonary disease etc. Besides this in case of patient with sleep apnea syndrome, myxedema, kyphoscoliosis, central nervous system (CNS) depression should have to be cautious prior administration of Tapentadol. Patients receiving other mu-opioid agonist analgesics, general anesthetics, phenothiazines, other tranquilizers, sedatives, hypnotics, or other CNS depressants (including alcohol) concomitantly with Tapentadol may exhibit additive CNS depression.

Increased risk of serotonin syndrome with other drugs that enhance monoaminergic neurotransmission (e.g. TCAs, triptans, SSRIs, serotonin and norepinephrine reuptake inhibitors). Enhanced sedative effect with benzodiazepines, barbiturates, antipsychotics, H1-antihistamines and other opioids. Increased potential for addiction with mixed μ-opioid agonists/antagonists (e.g. nalbuphine, pentazocine) or partial μ-opioid agonists (e.g. buprenorphine). Increased systemic exposure with strong inhibitors of UGT1A6, UGT1A9 and UGT2B7 isoenzymes. Decreased efficacy with strong enzyme inducers (e.g. rifampicin, phenobarbital).

Pregnancy Category C. There are no adequate and well-controlled studies in pregnant women. This preparation should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Neonates whose mothers have been taking Tapentadol should be monitored for respiratory depression.

Pediatric use: The safety and effectiveness of Tapentadol in pediatric patients less than 18 years of age have not been established.

Use in elderly patients: In general, recommended dosing for elderly patients with normal renal and hepatic function is the same as for younger adult patients with normal renal and hepatic function. consideration should be given to starting elderly patients with the lower range of recommended doses.

Use in Renal Disease: In patients with severe renal impairment, the safety and effectiveness of Tapentadol has not been established.

Use in Hepatic Disease: Tapentadol should be used with caution in patients with moderate hepatic impairment. Tapentadol has not been studied in patients with severe hepatic impairment.

Symptoms: Vomiting, miosis, CV collapse, consciousness disorders up to coma, convulsions and resp depression up to resp arrest.

Management: Re-establish a patent airway and institute assisted or controlled ventilation. GI decontamination with activated charcoal or by gastric lavage may be considered within 2 hr after intake. Pure opioid receptor antagonists (e.g. naloxone) may be given as antidote.

Store in a cool and dry place, protected from light and moisture. Keep the medicine out of the reach of children.

Tapentadol is indicated for the relief of moderate to severe acute pain in patients 18 years of age or older.

Opioid analgesics

Tapentadol is a centrally-acting synthetic analgesic. It is 18 times less potent than morphine in terms of binding to human mu-opioid receptors. It also increases norepinephrine concentrations in the brains of rats via inhibition of norepinephrine reuptake. Selective mu-opioid antagonists like naloxone can block analgesia from tapentadol. It also has not effect on the QT interval.

Tapendadol causes large increases in levels of extracellular norepinephrine (NE) due to a dual mechanism of action involving mu opioid receptor (MOR) agonism as well as noradrenaline reuptake inhibition.

As with many centrally-acting analgesic medications, the dosing regimen should be individualized according to the severity of pain being treated, the previous experience with similar drugs and the ability to monitor the patient.

The dose is 50 mg, 75 mg, or 100 mg every 4 to 6 hours depending upon pain intensity. On the first day of dosing, the second dose may be administered as soon as one hour after the first dose, if adequate pain relief is not attained with the first dose. Subsequent dosing is 50 mg, 75 mg, or 100 mg every 4 to 6 hours and should be adjusted to maintain adequate analgesia with acceptable tolerability.

Daily doses greater than 700 mg on the first day of therapy and 600 mg on subsequent days have not been studied and are not recommended.

The following treatment-emergent adverse events may happen: heart rate increased, heart rate decreased, visual disturbance, abdominal discomfort, impaired gastric emptying, irritability, edema, drug withdrawal syndrome, hypersensitivity, involuntary muscle contractions, sensation of heaviness, hypoesthesia, paresthesia, disturbance in attention, sedation, dysarthria, memory impairment, ataxia, presyncope, syncope, coordination abnormal, seizure, urticaria, blood pressure decreased etc.

This drug is contraindicated in patients with impaired Pulmonary Function, It is also contraindicated in patients with acute or severe bronchial asthma or hypercapnia in unmonitored settings or the absence of resuscitative equipment. This drug is contraindicated in any patient who has or is suspected of having paralytic ileus.

Tapentadol should be administered with caution to patients with conditions accompanied by hypoxia, hypercapnia respiratory problems such as: asthma, chronic obstructive pulmonary disease etc. Besides this in case of patient with sleep apnea syndrome, myxedema, kyphoscoliosis, central nervous system (CNS) depression should have to be cautious prior administration of Tapentadol. Patients receiving other mu-opioid agonist analgesics, general anesthetics, phenothiazines, other tranquilizers, sedatives, hypnotics, or other CNS depressants (including alcohol) concomitantly with Tapentadol may exhibit additive CNS depression.

Increased risk of serotonin syndrome with other drugs that enhance monoaminergic neurotransmission (e.g. TCAs, triptans, SSRIs, serotonin and norepinephrine reuptake inhibitors). Enhanced sedative effect with benzodiazepines, barbiturates, antipsychotics, H1-antihistamines and other opioids. Increased potential for addiction with mixed μ-opioid agonists/antagonists (e.g. nalbuphine, pentazocine) or partial μ-opioid agonists (e.g. buprenorphine). Increased systemic exposure with strong inhibitors of UGT1A6, UGT1A9 and UGT2B7 isoenzymes. Decreased efficacy with strong enzyme inducers (e.g. rifampicin, phenobarbital).

Pregnancy Category C. There are no adequate and well-controlled studies in pregnant women. This preparation should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Neonates whose mothers have been taking Tapentadol should be monitored for respiratory depression.

Pediatric use: The safety and effectiveness of Tapentadol in pediatric patients less than 18 years of age have not been established.

Use in elderly patients: In general, recommended dosing for elderly patients with normal renal and hepatic function is the same as for younger adult patients with normal renal and hepatic function. consideration should be given to starting elderly patients with the lower range of recommended doses.

Use in Renal Disease: In patients with severe renal impairment, the safety and effectiveness of Tapentadol has not been established.

Use in Hepatic Disease: Tapentadol should be used with caution in patients with moderate hepatic impairment. Tapentadol has not been studied in patients with severe hepatic impairment.

Symptoms: Vomiting, miosis, CV collapse, consciousness disorders up to coma, convulsions and resp depression up to resp arrest.

Management: Re-establish a patent airway and institute assisted or controlled ventilation. GI decontamination with activated charcoal or by gastric lavage may be considered within 2 hr after intake. Pure opioid receptor antagonists (e.g. naloxone) may be given as antidote.

Store in a cool and dry place, protected from light and moisture. Keep the medicine out of the reach of children.

Angiotensin-ll receptor blocker

Losartan Potassium is the first non-peptide orally active angiotensin II receptor blocker. It binds to the AT1 receptor found in many tissues (e.g. vascular smooth muscle, adrenal gland, kidneys and the heart) and reduces several important biological actions including vasoconstriction and the release of aldosterone responsible for hypertension.

The usual starting and maintenance dose is 50 mg once daily for most patients. If the antihypertensive effect using 50 mg once daily is inadequate, 25 mg twice daily is recommended prior to increasing the dose. For patients with intravascular volume-depletion (e.g., those treated with high-dose diuretics), a starting dose of 25 mg once daily should be considered. Losartan Potassium can be administered once or twice daily. The total daily dose ranges from 25 mg to 100 mg.

The side effects with the use of Losartan Potassium are mild and transient in nature. The most common side effects are dizziness, diarrhea, nasal congestion, cough, upper respiratory infection. Other side effects are fatigue, oedema, abdominal pain, chest pain, nausea, headache & pharyngitis.

Losartan Potassium is contraindicated in pregnant women and in patients who are hypersensitive to any component of this product. Losartan Potassium should not be administered with Aliskiren in patients with diabetes.

Use of Losartan Potassium during the second and third trimesters of pregnancy reduces fetal renal function and increases fetal and neonatal morbidity and death. In patients who are intravascularly volume-depleted (e.g., those treated with high-dose diuretics), symptomatic hypotension may occur. Plasma concentration of Losartan Potassium is significantly increased in cirrhotic patients. Changes in renal function including renal failure have been reported in renal impaired patient.

Rifampicin and fluconazole reduce levels of active metabolite of Losartan Potassium. Concomitant use of Losartan Potassium and hydrochlorothiazide may lead to potentiation of the antihypertensive effects. Concomitant use of potassium-sparing diuretics (eg, spironolactone, triamterene, amiloride), potassium supplements or salt substitutes containing potassium may lead to increases in serum potassium. The antihypertensive effect of losartan may be attenuated by the non-steroidal anti-inflammatory drug indomethacin. The use of ACE-inhibitor, angiotensin receptor antagonist, an anti-inflammatory drug and a thiazide diuretic at the same time increases the risk of renal impairment.

Pregnancy Category D. The risk to the fetus increases if Losartan Potassium is administered during the second or third trimesters of pregnancy. It is not known whether Losartan Potassium is excreted in human milk, as many drugs are excreted in human milk and because of the potential for adverse effects on the nursing infant, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.

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

Benzodiazepine sedatives

Bromazepam is a powerful psychotropic agent. In lower dosage, it selectively reduces tension and anxiety. In higher dosage, it shows sedative and muscle-relaxant properties. Bromazepam binds to the GABA-A receptor producing a conformational change and potentiating its inhibitory effects. Other neurotransmitters are not influenced.

Standard dosage: Average dosage for outpatient therapy is 1.5-3 mg up to three times daily. Treatment of outpatients should begin with low doses, gradually increasing to the optimum level.

In severe cases, especially in hospital: 6-12 mg 2 or 3 times daily. The overall treatment generally should not be more than 8-12 weeks. In certain cases extension beyond the maximum treatment period may be necessary; if so, it should be taken with re-evaluation of the patient's status with special expertise.

Elderly and debilitated patients: Elderly patients and those with impaired hepatic functions require lower doses.

Children: Bromazepam is usually not indicated in children, but if the physician feels bromazepam treatment is appropriate, then the dose should be adjusted to their low bodyweight (about 0.1-0.3 mg/kg bodyweight)

Bromazepam tablets are for oral administration

Common side-effects include fatigue, drowsiness, muscle weakness, numbed muscle, reduced alertness, confusion, headache, ataxia etc. These phenomena occur predominantly at the start of therapy and usually disappear with prolonged administration. Anterograde amnesia may occur using therapeutic doses.

Bromazepam is contraindicated in patients with known hypersensitivity to bromazepam, severe respiratory insufficiency, severe hepatic insufficiency or sleep apnea syndrome.

The use of benzodiazepines and benzodiazepine like agents may lead to the development of physical and psychological dependence upon these products. This dependence depends on the dose and duration of treatment; it is also greater in predisposed patients with a history of alcohol. Once physical dependence has developed, termination of the treatment will be accompanied by withdrawal symptoms. These may consist of headache, muscle pain, extreme anxiety, tension, confusion and irritability. Since the risk of withdrawal phenomena and rebound phenomena is greater after abrupt discontinuation of the treatment, it is recommended that the dosage be decreased gradually. Bromazepam is not recommended for the primary treatment of sleeplessness caused by psychotic illness. Caution should be exercised while driving cars or using machineries.

If bromazepam is combined with other centrally active drugs, its sedative effects may be enhanced. These drugs are antidepressants, hypnotics, narcotics, antipsychotics, sedatives, antiepileptic drugs, sedative antihistamines and anesthetics. Co-administration of cimetidine may prolong the eliminiation half-life of bromazepam. Concomitant intake of bromazepam with alcohol should be avoided, because the sedative effect of bromazepam may be intensified by alcohol.

The safety of bromazepam during pregnancy has not been established. As bromazepam is excreted in breast milk, use should be avoided during lactation.

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

Targeted Cancer Therapy

NSCLC: The recommended daily dose of Erlotinib for NSCLC is 150 mg taken on an empty stomach, i.e., at least one hour before or two hours after the ingestion of food. Treatment should continue until disease progression or unacceptable toxicity occurs.

Pancreatic Cancer: The recommended daily dose of Erlotinib for pancreatic cancer is 100 mg taken once daily in combination with gemcitabine. Take Erlotinib on an empty stomach, i.e., at least one hour before or two hours after the ingestion of food. Treatment should continue until disease progression or unacceptable toxicity occurs.

Reduce Erlotinib by 50 mg decrements: If severe reactions occur with concomitant use of strong CYP3A4 inhibitors (such as atazanavir, Clarithromycin, Indinavir, Itraconazole, Ketoconazole, Nefazodone, Nelfinavir, Ritonavir, Saquinavir, Telithromycin, Voriconazole or grapefruit or grapefruit juice] or when using concomitantly with an inhibitor of both CYP3A4 and CYP1A2 (e.g., Ciprofloxacin).

Increase Erlotinib by 50 mg increments as tolerated for: Concomitant use with CYP3A4 inducers, such as rifampin, rifabutin, rifapentine, phenytoin, carbamazepine, phenobarbital, or St. John's Wort. Increase doses by 50 mg increments at 2 week intervals to a maximum of 450 mg. Avoid concomitant use, if possible.

Concurrent cigarette smoking: Increase by 50 mg increments at 2 week intervals to a maximum of 300 mg. Immediately reduce the dose of Erlotinib to the recommended dose (150 mg or 100 mg daily) upon cessation of smoking.

The most common adverse reactions (20%) with Erlotinib from a pooled analysis of studies were rash, diarrhea, anorexia, fatigue, dyspnea, cough, nausea, and vomiting. The following serious adverse reactions, which may include fatalities.

• Interstitial Lung Disease (ILD)
• Renal Failure
• Hepatotoxicity with or without Hepatic Impairment
• Gastrointestinal Perforation
• Bullous and Exfoliative Skin Disorders
• Myocardial Infarction/Ischemia
• Cerebrovascular Accident
• Microangiopathic Hemolytic Anemia with Thrombocytopenia
• Ocular Disorders
• Hemorrhage in Patients Taking Warfarin

Anticoagulants: Interaction with coumarin-derived anticoagulants, including warfarin, leading to increased International Normalized Ratio (INR) and bleeding adverse reactions.

CYP3A4 inhibitors: Erlotinib is metabolized predominantly by CYP3A4. Co-treatment with the potent CYP3A4 inhibitor ketoconazole increased Erlotinib AUC by 67%. When Erlotinib was co-administered with Ciprofloxacin, an inhibitor of both CYP3A4 and CYP1A2, the Erlotinib exposure [AUC] and maximum concentration [Cmax] increased by 39% and 17%, respectively.

CYP3A4 inducers: Pre-treatment with the CYP3A4 inducer Rifampicin for 7-11 days prior to Erlotinib decreased Erlotinib AUC by 58% to 80%. Dose modifications are recommended.

Drugs affecting gastric pH: Co-administration of Erlotinib with omeprazole decreased Erlotinib AUC by 46% and co-administration of Erlotinib with Ranitidine 300 mg decreased Erlotinib AUC by 33%.

Pregnancy category D. Based on its mechanism of action, Erlotinib can cause fetal harm when administered to a pregnant woman. It is not known whether Erlotinib is present in human milk. Because many drugs are present in human milk and because of the potential for serious adverse reactions in nursing infants from Erlotinib, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.

Pediatric use: The safety and effectiveness of Erlotinib in pediatric patients have not been established.

Geriatric use: No overall differences in safety or efficacy were observed between subjects 65 years and older and those younger than 65.

Single oral doses of Erlotinib up to 1,000 mg in healthy subjects and weekly doses up to 1,600 mg in cancer patients have been tolerated. Repeated twice-daily doses of 200 mg single-agent Erlotinib in healthy subjects were poorly tolerated after only a few days of dosing. Based on the data from these studies, an unacceptable incidence of severe adverse reactions, such as diarrhea, rash, and liver transaminase elevation, may occur above the recommended dose. In case of suspected overdose, Erlotinib should be withheld and symptomatic treatment instituted.

Store at a temperature not exceeding 30°C in a dry place. Protect from light and moisture.

Targeted Cancer Therapy

NSCLC: The recommended daily dose of Erlotinib for NSCLC is 150 mg taken on an empty stomach, i.e., at least one hour before or two hours after the ingestion of food. Treatment should continue until disease progression or unacceptable toxicity occurs.

Pancreatic Cancer: The recommended daily dose of Erlotinib for pancreatic cancer is 100 mg taken once daily in combination with gemcitabine. Take Erlotinib on an empty stomach, i.e., at least one hour before or two hours after the ingestion of food. Treatment should continue until disease progression or unacceptable toxicity occurs.

Reduce Erlotinib by 50 mg decrements: If severe reactions occur with concomitant use of strong CYP3A4 inhibitors (such as atazanavir, Clarithromycin, Indinavir, Itraconazole, Ketoconazole, Nefazodone, Nelfinavir, Ritonavir, Saquinavir, Telithromycin, Voriconazole or grapefruit or grapefruit juice] or when using concomitantly with an inhibitor of both CYP3A4 and CYP1A2 (e.g., Ciprofloxacin).

Increase Erlotinib by 50 mg increments as tolerated for: Concomitant use with CYP3A4 inducers, such as rifampin, rifabutin, rifapentine, phenytoin, carbamazepine, phenobarbital, or St. John's Wort. Increase doses by 50 mg increments at 2 week intervals to a maximum of 450 mg. Avoid concomitant use, if possible.

Concurrent cigarette smoking: Increase by 50 mg increments at 2 week intervals to a maximum of 300 mg. Immediately reduce the dose of Erlotinib to the recommended dose (150 mg or 100 mg daily) upon cessation of smoking.

The most common adverse reactions (20%) with Erlotinib from a pooled analysis of studies were rash, diarrhea, anorexia, fatigue, dyspnea, cough, nausea, and vomiting. The following serious adverse reactions, which may include fatalities.

• Interstitial Lung Disease (ILD)
• Renal Failure
• Hepatotoxicity with or without Hepatic Impairment
• Gastrointestinal Perforation
• Bullous and Exfoliative Skin Disorders
• Myocardial Infarction/Ischemia
• Cerebrovascular Accident
• Microangiopathic Hemolytic Anemia with Thrombocytopenia
• Ocular Disorders
• Hemorrhage in Patients Taking Warfarin

Anticoagulants: Interaction with coumarin-derived anticoagulants, including warfarin, leading to increased International Normalized Ratio (INR) and bleeding adverse reactions.

CYP3A4 inhibitors: Erlotinib is metabolized predominantly by CYP3A4. Co-treatment with the potent CYP3A4 inhibitor ketoconazole increased Erlotinib AUC by 67%. When Erlotinib was co-administered with Ciprofloxacin, an inhibitor of both CYP3A4 and CYP1A2, the Erlotinib exposure [AUC] and maximum concentration [Cmax] increased by 39% and 17%, respectively.

CYP3A4 inducers: Pre-treatment with the CYP3A4 inducer Rifampicin for 7-11 days prior to Erlotinib decreased Erlotinib AUC by 58% to 80%. Dose modifications are recommended.

Drugs affecting gastric pH: Co-administration of Erlotinib with omeprazole decreased Erlotinib AUC by 46% and co-administration of Erlotinib with Ranitidine 300 mg decreased Erlotinib AUC by 33%.

Pregnancy category D. Based on its mechanism of action, Erlotinib can cause fetal harm when administered to a pregnant woman. It is not known whether Erlotinib is present in human milk. Because many drugs are present in human milk and because of the potential for serious adverse reactions in nursing infants from Erlotinib, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.

Pediatric use: The safety and effectiveness of Erlotinib in pediatric patients have not been established.

Geriatric use: No overall differences in safety or efficacy were observed between subjects 65 years and older and those younger than 65.

Single oral doses of Erlotinib up to 1,000 mg in healthy subjects and weekly doses up to 1,600 mg in cancer patients have been tolerated. Repeated twice-daily doses of 200 mg single-agent Erlotinib in healthy subjects were poorly tolerated after only a few days of dosing. Based on the data from these studies, an unacceptable incidence of severe adverse reactions, such as diarrhea, rash, and liver transaminase elevation, may occur above the recommended dose. In case of suspected overdose, Erlotinib should be withheld and symptomatic treatment instituted.

Store at a temperature not exceeding 30°C in a dry place. Protect from light and moisture.

Targeted Cancer Therapy

NSCLC: The recommended daily dose of Erlotinib for NSCLC is 150 mg taken on an empty stomach, i.e., at least one hour before or two hours after the ingestion of food. Treatment should continue until disease progression or unacceptable toxicity occurs.

Pancreatic Cancer: The recommended daily dose of Erlotinib for pancreatic cancer is 100 mg taken once daily in combination with gemcitabine. Take Erlotinib on an empty stomach, i.e., at least one hour before or two hours after the ingestion of food. Treatment should continue until disease progression or unacceptable toxicity occurs.

Reduce Erlotinib by 50 mg decrements: If severe reactions occur with concomitant use of strong CYP3A4 inhibitors (such as atazanavir, Clarithromycin, Indinavir, Itraconazole, Ketoconazole, Nefazodone, Nelfinavir, Ritonavir, Saquinavir, Telithromycin, Voriconazole or grapefruit or grapefruit juice] or when using concomitantly with an inhibitor of both CYP3A4 and CYP1A2 (e.g., Ciprofloxacin).

Increase Erlotinib by 50 mg increments as tolerated for: Concomitant use with CYP3A4 inducers, such as rifampin, rifabutin, rifapentine, phenytoin, carbamazepine, phenobarbital, or St. John's Wort. Increase doses by 50 mg increments at 2 week intervals to a maximum of 450 mg. Avoid concomitant use, if possible.

Concurrent cigarette smoking: Increase by 50 mg increments at 2 week intervals to a maximum of 300 mg. Immediately reduce the dose of Erlotinib to the recommended dose (150 mg or 100 mg daily) upon cessation of smoking.

The most common adverse reactions (20%) with Erlotinib from a pooled analysis of studies were rash, diarrhea, anorexia, fatigue, dyspnea, cough, nausea, and vomiting. The following serious adverse reactions, which may include fatalities.

• Interstitial Lung Disease (ILD)
• Renal Failure
• Hepatotoxicity with or without Hepatic Impairment
• Gastrointestinal Perforation
• Bullous and Exfoliative Skin Disorders
• Myocardial Infarction/Ischemia
• Cerebrovascular Accident
• Microangiopathic Hemolytic Anemia with Thrombocytopenia
• Ocular Disorders
• Hemorrhage in Patients Taking Warfarin

Anticoagulants: Interaction with coumarin-derived anticoagulants, including warfarin, leading to increased International Normalized Ratio (INR) and bleeding adverse reactions.

CYP3A4 inhibitors: Erlotinib is metabolized predominantly by CYP3A4. Co-treatment with the potent CYP3A4 inhibitor ketoconazole increased Erlotinib AUC by 67%. When Erlotinib was co-administered with Ciprofloxacin, an inhibitor of both CYP3A4 and CYP1A2, the Erlotinib exposure [AUC] and maximum concentration [Cmax] increased by 39% and 17%, respectively.

CYP3A4 inducers: Pre-treatment with the CYP3A4 inducer Rifampicin for 7-11 days prior to Erlotinib decreased Erlotinib AUC by 58% to 80%. Dose modifications are recommended.

Drugs affecting gastric pH: Co-administration of Erlotinib with omeprazole decreased Erlotinib AUC by 46% and co-administration of Erlotinib with Ranitidine 300 mg decreased Erlotinib AUC by 33%.

Pregnancy category D. Based on its mechanism of action, Erlotinib can cause fetal harm when administered to a pregnant woman. It is not known whether Erlotinib is present in human milk. Because many drugs are present in human milk and because of the potential for serious adverse reactions in nursing infants from Erlotinib, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.

Pediatric use: The safety and effectiveness of Erlotinib in pediatric patients have not been established.

Geriatric use: No overall differences in safety or efficacy were observed between subjects 65 years and older and those younger than 65.

Single oral doses of Erlotinib up to 1,000 mg in healthy subjects and weekly doses up to 1,600 mg in cancer patients have been tolerated. Repeated twice-daily doses of 200 mg single-agent Erlotinib in healthy subjects were poorly tolerated after only a few days of dosing. Based on the data from these studies, an unacceptable incidence of severe adverse reactions, such as diarrhea, rash, and liver transaminase elevation, may occur above the recommended dose. In case of suspected overdose, Erlotinib should be withheld and symptomatic treatment instituted.

Store at a temperature not exceeding 30°C in a dry place. Protect from light and moisture.

Glycopeptide

Teicoplanin is a glycopeptide antibiotic that has shown in vitro bactericidal activity against both anaerobic and aerobic gram-positive organisms. Teicoplanin inhibits the growth of susceptible organisms by interfering with cell-wall biosynthesis at a site different from that affected by beta-lactams. It is active against staphylococci (including those resistant to methicillin and other beta-lactam antibiotics), streptococci, enterococci, Listeria monocytogenes, micrococci, group JK corynebacteria and gram-positive anaerobes including Clostridium difficile and peptococci.

Adult or elderly patients with normal renal function:

Intravenously: Intravenous injection may be administered by rapid injection over 3-5 minutes, or slowly over a 30 minutes infusion by diluting with 0.9% Sodium Chloride or Hartmanns Solution or 5% Dextrose etc.

Intramascularly: An intramuscular injection of Teicoplanin should not exceed 3 ml at a single site.

3 ml water for injection should be added slowly down the side wall of the vial of Teicoplanin 200 mg or 400 mg. The vial should be rolled gently between the palms until the powder is completely dissolved. During the rolling, we have to be cautious about the solution that it does not become foamy. The solution must not be shaken. If foam formed then it should be allowed to stand for 15 minutes for the foam to be subsided. The entire contents from the vial should be withdrawn slowly into a syringe.

Teicoplanin is generally well tolerated. Serious side-effects are rare. Side-effects are gastrointestinal like nausea, vomiting, diarrhea, CNS associated with urticaria, rash, anaphylactic shock as well as hearing problems like vertigo, tinnitus and vestibular disorder may occur.

Teicoplanin is contraindicated in patients who have exhibited previous hypersensitivity to Teicoplanin.

Teicoplanin should be administered with caution in patients with renal insufficiency, patients who require concurrent use of drugs which have ototoxic and/or nephrotoxic properties.

Teicoplanin should be administered with caution in patients receiving concurrent nephrotoxic or ototoxic drugs such as Aminoglycosides, Amphotericin B, Cyclosporine and Frusemide.

There are no adequate and well-controlled studies in pregnant women about administration of Teicoplanin; this drug should be used during pregnancy only if clearly needed. Information about the excretion of Teicoplanin in milk is not known.

Patients with renal impairment: For patients with impaired renal function, reduction of dosage is not required until the fourth day of Teicoplanin treatment. From the fourth day of treatment-

In mild renal insufficiency: Teicoplanin dose should be halved either by administering the initial unit dose every two days, or by administering half of this dose once a day when creatinine clearance is 40-60 ml/min.

In severe renal insufficiency: Teicoplanin dose should be 1/3 of the normal either by administering the initial unit dose every third day or by administering 1/3 of this dose once a day when creatinine clearance is less than 40 ml/min and in haemodialysed patients. Teicoplanin is not removed by dialysis.

3 ml water for injection should be added slowly down the side wall of the vial of Teicoplanin 200 mg or 400 mg. The vial should be rolled gently between the palms until the powder is completely dissolved. During the rolling, we have to be cautious about the solution that it does not become foamy. The solution must not be shaken. If foam formed then it should be allowed to stand for 15 minutes for the foam to be subsided. The entire contents from the vial should be withdrawn slowly into a syringe.

Glycopeptide

Teicoplanin is a glycopeptide antibiotic that has shown in vitro bactericidal activity against both anaerobic and aerobic gram-positive organisms. Teicoplanin inhibits the growth of susceptible organisms by interfering with cell-wall biosynthesis at a site different from that affected by beta-lactams. It is active against staphylococci (including those resistant to methicillin and other beta-lactam antibiotics), streptococci, enterococci, Listeria monocytogenes, micrococci, group JK corynebacteria and gram-positive anaerobes including Clostridium difficile and peptococci.

Adult or elderly patients with normal renal function:

Intravenously: Intravenous injection may be administered by rapid injection over 3-5 minutes, or slowly over a 30 minutes infusion by diluting with 0.9% Sodium Chloride or Hartmanns Solution or 5% Dextrose etc.

Intramascularly: An intramuscular injection of Teicoplanin should not exceed 3 ml at a single site.

3 ml water for injection should be added slowly down the side wall of the vial of Teicoplanin 200 mg or 400 mg. The vial should be rolled gently between the palms until the powder is completely dissolved. During the rolling, we have to be cautious about the solution that it does not become foamy. The solution must not be shaken. If foam formed then it should be allowed to stand for 15 minutes for the foam to be subsided. The entire contents from the vial should be withdrawn slowly into a syringe.

Teicoplanin is generally well tolerated. Serious side-effects are rare. Side-effects are gastrointestinal like nausea, vomiting, diarrhea, CNS associated with urticaria, rash, anaphylactic shock as well as hearing problems like vertigo, tinnitus and vestibular disorder may occur.

Teicoplanin is contraindicated in patients who have exhibited previous hypersensitivity to Teicoplanin.

Teicoplanin should be administered with caution in patients with renal insufficiency, patients who require concurrent use of drugs which have ototoxic and/or nephrotoxic properties.

Teicoplanin should be administered with caution in patients receiving concurrent nephrotoxic or ototoxic drugs such as Aminoglycosides, Amphotericin B, Cyclosporine and Frusemide.

There are no adequate and well-controlled studies in pregnant women about administration of Teicoplanin; this drug should be used during pregnancy only if clearly needed. Information about the excretion of Teicoplanin in milk is not known.

Patients with renal impairment: For patients with impaired renal function, reduction of dosage is not required until the fourth day of Teicoplanin treatment. From the fourth day of treatment-

In mild renal insufficiency: Teicoplanin dose should be halved either by administering the initial unit dose every two days, or by administering half of this dose once a day when creatinine clearance is 40-60 ml/min.

In severe renal insufficiency: Teicoplanin dose should be 1/3 of the normal either by administering the initial unit dose every third day or by administering 1/3 of this dose once a day when creatinine clearance is less than 40 ml/min and in haemodialysed patients. Teicoplanin is not removed by dialysis.

3 ml water for injection should be added slowly down the side wall of the vial of Teicoplanin 200 mg or 400 mg. The vial should be rolled gently between the palms until the powder is completely dissolved. During the rolling, we have to be cautious about the solution that it does not become foamy. The solution must not be shaken. If foam formed then it should be allowed to stand for 15 minutes for the foam to be subsided. The entire contents from the vial should be withdrawn slowly into a syringe.

Tart Cherry is indicated in-

• Gout
• Hyperuricemia

Herbal and Nutraceuticals

Once-daily dose with a glass of water or as advised by the physician. At least 3 months repeated course is feasible as advised by the physician.

Generally well-tolerated in the recommended dose. Occasionally may cause gastrointestinal discomfort

Known hypersensitivity to Tart cherry.

Avoid during pregnancy and lactation due to insufficient data.

Do not store above 30°C. Store away from light & moisture. Keep out of reach of children.

Targeted Cancer Therapy

NSCLC: The recommended daily dose of Erlotinib for NSCLC is 150 mg taken on an empty stomach, i.e., at least one hour before or two hours after the ingestion of food. Treatment should continue until disease progression or unacceptable toxicity occurs.

Pancreatic Cancer: The recommended daily dose of Erlotinib for pancreatic cancer is 100 mg taken once daily in combination with gemcitabine. Take Erlotinib on an empty stomach, i.e., at least one hour before or two hours after the ingestion of food. Treatment should continue until disease progression or unacceptable toxicity occurs.

Reduce Erlotinib by 50 mg decrements: If severe reactions occur with concomitant use of strong CYP3A4 inhibitors (such as atazanavir, Clarithromycin, Indinavir, Itraconazole, Ketoconazole, Nefazodone, Nelfinavir, Ritonavir, Saquinavir, Telithromycin, Voriconazole or grapefruit or grapefruit juice] or when using concomitantly with an inhibitor of both CYP3A4 and CYP1A2 (e.g., Ciprofloxacin).

Increase Erlotinib by 50 mg increments as tolerated for: Concomitant use with CYP3A4 inducers, such as rifampin, rifabutin, rifapentine, phenytoin, carbamazepine, phenobarbital, or St. John's Wort. Increase doses by 50 mg increments at 2 week intervals to a maximum of 450 mg. Avoid concomitant use, if possible.

Concurrent cigarette smoking: Increase by 50 mg increments at 2 week intervals to a maximum of 300 mg. Immediately reduce the dose of Erlotinib to the recommended dose (150 mg or 100 mg daily) upon cessation of smoking.

The most common adverse reactions (20%) with Erlotinib from a pooled analysis of studies were rash, diarrhea, anorexia, fatigue, dyspnea, cough, nausea, and vomiting. The following serious adverse reactions, which may include fatalities.

• Interstitial Lung Disease (ILD)
• Renal Failure
• Hepatotoxicity with or without Hepatic Impairment
• Gastrointestinal Perforation
• Bullous and Exfoliative Skin Disorders
• Myocardial Infarction/Ischemia
• Cerebrovascular Accident
• Microangiopathic Hemolytic Anemia with Thrombocytopenia
• Ocular Disorders
• Hemorrhage in Patients Taking Warfarin

Anticoagulants: Interaction with coumarin-derived anticoagulants, including warfarin, leading to increased International Normalized Ratio (INR) and bleeding adverse reactions.

CYP3A4 inhibitors: Erlotinib is metabolized predominantly by CYP3A4. Co-treatment with the potent CYP3A4 inhibitor ketoconazole increased Erlotinib AUC by 67%. When Erlotinib was co-administered with Ciprofloxacin, an inhibitor of both CYP3A4 and CYP1A2, the Erlotinib exposure [AUC] and maximum concentration [Cmax] increased by 39% and 17%, respectively.

CYP3A4 inducers: Pre-treatment with the CYP3A4 inducer Rifampicin for 7-11 days prior to Erlotinib decreased Erlotinib AUC by 58% to 80%. Dose modifications are recommended.

Drugs affecting gastric pH: Co-administration of Erlotinib with omeprazole decreased Erlotinib AUC by 46% and co-administration of Erlotinib with Ranitidine 300 mg decreased Erlotinib AUC by 33%.

Pregnancy category D. Based on its mechanism of action, Erlotinib can cause fetal harm when administered to a pregnant woman. It is not known whether Erlotinib is present in human milk. Because many drugs are present in human milk and because of the potential for serious adverse reactions in nursing infants from Erlotinib, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.

Pediatric use: The safety and effectiveness of Erlotinib in pediatric patients have not been established.

Geriatric use: No overall differences in safety or efficacy were observed between subjects 65 years and older and those younger than 65.

Single oral doses of Erlotinib up to 1,000 mg in healthy subjects and weekly doses up to 1,600 mg in cancer patients have been tolerated. Repeated twice-daily doses of 200 mg single-agent Erlotinib in healthy subjects were poorly tolerated after only a few days of dosing. Based on the data from these studies, an unacceptable incidence of severe adverse reactions, such as diarrhea, rash, and liver transaminase elevation, may occur above the recommended dose. In case of suspected overdose, Erlotinib should be withheld and symptomatic treatment instituted.

Store at a temperature not exceeding 30°C in a dry place. Protect from light and moisture.

Targeted Cancer Therapy

NSCLC: The recommended daily dose of Erlotinib for NSCLC is 150 mg taken on an empty stomach, i.e., at least one hour before or two hours after the ingestion of food. Treatment should continue until disease progression or unacceptable toxicity occurs.

Pancreatic Cancer: The recommended daily dose of Erlotinib for pancreatic cancer is 100 mg taken once daily in combination with gemcitabine. Take Erlotinib on an empty stomach, i.e., at least one hour before or two hours after the ingestion of food. Treatment should continue until disease progression or unacceptable toxicity occurs.

Reduce Erlotinib by 50 mg decrements: If severe reactions occur with concomitant use of strong CYP3A4 inhibitors (such as atazanavir, Clarithromycin, Indinavir, Itraconazole, Ketoconazole, Nefazodone, Nelfinavir, Ritonavir, Saquinavir, Telithromycin, Voriconazole or grapefruit or grapefruit juice] or when using concomitantly with an inhibitor of both CYP3A4 and CYP1A2 (e.g., Ciprofloxacin).

Increase Erlotinib by 50 mg increments as tolerated for: Concomitant use with CYP3A4 inducers, such as rifampin, rifabutin, rifapentine, phenytoin, carbamazepine, phenobarbital, or St. John's Wort. Increase doses by 50 mg increments at 2 week intervals to a maximum of 450 mg. Avoid concomitant use, if possible.

Concurrent cigarette smoking: Increase by 50 mg increments at 2 week intervals to a maximum of 300 mg. Immediately reduce the dose of Erlotinib to the recommended dose (150 mg or 100 mg daily) upon cessation of smoking.

The most common adverse reactions (20%) with Erlotinib from a pooled analysis of studies were rash, diarrhea, anorexia, fatigue, dyspnea, cough, nausea, and vomiting. The following serious adverse reactions, which may include fatalities.

• Interstitial Lung Disease (ILD)
• Renal Failure
• Hepatotoxicity with or without Hepatic Impairment
• Gastrointestinal Perforation
• Bullous and Exfoliative Skin Disorders
• Myocardial Infarction/Ischemia
• Cerebrovascular Accident
• Microangiopathic Hemolytic Anemia with Thrombocytopenia
• Ocular Disorders
• Hemorrhage in Patients Taking Warfarin

Anticoagulants: Interaction with coumarin-derived anticoagulants, including warfarin, leading to increased International Normalized Ratio (INR) and bleeding adverse reactions.

CYP3A4 inhibitors: Erlotinib is metabolized predominantly by CYP3A4. Co-treatment with the potent CYP3A4 inhibitor ketoconazole increased Erlotinib AUC by 67%. When Erlotinib was co-administered with Ciprofloxacin, an inhibitor of both CYP3A4 and CYP1A2, the Erlotinib exposure [AUC] and maximum concentration [Cmax] increased by 39% and 17%, respectively.

CYP3A4 inducers: Pre-treatment with the CYP3A4 inducer Rifampicin for 7-11 days prior to Erlotinib decreased Erlotinib AUC by 58% to 80%. Dose modifications are recommended.

Drugs affecting gastric pH: Co-administration of Erlotinib with omeprazole decreased Erlotinib AUC by 46% and co-administration of Erlotinib with Ranitidine 300 mg decreased Erlotinib AUC by 33%.

Pregnancy category D. Based on its mechanism of action, Erlotinib can cause fetal harm when administered to a pregnant woman. It is not known whether Erlotinib is present in human milk. Because many drugs are present in human milk and because of the potential for serious adverse reactions in nursing infants from Erlotinib, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.

Pediatric use: The safety and effectiveness of Erlotinib in pediatric patients have not been established.

Geriatric use: No overall differences in safety or efficacy were observed between subjects 65 years and older and those younger than 65.

Single oral doses of Erlotinib up to 1,000 mg in healthy subjects and weekly doses up to 1,600 mg in cancer patients have been tolerated. Repeated twice-daily doses of 200 mg single-agent Erlotinib in healthy subjects were poorly tolerated after only a few days of dosing. Based on the data from these studies, an unacceptable incidence of severe adverse reactions, such as diarrhea, rash, and liver transaminase elevation, may occur above the recommended dose. In case of suspected overdose, Erlotinib should be withheld and symptomatic treatment instituted.

Store at a temperature not exceeding 30°C in a dry place. Protect from light and moisture.

Nilotinib is indicated in advanced renal cell carcinoma (RCC), advanced soft tissue sarcoma (STS) who have received prior chemotherapy. The efficacy of Nilotinib 200 for the treatment of patients with adipocytic STS or gastrointestinal stromal tumors has not been demonstrated.

Targeted Cancer Therapy

Pazopanib is a multi-tyrosine kinase inhibitor of vascular endothelial growth factor receptor (VEGFR)-1, VEGFR-2, VEGFR-3, platelet-derived growth factor receptor (PDGFR) and fibroblast growth factor receptor (FGFR)-1 and -3, cytokine receptor (Kit), interleukin-2 receptor-inducible T- cell kinase (Itk), lymphocyte-specific protein tyrosine kinase (Lck), and transmembrane glycoprotein receptor tyrosine kinase (c-Fms). In vitro, Pazopanib inhibited ligand-induced autophosphorylation of VEGFR-2, Kit, and PDGFR receptors.

Absorption: Pazopanib is absorbed orally with the median time to achieve peak concentrations of 2 to 4 hours after the dose. Daily dosing at 800 mg results in geometric mean AUC and Cmax of 1,037 mcg/mL and 58.1 mcg/mL (equivalent to 132 μM), respectively. There was no consistent increase in AUC or Cmax at Pazopanib doses above 800 mg.

Distribution: Binding of Pazopanib to human plasma protein in vivo was greater than 99% with no concentration dependence over the range of 10 to 100 mcg/mL. In vitro, studies suggest that Pazopanib is a substrate for P-gp and BCRP.

Metabolism: In vitro studies demonstrated that Pazopanib is metabolized by CYP3A4 with a minor contribution from CYP1A2 and CYP2C8.

Elimination: Pazopanib has a mean half-life of 30.9 hours after administration of the recommended dose of 800 mg. Elimination is primarily via feces with renal elimination accounting for less than 4% of the administered dose.

The recommended starting dose of Pazopanib is 800 mg orally once daily without food (at least 1 hour before or 2 hours after a meal). The dose of Pazopanib should not exceed 800 mg. Tablets should not be crushed due to the potential for an increased rate of absorption which may affect systemic exposure. If a dose is missed, it should not be taken if it is less than 12 hours until the next dose or as directed by the registered physicians.

Pediatric Use: The safety and effectiveness of Pazopanib in pediatric patients have not been established.

Should be taken on an empty stomach. Avoid food at least 2 hr before & at least 1 hr after a dose. Swallow whole, do not chew/crush. Avoid grapefruit products.

Rash, pruritus, hepatotoxicity, headache, fever, fatigue, GI disturbances (nausea, constipation, diarrhoea), alopecia, asthenia, muscle spasms, arthralgia, myalgia, pain (e.g. musculoskeletal or chest pain), oedema, folliculitis, papilloma, insomnia, dizziness, vertigo, anxiety, paraesthesia, hyperhidrosis, dry skin, urticaria, acne, conjunctivitis, dry eye, flushing, dyspnoea, cough, myelosuppression (e.g. thrombocytopenia, neutropenia, and anaemia), thrombotic disorders or haemorrhage, arrhythmias, heart failure, pericarditis, palpitations, HTN, angina, MI; elevated AST/ALT, serum lipase; electrolyte imbalances.

It is contraindicated in patients with known hypersensitivity to Pazopanib or any other components of this product.

Hepatic Toxicity and Hepatic Impairment: In clinical trials with Pazopanib, hepatotoxicity, manifested as increases in serum transaminases (alanine transferase [ALT], aspartate aminotransferase [AST]) and bilirubin, was observed. This hepatotoxicity can be severe and fatal. Patients older than 65 years are at greater risk for hepatotoxicity. Transaminase elevations occur early in the course of treatment (92.5% of all transaminase elevations of any grade occurred in the first 18 weeks).

QT Prolongation and Torsades De Pointes: In the RCC trials of Pazopanib, QT prolongation (greater than or equal to 500 msec) was identified on routine electrocardiogram (ECG) monitoring in 2% (11/558) of patients. Torsades de pointes occurred in less than 1% (2/977) of patients who received Pazopanib in the monotherapy trials. Pazopanib should be used with caution in patients with a history of QT interval prolongation, in patients taking antiarrhythmics or other medications that may prolong QT interval, and those with relevant pre-existing cardiac disease. When using Pazopanib, baseline and periodic monitoring of ECGs and maintenance of electrolytes (e.g., calcium, magnesium, potassium) within the normal range should be performed.

Hemorrhagic Events: Fatal hemorrhage occurred in 0.9% (5/586) in the RCC trials; there were no reports of fatal hemorrhage in the STS trials. In the randomized RCC trial, 13% (37/290) of patients treated with Pazopanib and 5% (7/145) of patients on placebo experienced at least 1 hemorrhagic event. The most common hemorrhagic events in the patients treated with Pazopanib were hematuria (4%), epistaxis (2%), hemoptysis (2%), and rectal hemorrhage (1%). Nine of 37 patients treated with Pazopanib, who had hemorrhagic events, experienced serious events including pulmonary, gastrointestinal, and genitourinary hemorrhage. One percent (4/290) of patients treated with Pazopanib died from hemorrhage compared with no (0/145) patients on placebo. In the overall safety population in RCC (N = 586), cerebral/intracranial hemorrhage was observed in less than 1% (2/586) of patients treated with Pazopanib.

Arterial Thromboembolic Events: Fatal arterial thromboembolic events were observed in 0.3% (2/586) of patients in the RCC trials and in no patients in the STS trials. In the randomized RCC trial, 2% (5/290) of patients receiving Pazopanib experienced myocardial infarction or ischemia, 0.3% (1/290) had a cerebrovascular accident, and 1% (4/290) had an event of transient ischemic attack. In the randomized STS trial, 2% (4/240) of patients receiving Pazopanib experienced a myocardial infarction or ischemia, 0.4% (1/240) had a cerebrovascular accident, and there were no incidents of transient ischemic attack. No arterial thromboembolic events were reported in patients who received placebo in either trial. Pazopanib should be used with caution in patients who are at increased risk for these events or who have had a history of these events. Pazopanib has not been studied in patients who have had an arterial thromboembolic event within the previous 6 months and should not be used in those patients.

Venous Thromboembolic Events: In RCC and STS trials of Pazopanib, venous thromboembolic events (VTEs), including venous thrombosis and fatal pulmonary embolus (PE), have occurred. In the randomized STS trial, VTEs were reported in 5% of patients treated with Pazopanib compared with 2% with placebo. In the randomized RCC trial, the rate was 1% in both arms. Fatal PE occurred in 1% (2/240) of STS patients receiving Pazopanib and in no patients receiving placebo. There were no fatal pulmonary emboli in the RCC trial. Monitor for signs and symptoms of VTE and PE.

Thrombotic Microangiopathy: Thrombotic microangiopathy (TMA), including thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS), has been reported in clinical trials of Pazopanib as monotherapy, in combination with Bevacizumab, and in combination with Topotecan. Pazopanib is not indicated for use in combination with other agents. Six of the 7 TMA cases occurred within 90 days of the initiation of Pazonib-200. Improvement of TMA was observed after treatment was discontinued. Monitor for signs and symptoms of TMA. Permanently discontinue Pazopanib in patients developing TMA. Manage as clinically indicated.

Gastrointestinal Perforation and Fistula: In the RCC and STS trials, gastrointestinal perforation or fistula occurred in 0.9% (5/586) of patients and 1% (4/382) of patients receiving Pazopanib, respectively. Fatal perforations occurred in 0.3% (2/586) of these patients in the RCC trials and in 0.3% (1/382) of these patients in the STS trials. Monitor for signs and symptoms of gastrointestinal perforation or fistula.

Interstitial Lung Disease/Pneumonitis: Interstitial lung disease (ILD)/pneumonitis, which can be fatal, has been reported in association with Pazopanib. In clinical trials, ILD/pneumonitis occurred in 0.1% of patients treated with Pazopanib.. Monitor patients for pulmonary symptoms indicative of ILD/pneumonitis and discontinue Pazopanib in patients developing ILD or pneumonitis.

Reversible Posterior Leukoencephalopathy Syndrome: Reversible Posterior Leukoencephalopathy Syndrome (RPLS) has been reported in patients receiving Pazopanib and may be fatal. RPLS is a neurological disorder that can present with headache, seizure, lethargy, confusion, blindness, and other visual and neurologic disturbances. Mild to severe hypertension may be present. The diagnosis of RPLS is optimally confirmed by magnetic resonance imaging. Permanently discontinue Pazopanib in patients developing RPLS.

Wound Healing: No formal trials on the effect of Pazopanib on wound healing have been conducted. Since vascular endothelial growth factor receptor (VEGFR) inhibitors such as Pazopanib may impair wound healing, treatment with Pazopanib should be stopped at least 7 days prior to scheduled surgery. The decision to resume Pazopanib after surgery should be based on clinical judgment of adequate wound healing. Pazopanib should be discontinued in patients with wound dehiscence.

Hypothyroidism: Hypothyroidism, confirmed based on a simultaneous rise of TSH and decline of T4, was reported in 7% (19/290) of patients treated with Pazopanib in the randomized RCC trial and in 5% (11/240) of patients treated with Pazopanib in the randomized STS trial. No patients on the placebo arm of either trial had hypothyroidism. In RCC and STS trials of Pazopanib, hypothyroidism was reported as an adverse reaction in 4% (26/586) and 5% (20/382) of patients, respectively. Proactive monitoring of thyroid function tests is recommended.

Tumor Lysis Syndrome: Cases of tumor lysis syndrome (TLS), including fatal cases, have been reported in RCC and STS patients treated with Pazopanib. Patients may be at risk of TLS if they have rapidly growing tumors, a high tumor burden, renal dysfunction, or dehydration. Closely monitor patients at risk, consider appropriate prophylaxis, and treat as clinically indicated.

Infection: Serious infections (with or without neutropenia), including some with fatal outcome, have been reported. Monitor patients for signs and symptoms of infection. Institute appropriate anti-infective therapy promptly and consider interruption or discontinuation of Pazopanib for serious infections. Increased Toxicity with other Cancer Therapy: Pazopanib is not indicated for use in combination with other agents. Clinical trials of Pazopanib in combination with Pemetrexed and Lapatinib were terminated early due to concerns over increased toxicity and mortality. The fatal toxicities observed included pulmonary hemorrhage, gastrointestinal hemorrhage, and sudden death. A safe and effective combination dose has not been established with these regimens.

Drugs that Inhibit or Induce Cytochrome P450 3A4 Enzymes: In vitro studies suggested that the oxidative metabolism of Pazopanib in human liver microsomes is mediated primarily by CYP3A4, with minor contributions from CYP1A2 and CYP2C8. Therefore, inhibitors and inducers of CYP3A4 may alter the metabolism of Pazopanib.

CYP3A4 Inhibitors: Co-administration of Pazopanib with strong inhibitors of CYP3A4 (e.g., Ketoconazole, Ritonavir, Clarithromycin) increases Pazopanib concentrations and should be avoided. Consider an alternate concomitant medication with no or minimal potential to inhibit CYP3A4. If co-administration of a strong CYP3A4 inhibitor is warranted, reduce the dose of Pazopanib to 400 mg. Grapefruit or grapefruit juice should be avoided as it inhibits CYP3A4 activity and may also increase plasma concentrations of Pazopanib.

CYP3A4 Inducers: CYP3A4 inducers, such as Rifampin, may decrease plasma Pazopanib concentrations. Consider an alternate concomitant medication with no or minimal enzyme induction potential. Pazopanib should not be used if chronic use of strong CYP3A4 inducers cannot be avoided.

Drugs that Inhibit Transporters: In vitro studies suggested that Pazopanib is a substrate of P- glycoprotein (P gp) and breast cancer resistance protein (BCRP). Therefore, absorption and subsequent elimination of Pazopanib may be influenced by products that affect P-gp and BCRP. Concomitant treatment with strong inhibitors of P-gp or BCRP should be avoided due to the risk of increased exposure to Pazopanib. The selection of alternative concomitant medicinal products with no or minimal potential to inhibit P-gp or BCRP should be considered.

Effects of Pazopanib on CYP Substrates: Results from drug-drug interaction trials conducted in cancer patients suggest that Pazopanib is a weak inhibitor of CYP3A4, CYP2C8, and CYP2D6 in vivo, but had no effect on CYP1A2, CYP2C9, or CYP2C19. Concomitant use of Pazopanib with agents with narrow therapeutic windows that are metabolized by CYP3A4, CYP2D6, or CYP2C8 is not recommended. Co-administration may result in inhibition of the metabolism of these products and create the potential for serious adverse events.

Effect of Concomitant Use of Pazopanib and Simvastatin: Concomitant use of Pazopanib and Simvastatin increases the incidence of ALT elevations. Across monotherapy trials with Pazopanib, ALT greater than 3 x ULN was reported in 126/895 (14%) of patients who did not use statins, compared with 11/41 (27%) of patients who had concomitant use of Simvastatin. If a patient receiving concomitant Simvastatin develops ALT elevations, follow dosing guidelines for Pazopanib or consider alternatives to Pazopanib. Alternatively, consider discontinuing Simvastatin. Insufficient data are available to assess the risk of concomitant administration of alternative statins and Pazopanib.

Pazopanib can cause fetal harm when administered to a pregnant woman. There are no available data in pregnant women to inform a drug-associated risk. Pregnant women or women should be advised of the childbearing potential of the risk to a fetus. There is no information regarding the presence of Pazopanib or its metabolites in human milk, or their effects on the breastfed infant, or on milk production. Because of the potential for serious adverse reactions in breastfed infants from Pazopanib, a lactating woman should be advised not to breastfeed during treatment with Pazopanib and for 2 weeks after the final dose.

Females contraception: Females of reproductive potential should be advised to use effective contraception during treatment and for at least 2 weeks after the last dose of Pazopanib.

Males contraception: To avoid potential drug exposure to pregnant partners and female partners of reproductive potential, male patients (including those who have had vasectomies) with female partners of reproductive potential should be advised to use condoms during treatment with Pazopanib and for at least 2 weeks after the last dose.

Pazopanib doses up to 2000 mg have been evaluated in clinical trials. Dose-limiting toxicity (Grade 3 fatigue) and Grade 3 hypertension were each observed in 1 of 3 patients dosed at 2000 mg daily and 1000 mg daily, respectively. Treatment of overdose with Nilotinib should consist of general supportive measures. There is no specific antidote for overdosage of Nilotinib. Hemodialysis is not expected to enhance the elimination of Nilotinib because Pazopanib is not significantly renally excreted and is highly bound to plasma proteins.

Store in a cool (not above 30°C) and dry place, away from sunlight. Keep out of reach of children.

Atenolol is indicated-

• In the management of hypertension. It may be used alone or concomitantly with other antihypertensive agents, particularly with a thiazide-type diuretic.
• For the long-term management of patients with angina pectoris.
• In the management of hemodynamically stable patients with defnite or suspected acute myocardial infarction to reduce cardiovascular mortality.

Beta-adrenoceptor blocking drugs, Beta-blockers

The synthesis of atenolol resulted from attempts to produce a β-adrenoceptor antagonist that would competitively block β1 (cardiac) receptors but have no effect on β2-receptors. It is classified as a β1 selective (cardioselective) β-adrenergic receptor antagonist with no membranestability activity and no partial agonist activity. It is markedly the most hydrophilic of the currently available β- blockers and thus penetrates the lipid of cell membranes poorly

Hypertension: The initial dose of Atenolol is 50 mg given as one tablet a day either alone or added to diuretic therapy. The full effect of this dose will usually be seen within one to two weeks. If an optimal response is not achieved, the dosage should be increased to Atenolol 100 mg given as one tablet a day. Increasing the dosage beyond 100 mg a day is unlikely to produce any further benefit.

Angina Pectoris: The initial dose of Atenolol is 50 mg given as one tablet a day. If an optimal response is not achieved within one week, the dosage should be increased to Atenolol 100 mg given as one tablet a day. Some patients may require a dosage of 200 mg once a day for optimal effect. Twenty-four hour control with once daily dosing is achieved by giving doses larger than necessary to achieve an immediate maximum effect. The maximum early effect on exercise tolerance occurs with doses of 50 to 100 mg, but at these doses the effect at 24 hours is attenuated, averaging about 50% to 75% of that observed with once a day oral doses of 200 mg.

Acute Myocardial Infarction: In patients with definite or suspected acute myocardial infarction, treatment with Atenolol I.V. Injection should be initiated as soon as possible after the patient's arrival in the hospital and after eligibility is established. Treatment should begin with the intravenous administration of 5 mg Atenolol over 5 minutes followed by another 5 mg intravenous injection 10 minutes later. In patients who tolerate the full intravenous dose (10 mg), Atenolol Tablets 50 mg should be initiated 10 minutes after the last intravenous dose followed by another 50 mg oral dose 12 hours later. Thereafter, Atenolol can be given orally either 100 mg once daily or 50 mg twice a day for a further 6-9 days or until discharge from the hospital. If bradycardia or hypotension requiring treatment or any other untoward effects occur, Atenolol should be discontinued.

In a series of investigations in the treatment of acute myocardial infarction, bradycardia and hypotension occurred more commonly, as expected for any beta blocker. In addition, a variety of adverse efects has been reported with other beta-adrenergic blocking agents, and may be considered potential adverse efects of Atenolol.

• Hematologic: Agranulocytosis.
• Allergic: Fever, combined with aching and sore throat, laryngospasm, and respiratory distress.
• Central Nervous System: Reversible mental depression progressing to catatonia; an acute reversible syndrome characterized by disorientation of time and place; short term memory loss; emotional lability with slightly clouded sensorium; and, decreased performance on neuropsychometrics.
• Gastrointestinal: Mesenteric arterial thrombosis, ischemic colitis.
• Miscellaneous: There have been reports of skin rashes and/or dry eyes associated with the use of beta-adrenergic blocking drugs. Discontinuance of the drug should be considered if any such reaction is not otherwise explicable. Patients should be closely monitored following cessation of therapy.
• Other: Erythematous rash

Atenolol is contraindicated in-

• Sinus bradycardia, heart block greater than first degree, cardiogenic shock, and overt cardiac failure.
• Those patients with a history of hypersensitivity to the atenolol or any of the drug product’s components.

General: Patients already on a beta blocker must be evaluated carefully before Atenolol is administered. Initial and subsequent Atenolol dosages can be adjusted downward depending on clinical observations including pulse and blood pressure. Atenolol may aggravate peripheral arterial circulatory disorders.

Impaired Renal Function: The drug should be used with caution in patients with impaired renal function.

Geriatric Use:

• Hypertension and Angina Pectoris: Due to Coronary Atherosclerosis: Dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.
• Acute Myocardial Infarction: Dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. Evaluation of patients with hypertension or myocardial infarction should always include assessment of renal function.

Pregnancy Category D. Caution should be exercised when Atenolol is administered to a nursing woman. Clinically significant bradycardia has been reported in breast-fed infants. Premature infants, or infants with impaired renal function, may be more likely to develop adverse effects.

Elderly Patients or Patients with Renal Impairment: Atenolol is excreted by the kidneys; consequently dosage should be adjusted in cases of severe impairment of renal function. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, refecting greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. The following maximum oral dosages are recommended for elderly, renal impaired patients and for patients with renal impairment due to other causes:

• Creatinine clearance 15-35 ml/min/1.73 m²: Maximum dosage 50 mg daily
• Creatinine clearance <15 mL/min/1.73 m²: Maximum dosage 25 mg daily

Some renal impaired or elderly patients being treated for hypertension may require a lower starting dose of Atenolol: 25 mg given as one tablet a day. Patients on hemodialysis should be given 25 mg or 50 mg after each dialysis; this should be done under hospital supervision as marked falls in blood pressure can occur.

Overdosage with Atenolol has been reported with patients surviving acute doses as high as 5 g. One death was reported in a man who may have taken as much as 10 g acutely. The predominant symptoms reported following Atenolol overdose are lethargy, disorder of respiratory drive, wheezing, sinus pause and bradycardia. Additionally, common efects associated with overdosage of any beta-adrenergic blocking agent and which might also be expected in Atenolol overdose are congestive heart failure, hypotension, bronchospasm and/or hypoglycemia. Treatment of overdose should be directed to the removal of any unabsorbed drug by induced emesis, gastric lavage, or administration of activated charcoal. Atenolol can be removed from the general circulation by hemodialysis. Based on the severity of symptoms, management may require intensive support care and facilities for applying cardiac and respiratory support.

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.

Tamsulosin Hydrochloride is indicated for the treatment of functional symptoms of Benign Prostatic Hyperplasia (BPH).

BPH/ Urinary retention/ Urinary incontinence

Tamsulosin, a selective alpha1 adrenoceptor blocking agent, exhibits its selectivity for alpha1 A adrenoceptors in human prostate. Blockade of these adrenoceptors can cause smooth muscle in the bladder neck and prostate to relax, resulting in an improvement in urine flow rate and a reduction in symptoms of BPH. Absorption of Tamsulosin hydrochloride capsule 0.4mg is essentially complete (90%) following oral administration under fasting conditions. The time to maximum concentration (Tmax) is reached by four to five hours under fasting conditions and by six to seven hours when administered with food. Tamsulosin hydrochloride is extremely bound to human plasma protein (94% to 99%). Tamsulosin hydrochloride is extensively metabolized by cytochrome P 450 enzymes in the liver and less than 10% of the dose is excreted in urine as unchanged form. Following intravenous or oral administration of an immediate-release formulation the elimination half-life of Tamsulosin hydrochloride in plasma ranges from five to seven hours. Because of the absorption rate controlled pharmacokinetics with Prostam capsules, the apparent half-life of Tamsulosin hydrochloride is approximately 9 to 13 hours in healthy volunteers and 14 to 15 hours in the target population.

Tamsulosin Hydrochloride 0.4 mg (one capsule) daily, to be taken after meal at night. The dose may be increased after 2 to 4 weeks, if necessary, to Tamsulosin Hydrochloride 0.8 mg (two capsules) once daily. If Tamsulosin Hydrochloride administration is discontinued or interrupted for several days at either the 0.4 mg or 0.8 mg dose, therapy should be started again with the Tamsulosin Hydrochloride 0.4 mg (one capsule) once daily dose. The capsule should be swallowed whole with a glass of water (about 150 ml) in the standing or sitting position. The capsule should not be crunched or chewed, as this will interfere with the modified release of the active ingredient.

The following adverse reactions have been reported during the use of Tamsulosin: dizziness, abnormal ejaculation and; less frequently headache, asthenia, postural hypotension and palpitations.

Tamsulosin hydrochloride is contraindicated in patients with hypersensitivity to it; history of orthostatic hypotension; severe hepatic insufficiency.

As with other alpha1 blockers, a reduction in blood pressure can occur in individual cases during treatment with Tamsulosin, as a result of which, rarely, syncope can occur, at the first signs of orthostatic hypotension (dizziness, weakness) the patient should sit or lie down until the symptoms have disappeared. And they should be cautioned to avoid situations where injury could result (like driving, operating machinery or performing hazardous tasks).

Before therapy with Tamsulosin is initiated the patient should be examined in order to exclude the presence of other conditions which can cause the same symptoms as Benign Prostatic hyperplasia. Digital rectal examination and when the necessary determination of Prostate Specific Antigen (PSA) should be performed before treatment and at regular intervals afterwards.

Rarely, transient postural symptoms have occurred during orthostatic provocation testing after the first dose. Use in patients with micturition syncope is not advised.

Effects on ability to drive and use machines: No data is available on whether Tamsulosin adversely affects the ability to drive or operate machines. However, in this respect, patients should be aware of the fact that dizziness can occur.

Concurrent administration of other alfa1-adrenoceptor antagonists could lead to hypotensive effects. No interactions have been seen when Tamsulosin was given concomitantly with either atenolol, enalapril or nifedipine. Concomitant cimetidine brings about a rise and frusemide a fall in plasma levels of Tamsulosin, but as levels remain within the normal range posology need not be changed. No interactions at the level of hepatic metabolism have been seen during in vitro studies with liver microsomal fractions (representative of the cytochrome P450-linked drug-metabolizing enzyme system), involving amitriptyline, salbutamol, glibenclamide, and finasteride. Diclofenac and warfarin, however, may increase the elimination rate of Tamsulosin.

Use of Tamsulosin in pregnancy and lactation is not recommended.

No case of acute overdosage has been reported. However, acute hypotension is likely to occur after overdosage in which case cardiovascular support should be given. Blood pressure can be restored and the heart rate brought back to normal by lying the patient down. If this does not help then volume expanders, and when necessary, vasopressors could be employed. Renal function should be monitored and general supportive measures applied. Dialysis is unlikely to be of help as Tamsulosin is very highly bound to plasma proteins. Measures, such as emesis, can be taken to impede absorption. When large quantities are involved, gastric lavage can be applied and activated charcoal and an osmotic laxative, such as sodium sulphate, can be administered.

Store in a cool and dry place, below 30°C, protected from light.

Osimertinib is indicated for the treatment of patients with metastatic epidermal growth factor receptor (EGFR) T790M mutation-positive non-small cell lung cancer (NSCLC), as detected by an FDA-approved test, whose disease has progressed on or after EGFR tyrosine kinase inhibitor (TKI) therapy.

Cytotoxic Chemotherapy

Osimertinib is an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) that binds to certain mutant forms of EGFR (T790M, L858R, and exon 19 deletion) that predominate in non-small cell lung cancer (NSCLC) tumours following treatment with first-line EGFR-TKIs. As a third-generation tyrosine kinase inhibitor, osimertinib is specific for the gate-keeper T790M mutation which increases ATP binding activity to EGFR and results in poor prognosis for late-stage disease. Furthermore, osimertinib has been shown to spare wild-type EGFR during therapy, thereby reducing non-specific binding and limiting toxicity.

The recommended dose of Osimertinib is 80 mg once a day until disease progression or unacceptable toxicity. Osimertinib can be taken with or without food. If a dose of Osimertinib is missed, do not make up the missed dose and take the next dose as scheduled.

Administration To Patients Who Have Difficulty Swallowing Solids: Disperse tablet in 60 ml (2 ounces) of non-carbonated water only. Stir until tablet is dispersed into small pieces (the tablet will not completely dissolve) and swallow immediately. Do not crush, heat, or ultrasonicate during preparation. Rinse the container with 120 ml to 240 ml (4 to 8 ounces of) water and immediately drink.

If administration via nasogastric tube is required, disperse the tablet as above in 15 ml of non-carbonated water, and then use an additional 15 ml of water to transfer any residues to the syringe. The resulting 30 ml liquid should be administered as per the nasogastric tube instructions with appropriate water flushes (approximately 30 ml).

Common side effects are Interstitial Lung Disease or Pneumonitis, QTc Interval Prolongation, Cardiomyopathy, Keratitis

Strong CYP3A4 Inducers: If concurrent use is unavoidable, increase Osimertinib dosage to 160 mg daily when coadministering with a strong CYP3A inducer. Resume Osimertinib at 80 mg 3 weeks after discontinuation of the strong CYP3A4 inducer

Use in Pregnancy: There are no or limited amount of data from the use of Osimertinib in pregnant women. Studies in animals have shown reproductive toxicity. Based on its mechanism of action and preclinical data, Osimertinib may cause foetal harm when administered to a pregnant woman. Administration of osimertinib to pregnant rats was associated with embryolethality, reduced foetal growth and neonatal death at exposures similar to what is expected in humans. Osimertinib is not recommended during pregnancy and in women of childbearing potential not using contraception.

Use in Lactation: It is not known whether osimertinib or its metabolites are excreted in human milk. Administration to rats during gestation and early lactation was associated with adverse effects, including reduced growth rates and neonatal death. There is insufficient information on the excretion of osimertinib or its metabolites in animal milk. A risk to the suckling child cannot be excluded. Breast-feeding should discontinue during treatment with Osimertinib.

Fertility: There are no data on the effect of Osimertinib on human fertility. Results from animal studies have shown that Osimertinib has effects on male and female reproductive organs and could impair fertility

Store Osimertinib at room temperature between 20°C to 25°C. Safely throw away medicine that is out of date or that you no longer need. Keep Osimertinib and all medicines out of the reach of children.

Osimertinib is indicated for the treatment of patients with metastatic epidermal growth factor receptor (EGFR) T790M mutation-positive non-small cell lung cancer (NSCLC), as detected by an FDA-approved test, whose disease has progressed on or after EGFR tyrosine kinase inhibitor (TKI) therapy.

Cytotoxic Chemotherapy

Osimertinib is an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) that binds to certain mutant forms of EGFR (T790M, L858R, and exon 19 deletion) that predominate in non-small cell lung cancer (NSCLC) tumours following treatment with first-line EGFR-TKIs. As a third-generation tyrosine kinase inhibitor, osimertinib is specific for the gate-keeper T790M mutation which increases ATP binding activity to EGFR and results in poor prognosis for late-stage disease. Furthermore, osimertinib has been shown to spare wild-type EGFR during therapy, thereby reducing non-specific binding and limiting toxicity.

The recommended dose of Osimertinib is 80 mg once a day until disease progression or unacceptable toxicity. Osimertinib can be taken with or without food. If a dose of Osimertinib is missed, do not make up the missed dose and take the next dose as scheduled.

Administration To Patients Who Have Difficulty Swallowing Solids: Disperse tablet in 60 ml (2 ounces) of non-carbonated water only. Stir until tablet is dispersed into small pieces (the tablet will not completely dissolve) and swallow immediately. Do not crush, heat, or ultrasonicate during preparation. Rinse the container with 120 ml to 240 ml (4 to 8 ounces of) water and immediately drink.

If administration via nasogastric tube is required, disperse the tablet as above in 15 ml of non-carbonated water, and then use an additional 15 ml of water to transfer any residues to the syringe. The resulting 30 ml liquid should be administered as per the nasogastric tube instructions with appropriate water flushes (approximately 30 ml).

Common side effects are Interstitial Lung Disease or Pneumonitis, QTc Interval Prolongation, Cardiomyopathy, Keratitis

Strong CYP3A4 Inducers: If concurrent use is unavoidable, increase Osimertinib dosage to 160 mg daily when coadministering with a strong CYP3A inducer. Resume Osimertinib at 80 mg 3 weeks after discontinuation of the strong CYP3A4 inducer

Use in Pregnancy: There are no or limited amount of data from the use of Osimertinib in pregnant women. Studies in animals have shown reproductive toxicity. Based on its mechanism of action and preclinical data, Osimertinib may cause foetal harm when administered to a pregnant woman. Administration of osimertinib to pregnant rats was associated with embryolethality, reduced foetal growth and neonatal death at exposures similar to what is expected in humans. Osimertinib is not recommended during pregnancy and in women of childbearing potential not using contraception.

Use in Lactation: It is not known whether osimertinib or its metabolites are excreted in human milk. Administration to rats during gestation and early lactation was associated with adverse effects, including reduced growth rates and neonatal death. There is insufficient information on the excretion of osimertinib or its metabolites in animal milk. A risk to the suckling child cannot be excluded. Breast-feeding should discontinue during treatment with Osimertinib.

Fertility: There are no data on the effect of Osimertinib on human fertility. Results from animal studies have shown that Osimertinib has effects on male and female reproductive organs and could impair fertility

Store Osimertinib at room temperature between 20°C to 25°C. Safely throw away medicine that is out of date or that you no longer need. Keep Osimertinib and all medicines out of the reach of children.

Anti-oxidant Multivitamin preparations

Beta carotene of this tablet is converted to vitamin A (Retinol) when required. Retinol has several biochemical functions e.g. on retina, growth, tissue differentiation, immunological response. It has also some anti-cancer activity.

Vitamin C is the most powerful reducing agent known to be present in living tissues. Vitamin C deficiency produces scurvy. It is a cofactor in numerous biological processes. Vitamin C and molecular oxygen are essential for the conversion of proline to hydroxyproline, dopamine to noradrenaline . Vitamin C is also essential for the synthesis of adrenal steroid hormones. Vitamin C is important in the defense against infection and studies shown that vitamin C is important for the normal functioning of T-lymphocyte and leukocyte. Ascorbic acid has some antiinflammatory activity and protects cells against oxidation of essential molecules. In high doses, (1-2 g daily) ascorbic acid increases iron absorption.

vitamin E seems to be as a defense against oxidative stress and lipid peroxidation. In most cell membranes there is one molecule of tocopherol for every 1000 lipid molecules. Tocopherol mops up peroxide radicals and then needs a supply of reduced hydrogen to restore the steady-state situation. This is usually supplied by ascorbic acid or reduced glutathione.

This tablet is administered orally. The adult dose of this combination of antioxidant vitamin tablet is 1 tablet daily or as prescribed by the physician.

β carotene is comparatively safe even at high and prolonged exposure. Individuals who routinely ingest large amounts of carotenoids can develop hypercarotenosis, which is characterised by a yellowish colouration of the skin and a very high concentration of carotenoids in the plasma. This benign condition, although resembling jaundice, gradually disappears upon correcting the excessive intake of carotenoids.

Vitamin C is generally a safe drug for human use in normal doses. Larger doses may lead to gastrointestinal tract upset and renal stone formation.

Vitamin E is considered safe even in large doses. Doses over 800 mg may cause diarrhoea, abdominal pain or cramps, fatigue and reduced resistance to bacterial infection and transiently raised blood pressure.

Carocet is contraindicated in patients with hypersensitivity to any of its components.

There are some evidences that β carotene may cause harm to heavy smokers and alcoholics. Therefore, caution should be exercised in these cases. Vitamin C should be given with caution to patients with hyperoxaluria. Vitamin E should be used with caution in patients taking anticoagulant drugs, because vitamin E may enhance the anticoagulant activity of these drugs.

Cholestyramine, Colestipol, Neomycin cause decreased absorption of β carotene. Circulating vitamin C levels have been shown to be reduced during prolonged administration of oral contraceptives containing Oestrogen, Tetracycline and Aspirin. The decrease in vitamin C level may be due to drug induced impaired absorption or increased utilization of the vitamin for drug metabolism. Vitamin E may enhance the anticoagulant activity of anticoagulant drugs. High doses of vitamin E can impair intestinal absorption of vitamins A and K.

β carotene, vitamin C and vitamin E have no teratogenic effects in humans. However, like any other drugs caution should be taken in prescribing to pregnant women.

Should be stored in a dry place below 30˚C.