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Famotidine is indicated in-

• Gastric ulcer
• Duodenal ulcer
• Anastomotic ulcer
• Acute stress ulcer
• Reflux esophagitis and
• Zollinger-Ellison syndrome.

Famotidine is also indicated for the treatment of acute gastritis, chronic gastritis in the acute exacerbation stage.

Famotidine is a histamine H2-receptor antagonist. Famotidine completely inhibits the action of histamine on H2- receptors of parietal cell. It inhibits basal, overnight and pentagastrin stimulated gastric acid secretion. The H2- receptor antagonist activity of Famotidine is slowly reversible, since the drug dissociates slowly from H2-receptor.

Tablet:

• For gastric ulcer, duodenal ulcer, anastomotic ulcer, upper gastro-intestinal hemorrhage, reflux esophagitis and Zollinger-Ellison syndrome: Usual dose for adults: Famotidine 20 mg twice daily (after breakfast and after supper or before bed time) or Famotidine 40 mg can be administered orally once daily at bed time.
• For the treatment of acute gastritis, chronic gastritis in acute exacerbation stage: Usual dosage for adults is Famotidine 20 mg orally twice a day (after breakfast and after supper or before bed time). Also Famotidine 40 mg can be orally administered once a day (before bed time), dosage should be adjusted according to age and symptoms. Most ulcer patients heal within 4-8 weeks. For maintenance therapy the recommended oral dose is 20 mg once daily. Or, as directed by the registered physician.

Powder for Suspension: Gastroesophageal Reflux Disease(GERD):

• <1 year of age: 0.5 mg/kg/dose of famotidine oral suspension up to 8 weeks once daily in patients
• Age 3 to 11 months: 0.5 mg/kg/dose twice daily up to 8 weeks
• Age 1 to 2 months: 0.5 mg/kg/dose once daily up to 8 weeks
• Neonates: 0.5 mg/kg/dose maximum once daily up to 8 weeks

Patients 1-16 years of age:

• Gastroesophageal Reflux Disease(GERD): 1 mg/kg/day p.o. divided b.i.d. up to 40 mg b.i.d.
• Duodonal ulcer: 0.5 mg/kg/day p.o. at bedtime or divided b.i.d. up to 40 mg/day.
• Peptic ulcer: 0.5 mg/kg/day p.o. at bedtime or divided b.i.d. up to 40 mg/day.
• Maintenance therapy: 40 mg at daily night.
• Reflux esophagitis: 2 mg/kg/day
• Zollinger-Ellison Syndrome: 40 mg 3 times daily.

Intravenous Injection: In some hospitalized patients with pathological hypersecretory conditions or intractable ulcers, or in patients who are unable to take oral medication, Famotidine Injection Premixed or Famotidine Injection may be administered until oral therapy can be instituted. The recommended dosage for Famotidine Injection Premixed and Famotidine Injection in adult patients is 20 mg intravenously q 12 h. The doses and regimen for parenteral administration in patients with GERD have not been established.

Dosage for Pediatric Patients: Pediatric Patients suggest that the starting dose in pediatric patients 1-16 years of age is 0.25 mg/kg intravenously (injected over a period of not less than two minutes or as a 15-minute infusion) q 12 h up to 40 mg/day. While published uncontrolled clinical studies suggest the effectiveness of famotidine in the treatment of peptic ulcer, data in pediatric patients are insufficient to establish percent response with dose and duration of therapy. Therefore, treatment duration (initially based on adult duration recommendations) and dose should be individualized based on clinical response and/or gastric pH determination and endoscopy. Published uncontrolled studies in pediatric patients have demonstrated gastric acid suppression with doses up to 0.5 mg/kg intravenously q 12 h. No pharmacokinetic or pharmacodynamic data are available on pediatric patients under 1 year of age.

Eruption, constipation, diarrhoea, dry mouth, nausea, vomiting, tachycardia, high blood pressure, headache, drowsiness or insomnia may rarely occur.

Known hypersensitivity to any component of the drug.

The drug should be used in the minimum required amount depending upon the conditions of the diseases. The drug should be administered carefully with elderly patients, patients with renal failure and hepatic disorders.

No clinically important drug interactions have been identified. Famotidine does not interact with the cytochrome P450-linked drug-metabolizing enzyme system.

Pregnancy category B. There are no adequate and well-controlled studies in pregnant women. This drug should be used during pregnancy only if clearly needed. Caution should be exercised when Famotid is administered to a nursing woman.

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

Ketotifen is indicated in the following conditions-

• For the prophylactic treatment of bronchial asthma.
• Symptomatic treatment of allergic conditions including rhinitis and conjunctivitis.
• For alleviating the complications of itching, pain and tenderness associated with neurofibroma.
• Symptomatic treatment of allergy such as hayfever, urticaria.

Cromoglycate & related drugs

Ketotifen has anti-allergic properties and has been used similarly, to sodium chromoglycate in the prophylactic treatment of asthma. It also has the properties of an antihistamine. Ketotifen possesses marked anti-anaphylactic properties and is effective in preventing an asthmatic attacks. Ketotifen exerts as sustained inhibitory effect on histamine reactions, which can be clearly dissociated from its anti-anaphylactic properties. Experimental investigations in asthmatic subjects have shown that Ketotifen is as effective orally as a selective mast cell stabilizer administered by inhalation. Antihistamines were ineffective in those tests. The effectiveness of Ketotifen has been studied in long-term clinical trials. Asthma attacks were reduced in number, severity and duration and in some cases, the patients were completely freed from attacks. Progressive reduction of corticosteroids and/or bronchodilators was also possible. The prophylactic activity of Ketotifen may take several weeks to become fully established. Ketotifen will not abort established attacks of asthma.

Adults: 1 mg twice daily with food. If necessary the dose may be increased to 2 mg twice daily in severe cases.

Children above 3 years: 1 mg twice daily with food. Patients known to be easily sedated should begin treatment with 0.5 to 1 mg at night for the first few days or as directed by the physician.

Use in elderly: Same as adult dose or as advised by the physician.

Drowsiness and in isolated cases, dry mouth and slight dizziness may occur at the beginning of treatment but usually disappear spontaneously after a few days.

A reversible fall in the platelet count has been observed in a few patients receiving Ketotifen concomitantly with oral antidiabetic agent and it has been suggested that this combination should therefore be avoided. Although there is no evidence of any teratogenic effect, recommendations for Ketotifen in pregnancy or when breast feeding can not be given.

It is important to continue the previous treatment for a minimum of two weeks after starting Ketotifen to avoid the possibility of exacerbation of asthma. This applies specially to systemic corticosteroids and ACTH because of the possible existence of adrenocortical insufficiency in steroid dependent patient. If inter current infection occurs, Ketotifen treatment must be supplemented by specific antimicrobial therapy. During the first day of treatment with Ketotifen, reactions may be impaired and patients should be warned not to take charge of vehicle or machinery until the effect of Ketotifen treatment on the individual is known. Patients should be advised to avoid alcoholic drinks. Ketotifen may potentiate the effects of sedatives, hypnotics, antihistamines and alcohol.

Ketotifen may potentiate the effects of sedatives, hypnotics, antihistamines and alcohols. A reversible fall in the platelet count has been observed in a few patients receiving Tifen concomitantly with oral antidiabetic agents and it has been suggested that this combination should therefore be avoided.

Although there is no evidence of any teratogenic effect, Ketotifen in pregnancy and lactation is not recommended.

The reported features of overdosage include confusion, drowsiness, headache, bradycardia, respiratory depression etc. should be watched for. Elimination of the drug with gastric lavage or emessis is recommended. Otherwise, general supportive treatment is all that is required shall be instituted.

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

Ketotifen is indicated in the following conditions-

• For the prophylactic treatment of bronchial asthma.
• Symptomatic treatment of allergic conditions including rhinitis and conjunctivitis.
• For alleviating the complications of itching, pain and tenderness associated with neurofibroma.
• Symptomatic treatment of allergy such as hayfever, urticaria.

Cromoglycate & related drugs

Ketotifen has anti-allergic properties and has been used similarly, to sodium chromoglycate in the prophylactic treatment of asthma. It also has the properties of an antihistamine. Ketotifen possesses marked anti-anaphylactic properties and is effective in preventing an asthmatic attacks. Ketotifen exerts as sustained inhibitory effect on histamine reactions, which can be clearly dissociated from its anti-anaphylactic properties. Experimental investigations in asthmatic subjects have shown that Ketotifen is as effective orally as a selective mast cell stabilizer administered by inhalation. Antihistamines were ineffective in those tests. The effectiveness of Ketotifen has been studied in long-term clinical trials. Asthma attacks were reduced in number, severity and duration and in some cases, the patients were completely freed from attacks. Progressive reduction of corticosteroids and/or bronchodilators was also possible. The prophylactic activity of Ketotifen may take several weeks to become fully established. Ketotifen will not abort established attacks of asthma.

Adults: 1 mg twice daily with food. If necessary the dose may be increased to 2 mg twice daily in severe cases.

Children above 3 years: 1 mg twice daily with food. Patients known to be easily sedated should begin treatment with 0.5 to 1 mg at night for the first few days or as directed by the physician.

Use in elderly: Same as adult dose or as advised by the physician.

Drowsiness and in isolated cases, dry mouth and slight dizziness may occur at the beginning of treatment but usually disappear spontaneously after a few days.

A reversible fall in the platelet count has been observed in a few patients receiving Ketotifen concomitantly with oral antidiabetic agent and it has been suggested that this combination should therefore be avoided. Although there is no evidence of any teratogenic effect, recommendations for Ketotifen in pregnancy or when breast feeding can not be given.

It is important to continue the previous treatment for a minimum of two weeks after starting Ketotifen to avoid the possibility of exacerbation of asthma. This applies specially to systemic corticosteroids and ACTH because of the possible existence of adrenocortical insufficiency in steroid dependent patient. If inter current infection occurs, Ketotifen treatment must be supplemented by specific antimicrobial therapy. During the first day of treatment with Ketotifen, reactions may be impaired and patients should be warned not to take charge of vehicle or machinery until the effect of Ketotifen treatment on the individual is known. Patients should be advised to avoid alcoholic drinks. Ketotifen may potentiate the effects of sedatives, hypnotics, antihistamines and alcohol.

Ketotifen may potentiate the effects of sedatives, hypnotics, antihistamines and alcohols. A reversible fall in the platelet count has been observed in a few patients receiving Tifen concomitantly with oral antidiabetic agents and it has been suggested that this combination should therefore be avoided.

Although there is no evidence of any teratogenic effect, Ketotifen in pregnancy and lactation is not recommended.

The reported features of overdosage include confusion, drowsiness, headache, bradycardia, respiratory depression etc. should be watched for. Elimination of the drug with gastric lavage or emessis is recommended. Otherwise, general supportive treatment is all that is required shall be instituted.

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

Ketotifen eye drop is indicated for the treatment of signs & symptoms (itchy, watery, red & swollen eyes and eyelids) of allergic conjunctivitis including vernal kerato-conjunctivitis, vernal-keratitis, blepharitis, blepharo-conjunctivitis, and giant papillary conjunctivitis.

Ophthalmic Non-Steroid drugs

Ketotifen is a potent anti-allergic substance possessing a powerful and sustained non-competitive histamine (H1) receptor blocking property. Ketotifen inhibits the release of mediators (e.g histamine, leukotrienes and prostaglandins) from cells responsible for type-(I) allergic reactions. Ketotifen also stabilizes mast cells, decreases chemotaxis, activation of degranulation of eosinophils.

Adults and children 3 years and older: 1 drop in the affected eye(s) twice daily, every 8-12 hours, not more than twice per day.

Children under 3 years of age: Consult with a doctor.

Common side effects are burning, stinging, punctate corneal epithelial erosion, Blurring of vision upon drug instillation, dry eyes, eyelid disorder, conjunctivitis, eye pain, photophobia, subconjunctival haemorrhage.

Hypersensitivity to Ketotifen or any of the components

The formulation of Ketotifen 0.025% eye drops contains benzalkonium chloride as a preservative, which may be deposited in soft contact lenses; therefore this eye drops should not be instilled while the patient is wearing lenses. The lenses should be removed before application of the drops and not reinserted earlier than 15 minutes after use.

If Ketotifen eye drops is used concomitantly with other eye medications there must be an interval of at least 5 minutes between the two medications.

There are no adequate data from the use of ketotifen eye drops in pregnant women. Systemic levels after ocular administration are much lower than after oral use. Caution should be exercised when prescribing to pregnant women. Although animal data following oral administration show excretion into breast milk, topical administration to humans is unlikely to produce detectable quantities in breast milk. ketotifen 0.25% eye drops can be used during lactation.

No case of overdose has been reported. Oral ingestion of the contents of a 5 ml bottle would be equivalent to 1.25 mg of Ketotifen which is 60% of a recommended oral daily dose for a 3 years old child. Clinical results have shown no serious signs or symptoms after oral ingestion of up to 20 mg of Ketotifen.

Store in a cool and dry place protected from light and moisture. Keep out of reach of children. Do not touch the dropper tip to any surface since this may contaminate the solution. Do not use after 30 days of first opening.

Ketotifen is indicated in the following conditions-

• For the prophylactic treatment of bronchial asthma.
• Symptomatic treatment of allergic conditions including rhinitis and conjunctivitis.
• For alleviating the complications of itching, pain and tenderness associated with neurofibroma.
• Symptomatic treatment of allergy such as hayfever, urticaria.

Cromoglycate & related drugs

Ketotifen has anti-allergic properties and has been used similarly, to sodium chromoglycate in the prophylactic treatment of asthma. It also has the properties of an antihistamine. Ketotifen possesses marked anti-anaphylactic properties and is effective in preventing an asthmatic attacks. Ketotifen exerts as sustained inhibitory effect on histamine reactions, which can be clearly dissociated from its anti-anaphylactic properties. Experimental investigations in asthmatic subjects have shown that Ketotifen is as effective orally as a selective mast cell stabilizer administered by inhalation. Antihistamines were ineffective in those tests. The effectiveness of Ketotifen has been studied in long-term clinical trials. Asthma attacks were reduced in number, severity and duration and in some cases, the patients were completely freed from attacks. Progressive reduction of corticosteroids and/or bronchodilators was also possible. The prophylactic activity of Ketotifen may take several weeks to become fully established. Ketotifen will not abort established attacks of asthma.

Adults: 1 mg twice daily with food. If necessary the dose may be increased to 2 mg twice daily in severe cases.

Children above 3 years: 1 mg twice daily with food. Patients known to be easily sedated should begin treatment with 0.5 to 1 mg at night for the first few days or as directed by the physician.

Use in elderly: Same as adult dose or as advised by the physician.

Drowsiness and in isolated cases, dry mouth and slight dizziness may occur at the beginning of treatment but usually disappear spontaneously after a few days.

A reversible fall in the platelet count has been observed in a few patients receiving Ketotifen concomitantly with oral antidiabetic agent and it has been suggested that this combination should therefore be avoided. Although there is no evidence of any teratogenic effect, recommendations for Ketotifen in pregnancy or when breast feeding can not be given.

It is important to continue the previous treatment for a minimum of two weeks after starting Ketotifen to avoid the possibility of exacerbation of asthma. This applies specially to systemic corticosteroids and ACTH because of the possible existence of adrenocortical insufficiency in steroid dependent patient. If inter current infection occurs, Ketotifen treatment must be supplemented by specific antimicrobial therapy. During the first day of treatment with Ketotifen, reactions may be impaired and patients should be warned not to take charge of vehicle or machinery until the effect of Ketotifen treatment on the individual is known. Patients should be advised to avoid alcoholic drinks. Ketotifen may potentiate the effects of sedatives, hypnotics, antihistamines and alcohol.

Ketotifen may potentiate the effects of sedatives, hypnotics, antihistamines and alcohols. A reversible fall in the platelet count has been observed in a few patients receiving Tifen concomitantly with oral antidiabetic agents and it has been suggested that this combination should therefore be avoided.

Although there is no evidence of any teratogenic effect, Ketotifen in pregnancy and lactation is not recommended.

The reported features of overdosage include confusion, drowsiness, headache, bradycardia, respiratory depression etc. should be watched for. Elimination of the drug with gastric lavage or emessis is recommended. Otherwise, general supportive treatment is all that is required shall be instituted.

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

Zafirlukast is indicated for the prophylaxis and chronic treatment of asthma in adults and children 5 years of age and older.

Leukotriene receptor antagonists

Zafirlukast is a selective and competitive leukotriene-receptor antagonist (LTRA) of leukotriene D4 and E4 (LTD4 and LTE4), components of slow-reacting substance of anaphylaxis (SRSA). Cysteinyl leukotriene production and receptor occupation have been correlated with the pathophysiology of asthma, including airway oedema, smooth muscle constriction, and altered cellular activity associated with the inflammatory process, which contribute to the signs and symptoms of asthma.

Zafirlukast should be taken continuously.

Children under 7 years of age: There is no clinical experience of the use of Zafirlukast in children under 7 years of age until safety information is available.

Children over 7 years through 11 years of age: The recommended dose of Zafirlukast in this age group is 10 mg twice daily.

Adult and children aged 12 years and over: The dosage is one 20 mg tablet twice daily. This dosage should not be exceeded. Higher doses may be associated with elevations of one or more liver enzymes consistent with hepatotoxicity. As food may reduce the bioavailability of Zafirlukast, Zafirlukast should not be taken with meals

Elderly: The clearance of Zafirlukast is significantly reduced in elderly patients (over 65 years old), and Cmax and AUC are approximately double than those of younger adults. However, accumulation of Zafirlukast is not greater than that seen in multiple dose trials conducted in adult subjects with asthma and the consequences of the altered kinetic in the elderly are unknown. Clinical experience with Zafirlukast in the elderly (over 65 years) is limited and caution is recommended until further information is available.

Renal impairment: No dosage adjustment is necessary in patients with mild renal impairment.

Effect on ability to drive or operate machinery: There is no evidence that Zafirlukast affects the ability to drive and use machinery. Administration of Zafirlukast in clinical trials against placebo has been associated with headache (9.9% vs. 9.0%) or gastrointestinal disturbance (nausea 2.6% vs. 2.2%, vomiting 1.2% vs. 1.0%, diarrhoea 2.3% vs. 1.8%, abdominal pain 1.6% vs. 1.2%). These symptoms are usually mild and do not necessitate withdrawal from therapy. During post-marketing experience, bruising, bleeding disorders, including menorrhagia (rare), thrombocytopaenia and agranulocytosis (very rare) have also been reported.

Hypersensitivity reactions, including urticaria and angio-oedema have been reported. Rashes, including blistering, have also been reported. The above events have usually resolved during continued treatment or following cessation of therapy.

Infrequently, elevated serum transaminase levels have been observed in clinical trials against placebo with Zafirlukast (increased AST 1.0% vs. 0.9%, increased AST 0.6% vs. 0.6%); at recommended doses the incidence was equivalent to placebo. Rarely the transaminase profile has been consistent with drug-induced hepatitis, which resolved following cessation of Zafirlukast therapy. During post-marketing experience there have been rare reports of hepatitis, with or without elevated bilirubin levels. These cases were usually reversible.

In placebo controlled clinical trials, an increased incidence of infection has been observed in elderly patients given Zafirlukast (7.8% vs. 1.4%). Infections were usually mild, predominantly affecting the respiratory tract.

Zafirlukast should not be given to patients who have previously experienced hypersensitivity to the product or any of its ingredients. Zafirlukast is contraindicated in patients with a history of moderate or severe renal impairment. Zafirlukast is contraindicated in patients with hepatic impairment or cirrhosis; it has not been studied in patients with hepatitis or in long term studies of patients with cirrhosis. Zafirlukast is contraindicated in children under 7 years of age until safety information is available.

Zafirlukast should be taken regularly to achieve benefit, even during symptom free periods. Zafirlukast therapy should normally be continued during acute exacerbations of asthma. Zafirlukast does not allow a reduction in existing steroid treatment. As with inhaled steroids and hormones (disodium cromoglycate, nedocromil sodium), Zafirlukast is not indicated for use in the reversal of bronchospasm in acute asthma attacks. Zafirlukast has not been evaluated in the treatment of labile (brittle) or unstable asthma.

Cases of Churg Strauss syndrome have been reported in association with Zafirlukast usage. A causal relationship has neither been confirmed nor refuted. If a patient develops a Churg Strauss syndrome type illness, Zafirlukast should be stopped, a re-challenge test should not be performed and treatment should not be restarted.

Elevations in serum transaminases can occur during treatment with Zafirlukast. These are usually asymptomatic and transient but could represent early evidence of hepatotoxicity.

If clinical symptoms or signs suggestive of liver dysfunction occur (e.g., nausea, vomiting, right upper quadrant pain, fatigue, lethargy, flu-like symptoms, enlarged liver, pruritus and jaundice), the serum transaminases, in particular serum ALT, should be measured and the patient managed accordingly. A decision to discontinue Zafirlukast should be individualized to the patient’s condition, weighing the risk of hepatic dysfunction against the clinical benefit of Zafirlukast to the patient.

Zafirlukast may be administered with other therapies routinely used in the management of asthma and allergy. Inhaled steroids, inhaled and oral bronchodilator therapy, antibiotics and antihistamines are examples of agents which have been co-administered with Zafirlukast without adverse interaction.

Zafirlukast may be administered with oral contraceptives without adverse interaction. Co-administration with Warfarin results in an increase in maximum prothrombin time by approximately 35%. It is therefore recommended that if Zafirlukast is co-administered with Warfarin, prothrombin time should be closely monitored. The interaction is probably due to an inhibition by Zafirlukast of the cytochrome P450 2C9 enzyme system. In clinical trials co-administration with Theophylline resulted in decreased plasma levels of Zafirlukast, by approximately 30%, but with no effect on plasma Theophylline levels. However, during postmarketing surveillance, there have been rare cases of patients experiencing increased Theophylline levels when co-administered with Zafirlukast.

Co-administration with Terfenadine resulted in a 54% decrease in AUC for Zafirlukast, but with no effect on plasma Terfenadine levels. Coadministration with Acetylsalicylic acid (650 mg four times a day) may result in increased plasma levels of Zafirlukast, by approximately 45%.

Co-administration with Erythromycin will result in decreased plasma levels of Zafirlukast, by approximately 40%. The clearance of Zafirlukast in smokers may be increased by approximately 20%

Pregnancy: The safety of Zafirlukast in human pregnancy has not been established. In animal studies, Zafirlukast did not have any apparent effect on fertility and did not appear to have any teratogenic or selective toxic effect on the foetus. The potential risks should be weighed against the benefits of continuing therapy during pregnancy and Zafirlukast should be used during pregnancy only if clearly needed.

Lactation: Zafirlukast is excreted in human breast milk. Zafirlukast should not be administered to nursing mothers.

Store between 20-25° C. Protect from light and moisture.

Aflibercept, in combination with 5-fluorouracil, leucovorin, irinotecan-(FOLFIRI), is indicated for patients with metastatic colorectal cancer (mCRC) that is resistant to or has progressed following an oxaliplatin-containing regimen.

Cytotoxic Chemotherapy

Ablibercept is a recombinant fusion protein that acts as a decoy receptor for the ligands, vascular endothelial growth factor-A (VEGF-A) and placental growth factor (PIGF). It prevents these ligands to binding to endothelial receptors, VEGFR-1 and VEGFR-2, to suppress neovascularization and decrease vascular permeability. This ultimately will slow vision loss or the progression of metastatic colorectal cancer.

4 mg/kg as an intravenous infusion over 1 hour every 2 weeks. Do not administer as an intravenous (IV) push or bolus.

Preparation for Administration: Inspect vials visually prior to use. Aflibercept is a clear, colorless to pale yellow solution. Do not use vial if the solution is discolored or cloudy or if the solution contains particles. Do not re-enter the vial after the initial puncture. Discard any unused portion left in the vial. Withdraw the prescribed dose of Aflibercept and dilute in 0.9% sodium chloride solution, 5% dextrose solution for injection, to achieve a final concentration of 0.6–8 mg/mL.

Use polyvinyl chloride (PVC) infusion bags containing bis (2-ethylhexyl) phthalate (DEHP) or polyolefin infusion bags. Store diluted Aflibercept at 2°–8°C for up to 24 hours, or at controlled room temperature 20°–25°C for up to 8 hours. Discard any unused portion left in the infusion bag.

Administration: Administer the diluted Aflibercept solution as an intravenous infusion over 1 hour through a 0.2 micron polyethersulfone filter. Do not use filters made of polyvinylidene fluoride (PVDF) or nylon. Do not administer as an intravenous (IV) push or bolus. Do not combine Aflibercept with other drugs in the same infusion bag or intravenous line.

Most common adverse reactions (all grades, ≥20% incidence and at least 2% greater incidence for the Aflibercept/FOLFIRI regimen) were leukopenia, diarrhea, neutropenia, proteinuria, AST increased, stomatitis, fatigue, thrombocytopenia, ALT increased, hypertension, weight decreased, decreased appetite, epistaxis, abdominal pain, dysphonia, serum creatinine increased, and headache

Adverse reactions, sometimes severe and life-threatening or fatal, have been seen in clinical trials with Aflibercept, including:

• Fistula Formation: Discontinue Aflibercept if fistula occurs.
• Hypertension: Monitor blood pressure and treat hypertension. Temporarily suspend Aflibercept if hypertension is not controlled. Discontinue Aflibercept if hypertensive crisis develops.
• Arterial Thromboembolic Events (ATE) (e.g., transient ischemic attacks, cerebrovascular accident, angina pectoris): Discontinue Aflibercept if ATE develops.
• Proteinuria: Monitor urine protein. Suspend Aflibercept when proteinuria ≥ 2 grams per 24 hours. Discontinue Aflibercept if nephrotic syndrome or thrombotic microangiopathy (TMA) develops.
• Neutropenia and Neutropenic Complications: Delay administration of Aflibercept/FOLFIRI until neutrophil count is ≥ 1.5 × 109/L.
• Diarrhea and Dehydration: Incidence of severe diarrhea and dehydration is increased. Monitor elderly patients more closely.
• Reversible Posterior Leukoencephalopathy Syndrome (RPLS): Discontinue Aflibercept.

No dedicated drug-drug interaction studies have been conducted for Aflibercept. No clinically important pharmacokinetic drug-drug interactions were found between ziv-aflibercept and irinotecan/SN-38 or 5-FU, based on cross-study comparisons and population pharmacokinetic analyses.

Pregnancy category C. There are no adequate and well-controlled studies with Aflibercept in pregnant women. Aflibercept was embryotoxic and teratogenic in rabbits at exposure levels lower than human exposures at the recommended dose, with increased incidences of external, visceral, and skeletal fetal malformations. Aflibercept should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

It is not known whether Aflibercept is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from Aflibercept, 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 in pediatric patients have not been established. In a dose-escalation, safety, and tolerability study, 21 patients ages 2 to 21 years (median age 12.9) with solid tumors received Aflibercept at doses ranging from 2 to 3 mg/kg, IV, every two weeks. The pharmacokinetics of free ziv-aflibercept were evaluated in 8 of these patients (ages 5 to 17 years). The maximum tolerated dose in the study was 2.5 mg/kg, below the dose known to be safe and effective in adults with mCRC.

Geriatric Use: Of the 611 patients with mCRC, patients treated with Aflibercept/FOLFIRI, 205 (34%) were 65 years or older, and 33 (5%) were 75 years or older. Elderly patients (≥65 years of age) experienced higher incidences (≥5%) of diarrhea, dizziness, asthenia, weight decrease, and dehydration when compared to younger patients. Monitor elderly patients more closely for diarrhea and dehydration

The effect of Aflibercept on overall survival was similar in patients <65 years old and ≥65 years old who received Aflibercept/FOLFIRI. No dose adjustment of Aflibercept is recommended for patients greater than or equal to 65 years of age.

Hepatic Impairment: No dedicated clinical studies have been conducted to evaluate the effect of hepatic impairment on the pharmacokinetics of ziv-aflibercept. Based on a population PK analysis with data from 1507 patients, ziv-aflibercept exposure in patients with mild and moderate hepatic impairment were similar to those in patients with normal hepatic function. There are no data available for patients with severe hepatic impairment.

Renal Impairment: No dedicated clinical studies have been conducted to evaluate the effect of renal impairment on the pharmacokinetics of ziv-aflibercept. Based on a population PK analysis with data from 1507 patients, ziv-aflibercept exposure in patients with mild, moderate, and severe renal impairment were similar to those in patients with normal renal function [see Clinical Pharmacology.

Females and Males of Reproductive Potential: Male and female reproductive function and fertility may be compromised during treatment with Aflibercept, as suggested by findings in monkeys [see Nonclinical Toxicology. These animal findings were reversible within 18 weeks after cessation of treatment. Females and males of reproductive potential should use highly effective contraception during and up to a minimum of 3 months after the last dose of treatment.

There have been no cases of overdose reported with Aflibercept. There is no information on the safety of Aflibercept given at doses exceeding 7 mg per kg every 2 weeks or 9 mg per kg every 3 weeks.

Store Aflibercept vials in a refrigerator at 2 to 8° C . Keep the vials in the original outer carton to protect from light.

H2 receptor antagonist

Ranitidine competitively blocks histamine at H2-receptors of the gastric parietal cells which inhibits gastric acid secretion. It does not affect pepsin secretion, pentagastrin-stimulated intrinsic factor secretion or serum gastrin.

Ranitidine Tablet & Syrup:

Duodenal and gastric ulcer: The usual dosage is 150 mg twice daily taken in the morning and evening or 300 mg as a single daily dose at night for 4 to 8 weeks.

Reflux oesophagitis: 150 mg twice daily or 300 mg at bed time for up to 8 weeks.

Zollinger Ellison syndrome: 150 mg 3 times daily and increased if necessary up to 6 g daily in divided doses. Dosage should be continued as long as clinically indicated.

Episodic dyspepsia: 150 mg twice daily or 300 mg at bed time for up to 6 weeks.

Maintenance: 150 mg at night for preventing recurrences.

Child (peptic ulcer): 2-4 mg/kg twice daily, maximum 300 mg daily.

Ranitidine IV injection & IV Infusion:

Ranitidine injection may be given either as a slow (over a period of at least two minutes) intravenous injection of 50 mg, after dilution to a volume of 20 ml per 50 mg dose, which may be repeated every six to eight hours; or as an intermittent intravenous infusion at a rate of 25 mg per hour for two hours; the infusion may be repeated at six to eight hour intervals; or as an intramuscular injection of 50 mg (2 ml) every six to eight hours. In the prophylaxis of haemorrhage from stress ulceration in seriously ill patients or the prophylaxis of recurrent haemorrhage in patients bleeding from peptic ulceration, parenteral administration may be continued until oral feeding commences.

In the prophylaxis of upper gastrointestinal haemorrhage from stress ulceration in seriously ill patient sapriming dose of 50 mg as low as intravenous injection followed by a continuous intravenous infusion of 0.125-0.250 mg/kg/hour may be preferred. In patients considered to be at risk of developing aspiration syndrome Ranitidine injection 50 mg may be given intramuscularly or by slow intravenous injection 45 to 60 minutes before induction of general anaesthesia.

Children: The recommended oral dose for the treatment of peptic ulcer in children is 2 mg/kg to 4 mg/kg twice daily to a maximum of 300 mg ranitidine per day. Safety and effectiveness of Ranitidine injection have not been established in case of children.

Ranitidine is well tolerated and side effects are usually uncommon. Altered bowel habit, dizziness, rash, tiredness, reversible confusional states, headache, decreased blood counts, muscle or joint pain have rarely been reported.

Patients hypersensitive to Ranitidine

Ranitidine should be given in reduced dosage to patients with impaired renal and hepatic function.

Delayed absorption and increased peak serum concentration with propantheline bromide. Ranitidine minimally inhibits hepatic metabolism of coumarin anticoagulants, theophylline, diazepam and propanolol. May alter absorption of pH-dependent drugs (e.g. ketoconazole, midazolam, glipizide). May reduce bioavailability with antacids.

Pregnancy: Ranitidine crosses the placenta. But there is no evidence of impaired fertility or harm to the foetus due to Ranitidine. Like other drugs, Ranitidine should only be used during pregnancy if considered essential.

Lactation: Ranitidine is excreted in human breast milk. Caution should be exercised when the drug is administered to a nursing mother.

Use in elderly patients: In clinical trial the ulcer healing rates have been found similar in patients age 65 and over with those in younger patients. Additionally, there was no difference in the incidence of adverse effects.

Ranitidine is very specific in action and accordingly no particular problems are expected following overdosage with the drug. Symptomatic and supportive therapy should be given as appropriate. If required, the drug may be removed from the plasma by haemodiaiysis.

Slow IV inj: Ranitidine 50 mg diluted to a concentration ≤2.5 mg/mL (e.g. total of 20 mL) with NaCl 0.9% inj or dextrose 5% or 10%, lactated Ringer's, Na bicarbonate 5% soln.

Intermittent slow IV infusion: Ranitidine 50 mg diluted to a concentration ≤0.5 mg/mL (e.g. total of 100 mL) of dextrose 5% inj or NaCl 0.9%, lactated Ringer's, Na bicarbonate 5% soln.

Continuous IV infusion: Ranitidine 150 mg diluted in 250 mL of dextrose 5% inj or NaCl 0.9%, lactated Ringer's, Na bicarbonate 5% soln.

Patients with Zollinger-Ellison syndrome or other hypersecretory conditions: Ranitidine should be diluted to a concentration ≤2.5 mg/mL with dextrose 5% or NaCl 0.9%, lactated Ringer's, Na bicarbonate 5% soln.

Store in a cool and dry place. protect from light.

Supplements & adjuvant therapy

Astaxanthin acts as an antioxidant by dual mode of action. It suppresses singlet oxygen and also inhibits lipid peroxidation. By these actions it reduces the harmful free radicals. Therefore acts as a very strong antioxidant. Astaxanthin is absorbed by passive diffusion into the intestinal epithelium alongside fatty acids. Then it is incorporated into lipoproteins, transported to the liver, via lymph and blood and partly resecreted with lipoproteins. More than 70% of the Astaxanthin is contained in high-density lipoprotein part of plasma. Highest concentration of Astaxanthin is in the small intestine, followed by subcutaneous fat, abdominal fat, spleen, liver, heart, kidney and skin and lowest in the muscles.

Adults (18 years and older): Daily dose is 4 mg. Should be taken along with or immediately prior to meals in the morning.

• 4 mg: As a strong antioxidant, improves cardiovascular health (Atherosclerosis, reduce cholesterol), improves immune function.
• 4-8 mg: Improves condition of skin, protects skin from sun damage (Reduce wrinkles, pimples and other signs of aging), improves recovery from central nervous systehn injuries and protects eyes from cataracts and macular degeneration.
• 8-12 mg: Reduces inflammation (Arthritis)
• 16 mg: Reduces risk of infertility

No severe side effects have been reported yet.

Contraindicated for those with known allergies to Astaxanthin.

Concomitant intake of Astaxanthin with Cholestyramine, Colestipol, Mineral oil, Orlistat may reduce the absorption rate of Astaxanthin.

Both pregnant women and lactating mothers should avoid Astaxanthin supplements as no data on safety has been found yet.

No case of overdose has occurred with Astaxanthin.

Store in cool and dry place, away from direct light. Keep out of reach of children.

Supplements & adjuvant therapy

Astaxanthin acts as an antioxidant by dual mode of action. It suppresses singlet oxygen and also inhibits lipid peroxidation. By these actions it reduces the harmful free radicals. Therefore acts as a very strong antioxidant. Astaxanthin is absorbed by passive diffusion into the intestinal epithelium alongside fatty acids. Then it is incorporated into lipoproteins, transported to the liver, via lymph and blood and partly resecreted with lipoproteins. More than 70% of the Astaxanthin is contained in high-density lipoprotein part of plasma. Highest concentration of Astaxanthin is in the small intestine, followed by subcutaneous fat, abdominal fat, spleen, liver, heart, kidney and skin and lowest in the muscles.

Adults (18 years and older): Daily dose is 4 mg. Should be taken along with or immediately prior to meals in the morning.

• 4 mg: As a strong antioxidant, improves cardiovascular health (Atherosclerosis, reduce cholesterol), improves immune function.
• 4-8 mg: Improves condition of skin, protects skin from sun damage (Reduce wrinkles, pimples and other signs of aging), improves recovery from central nervous systehn injuries and protects eyes from cataracts and macular degeneration.
• 8-12 mg: Reduces inflammation (Arthritis)
• 16 mg: Reduces risk of infertility

No severe side effects have been reported yet.

Contraindicated for those with known allergies to Astaxanthin.

Concomitant intake of Astaxanthin with Cholestyramine, Colestipol, Mineral oil, Orlistat may reduce the absorption rate of Astaxanthin.

Both pregnant women and lactating mothers should avoid Astaxanthin supplements as no data on safety has been found yet.

No case of overdose has occurred with Astaxanthin.

Store in cool and dry place, away from direct light. Keep out of reach of children.

Clozapine is indicated in-

• Schizophrenia in patients unresponsive to, or intolerant of, conventional antipsychotic drugs.
• Psychosis in Parkinson's disease.

Atypical neuroleptic drugs

Clozapine is classified as an 'atypical' antipsychotic drug because of its profile of binding to dopamine receptors and its effects on various dopamine-mediated behaviors differ from those exhibited by other typical antipsychotic drug products. In particular, although Clozapine does interfere with the binding of dopamine at D1, D2, D3 and D5 receptors, and has a high affinity for the D4 receptor. This evidence, consistent with the view that Clozapine is preferentially more active at limbic than at striatal dopamine receptors. This may explain the relative freedom of Clozapine from extrapyramidal side effects. Clozapine also acts as an antagonist at adrenergic, cholinergic, histaminergic and serotonergic receptors.

Schizophrenia: Adult over 16 years, 12.5 mg once or twice (elderly 12.5 mg once) on first day then 25-50 mg (elderly 25-37.5 mg) on second day then increased gradually (if well tolerated) in steps of 25-50 mg daily (elderly max. increment 25 mg daily) over 14-21 days up to 300 mg daily in divided doses (larger dose at night, up to 200 mg daily may be taken as a single dose at bedtime); if necessary may be further increased in steps of 50-100 mg once (preferably) or twice weekly; usual dose 200-450 mg daily (max. 900 mg daily)

Psychosis in Parkinson's disease: Adult over 16 years, 12.5 mg at bedtime then increased according to response in steps of 12.5 mg up to twice weekly; usual dose range 25-37.5 mg at bedtime, usual maximum 50 mg daily; exceptionally, dose may be increased further in steps of 12.5 mg weekly to maximum 100 mg daily in 1-2 divided doses.

Common side effects are constipation, dizziness or lightheadedness (mild), drowsiness, headache (mild), increased watering of mouth, nausea or vomiting, unusual weight gain. Less common side effects include abdominal discomfort or heartburn, dryness of mouth.

Severe cardiac disorders (e.g. myocarditis); renal impairment (avoid if creatinine clearance less than 10 ml/minute); history of neutropenia or agranulocytosis; bone-marrow disorders; paralytic ileus; alcoholic and toxic psychoses; history of circulatory collapse; drug intoxication; coma or severe CNS depression; uncontrolled epilepsy; breast-feeding.

Medication should not be stopped abruptly; should be tapered off over 1-2 weeks. If conditions warrant abrupt discontinuation (leukopenia, myocarditis, cardiomyopathy), monitor patient for psychosis and cholinergic rebound (headache, nausea, vomiting, diarrhea). Elderly patients are more susceptible to adverse effects  (including agranulocytosis, cardiovascular, anticholinergic, and tardive dyskinesia). Significant risk of agranulocytosis, potentially life-threatening. WBC testing should occur weekly for the first 6 months of therapy; thereafter, if acceptable WBC counts are maintained (WBC 3000/mm3, ANC 1500/mm3) then WBC counts can be monitored every other week. WBCs must be monitored weekly for the first 4 weeks after therapy discontinuation. Use with caution in patients receiving other marrow suppressive agents. Eosinophilia has been reported to occur with Clozapine and may require temporary or permanent interruption of therapy.

Cognitive and/or motor impairment (sedation) is common with Clozapine, resulting in impaired performance of tasks requiring alertness (eg, operating machinery or driving). Use with caution in patients at risk of seizures, including those with a history of seizures, head trauma, brain damage, alcoholism, or concurrent therapy with medications which may lower seizure threshold. Has been associated with benign, self-limiting fever (<100.4°F, usually within first 3 weeks). However, dozapine may also be associated with severe febrile reactions, including neuroleptic malignant syndrome (NMS). Clozapine's potential for extrapyramidal symptoms appear to be extremely low.

May cause anticholinergic effects; should be used with caution in patients with urinary retention, benign prostatic hyperplasia, narrow-angle glaucoma, xerostomia, visual problems, constipation, or history of bowel obstruction. May cause hyperglycemia; in some cases may be extreme and associated with ketoacidosis, hyperosmolar coma, or death. Use with caution in patients with diabetes or other disorders of glucose regulation; monitor for worsening of glucose control. Use with caution in patients with hepatic disease or impairment; hepatitis has been reported as a consequence of therapy.

May cause orthostatic hypotension and tachycardia; should be used with caution in patients at risk of hypotension or in patients where transient hypotensive episodes would be poorly tolerated (cardiovascular disease or cerebrovascular disease). Concurrent use of psychotropics and benzodiazepines may increase the risk of severe cardiopulmonary reactions.

Myocarditis, pericarditis, pericardial effusion, cardiomyopathy, and CHF have also been associated with clozapine. Fatalities due to myocarditis have been reported; highest risk in the first month of therapy, however, later cases also reported. Myocarditis or cardiomyopathy should be considered in patients who present with signs/symptoms of heart failure (dyspnea, fatigue, orthopnea, paroxysmal nocturnal dyspnea, peripheral edema), chest pain, palpitations, new electrocardiographic abnormalities (arrhythmias, ST-T wave abnormalities), or unexplained fever. Patients with tachycardia during the first month of therapy should be closely monitored for other signs of myocarditis. Discontinue clozapine if myocarditis is suspected; do not rechallenge in patients with clozapine-related myocarditis. The reported rate of cardiomyopathy in clozapine treated patients is similar to that in the general population. The majority of patients were over 50 years of age and were taking clozapine for >6 months. Clozapine should be discontinued in patients with confirmed cardiomyopathy unless benefit clearly outweighs risk. Rare cases of thromboembolism, including pulmonary embolism and stroke resulting in fatalities, have been associated with clozapine.

Myelosuppression may be aggravated with concomitant use of myelosuppressants. Clozapine may interact with other CNS active drugs or alcohol. Orthostatic hypotension may occur with benzodiazepine usage or other psychotropics. Since Clozapine is highly bound to proteins. It may be displaced by other drugs, which are also highly protein bound. Conversely, Clozapine may also displace protein bound drugs (e.g. warfarin, digoxin). Cimetidine may decrease plasma Clozapine levels.

Although concomitant administration of Carbamazepine and Clozapine is not recommended, it should be noted that discontinuation of concomitant Carbamazepine may result in an increase in plasma Clozapine levels. A reduced Clozapine dosage should be used when it is combined with drugs like fluvoxamine, paroxetine and sertraline. The action of hypotensive drugs may be potentiated. Other anticholinergic drug action may also be increased. Administration of adrenaline should generally be avoided due to possibility of reversal of adrenaline effect due to alpha adrenergic blockade by Clozapine. Concomitant use of Clozapine with other drugs metabolized by cytochrome P450 2D6 (such as phenothiazines, antidepressants, propafenone, flecainide and encainide) or those that inhibit this enzyme such as quinidine; require lower doses of either Clozapine or the other drugs.

There are no adequate studies of Clozapine in pregnant women. Studies in animals suggest no important effects on the fetus. Clozapine can be used in pregnancy if the physician feels that it is necessary. Animal studies suggest that Clozapine is secreted in breast milk. Therefore, women taking Clozapine should not nurse their infants.

The most commonly reported signs and symptoms associated with Clozapine overdose are: altered states of consciousness, including drowsiness, delirium and coma; tachycardia; hypotension; respiratory depression or failure; hypersalivation. Aspiration pneumonia and cardiac arrhythmias have also been reported. Seizures have occurred in a minority of reported cases. Fatal overdoses have been reported with Clozapine, generally at doses above 2500 mg. There have also been reports of patients recovering from overdoses well in excess of 4 gm.

Management of Overdose: Should be established and maintained an airway; should be ensured adequate oxygenation and ventilation. Activated charcoal, which may be used with sorbitol, may be as or more effective than emesis or lavage, and should be considered in treating overdosage. Cardiac and vital signs monitoring is recommended along with general symptomatic and supportive measures. Additional surveillance should be continued for several days because of the risk of delayed effects. Avoid epinephrine and derivatives when treating hypotension, and quinidine and procainamide when treating cardiac arrhythmia. There are no specific antidotes for Clozapine. Forced diuresis, dialysis, hemoperfusion and exchange transfusion are unlikely to be of benefit. ln managing overdosage, the physician should consider the possibility of multiple drug involvement.

Do not store above 30°C. Keep away from light and out of the reach of children.

Clozapine is indicated in-

• Schizophrenia in patients unresponsive to, or intolerant of, conventional antipsychotic drugs.
• Psychosis in Parkinson's disease.

Atypical neuroleptic drugs

Clozapine is classified as an 'atypical' antipsychotic drug because of its profile of binding to dopamine receptors and its effects on various dopamine-mediated behaviors differ from those exhibited by other typical antipsychotic drug products. In particular, although Clozapine does interfere with the binding of dopamine at D1, D2, D3 and D5 receptors, and has a high affinity for the D4 receptor. This evidence, consistent with the view that Clozapine is preferentially more active at limbic than at striatal dopamine receptors. This may explain the relative freedom of Clozapine from extrapyramidal side effects. Clozapine also acts as an antagonist at adrenergic, cholinergic, histaminergic and serotonergic receptors.

Schizophrenia: Adult over 16 years, 12.5 mg once or twice (elderly 12.5 mg once) on first day then 25-50 mg (elderly 25-37.5 mg) on second day then increased gradually (if well tolerated) in steps of 25-50 mg daily (elderly max. increment 25 mg daily) over 14-21 days up to 300 mg daily in divided doses (larger dose at night, up to 200 mg daily may be taken as a single dose at bedtime); if necessary may be further increased in steps of 50-100 mg once (preferably) or twice weekly; usual dose 200-450 mg daily (max. 900 mg daily)

Psychosis in Parkinson's disease: Adult over 16 years, 12.5 mg at bedtime then increased according to response in steps of 12.5 mg up to twice weekly; usual dose range 25-37.5 mg at bedtime, usual maximum 50 mg daily; exceptionally, dose may be increased further in steps of 12.5 mg weekly to maximum 100 mg daily in 1-2 divided doses.

Common side effects are constipation, dizziness or lightheadedness (mild), drowsiness, headache (mild), increased watering of mouth, nausea or vomiting, unusual weight gain. Less common side effects include abdominal discomfort or heartburn, dryness of mouth.

Severe cardiac disorders (e.g. myocarditis); renal impairment (avoid if creatinine clearance less than 10 ml/minute); history of neutropenia or agranulocytosis; bone-marrow disorders; paralytic ileus; alcoholic and toxic psychoses; history of circulatory collapse; drug intoxication; coma or severe CNS depression; uncontrolled epilepsy; breast-feeding.

Medication should not be stopped abruptly; should be tapered off over 1-2 weeks. If conditions warrant abrupt discontinuation (leukopenia, myocarditis, cardiomyopathy), monitor patient for psychosis and cholinergic rebound (headache, nausea, vomiting, diarrhea). Elderly patients are more susceptible to adverse effects  (including agranulocytosis, cardiovascular, anticholinergic, and tardive dyskinesia). Significant risk of agranulocytosis, potentially life-threatening. WBC testing should occur weekly for the first 6 months of therapy; thereafter, if acceptable WBC counts are maintained (WBC 3000/mm3, ANC 1500/mm3) then WBC counts can be monitored every other week. WBCs must be monitored weekly for the first 4 weeks after therapy discontinuation. Use with caution in patients receiving other marrow suppressive agents. Eosinophilia has been reported to occur with Clozapine and may require temporary or permanent interruption of therapy.

Cognitive and/or motor impairment (sedation) is common with Clozapine, resulting in impaired performance of tasks requiring alertness (eg, operating machinery or driving). Use with caution in patients at risk of seizures, including those with a history of seizures, head trauma, brain damage, alcoholism, or concurrent therapy with medications which may lower seizure threshold. Has been associated with benign, self-limiting fever (<100.4°F, usually within first 3 weeks). However, dozapine may also be associated with severe febrile reactions, including neuroleptic malignant syndrome (NMS). Clozapine's potential for extrapyramidal symptoms appear to be extremely low.

May cause anticholinergic effects; should be used with caution in patients with urinary retention, benign prostatic hyperplasia, narrow-angle glaucoma, xerostomia, visual problems, constipation, or history of bowel obstruction. May cause hyperglycemia; in some cases may be extreme and associated with ketoacidosis, hyperosmolar coma, or death. Use with caution in patients with diabetes or other disorders of glucose regulation; monitor for worsening of glucose control. Use with caution in patients with hepatic disease or impairment; hepatitis has been reported as a consequence of therapy.

May cause orthostatic hypotension and tachycardia; should be used with caution in patients at risk of hypotension or in patients where transient hypotensive episodes would be poorly tolerated (cardiovascular disease or cerebrovascular disease). Concurrent use of psychotropics and benzodiazepines may increase the risk of severe cardiopulmonary reactions.

Myocarditis, pericarditis, pericardial effusion, cardiomyopathy, and CHF have also been associated with clozapine. Fatalities due to myocarditis have been reported; highest risk in the first month of therapy, however, later cases also reported. Myocarditis or cardiomyopathy should be considered in patients who present with signs/symptoms of heart failure (dyspnea, fatigue, orthopnea, paroxysmal nocturnal dyspnea, peripheral edema), chest pain, palpitations, new electrocardiographic abnormalities (arrhythmias, ST-T wave abnormalities), or unexplained fever. Patients with tachycardia during the first month of therapy should be closely monitored for other signs of myocarditis. Discontinue clozapine if myocarditis is suspected; do not rechallenge in patients with clozapine-related myocarditis. The reported rate of cardiomyopathy in clozapine treated patients is similar to that in the general population. The majority of patients were over 50 years of age and were taking clozapine for >6 months. Clozapine should be discontinued in patients with confirmed cardiomyopathy unless benefit clearly outweighs risk. Rare cases of thromboembolism, including pulmonary embolism and stroke resulting in fatalities, have been associated with clozapine.

Myelosuppression may be aggravated with concomitant use of myelosuppressants. Clozapine may interact with other CNS active drugs or alcohol. Orthostatic hypotension may occur with benzodiazepine usage or other psychotropics. Since Clozapine is highly bound to proteins. It may be displaced by other drugs, which are also highly protein bound. Conversely, Clozapine may also displace protein bound drugs (e.g. warfarin, digoxin). Cimetidine may decrease plasma Clozapine levels.

Although concomitant administration of Carbamazepine and Clozapine is not recommended, it should be noted that discontinuation of concomitant Carbamazepine may result in an increase in plasma Clozapine levels. A reduced Clozapine dosage should be used when it is combined with drugs like fluvoxamine, paroxetine and sertraline. The action of hypotensive drugs may be potentiated. Other anticholinergic drug action may also be increased. Administration of adrenaline should generally be avoided due to possibility of reversal of adrenaline effect due to alpha adrenergic blockade by Clozapine. Concomitant use of Clozapine with other drugs metabolized by cytochrome P450 2D6 (such as phenothiazines, antidepressants, propafenone, flecainide and encainide) or those that inhibit this enzyme such as quinidine; require lower doses of either Clozapine or the other drugs.

There are no adequate studies of Clozapine in pregnant women. Studies in animals suggest no important effects on the fetus. Clozapine can be used in pregnancy if the physician feels that it is necessary. Animal studies suggest that Clozapine is secreted in breast milk. Therefore, women taking Clozapine should not nurse their infants.

The most commonly reported signs and symptoms associated with Clozapine overdose are: altered states of consciousness, including drowsiness, delirium and coma; tachycardia; hypotension; respiratory depression or failure; hypersalivation. Aspiration pneumonia and cardiac arrhythmias have also been reported. Seizures have occurred in a minority of reported cases. Fatal overdoses have been reported with Clozapine, generally at doses above 2500 mg. There have also been reports of patients recovering from overdoses well in excess of 4 gm.

Management of Overdose: Should be established and maintained an airway; should be ensured adequate oxygenation and ventilation. Activated charcoal, which may be used with sorbitol, may be as or more effective than emesis or lavage, and should be considered in treating overdosage. Cardiac and vital signs monitoring is recommended along with general symptomatic and supportive measures. Additional surveillance should be continued for several days because of the risk of delayed effects. Avoid epinephrine and derivatives when treating hypotension, and quinidine and procainamide when treating cardiac arrhythmia. There are no specific antidotes for Clozapine. Forced diuresis, dialysis, hemoperfusion and exchange transfusion are unlikely to be of benefit. ln managing overdosage, the physician should consider the possibility of multiple drug involvement.

Do not store above 30°C. Keep away from light and out of the reach of children.

Other Anti-anginal & Anti-ischaemic drugs, Statins

Atorvastatin is a selective inhibitor of HMG-CoA reductase. This enzyme is the rate-limiting enzyme responsible for the conversion of HMG-CoA to mevalonate, a precursor of sterols, including cholesterol. Atorvastatin lowers plasma cholesterol and lipoprotein levels by inhibiting HMG-CoA reductase and cholesterol synthesis in the liver and increases the number of hepatic LDL receptors on the cell surface for enhanced uptake and catabolism of LDL.

Primary hypercholesterolaemia and combined hyperlipidaemia-

• Adults: Usually 10 mg once daily; if necessary, may be increased at intervals of at least 4 weeks to max. 80 mg once daily.
• Child (10-18 years): Initially 10 mg once daily, increased if necessary at intervals of at least 4 weeks to usual max. 20 mg once daily.

Familial hypercholesterolaemia-

• Adults: Initially 10 mg daily, increased at intervals of at least 4 weeks to 40 mg once daily; if necessary, further increased to max. 80 mg once daily (or 40 mg once daily combined with anion-exchange resin in heterozygous familial hypercholesterolaemia).
• Child (10-18 years): Initially 10 mg once daily, increased if necessary at intervals of at least 4 weeks to usual max. 80 mg once daily.

Prevention of cardiovascular events-

• Adults: Initially 10 mg once daily adjusted according to response.

Atorvastatin is generally well-tolerated. The most frequent side effects related to Atorvastatin are constipation, flatulence, dyspepsia, abdominal pain. Other side effects includes infection, headache, back pain, rash, asthenia, arthralgia, myalgia.

Atorvastatin should not be used in patient with hypersensitivity to any component of this medication. Atorvastatin is contraindicated in active liver disease or unexplained persistent elevations of serum transaminases. It is also contraindicated in patient with history of serious adverse reaction to prior administration of HMG-CoA reductase inhibitors.

Liver effects: Liver function tests should be performed before the initiation of treatment and periodically thereafter. Atorvastatin should be used with caution in patients who consume substantial quantities of alcohol or have a history of liver disease. Atorvastatin therapy should be discontinued if markedly elevated CPK levels occur or myopathy is diagnosed or suspected.

The risk of myopathy during treatment with Atorvastatin is increased with concurrent administration of cyclosporin, fibric acid derivatives, erythromycin, azole antifungals and niacin. No clinically significant interactions were seen when Atorvastatin was administered with antihypertensives or hypoglycemic agents. Patients should be closely monitored if Atorvastatin is added to digoxin, erythromycin, oral contraceptives, colestipol, antacid and warfarin.

Pregnancy: Atorvastatin is contraindicated during pregnancy. Safety in pregnant women has not been established. No controlled clinical trials with atorvastatin have been conducted in pregnant women. Rare reports of congenital anomalies following intrauterine exposure to HMG-CoA reductase inhibitors have been received. Animal studies have shown toxicity to reproduction. Maternal treatment with atorvastatin may reduce the fetal levels of mevalonate which is a precursor of cholesterol biosynthesis. Atorvastatin should not be used in women who are pregnant, trying to become pregnant or suspect they are pregnant. Treatment with atorvastatin should be suspended for the duration of pregnancy or until it has been determined that the woman is not pregnant

Lactation: It is not known whether atorvastatin or its metabolites are excreted in human milk. In rats, plasma concentrations of atorvastatin and its active metabolites are similar to those in milk. Because of the potential for serious adverse reactions, women taking atorvastatin should not breastfeed their infants. Atorvastatin is contraindicated during breastfeeding.

Hepatic impairment: Atorvastatin should be used with caution in patients with hepatic impairment.

Pediatric use: For patients aged 10 years and above, the recommended starting dose of atorvastatin is 10 mg per day with titration up to 20 mg per day. Atorvastatin is not indicated in the treatment of patients below the age of 10 years.

Specific treatment is not available for atorvastatin overdose. The patient should be treated symptomatically and supportive measures instituted, as required. Liver function tests should be performed and serum CK levels should be monitored. Due to extensive atorvastatin binding to plasma proteins, hemodialysis is not expected to significantly enhance atorvastatin clearance.

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

Other Anti-anginal & Anti-ischaemic drugs, Statins

Atorvastatin is a selective inhibitor of HMG-CoA reductase. This enzyme is the rate-limiting enzyme responsible for the conversion of HMG-CoA to mevalonate, a precursor of sterols, including cholesterol. Atorvastatin lowers plasma cholesterol and lipoprotein levels by inhibiting HMG-CoA reductase and cholesterol synthesis in the liver and increases the number of hepatic LDL receptors on the cell surface for enhanced uptake and catabolism of LDL.

Primary hypercholesterolaemia and combined hyperlipidaemia-

• Adults: Usually 10 mg once daily; if necessary, may be increased at intervals of at least 4 weeks to max. 80 mg once daily.
• Child (10-18 years): Initially 10 mg once daily, increased if necessary at intervals of at least 4 weeks to usual max. 20 mg once daily.

Familial hypercholesterolaemia-

• Adults: Initially 10 mg daily, increased at intervals of at least 4 weeks to 40 mg once daily; if necessary, further increased to max. 80 mg once daily (or 40 mg once daily combined with anion-exchange resin in heterozygous familial hypercholesterolaemia).
• Child (10-18 years): Initially 10 mg once daily, increased if necessary at intervals of at least 4 weeks to usual max. 80 mg once daily.

Prevention of cardiovascular events-

• Adults: Initially 10 mg once daily adjusted according to response.

Atorvastatin is generally well-tolerated. The most frequent side effects related to Atorvastatin are constipation, flatulence, dyspepsia, abdominal pain. Other side effects includes infection, headache, back pain, rash, asthenia, arthralgia, myalgia.

Atorvastatin should not be used in patient with hypersensitivity to any component of this medication. Atorvastatin is contraindicated in active liver disease or unexplained persistent elevations of serum transaminases. It is also contraindicated in patient with history of serious adverse reaction to prior administration of HMG-CoA reductase inhibitors.

Liver effects: Liver function tests should be performed before the initiation of treatment and periodically thereafter. Atorvastatin should be used with caution in patients who consume substantial quantities of alcohol or have a history of liver disease. Atorvastatin therapy should be discontinued if markedly elevated CPK levels occur or myopathy is diagnosed or suspected.

The risk of myopathy during treatment with Atorvastatin is increased with concurrent administration of cyclosporin, fibric acid derivatives, erythromycin, azole antifungals and niacin. No clinically significant interactions were seen when Atorvastatin was administered with antihypertensives or hypoglycemic agents. Patients should be closely monitored if Atorvastatin is added to digoxin, erythromycin, oral contraceptives, colestipol, antacid and warfarin.

Pregnancy: Atorvastatin is contraindicated during pregnancy. Safety in pregnant women has not been established. No controlled clinical trials with atorvastatin have been conducted in pregnant women. Rare reports of congenital anomalies following intrauterine exposure to HMG-CoA reductase inhibitors have been received. Animal studies have shown toxicity to reproduction. Maternal treatment with atorvastatin may reduce the fetal levels of mevalonate which is a precursor of cholesterol biosynthesis. Atorvastatin should not be used in women who are pregnant, trying to become pregnant or suspect they are pregnant. Treatment with atorvastatin should be suspended for the duration of pregnancy or until it has been determined that the woman is not pregnant

Lactation: It is not known whether atorvastatin or its metabolites are excreted in human milk. In rats, plasma concentrations of atorvastatin and its active metabolites are similar to those in milk. Because of the potential for serious adverse reactions, women taking atorvastatin should not breastfeed their infants. Atorvastatin is contraindicated during breastfeeding.

Hepatic impairment: Atorvastatin should be used with caution in patients with hepatic impairment.

Pediatric use: For patients aged 10 years and above, the recommended starting dose of atorvastatin is 10 mg per day with titration up to 20 mg per day. Atorvastatin is not indicated in the treatment of patients below the age of 10 years.

Specific treatment is not available for atorvastatin overdose. The patient should be treated symptomatically and supportive measures instituted, as required. Liver function tests should be performed and serum CK levels should be monitored. Due to extensive atorvastatin binding to plasma proteins, hemodialysis is not expected to significantly enhance atorvastatin clearance.

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

The is indicated in the following condition-

• Headache
• Migraine
• Toothache
• Neuralgia
• Feverishness
• Period pain
• Sore throat
• Backache
• Help to reduce the temperature
• Aches and pain of colds and flu

Non opioid analgesics

This is a combination of Paracetamol and Caffeine. Paracetamol has analgesic and antipyretic properties with weak anti-inflammatory activity. Caffeine is an alkaloid which is a theophylline-like xanthine derivative. By intermolecular association with Paracetamol, Caffeine increases the solubility and transmembrane permeation of Paracetamol. In addition, Caffeine increases the pain threshold and tolerance of pain. Caffeine has also an intrinsic power to raise vessel tone in the brain, which provides another benefit to treat migraine and headache.

Adult dose: 1-2 tablets every 4-6 hours. Maximum dose: 8 tablets daily.
Child dose: Not recommended for children below 12 years.

Side effects of paracetamol are usually mild, though haematological reactions including thrombocytopenia, leukopenia, pancytopenia, neutropenia, and agranulocytosis have been reported. Pancreatitis, skin rashes, and other allergic reactions occur occasionally.

Paracetamol is contraindicated in patients with severe renal function impairment and hepatic disease (Viral Hepatitis). Known hypersensitivity to paracetamol or caffeine.

Paracetamol & Caffeine should be given cautiously in the following cases: In patients with hepatic or renal failure, in patients taking other hepatotoxic medication. Prolonged use of the drug without consulting a physician should be avoided.

May reduce serum levels with anticonvulsants (e.g. phenytoin, barbiturates, carbamazepine). May enhance the anticoagulant effect of warfarin and other coumarins with prolonged use. Accelerated absorption with metoclopramide and domperidone. May increase serum levels with probenecid. May increase serum levels of chloramphenicol. May reduce absorption with colestyramine within 1 hr of admin. May cause severe hypothermia with phenothiazine.

Pregnant mothers should consult with doctors before taking Paracetamol & Caffeine. Paracetamol & Caffeine can be taken whilst breast feeding.

Symptoms of Paracetamol overdose in the first 24 hours are pallor, nausea, vomiting, anorexia and abdominal pain. Liver damage may become apparent 12 to 40 hours after ingestion. Abnormalities of glucose metabolism and metabolic acidosis may occur.

Store in a cool and dry place, protect from light and moisture.Keep all medicines out of the reach of the children.

Alfuzosin Hydrochloride is indicated for the treatment of the signs and symptoms of benign prostatic hyperplasia(BPH), lower urinary tract symptoms (LUTS) including urinary frequency, nocturia, incomplete emptying and urinary hesitancy associated with BPH.

BPH/ Urinary retention/ Urinary incontinence

Alfuzosin Hydrochloride is a selective antagonist of post-synaptic a1 adrenoreceptors, which are located in the prostate, bladder base, bladder neck, prostatic capsule, and prostatic urethra. Alfuzosin Hydrochloride relaxes the tone of the prostate smooth muscle, prostate capsule, bladder neck and proximal urethra. It competitively and selectively binds to the post synaptic a1-adrenergic receptors in the lower urinary tract. It also relaxes sympathetic nervous stimulation, reduces resting urethral pressure and inhibits urethral hypertonia-induced sympathetic nervous stimulation. As an uroselective agent, Alfuzosin Hydrochloride preferentially binds to prostatic a1 receptors, blockage of these receptors result in reduction of BPH symptoms, improvement of urine flow and decreased potential for hypertensive events.

Benign prostatic hyperplasia (BPH): The recommended dose is 10 mg to be taken once daily after a meal.

Acute urinary retention (AUR): In patients 65 years and older, 10 mg  daily after a meal to be taken from the first day of catheterisation. The treatment should be administered for 3-4 days, 2-3 days during catheterisation and 1 day after its removal. In this indication no benefit has been established in patients under 65 years of age or if treatment is extended beyond 4 days.

Alfuzosin Hydrochloride tablet should be swallowed whole.

Classification of expected frequencies: Very common (<1/10), common (<1/100 to <1/10), uncommon (<1/1,000 to <1/100), rare (<1/10,000 to <1/1,000), very rare (<1/10,000), not known (cannot be estimated from the available data). Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness. Nervous system disorders: Common: faintness/dizziness, headache; Uncommon: syncope, vertigo, malaise, drowsiness. Eye disorders: Uncommon: vision abnormal; Not known: intraoperative floppy iris syndrome. Cardiac disorders: Uncommon: tachycardia, palpitations, hypotension (postural); Very rare: New onset, aggravation or recurrence of angina pectoris in patients with pre-existing coronary artery disease; Not known: atrial fibrillation. Vascular disorders: Uncommon: hypotension (postural), flushing. Blood and lymphatic system disorders: Not known: neutropenia, thrombocytopenia. Respiratory, thoracic and mediastinal disorders: Uncommon: rhinitis. Gastro-intestinal disorders: Common: nausea, abdominal pain; Uncommon: diarrhoea, dry mouth, vomiting; Not known: vomiting. Hepatobiliary disorders: Frequency unknown: hepatocellular injury, cholestatic liver disease. Skin and subcutaneous tissue disorders: Uncommon: rash, pruritus; Very rare: urticaria, angioedema. Reproductive system and breast disorders: Frequency unknown: priapism. General disorders and administration site conditions: Common: asthenia; Uncommon: flushes, oedema, chest pain.

As with all alpha-1-blockers in some subjects, in particular patients receiving antihypertensive medications or nitrates, postural hypotension with or without symptoms (dizziness, fatigue, sweating) may develop within a few hours following administration. In such cases, the patient should lie down until the symptoms have completely disappeared. These effects are transient, occur at the beginning of treatment and do not usually prevent the continuation of treatment. The patient should be warned of the possible occurrence of such events. As with all alpha1-receptor blockers, Alfuzosin Hydrochloride should be used with caution in patients with acute cardiac failure. Care should be taken when Alfuzosin Hydrochloride is administered to patients who have had a pronounced hypotensive response to another alpha-1-blocker. Treatment should be initiated gradually in patients with hypersensitivity to alpha-1-blockers. Alfuzosin Hydrochloride should be administered carefully to patients being treated with antihypertensives. Blood pressure should be monitored regularly, especially at the beginning of treatment. Patients with congenital QTc prolongation, with a known history of acquired QTc prolongation or who are taking drugs known to increase the QTc interval should be evaluated before and during the administration of Alfuzosin Hydrochloride. In coronary patients, the specific treatment for coronary insufficiency should be continued. If angina pectoris reappears or worsens Alfuzosin Hydrochloride should be discontinued.  As there are no clinical safety data available in patients with severe renal impairment (creatinine clearance < 30ml/min), Alfuzosin Hydrochloride 10mg prolonged released tablets should not be administered to this patient group. Patients should be warned that the tablet should be swallowed whole. Any other mode of administration, such as crunching, crushing, chewing, grinding or pounding to powder should be prohibited. These actions may lead to inappropriate release and absorption of the drug and therefore possible early adverse reactions. The ‘Intraoperative Floppy Iris Syndrome’ (IFIS, a variant of small pupil syndrome) has been observed during cataract surgery in some patients on or previously treated with alpha-1-blockers. Although the risk of this event with Alfuzosin Hydrochloride appears very low, ophthalmic surgeons should be informed in advance of cataract surgery of current or past use of alpha-1-blockers, as IFIS may lead to increased procedural complications. The ophthalmologists should be prepared for possible modifications to their surgical technique. Alfuzosin Hydrochloride 10mg prolonged release tablets contain hydrogenated castor oil which may cause stomach upset and diarrhoea.

The administration of general anesthetics to patients receiving Alfuzosin could cause profound hypotension. It is recommended that the tablets be withdrawn 24 hours before surgery. If symptoms of angina pectoris start or get worse, taking Alfuzosin should be stopped.

Combinations contra-indicated: Alpha-1-receptor blockers. Combinations to be taken into account: Antihypertensive drugs, nitrates, potent CYP3A4 inhibitors such as ketoconazole, itraconazole and ritonavir. Repeated 200mg daily dosing of ketoconazole, for seven days resulted in a 2.1-fold increase in Cmax and a 2.5-fold increase in exposure of Alfuzosin Hydrochloride 10mg when administered as a single dose under fed conditions (high fat meal). Other parameters such as tmax and t1/2 were not modified. Cmax and AUC of Alfuzosin Hydrochloride 10mg, when administered as a single dose under fed conditions, increased 2.3- fold and 3.0- fold, respectively following 8-day repeated 400mg ketoconazole daily dosing. The administration of general anaesthetics to patients receiving Alfuzosin Hydrochloride could cause profound hypotension. It is recommended that the tablets be withdrawn 24 hours before surgery.

Other forms of interaction: No pharmacodynamic or pharmacokinetic interaction has been observed in healthy volunteers between Alfuzosin Hydrochloride and the following drugs: warfarin, digoxin, hydrochlorothiazide and atenolol.

Paediatric Population: Efficacy of Alfuzosin Hydrochloride has not been demonstrated in children aged 2 to 16 years. Therefore Alfuzosin Hydrochloride is not indicated for use in the paediatric population.

In case of overdosage, the patient should be hospitalised, kept in the supine position, and conventional treatment of hypotension should take place. In case of significant hypotension, the appropriate corrective treatment may be a vasoconstrictor that acts directly on vascular muscle fibres.

Store in a cool and dry place, protected from light

Ceftazidime inhibits bacterial peptidoglycan cell wall synthesis following binding to penicillin binding proteins (PBPs), which leads to bacterial cell lysis and death. Avibactam is a non β-lactam, β-lactamase inhibitor that acts by forming a covalent adduct with the enzyme that is stable to hydrolysis. It inhibits both Ambler class A and class C β-lactamases and some class D enzymes, including extended-spectrum β-lactamases (ESBLs), KPC and OXA-48 carbapenemases, and AmpC enzymes. Avibactam does not inhibit class B enzymes (metallo-β-lactamases) and is not able to inhibit many class D enzymes.

It is recommended that this should be used to treat infections due to aerobic Gram-negative organisms in adults and paediatric patients aged 3 months and older with limited treatment options only after consultation with a physician with appropriate experience in the management of infectious diseases.

• Complicated intra-abdominal infection: 2 g/0.5 g, every 8 hours for 5-14 days.
• Complicated urinary tract infection (cUTI), including pyelonephritis: 2 g/0.5 g every 8 hours for 5-10 days.
• Hospital-acquired pneumonia (HAP), including ventilator associated pneumonia (VAP): 2 g/0.5 g Every 8 hours for 7-14 days.
• Bacteraemia associated with, or suspected to be associated with any of the above infections: 2 g/0.5 g Every 8 hours. Duration of treatment should be in accordance with the site of infection.
• Infections due to aerobic Gram-negative organisms in patients with limited treatment options: 2 g/0.5 g Every 8 hours. Guided by the severity of the infection, the pathogen(s) and the patient’s clinical and bacteriological progress.

severe allergic reactions: signs include sudden swelling of your lips, face, throat or tongue, a severe rash or other severe skin reactions, difficulty swallowing or breathing. This reaction may be life-threatening. diarrhoea that keeps getting worse or does not go away, or stools that contains blood or mucus-this may happen during or after treatment is stopped with this combination. If this happens do not take medicines that stop or slow bowel movement.

Hypersensitivity to the active substances or to any of the excipients. Hypersensitivity to any cephalosporin antibacterial agent. Severe hypersensitivity (e.g. anaphylactic reaction, severe skin reaction) to any other type of β-lactam antibacterial agent (e.g. penicillins, monobactams or carbapenems).

This medicinal product does not require any special storage conditions. Store in the original package in order to protect from light.

Animal studies with ceftazidime do not indicate direct or indirect harmful effects with respect to pregnancy, embryonal/foetal development, parturition or postnatal development. Animal studies with avibactam have shown reproductive toxicity without evidence of teratogenic effects. Ceftazidime/avibactam should only be used during pregnancy if the potential benefit outweighs the possible risk. Ceftazidime is excreted in human milk in small quantities. It is unknown whether avibactam is excreted in human milk. A risk to newborns/infants cannot be excluded. A decision must be made whether to discontinue breast feeding or to discontinue/abstain from ceftazidime/avibactam therapy taking into account the benefit of breast feeding for the child and the benefit of therapy for the woman.

Elderly: No dosage adjustment is required in elderly patients.

Renal impairment: No dosage adjustment is required in patients with mild renal impairment.

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

This is indicated for the treatment and prevention of zinc and vitamin B deficiencies.

Specific mineral & vitamin combined preparations

Zinc is vital for many biological functions such as immunity enhancement, wound healing, digestion, reproduction, physical growth and mental development. Zinc supports normal growth and development during pregnancy, childhood, and adolescence. Zinc also has some antioxidant properties. Zinc is used to treat ADHD (Attention Deficit Hyper-activity Disorder) in children. In adult, due to zinc deficiency loss of appetite, poor sense of taste and smell, tendency towards depression, white marks on fingernails, frequent infections, low fertility, prostate problems, mental problems, poor wound healing, a poor immune system, diarrhoea, mental lethargy, rough skin and weight loss may occur.

B-Vitamins are needed to release energy from food. They play an important role in ensuring healthy brain and nerve function, healthy red blood cells formation in children & adults. They are specially needed for healthy growth and development of children. B-Vitamin deficiencies in adult cause profound fatigue and various types of neurologic manifestations, which may include weakness, poor balance, confusion, irritability, memory loss, nervousness, tingling of the limbs and loss of coordination. Additional symptoms of vitamin B deficiency are sleep disturbances, nausea, poor appetite, frequent infections, and skin lesions.

Syrup-

• Adults: 10 ml (2 teaspoonful) 2 to 3 times daily or as recommended by the physician.
• Children: 10 ml (2 teaspoonful) 1 to 3 times daily or as recommended by the physician.
• Infants: 5 ml (1 teaspoonful) 1 to 2 times daily or as recommended by the physician.

Tablet-

• Adults & Children over 30 kg: 1 to 2 tablets 2 to 3 times daily or as recommended by the physician.

This is generally well tolerated. However, a few side effects like nausea, vomiting, diarrhoea & stomach upset may occur. Side effects have been reported with specific vitamins but generally at levels substantially higher than recommended doses.

Vitamin B Complex & Zinc is contraindicated in patients with a known hypersensitivity to any of the ingredients of this product.

In acute renal failure, zinc accumulation may occur, so dosage adjustment is needed. This is not intended for the treatment of severe specific deficiencies.

Concomitant intake of tetracyclines and zinc may decrease the Gl absorption and serum levels of tetracyclines. Similarly concomitant administration of zinc and fluroquinolones may decrease the Gl absorption and serum  levels of some fluroquinolones. Coadministration of Niacin and HMG-CoA reductase inhibitors (eg. lovastatin) may result mayopathy and rhabdomyolysis. Pyridoxine reduces levodopa's effectiveness by increasing its peripheral metabolism. Co-administration of pyridoxine with phenytoin may decrease serum levels of phenytoin.

This is recommended in pregnancy and lactation.

In case of overdosage, initially epigastric pain, diarrhoea and vomiting can occur. In that case, one should seek emergency medical attention. Initially, an emetic should be given and then gastric lavage and general supportive measures should be employed.

Store in a cool & dry place, protected from light. Keep all medicines out of reach of children.

This is indicated for the prevention and treatment of Iron, vitamin B12 and Folic acid deficiency. Also indicated for the prevention of Iron deficiency during pregnancy and lactation and as prophylactic therapy of Iron deficiency to cover the recommended daily dietary allowance.

Iron & Vitamin Combined preparations

Vitamin B12 (cyanocobalamin): Required for the maintenance of normal erthropoiesis, nucleprotein and myelin synthesis, cell reproduction and normal growth; Coenzyme; metabolic functions include protein synthesis and carbohydrate metabolism. Plays role in cell replication and hematopoiesis.

Iron: Essential component in the formation of hemoglobin; adequate amounts of iron are necessary for effective erythropoiesis; also serves as a cofactor of several essential enzymes, including cytochromes that are involved in electron transport. Replacement of iron stores found in hemoglobin, myoglobin, and enzymes; works to transport oxygen via hemoglobin.

Folic acid: Required for nucleoprotein synthesis and the maintenance of normal erythropoiesis; folic acid is converted in the liver and plasma to its metabolically active form, tetrahydrofolic acid, by dihydrofolate reductase; prevents neural tube defects in women of childbearing potential and higher doses required during pregnancy.

Adult: 1-2 capsules daily; as recommended by the physician.
Children: 1 capsule daily; as recommended by the physician.
Infant: As recommended by the physician.

Generally well tolerated. In individual cases, a few side-effects occur to oral Iron preparation, such as nausea, vomiting, constipation or diarrhoea.

Contraindicated in patients with known hypersensivity to any of its ingredients.

Caution should be applied where there is a risk of Iron overload, e.g. Haemochromatosis, Thalassaemia, Haemosiderosis or Haemolytic anaemia.

Generally no interactions have been observed. Iron may decrease the absorption of antacids, tetracycline, quinolone antibiotics, levodopa, levothyroxine, methyldopa and pencillamine. Folic acid interacts with antiepileptic drugs, no plasma concentrations of Phenobarbital, phenytoin possibly reduced.

This preparation can be used in pregnancy and lactation.

Initially epigastric pain, diarrhea and vomiting can occur of overdose. Metabolic acidosis, convulsions and coma can occur after recovery. In case of overdose an emetic should be given followed by gastric lavage and general supportive measures.

Store in cool and dry place. Protect from light.

Specific mineral preparations

Zinc sulphate monohydrate is an essential trace element and is involved in a number of body enzyme systems. The body needs zinc for normal growth and health. Zinc is also vital for sexual maturation and reproduction, dark vision adaptation, olfactory and gustatory activity, insulin storage & release and for a variety of host immune defenses. Zinc deficiency may lead to impaired immune function, delayed wound healing, a decrease in sense of taste and smell, a reduced ability to fight infections, poor night vision, increased risk of abortion, alopecia, mental lethargy, skin changes and poor development of reproductive organs.

Child under 10 kg: 5 ml (1 teaspoonful) 2 times daily after food.
Child between 10-30 kg: 10 ml (2 teaspoonfuls) 1-3 times daily after food.
Adults and child over 30 kg: 20 ml (4 teaspoonfuls) 1-3 times daily after food.

This drug is most effective if they are taken at least 1 hour before or 2 hour after meals. However, if causes stomach upset, this may be taken with a meal.

For dispersible tablet-

• Place the tablet in a teaspoon
• Add adequate amount of water
• Let the tablet dissolve completely
• Give the entire spoonful solution

Zinc may cause nausea, vomiting, diarrhoea, stomach upset, heartburn and gastritis.

It is contraindicated in those who are hypersensitive to any component of the ingredient of this preparation.

In acute renal failure, zinc accumulation may occur in body; so dose adjustment is needed.

Concomitant intake of a tetracycline and zinc may decrease the absorption of both the tetracycline and zinc. Similarly concomitant administration of zinc and quinolone drug may also decrease the absorption of both. Concomitant intake of penicillamine and zinc may decrese absorption of zinc.

The safety of this product in human pregnancy has not been established. Zinc crosses the placenta and is present in breast milk.

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