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For the improvement of neurological outcome by reducing the incidence and severity of ischemic deficits in patients with subarachnoid hemorrhage from ruptured intracranial berry aneurysms regardless of their post ictus neurological condition.

Calcium-channel blockers

Nimodipine inhibits inflow of Calcium ions into cells by blocking Calcium channels or select voltage-sensitive areas resulting in relaxation of vascular smooth muscle and myocardium during depolarisation. Nimodipine has greater action on the cerebral vessels because of its high lipophilicity.

Adult: Initial dose is 60 mg in every four hours interval for 21 consecutive days, preferably not less than one hour before or two hours after meals. Oral Nimodipine therapy should be commence within 96 hours of the subarachnoid hemorrhage.

Use in Pediatric Patients: While there is no specific information on use of this medication in pediatric patients.

Although side effects from nimodipine are not common, the following can occur: headache, dizziness, flushing (feeling of warmth), heartburn, fast heartbeat, slow heartbeat, upset stomach, stomach pain, constipation, depression etc.

Use within 1 mth of MI or an episode of unstable angina. Concomitant use with potent CYP3A4 inhibitors (e.g. clarithromycin, ritonavir, ketoconazole, nefazodone).

Patients with cerebral oedema or severely raised intracranial pressure. Contents of oral capsules should be given only by mouth or through a feeding tube. It must never be administered IV or by any other parenteral route. Hepatic impairment. Pregnancy and lactation.

Plasma concentration and efficacy may be significantly reduced when administered with strong CYP3A4 inducers (e.g. rifampicin, carbamazepine, phenobarbital, phenytoin). May increase serum levels and toxicity of phenytoin. Increased plasma concentrations with cimetidine or sodium valproate.

Use in Pregnancy: Large doses of nimodipine have been shown to cause birth defects in animals. Human studies have not been done. Before you take nimodipine, tell your doctor if you are pregnant or plan to become pregnant.

Use in Nursing Mothers: Nimodipine may pass into breast milk but has not been reported to cause problems; caution is advised. Consult your doctor for advice.

Symptoms: Excessive peripheral vasodilation, systemic hypotension, tachycardia, bradycardia, GI complaints, nausea.

Management: Symptomatic and supportive treatment. Admin of vasopressor may be necessary if significant hypotension occurs. IV Ca salts have been also used for hypotension.

Store between 15-30° C. Protect from light.

Naproxen & Esomeprazole is indicated for the relief of signs & symptoms of-

• Osteoarthritis
• Rheumatoid arthritis
• Ankylosing spondylitis &
• To decrease the risk of developing gastric ulcers in patients at risk of developing NSAID-associated gastric ulcers.

Drugs for Osteoarthritis, Drugs used for Rheumatoid Arthritis, Non-steroidal Anti-inflammatory Drugs (NSAIDs)

This consists of an immediate release Esomeprazole Magnesium layer & an enteric-coated Naproxen core. As a result, Esomeprazole is released first into the stomach, prior to the dissolution of Naproxen in the small intestine.

Naproxen is a NSAID with analgesic & antipyretic properties. The mechanism of action of Naproxen is to inhibit the prostaglandin synthesis. Esomeprazole is a proton pump inhibitor that suppresses gastric acid secretion by specific inhibition of the H⁺/k⁺ -ATPase in the gastric parietal cell by acting specifically on the proton pump, Esomeprazole blocks the final step in acid production, thus reducing gastric acidity.

Carefully consider the potential benefits & risks of this tablet & other treatment options before deciding to use this tablet. Use the lowest effective dose for the shortest duration consistent with individual patient treatment goals. If a dose of Esomeprazole lower than a total daily dose of 40 mg is more appropriate, a different treatment should be considered.

Rheumatoid Arthritis, Osteoarthritis and Ankylosing Spondylitis-

• Adults: One tablet twice daily of either: 375 mg naproxen/20 mg of esomeprazole; or 500 mg naproxen/20 mg of esomeprazole

Juvenile Idiopathic Arthritis in Adolescent Patients 12 Years of Age & Older-

• Weight greater than 50 kg: 375 mg naproxen/20 mg of esomeprazole; or 500 mg naproxen/20 mg of esomeprazole
• Weight 38 kg to less than 50 kg: One tablet twice daily of 375 mg naproxen/20 mg of esomeprazole.

Do not split, chew, crush or dissolve the tablet. This tablet is to be taken at least 30 minutes before meals.

In general, this preparation is well tolerated. The most common adverse reactions in clinical trials (>5%): erosive gastritis, dyspepsia, gastritis, diarrhea, gastric ulcer, upper abdominal pain, nausea etc.

Patients with known CV disease/risk factors may be at greater risk. This tablet should be used with caution in patients with fluid retention or heart failure.

With medicine:

• Concomitant use of NSAIDs may reduce the antihypertensive effect of ACE inhibitors, diuretics & beta-blockers
• Concomitant use of this tablet and warfarin may result in an increased risk of a bleeding complication.
• Esomeprazole inhibits gastric acid secretion & may interfere with the absorption of drugs where gastric pH is an important determinant of bioavailability (eg. Ketoconazole, iron salts and digoxin).

With food & others: Administration of Naproxen & Esomeprazole together with high-fat food in healthy volunteers does not affect the extent of absorption of naproxen but significantly prolongs t_max by 10 hours and decreases peak plasma concentration (C_max) by about 12%

Pregnancy category C. In late pregnancy, it should be avoided because it may cause premature closure of the ductus arteriosus. This tablet should not be used in nursing mothers due to the Naproxen component.

Elderly patients: Studies indicate that although the total plasma concentration of naproxen is unchanged, the unbound plasma fraction of naproxen is increased in the elderly. Use caution when high doses are required & some adjustment of dosage may be required in elderly patients. As with other drugs used in the elderly use the lowest effective dose.

Patients with Moderate to Severe Renal impairment: Naproxen-containing products are not recommended for use in patients with moderate to severe or severe renal impairment (creatinine clearance <30 ml/min).

Hepatic insufficiency: Monitor patients with mild to moderate hepatic impairment closely & consider a possible dose reduction based on the Naproxen component of this tablet. This is not recommended in patients with severe hepatic impairment because Esomeprazole dosage should not exceed 20 mg daily in these patients.

There is no clinical data on overdosage with this tablet.

Overdose of Naproxen: Significant naproxen overdosage may be characterized by lethargy, drowsiness, epigastric pain, abdominal discomfort, heartburn, indigestion, nausea, transient alteration in liver function, hypoprothrombinemia, renal dysfunction, metabolic acidosis, apnea, vomiting etc.

Overdose of Esomeprazole: The major signs of acute toxicity were reduced motor activity, changes in respiratory frequency, tremor and intermittent clonic convulsions etc.

Store at temperature of below 30°C, protect from light & moisture. Keep out of reach of children.

Echinacea is used to treat common cold, cough, bronchitis and other upper respiratory tract infections, fever & cold, stimulate the immune system to prevent the tendency of infection.

Herbal and Nutraceuticals

Echinacea products contain a variety of bioactive ingredients including echinacosides, caffeic acids, alkylamides, polysaccharides, and glycoproteins. Though several echinacea products are standardized to the amount of echinacosides, there is no general consensus on the active component of echinacea responsible for its purported medicinal properties. 

In vitro, echinacea causes macrophage activation and the release of tumor necrosis factor, interleukin 1, interleukin 6, and interferon. Echinacea has been noted to have antiviral activity against influenza, herpes, and poliovirus. Phenolic compounds present in echinacea demonstrate antioxidant activity. It has also been reported to have antiinflammatory activity through inhibition of lipoxygenase and cyclooxygenase and is able to stimulate the anterior pituitary-adrenal cortex.

The dose is 1-2 capsule 3 times daily.

Echinacea is generally safe for most people. Some side effects have been reported such as fever, nausea, vomiting, diarrhea, dry mouth, headache, dizziness, joint and muscle aches.

The drug should be used cautiously in patients with autoimmune disease

Echinacea is not recommended for use during pregnancy.

Echinacea capsule should be stored at room temperature. Protect from moisture and light.

Tyrosine Kinase Inhibitor

Nintedanib is a small molecule, competitive, triple angiokinase inhibitor that targets multiple receptor tyrosine kinases (RTKs) and non-receptor tyrosine kinases (nRTKs). Many of these RTKs are implicated in lung fibrosis and tumour angiogenesis, so nintedanib is therefore used in the treatment of proliferative diseases such as idiopathic pulmonary fibrosis, non-small cell lung cancer, and systemic sclerosis-associated interstitial lung disease. The specific RTKs that nintedanib inhibits are platelet-derived growth factor (PDGFR) α and β, fibroblast growth factor receptor (FGFR) 1-3, vascular endothelial growth factor receptor (VEGFR), and Fns-Like tyrosine kinase-3 (FLT3). Nintedanib binds to the ATP-binding pocket of these receptors and inhibits their activity, thereby blocking signalling cascades that result in the proliferation and migration of lung fibroblasts. Nintedanib also inhibits kinase signalling pathways in various cells within tumour tissues, including endothelial cells, pericytes, smooth muscle cells, and cells contributing to angiogenesis, culminating in an inhibition of cell proliferation and apoptosis of affected tumour cells.

In addition to RTK inhibition, nintedanib also prevents the actions of the nRTKs Lck, Lyn, and Src. The contribution of the inhibition of Lck and Lyn towards the therapeutic efficacy of nintedanib is unclear, but inhibition of the Src pathway by nintedanib has been shown to reduce lung fibrosis.

Treatment with Nintedanib should be initiated by physicians experienced in the diagnosis and treatment of IPF.

Posology: The recommended dose is 150 mg Nintedanib twice daily administered approximately 12 hours apart. The 100 mg twice daily dose is only recommended to be used in patients who do not tolerate the 150 mg twice daily dose. If a dose is missed, administration should resume at the next scheduled time at the recommended dose. If a dose is missed the patient should not take an additional dose. The recommended maximum daily dose of 300 mg should not be exceeded.

For NSCLC:

• The recommended dose of nintedanib is 200 mg twice daily administered approximately 12 hours apart, on days 2 to 21 of a standard 21 day docetaxel treatment cycle.
• Nintedanib must not be taken on the same day of docetaxel chemotherapy administration (= day 1). If a dose of nintedanib is missed, administration should resume at the next scheduled time at the recommended dose. The individual daily doses of nintedanib should not be increased beyond the recommended dose to make up for missed doses. The recommended maximum daily dose of 400 mg should not be exceeded.
• Patients may continue therapy with nintedanib after discontinuation of docetaxel for as long as clinical benefit is observed or until unacceptable toxicity occurs.
• Dose adjustments: In addition to symptomatic treatment if applicable, the management of adverse reactions to Nintedanib could include dose reduction and temporary interruption until the specific adverse reaction has resolved to levels that allow continuation of therapy. Nintedanib treatment may be resumed at the full dose (150 mg twice daily) or a reduced dose (100 mg twice daily). If a patient does not tolerate 100 mg twice daily, treatment with Nintedanib should be discontinued.
• In case of interruptions due to aspartate aminotransferase (AST) or alanine aminotransferase (ALT) elevations > 3x upper limit of normal (ULN), once transaminases have returned to baseline values, treatment with Nintedanib may be reintroduced at a reduced dose (100 mg twice daily) which subsequently may be increased to the full dose (150 mg twice daily).

Nintedanib is for oral use. The capsules should be taken with food, swallowed whole with water, and should not be chewed or crushed.

Summary of the safety profile: Nintedanib has been studied in clinical trials of 1,529 patients suffering from IPF. The safety data provided in the following are based on the two Phase III, randomized, double-blind, placebo-controlled studies in 1,061 patients comparing treatment with Nintedanib 150 mg twice daily to placebo for 52 weeks (INPULSIS-1 and INPULSIS-2) and based on data observed during the post-marketing period.

The most frequently reported adverse reactions associated with the use of Nintedanib included diarrhea, nausea and vomiting, abdominal pain, decreased appetite, weight decreased and hepatic enzyme increased.

Tabulated list of adverse reactions: The below table provides a summary of the adverse reactions by MedDRA System Organ Class (SOC) and frequency category.

Below table summarizes the frequencies of adverse drug reactions (ADRs) that were reported in the Nintedanib group (638 patients) pooled from the two placebo-controlled Phase III clinical trials of 52 weeks duration or from the post-marketing period.

Frequency categories are defined using the following convention: Very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to < 1/100), rare (≥ 1/10,000 to < 1/1,000), very rare (< 1/10,000), not known (cannot be estimated from the available data).

Hypersensitivity to Nintedanib, to peanut or soya, or to any of the excipients.

Diarrhoea: In the INPULSIS trials, diarrhoea was the most frequent gastro-intestinal adverse reaction reported in 62.4% versus 18.4% of patients treated with Nintedanib and placebo, respectively. In most patients the adverse reaction was of mild to moderate intensity and occurred within the first 3 months of treatment. Diarrhoea led to dose reduction in 10.7% of the patients and to discontinuation of Nintedanib in 4.4% of the patients in clinical trials. Serious cases of diarrhoea leading to dehydration and electrolyte disturbances have been reported in the post-marketing. Patients should be treated at first signs with adequate hydration and anti-diarrhoeal medicinal products, e.g. loperamide, and may require treatment interruption. Nintedanib treatment may be resumed at a reduced dose (100 mg twice daily) or at the full dose (150 mg twice daily). In case of persisting severe diarrhoea despite symptomatic treatment, therapy with Nintedanib should be discontinued.

Nausea and vomiting: Nausea and vomiting were frequently reported gastrointestinal adverse reactions. In most patients with nausea and vomiting, the event was of mild to moderate intensity. Nausea led to discontinuation of Nintedanib in 2.0% of patients. Vomiting led to discontinuation in 0.8% of the patients. If symptoms persist despite appropriate supportive care (including anti-emetic therapy), dose reduction or treatment interruption may be required. The treatment may be resumed at a reduced dose (100 mg twice daily) or at the full dose (150 mg twice daily). In case of persisting severe symptoms therapy with Nintedanib should be discontinued.

Hepatic function: The safety and efficacy of Nintedanib has not been studied  in patients with moderate (Child Pugh B) or severe (Child Pugh C) hepatic impairment. Therefore, treatment with Nintedanib is not recommended in such patients. Based on increased exposure, the risk for adverse events may be increased in patients with mild hepatic impairment (Child Pugh A). Patients with mild hepatic impairment (Child Pugh A) should be treated with a reduced dose of Nintedanib. Cases of drug-induced liver injury have been observed with Nintedanib treatment, including severe liver injury with fatal outcome. The majority of hepatic events occur within the first three months of treatment. Therefore, hepatic transaminase and bilirubin levels should be investigated before treatment initiation and during the first month of treatment with Nintedanib. Patients should then be monitored at regular intervals during the subsequent two months of treatment and periodically thereafter, e.g. at each patient visit or as clinically indicated. Elevations of liver enzymes (ALT, AST, ALKP, gamma-glutamyl-transferase (GGT) and bilirubin were reversible upon dose reduction or interruption in the majority of cases. If transaminase (AST or ALT) elevations > 3x ULN are measured, dose reduction or interruption of the therapy with Nintedanib is recommended and the patient should be monitored closely. Once transaminases have returned to baseline values, treatment with Nintedanib may be resumed at the full dose (150 mg twice daily) or reintroduced at a reduced dose (100 mg twice daily) which subsequently may be increased to the full dose. If any liver test elevations are associated with clinical signs or symptoms of liver injury, e.g. jaundice, treatment with Nintedanib should be permanently discontinued. Alternative causes of the liver enzyme elevations should be investigated.

Patients with low body weight (<65 kg), Asian and female patients have a higher risk of elevations of liver enzymes. Nintedanib exposure increased linearly with patient age, which may also result in a higher risk of developing liver enzyme elevations. Close monitoring is recommended in patients with these risk factors.

Renal Function: Cases of renal impairment/failure, in some cases with fatal outcome, have been reported with Nintedanib use. Patients should be monitored during Nintedanib therapy, with particular attention to those patients exhibiting risk factors for renal impairment/failure. In case of renal impairment/failure, therapy adjustment should be considered.

Haemorrhage: Vascular endothelial growth factor receptor (VEGFR) inhibition might be associated with an increased risk of bleeding. In the INPULSIS trials with Nintedanib, the frequency of patients who experienced bleeding AEs was slightly higher in the Nintedanib arm (10.3%) than in the placebo arm (7.8%). Non-serious epistaxis was the most frequent bleeding event. Serious bleeding events occurred with low and similar frequencies in the 2 treatment groups (placebo: 1.4%; Nintedanib: 1.3%). Patients at known risk for bleeding including patients with inherited predisposition to bleeding or patients receiving a full dose of anti-coagulative treatment were not included in the INPULSIS studies. Non-serious and serious bleeding events, some of which were fatal, have been reported in the post-marketing period (including patients with or without anticoagulant therapy or other drugs that could cause bleeding). Therefore, these patients should only be treated with Nintedanib if the anticipated benefit outweighs the potential risk. Post-marketing bleeding events include but are not limited to gastrointestinal, respiratory and central nervous organ systems, with the most frequent being gastrointestinal.

Arterial thromboembolic events: Patients with a recent history of myocardial infarction or stroke were excluded from the INPULSIS trials. Arterial thromboembolic events were infrequently reported: in 0.7% of patients in the placebo and 2.5% in the Nintedanib treated group. While adverse events reflecting ischemic heart disease were balanced between the Nintedanib and placebo groups, a higher percentage of patients experienced myocardial infarctions in the Nintedanib group (1.6%) compared to the placebo group (0.5%). Caution should be used when treating patients at higher cardiovascular risk including known coronary artery disease. Treatment interruption should be considered in patients who develop signs or symptoms of acute myocardial ischemia.

Venous thromboembolism: In the INPULSIS trials no increased risk of venous thromboembolism was observed in Nintedanib treated patients. Due to the mechanism of action of Nintedanib patients might have an increased risk of thromboembolic events.

Gastrointestinal perforations: In the INPULSIS trials, the frequency of patients with perforation was very low in both treatment groups: 0% placebo, 0.3% Nintedanib (involving two patients). Due to the mechanism of action of Nintedanib patients might have an increased risk of gastrointestinal perforation. Cases of gastrointestinal perforations, some of which were fatal, have been reported in the post-marketing period. Particular caution should be exercised when treating patients with previous abdominal surgery, previous history of peptic ulceration, diverticular disease or receiving concomitant corticosteroids or NSAIDs. Nintedanib should only be initiated at least 4 weeks after abdominal surgery. Therapy with Nintedanib should be permanently discontinued in patients who develop gastrointestinal perforation.

Hypertension: Administration of Nintedanib may increase blood pressure. Systemic blood pressure should be measured periodically and as clinically indicated.

Wound healing complication: No increased frequency of impaired wound healing was observed in the INPULSIS trials. Based on the mechanism of action Nintedanib may impair wound healing. No dedicated studies investigating the effect of Nintedanib on wound healing were performed. Treatment with Nintedanib should therefore only be initiated or – in case of perioperative interruption – resumed based on clinical judgement of adequate wound healing.

Co-administration with Pirfenidone: In a dedicated pharmacokinetic study, concomitant treatment of Nintedanib with Pirfenidone was investigated in patients with IPF. Based on these results, there is no evidence of a relevant pharmacokinetic drug-drug interaction between Nintedanib and Pirfenidone when administered in combination. In view of the limited number of patients, this study detected only the most frequent adverse events and showed an increase in gastrointestinal adverse events and a trend toward increased hepatic adverse events. Given the similarity in safety profiles for both medicinal products, additive adverse events, including gastrointestinal and hepatic adverse events, may be expected. The benefit-risk balance of concomitant treatment with Pirfenidone has not been established.

Effect on QT interval: No evidence of QT prolongation was observed for Nintedanib in the clinical trial programme. As some other tyrosine kinase inhibitors are known to exert an effect on QT, caution should be exercised when administered Nintedanib in patients who may develop QTc prolongation.

Allergic reaction: Dietary soya products are known to cause allergic reactions including severe anaphylaxis in persons with soya allergy. Patients with known allergy to peanut protein carry an enhanced risk for severe reactions to soya preparations.

P-glycoprotein (P-gp): Nintedanib is a substrate of P-gp. Co-administration with the potent P-gp inhibitor ketoconazole increased exposure to Nintedanib 1.61-fold based on AUC and 1.83-fold based on Cmax in a dedicated drug-drug interaction study. In a drug-drug interaction study with the potent P-gp inducer rifampicin, exposure to Nintedanib decreased to 50.3% based on AUC and to 60.3% based on Cmax upon co-administration with rifampicin compared to administration of Nintedanib alone. If co-administered with Nintedanib, potent P-gp inhibitors (e.g. ketoconazole, erythromycin or cyclosporine) may increase exposure to Nintedanib. In such cases, patients should be monitored closely for tolerability of Nintedanib. Management of side effects may require interruption, dose reduction, or discontinuation of therapy with Nintedanib. Potent P-gp inducers (e.g. rifampicin, carbamazepine, phenytoin, and St. John’s Wort) may decrease exposure to Nintedanib. Selection of an alternate concomitant medicinal product with no or minimal P-gp induction potential should be considered.

Cytochrome (CYP)-enzymes: Only a minor extent of the biotransformation of Nintedanib consisted of CYP pathways. Nintedanib and its metabolites, the free acid moiety BIBF 1202 and its glucuronide BIBF 1202 glucuronide, did not inhibit or induce CYP enzymes in preclinical studies. The likelihood of drug-drug interactions with Nintedanib based on CYP metabolism is therefore considered to be low.

Co-administration with other medicinal products: The potential for interactions of Nintedanib with hormonal contraceptives was not explored.

Women of childbearing potential/Contraception: Nintedanib may cause foetalharm in humans. Women of childbearing potential should be advised to avoid becoming pregnant while receiving treatment with Nintedanib. They should be advised to use adequate contraception during and at least 3 months after the last dose of Nintedanib. Since the effect of Nintedanib on the metabolism and efficacy of hormonal contraceptives has not been investigated, barrier methods should be applied as a second form of contraception, to avoid pregnancy.

Pregnancy: There is no information on the use of Nintedanib in pregnant women, but pre-clinical studies in animals have shown reproductive toxicity of this active substance. As Nintedanib may cause foetal harm also in humans, it must not be used during pregnancy. Female patients should be advised to notify their doctor or pharmacist if they become pregnant during therapy with Nintedanib. If the patient becomes pregnant while receiving Nintedanib, she should be apprised of the potential hazard to the foetus. Termination of the treatment with Nintedanib should be considered.

Lactation: There is no information on the excretion of Nintedanib and its metabolites in human milk. Pre-clinical studies showed that small amounts of Nintedanib and its metabolites (≤ 0.5% of the administered dose) were secreted into milk of lactating rats. A risk to the newborns/infants cannot be excluded. Breast-feeding should be discontinued during treatment with Nintedanib.

Fertility: Based on preclinical investigations there is no evidence for impairment of male fertility. From subchronic and chronic toxicity studies, there is no evidence that female fertility in rats is impaired at a systemic exposure level comparable with that at the maximum recommended human dose (MRHD) of 150 mg twice daily.

Elderly patients (≥65 years): No overall differences in safety and efficacy were observed for elderly patients. No a-priori dose adjustment is required on the basis of a patient’s age. Patients ≥75 years may be more likely to require dose reduction to manage adverse effects.

Renal impairment: Less than 1% of a single dose of Nintedanib is excreted via the kidney. Adjustment of the starting dose in patients with mild to moderate renal impairment is not required. The safety, efficacy, and pharmacokinetics of Nintedanib have not been studied in patients with severe renal impairment (<30 ml/min creatinine clearance).

Hepatic impairment: Nintedanib is predominantly eliminated via biliary/faecal excretion (> 90%). Exposure increased in patients with hepatic impairment (Child Pugh A, Child Pugh B). In patients with mild hepatic impairment (Child Pugh A), the recommended dose of Nintedanib is 100 mg twice daily approximately 12 hours apart. In patients with mild hepatic impairment (Child Pugh A), treatment interruption or discontinuation for management of adverse reactions should be considered. The safety and efficacy of Nintedanib have not been investigated in patients with hepatic impairment classified as Child Pugh B and C. Treatment of patients with moderate (Child Pugh B) and severe (Child Pugh C) hepatic impairment with Nintedanib is not recommended.

Paediatric population: The safety and efficacy of Nintedanib in children aged 0-18 years have not been established. No data are available.

Store in a cool and dry place, protected from light. Do not store above 25°C.

Tyrosine Kinase Inhibitor

Nintedanib is a small molecule, competitive, triple angiokinase inhibitor that targets multiple receptor tyrosine kinases (RTKs) and non-receptor tyrosine kinases (nRTKs). Many of these RTKs are implicated in lung fibrosis and tumour angiogenesis, so nintedanib is therefore used in the treatment of proliferative diseases such as idiopathic pulmonary fibrosis, non-small cell lung cancer, and systemic sclerosis-associated interstitial lung disease. The specific RTKs that nintedanib inhibits are platelet-derived growth factor (PDGFR) α and β, fibroblast growth factor receptor (FGFR) 1-3, vascular endothelial growth factor receptor (VEGFR), and Fns-Like tyrosine kinase-3 (FLT3). Nintedanib binds to the ATP-binding pocket of these receptors and inhibits their activity, thereby blocking signalling cascades that result in the proliferation and migration of lung fibroblasts. Nintedanib also inhibits kinase signalling pathways in various cells within tumour tissues, including endothelial cells, pericytes, smooth muscle cells, and cells contributing to angiogenesis, culminating in an inhibition of cell proliferation and apoptosis of affected tumour cells.

In addition to RTK inhibition, nintedanib also prevents the actions of the nRTKs Lck, Lyn, and Src. The contribution of the inhibition of Lck and Lyn towards the therapeutic efficacy of nintedanib is unclear, but inhibition of the Src pathway by nintedanib has been shown to reduce lung fibrosis.

Treatment with Nintedanib should be initiated by physicians experienced in the diagnosis and treatment of IPF.

Posology: The recommended dose is 150 mg Nintedanib twice daily administered approximately 12 hours apart. The 100 mg twice daily dose is only recommended to be used in patients who do not tolerate the 150 mg twice daily dose. If a dose is missed, administration should resume at the next scheduled time at the recommended dose. If a dose is missed the patient should not take an additional dose. The recommended maximum daily dose of 300 mg should not be exceeded.

For NSCLC:

• The recommended dose of nintedanib is 200 mg twice daily administered approximately 12 hours apart, on days 2 to 21 of a standard 21 day docetaxel treatment cycle.
• Nintedanib must not be taken on the same day of docetaxel chemotherapy administration (= day 1). If a dose of nintedanib is missed, administration should resume at the next scheduled time at the recommended dose. The individual daily doses of nintedanib should not be increased beyond the recommended dose to make up for missed doses. The recommended maximum daily dose of 400 mg should not be exceeded.
• Patients may continue therapy with nintedanib after discontinuation of docetaxel for as long as clinical benefit is observed or until unacceptable toxicity occurs.
• Dose adjustments: In addition to symptomatic treatment if applicable, the management of adverse reactions to Nintedanib could include dose reduction and temporary interruption until the specific adverse reaction has resolved to levels that allow continuation of therapy. Nintedanib treatment may be resumed at the full dose (150 mg twice daily) or a reduced dose (100 mg twice daily). If a patient does not tolerate 100 mg twice daily, treatment with Nintedanib should be discontinued.
• In case of interruptions due to aspartate aminotransferase (AST) or alanine aminotransferase (ALT) elevations > 3x upper limit of normal (ULN), once transaminases have returned to baseline values, treatment with Nintedanib may be reintroduced at a reduced dose (100 mg twice daily) which subsequently may be increased to the full dose (150 mg twice daily).

Nintedanib is for oral use. The capsules should be taken with food, swallowed whole with water, and should not be chewed or crushed.

Summary of the safety profile: Nintedanib has been studied in clinical trials of 1,529 patients suffering from IPF. The safety data provided in the following are based on the two Phase III, randomized, double-blind, placebo-controlled studies in 1,061 patients comparing treatment with Nintedanib 150 mg twice daily to placebo for 52 weeks (INPULSIS-1 and INPULSIS-2) and based on data observed during the post-marketing period.

The most frequently reported adverse reactions associated with the use of Nintedanib included diarrhea, nausea and vomiting, abdominal pain, decreased appetite, weight decreased and hepatic enzyme increased.

Tabulated list of adverse reactions: The below table provides a summary of the adverse reactions by MedDRA System Organ Class (SOC) and frequency category.

Below table summarizes the frequencies of adverse drug reactions (ADRs) that were reported in the Nintedanib group (638 patients) pooled from the two placebo-controlled Phase III clinical trials of 52 weeks duration or from the post-marketing period.

Frequency categories are defined using the following convention: Very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to < 1/100), rare (≥ 1/10,000 to < 1/1,000), very rare (< 1/10,000), not known (cannot be estimated from the available data).

Hypersensitivity to Nintedanib, to peanut or soya, or to any of the excipients.

Diarrhoea: In the INPULSIS trials, diarrhoea was the most frequent gastro-intestinal adverse reaction reported in 62.4% versus 18.4% of patients treated with Nintedanib and placebo, respectively. In most patients the adverse reaction was of mild to moderate intensity and occurred within the first 3 months of treatment. Diarrhoea led to dose reduction in 10.7% of the patients and to discontinuation of Nintedanib in 4.4% of the patients in clinical trials. Serious cases of diarrhoea leading to dehydration and electrolyte disturbances have been reported in the post-marketing. Patients should be treated at first signs with adequate hydration and anti-diarrhoeal medicinal products, e.g. loperamide, and may require treatment interruption. Nintedanib treatment may be resumed at a reduced dose (100 mg twice daily) or at the full dose (150 mg twice daily). In case of persisting severe diarrhoea despite symptomatic treatment, therapy with Nintedanib should be discontinued.

Nausea and vomiting: Nausea and vomiting were frequently reported gastrointestinal adverse reactions. In most patients with nausea and vomiting, the event was of mild to moderate intensity. Nausea led to discontinuation of Nintedanib in 2.0% of patients. Vomiting led to discontinuation in 0.8% of the patients. If symptoms persist despite appropriate supportive care (including anti-emetic therapy), dose reduction or treatment interruption may be required. The treatment may be resumed at a reduced dose (100 mg twice daily) or at the full dose (150 mg twice daily). In case of persisting severe symptoms therapy with Nintedanib should be discontinued.

Hepatic function: The safety and efficacy of Nintedanib has not been studied  in patients with moderate (Child Pugh B) or severe (Child Pugh C) hepatic impairment. Therefore, treatment with Nintedanib is not recommended in such patients. Based on increased exposure, the risk for adverse events may be increased in patients with mild hepatic impairment (Child Pugh A). Patients with mild hepatic impairment (Child Pugh A) should be treated with a reduced dose of Nintedanib. Cases of drug-induced liver injury have been observed with Nintedanib treatment, including severe liver injury with fatal outcome. The majority of hepatic events occur within the first three months of treatment. Therefore, hepatic transaminase and bilirubin levels should be investigated before treatment initiation and during the first month of treatment with Nintedanib. Patients should then be monitored at regular intervals during the subsequent two months of treatment and periodically thereafter, e.g. at each patient visit or as clinically indicated. Elevations of liver enzymes (ALT, AST, ALKP, gamma-glutamyl-transferase (GGT) and bilirubin were reversible upon dose reduction or interruption in the majority of cases. If transaminase (AST or ALT) elevations > 3x ULN are measured, dose reduction or interruption of the therapy with Nintedanib is recommended and the patient should be monitored closely. Once transaminases have returned to baseline values, treatment with Nintedanib may be resumed at the full dose (150 mg twice daily) or reintroduced at a reduced dose (100 mg twice daily) which subsequently may be increased to the full dose. If any liver test elevations are associated with clinical signs or symptoms of liver injury, e.g. jaundice, treatment with Nintedanib should be permanently discontinued. Alternative causes of the liver enzyme elevations should be investigated.

Patients with low body weight (<65 kg), Asian and female patients have a higher risk of elevations of liver enzymes. Nintedanib exposure increased linearly with patient age, which may also result in a higher risk of developing liver enzyme elevations. Close monitoring is recommended in patients with these risk factors.

Renal Function: Cases of renal impairment/failure, in some cases with fatal outcome, have been reported with Nintedanib use. Patients should be monitored during Nintedanib therapy, with particular attention to those patients exhibiting risk factors for renal impairment/failure. In case of renal impairment/failure, therapy adjustment should be considered.

Haemorrhage: Vascular endothelial growth factor receptor (VEGFR) inhibition might be associated with an increased risk of bleeding. In the INPULSIS trials with Nintedanib, the frequency of patients who experienced bleeding AEs was slightly higher in the Nintedanib arm (10.3%) than in the placebo arm (7.8%). Non-serious epistaxis was the most frequent bleeding event. Serious bleeding events occurred with low and similar frequencies in the 2 treatment groups (placebo: 1.4%; Nintedanib: 1.3%). Patients at known risk for bleeding including patients with inherited predisposition to bleeding or patients receiving a full dose of anti-coagulative treatment were not included in the INPULSIS studies. Non-serious and serious bleeding events, some of which were fatal, have been reported in the post-marketing period (including patients with or without anticoagulant therapy or other drugs that could cause bleeding). Therefore, these patients should only be treated with Nintedanib if the anticipated benefit outweighs the potential risk. Post-marketing bleeding events include but are not limited to gastrointestinal, respiratory and central nervous organ systems, with the most frequent being gastrointestinal.

Arterial thromboembolic events: Patients with a recent history of myocardial infarction or stroke were excluded from the INPULSIS trials. Arterial thromboembolic events were infrequently reported: in 0.7% of patients in the placebo and 2.5% in the Nintedanib treated group. While adverse events reflecting ischemic heart disease were balanced between the Nintedanib and placebo groups, a higher percentage of patients experienced myocardial infarctions in the Nintedanib group (1.6%) compared to the placebo group (0.5%). Caution should be used when treating patients at higher cardiovascular risk including known coronary artery disease. Treatment interruption should be considered in patients who develop signs or symptoms of acute myocardial ischemia.

Venous thromboembolism: In the INPULSIS trials no increased risk of venous thromboembolism was observed in Nintedanib treated patients. Due to the mechanism of action of Nintedanib patients might have an increased risk of thromboembolic events.

Gastrointestinal perforations: In the INPULSIS trials, the frequency of patients with perforation was very low in both treatment groups: 0% placebo, 0.3% Nintedanib (involving two patients). Due to the mechanism of action of Nintedanib patients might have an increased risk of gastrointestinal perforation. Cases of gastrointestinal perforations, some of which were fatal, have been reported in the post-marketing period. Particular caution should be exercised when treating patients with previous abdominal surgery, previous history of peptic ulceration, diverticular disease or receiving concomitant corticosteroids or NSAIDs. Nintedanib should only be initiated at least 4 weeks after abdominal surgery. Therapy with Nintedanib should be permanently discontinued in patients who develop gastrointestinal perforation.

Hypertension: Administration of Nintedanib may increase blood pressure. Systemic blood pressure should be measured periodically and as clinically indicated.

Wound healing complication: No increased frequency of impaired wound healing was observed in the INPULSIS trials. Based on the mechanism of action Nintedanib may impair wound healing. No dedicated studies investigating the effect of Nintedanib on wound healing were performed. Treatment with Nintedanib should therefore only be initiated or – in case of perioperative interruption – resumed based on clinical judgement of adequate wound healing.

Co-administration with Pirfenidone: In a dedicated pharmacokinetic study, concomitant treatment of Nintedanib with Pirfenidone was investigated in patients with IPF. Based on these results, there is no evidence of a relevant pharmacokinetic drug-drug interaction between Nintedanib and Pirfenidone when administered in combination. In view of the limited number of patients, this study detected only the most frequent adverse events and showed an increase in gastrointestinal adverse events and a trend toward increased hepatic adverse events. Given the similarity in safety profiles for both medicinal products, additive adverse events, including gastrointestinal and hepatic adverse events, may be expected. The benefit-risk balance of concomitant treatment with Pirfenidone has not been established.

Effect on QT interval: No evidence of QT prolongation was observed for Nintedanib in the clinical trial programme. As some other tyrosine kinase inhibitors are known to exert an effect on QT, caution should be exercised when administered Nintedanib in patients who may develop QTc prolongation.

Allergic reaction: Dietary soya products are known to cause allergic reactions including severe anaphylaxis in persons with soya allergy. Patients with known allergy to peanut protein carry an enhanced risk for severe reactions to soya preparations.

P-glycoprotein (P-gp): Nintedanib is a substrate of P-gp. Co-administration with the potent P-gp inhibitor ketoconazole increased exposure to Nintedanib 1.61-fold based on AUC and 1.83-fold based on Cmax in a dedicated drug-drug interaction study. In a drug-drug interaction study with the potent P-gp inducer rifampicin, exposure to Nintedanib decreased to 50.3% based on AUC and to 60.3% based on Cmax upon co-administration with rifampicin compared to administration of Nintedanib alone. If co-administered with Nintedanib, potent P-gp inhibitors (e.g. ketoconazole, erythromycin or cyclosporine) may increase exposure to Nintedanib. In such cases, patients should be monitored closely for tolerability of Nintedanib. Management of side effects may require interruption, dose reduction, or discontinuation of therapy with Nintedanib. Potent P-gp inducers (e.g. rifampicin, carbamazepine, phenytoin, and St. John’s Wort) may decrease exposure to Nintedanib. Selection of an alternate concomitant medicinal product with no or minimal P-gp induction potential should be considered.

Cytochrome (CYP)-enzymes: Only a minor extent of the biotransformation of Nintedanib consisted of CYP pathways. Nintedanib and its metabolites, the free acid moiety BIBF 1202 and its glucuronide BIBF 1202 glucuronide, did not inhibit or induce CYP enzymes in preclinical studies. The likelihood of drug-drug interactions with Nintedanib based on CYP metabolism is therefore considered to be low.

Co-administration with other medicinal products: The potential for interactions of Nintedanib with hormonal contraceptives was not explored.

Women of childbearing potential/Contraception: Nintedanib may cause foetalharm in humans. Women of childbearing potential should be advised to avoid becoming pregnant while receiving treatment with Nintedanib. They should be advised to use adequate contraception during and at least 3 months after the last dose of Nintedanib. Since the effect of Nintedanib on the metabolism and efficacy of hormonal contraceptives has not been investigated, barrier methods should be applied as a second form of contraception, to avoid pregnancy.

Pregnancy: There is no information on the use of Nintedanib in pregnant women, but pre-clinical studies in animals have shown reproductive toxicity of this active substance. As Nintedanib may cause foetal harm also in humans, it must not be used during pregnancy. Female patients should be advised to notify their doctor or pharmacist if they become pregnant during therapy with Nintedanib. If the patient becomes pregnant while receiving Nintedanib, she should be apprised of the potential hazard to the foetus. Termination of the treatment with Nintedanib should be considered.

Lactation: There is no information on the excretion of Nintedanib and its metabolites in human milk. Pre-clinical studies showed that small amounts of Nintedanib and its metabolites (≤ 0.5% of the administered dose) were secreted into milk of lactating rats. A risk to the newborns/infants cannot be excluded. Breast-feeding should be discontinued during treatment with Nintedanib.

Fertility: Based on preclinical investigations there is no evidence for impairment of male fertility. From subchronic and chronic toxicity studies, there is no evidence that female fertility in rats is impaired at a systemic exposure level comparable with that at the maximum recommended human dose (MRHD) of 150 mg twice daily.

Elderly patients (≥65 years): No overall differences in safety and efficacy were observed for elderly patients. No a-priori dose adjustment is required on the basis of a patient’s age. Patients ≥75 years may be more likely to require dose reduction to manage adverse effects.

Renal impairment: Less than 1% of a single dose of Nintedanib is excreted via the kidney. Adjustment of the starting dose in patients with mild to moderate renal impairment is not required. The safety, efficacy, and pharmacokinetics of Nintedanib have not been studied in patients with severe renal impairment (<30 ml/min creatinine clearance).

Hepatic impairment: Nintedanib is predominantly eliminated via biliary/faecal excretion (> 90%). Exposure increased in patients with hepatic impairment (Child Pugh A, Child Pugh B). In patients with mild hepatic impairment (Child Pugh A), the recommended dose of Nintedanib is 100 mg twice daily approximately 12 hours apart. In patients with mild hepatic impairment (Child Pugh A), treatment interruption or discontinuation for management of adverse reactions should be considered. The safety and efficacy of Nintedanib have not been investigated in patients with hepatic impairment classified as Child Pugh B and C. Treatment of patients with moderate (Child Pugh B) and severe (Child Pugh C) hepatic impairment with Nintedanib is not recommended.

Paediatric population: The safety and efficacy of Nintedanib in children aged 0-18 years have not been established. No data are available.

Store in a cool and dry place, protected from light. Do not store above 25°C.

Anti-viral drugs

Remdesivir is a preparation of Remdesivir. It is an adenosine nucleotide prodrug that distributes into cells where it is metabolized to form the pharmacologically active nucleoside triphosphate metabolite. Metabolism of Remdesivir to Remdesivir Triphosphate has been demonstrated in multiple cell types. Remdesivir Triphosphate act as an analogue of adenosine triphosphate (ATP) and competes with the natural ATP substrate for incorporation into nascent RNA chains by the SARS-CoV-2 RNA-dependent RNA polymerase, which results in delayed chain termination during replication of the viral RNA. Remdesivir triphosphate is a weak inhibitor of mammalian DNA and RNA polymerase with low potential for mitochondrial toxicity.

General Information-

• Adult and pediatric patients (>28 days and old) must have an eGFR determined and full-term neonates (≥7 days to ≤28 days old) must have serum creatinine determined before dosing of Remdesivir.
• Hepatic laboratory testing should be performed in all patients prior to starting Remdesivir and daily while receiving Remdesivir.
• Remdesivir should be administered via intravenous infusion only. Do not administer as intramuscular injection.

Adult Patients-

• The recommended dosage in adults requiring invasive mechanical ventilation and/or ECMO is a single loading dose of Remdesivir 200 mg on day 1 followed by once daily maintenance dose of Remdesivir 100 mg for 9 days.
• The recommended dose in adults not requiring invasive mechanical ventilation and/or ECMO is a single dose of Remdesivir 200 mg on day 1 followed by once daily maintenance dose of Remdesivir 100 mg for 4 days. If a patient dose not demonstrate clinical improvement, treatment may be extended for up to 5 additional days (i.e. up to a total of 10 days)
• Remdesivir is to be administered via intravenous infusion in a total volume of up to 250 ml 0.9% saline over 30 to 120 minutes.

Pediatric Patients-

• The recommended pediatric dose for pediatric patients weighing between 3.5 kg <40 kg should be calculated using the mg/kg dose according to the patient’s weight.
• For pediatric patients with body weight between 3.5 kg <40 kg use Remdesivir for injection 100 mg lyophilized powder only. Administer a body weight-based dosing regimen of one loading dose of Remdesivir 5 mg/kg IV (infused over 30 to 120 minutes) on day 1 followed by Remdesivir 2.5 mg/kg IV (infused over 30 to 120 minutes) once daily for 9 days (for pediatric patients requiring invasive mechanical ventilation and/or ECMO, days 2 through 5). If a patient dose not demonstrate clinical improvement, treatment may be extended for up to 5 additional days (i.e. up to a total of 10 days)
• For pediatric patients with body weight ≥40 kg requiring invasive mechanical ventilation and/or ECMO, the adult dosage regimen of one loading dose of Remdesivir 200 mg IV (infused over 30 to 120 minutes) on day 1 followed by Remdesivir 100 mg IV (infused over 30 to 120 minutes) once daily for 9 days will be administered.
• For pediatric patients with body weight ≥40 kg requiring invasive mechanical ventilation and/or ECMO, the adult dosage regimen of one loading dose of Remdesivir 200 mg IV (infused over 30 to 120 minutes) on day 1 followed by Remdesivir 100 mg IV (infused over 30 to 120 minutes) once daily for 4 days (days 2 through 5) will be administered. If a patient does not demonstrate clinical improvement, treatment may be extended for up to 5 additional days (i.e. up to a total of 10 days).

The prepared dilution should not be administered simultaneously with any other medication. The compatibility of Remdesivir injection with IV solutions and medications other than saline is not known. Please administered the diluted solution with the infusion rate described in the below table. Recommended Rate of Infusion- Diluted Remdesivir for Injection Lyophilized Powder in Adults and Pediatric Patients Weighing > 40 kg

Infusion bag 250 ml:

• Infusion Time: 30 min, Rate of Infusion: 8.33 ml/min
• Infusion Time: 60 min, Rate of Infusion: 4.17 ml/min
• Infusion Time: 120 min, Rate of Infusion: 2.08 ml/min

Infusion bag 100 ml:

• Infusion Time: 30 min, Rate of Infusion: 3.33 ml/min
• Infusion Time: 60 min, Rate of Infusion: 1.67 ml/min
• Infusion Time: 120 min, Rate of Infusion: 0.83 ml/min

An adverse reaction associated with Remdesivir in clinical trials in healthy adult subjects was increased liver transaminases.

Remdesivir is contraindicated in patients with known hypersensitivity to Remdesivir.

There are limited clinical data available for Remdesivir. Serious and unexpected adverse events may occur that have not been previously reported with Remdesivir use.

No adequate and well controlled studies of Remdesivir use in pregnant women have been conducted. Remdesivir should be used in pregnancy only if the potential benefit justifies the potential risk for the mother fetus. There is no information regarding the presence of Remdesivir in human milk, the effects on the breastfeed infants, or the effects on milk production. Because of the potential for viral transmission of SARS-CoV-2 negative infants and adverse reactions from the drug in breastfeeding infants, the development and health benefits of breastfeeding should be considered along with the mother's clinical need for Remdesivir and any potential adverse effects on the breastfed child from Remdesivir or from the underlying maternal condition.

Reconstitution instructions:

• Aseptically reconstitute Remdesivir lyophilized powder by addition of 19 ml of sterile water for injection using a suitably sized syringe and needle per vial.
• Discard the vial if a vacuum does not pull the sterile water for injection into the vial.
• Immediately shake the vial for 30 seconds.
• Allow the contents of the vial to settle for 2 to 3 minutes. A clear solution should result.
• If the content of the vial is not completely dissolved, shake the vial again for 30 seconds and allow the contents to settle for 2 to 3 minutes. Repeat this procedure as necessary until the contents of the vial are completely dissolved.
• Following reconstitution, each vial contains 100 mg/20 ml (5 mg/ml).
• Parenteral drug products should be inspected virtually for particulate matter and and discoloration prior to administration, whenever solution and container permit.

Please do not reuse or save unused Remdesivir Lyophilized powder, injection solution or diluted solution for infusion for further use. This product contains no preservatives.

Lyophilized Powder: Please store Remdesivir for injection, 100 mg, vials at temperature not exceeding 30°C in a dry place until required for use. Protect from light & moisture. Do not use after expiration date.

After reconstitution: vials can be stored up to 4 hours at room temperature (20°C-25°C) prior to administration or 24 hours at refrigerated temperature (2°C-8°C). Please dilute within the same day as administration.

Diluted Solution for Infusion: Please store diluted Remdesivir solution for infusion up to 4 hours at room temperature (20°C-25°C) or 24 hours at refrigerated temperature (2°C-8°C).

Specific combined vitamin preparations

This preparation contains 8 essential vitamins with Cod Liver Oil. This provides extra protection for the children. It ensures for getting enough vitamins for children that help them to be grown up strong & stay healthy. Cod Liver Oil contains Vitamin A, Vitamin D, EPA & DHA. Vitamin A is essential for the immune system, bone growth, night vision, cellular growth, testicular and ovarian function, Vitamin D is essential for the absorption and utilization of calcium, which is also required for skeletal growth. EPA and DHA; omega-3 fatty acids, which are converted in the body to produce prostaglandins that affect a wide variety of physiological processes due to their modulating effect on the action of hormones. Omega-3 fatty acids relieve the symptoms of osteoarthritis, rheumatoid arthritis which also enhances immune function and promotes healthy blood circulation. It is thought that EPA and DHA may reduce the risk of coronary heart disease. DHA seems essential for normal brain development in unborn babies.

1-12 Months: 2.5 ml (½ teaspoon) daily
1-4 Years: 5 ml (1 teaspoon) daily
4 years up: 7.5 ml (1½ teaspoon) daily
Adult: 10 ml (2 teaspoons) daily.

This syrup can be taken with water or milk.

Generally well tolerated. However, a few allergic reactions may be seen.

This product is contraindicated in patients with a known hypersensitivity to any of the ingredients.

This medicine may accumulate in the body. So, should not be taken in overdose.

Some drug interaction may occur with- Erythromycin, Conjugated estrogens, Sodium bicarbonate, Chloramphenicol etc.

Should be taken on physician's advice.

Keep in cool and dry place and away from light. Keep away from children

Vitamin B1, B6 & B12 is indicated for the treatment of vitamin B1, B6 & B12 deficiency syndrome. It is also indicated for the supportive treatment of neuritis & non-inflammatory diseases of the nerves, e.g.- Diabetic neuropathy, Peripheral neuralgin, Lumbago, Myalgia, Optic neuritis, Sciatica, Facial neuralgia, Intercostal neuralgia, Spinal pain.

Specific combined vitamin preparations

Vitamin B1 converts carbohydrates, fatty acids and amino acids into energy, promotes healthy nerves, improves mood, strengthens the heart. Vitamin B6 forms RBCs, helps cells to make proteins, manufactures neurotransmitters e.g. serotonin and releases stored forms of energy, helps to prevent CVS diseases and stroke, helps to lift depression and eases insomnia. Vitamin B12 is essential for cell replication and important for RBC production, prevents anemia, helps to prevent depression, reduces nerve pain, numbness, tingling and lowers the risk of heart diseases.

The vitamin ingredients are absorbed well in per oral reception. It is widely distributed to most tissues and appears in breast milk. Within the cell, thiamine is mostly present as diphosphate. Thiamine is not stored to any appreciable extent in the body and amounts in excess of the body’s requirements are excreted in the urine as unchanged thiamine or as metabolites. Pyridoxine, pyridoxal and pyridoxamine are readily absorbed from the GIT following oral administration and are converted to the active forms of pyridoxal phosphate an pyridoxamine phosphate. They are stored mainly in liver where there is oxidation to 4-pyridoxic acid and other inactive metabolites, which are excreted in urine. As the dose increases, proportionally greater amounts are excreted unchanged in the urine.

Tablet: 1-3 Tablets per day or as advised by the physician.

Injection:

• In severe (acute) cases: 1 injection daily until the acute symptoms subside or taken as advised by the physician.
• In mild cases: 1 injection 2-3 times per week. Ampoules are preferably injected intramuscularly.

Use in children: There is no information on the use of this drug in children.

Generally well tolerated but allergic reactions may be observed in few cases.

Vitamin B1, Vitamin B6 and Vitamin B12 is contraindicated in patients on levodopa therapy, and in patients with hypersensitivity to any of the ingredients of the preparation.

Cyanocobalamin should not be given in patients with subacute degeneration of the spinal cord. Cyanocobalamin is not suitable form of vitamin B12 for the treatment of optic neuropathies associated with raised plasma concentrations of cyanocobalamin.

No drug interaction has been reported yet.

Oral tablet form is recommended but due to the presence of benzyl alcohol, injection is not recommended during pregnancy & lactation.

No overdosage symptoms are to be expected in the recommended dosage. If there is known overdose then treatment is symptomatic & supportive.

Keep out of reach of children. Store in a cool (below 25°C temperature) and dry place, protected from light.

Nitrofurantoin is specifically indicated for the treatment & prophylaxis of urinary tract infections caused by susceptible strains of Escherichia coli, Enterococci, Staphylococcus aureus, Staphylococcus saprophyticus and certain susceptible strains of Klebsiella and Enterobacter species.

Systemic Urinary Anti- infective

Nitrofurantoin is an antibacterial agent specific for urinary tract infections. Nitrofurantoin is highly soluble in urine, to which it may impart a brown color. Nitrofurantoin inactivates or alters bacterial ribosomal proteins and other macromolecules. Nitrofurantoin has been shown to be active against the following bacteria: Gram-Positive Aerobes Staphylococcus saprophyticus, Coagulase-negative staphylococci (including Staphylococcus epidermidis), Enterococcus faecalis, Staphylococcus aureus, Streptococcus agalactiae, Group D streptococci, Viridans group streptococci. Gram-Negative Aerobes- Escherichia coli, Citrobacter amalonaticus, Citrobacter diversus, Citrobacter freundii, Klebsiella oxytoca, Klebsiella ozaenae.

Nitrofurantoin tablet (In adults):

• Uncomplicated urinary tract infections: 50-100 mg four times a day- the lower dosage level is recommended. Therapy should be continued for one week or for at least 3 days after sterility of the urine is obtained.
• For long-term suppressive therapy: In adults, a reduction of dosage to 50-100 mg at bedtime may be adequate.

Nitrofurantoin capsule (In adults):

• Acute Uncomplicated Urinary Tract Infections (UTIs): 50 mg four times daily for 7 days.
• Long term suppression: 50-100 mg once a day.
• Prophylaxis: 50 mg four times daily for the duration of procedure and for three days thereafter.

Nitrofurantoin SR capsule:

• Adults and Children over 12 years: One 100 mg capsule every 12 hours for seven days.
• Genito-urinary surgical prophylaxis: One capsule twice daily on day of procedure and for next 3 days.

Nitrofurantoin suspension: Children: 5-7 mg/kg/day in four divided doses (contraindicated under one month of age). The average dose of Nintoin suspension for pediatric patients are as follows-

• 7 to 11 kg: ½ (2.5 ml) teaspoonfuls 4 times daily.
• 12 to 21 kg: 1 (5 ml) teaspoonfuls 4 times daily.
• 22 to 30 kg: 1½ (7.5 ml) teaspoonfuls 4 times daily.
• 31 to 41 kg: 2 (10 ml) teaspoonfuls 4 times daily.

Therapy should be continued for one week or for at least 3 days after sterility of the urine is obtained. For long-term suppressive therapy in children, doses as low as 1 mg/kg per 24 hours, given in a single dose or in two divided doses, may be adequate.

Nitrofurantoin should be taken with food.

The most frequent clinical adverse events are nausea, headache, and flatulence. Other less occurred adverse events are diarrhea, dyspepsia, abdominal pain, constipation, emesis, dizziness and drowsiness.

Anuria, oliguria or significant impairment of renal function are contraindications. This drug is contraindicated in pregnant patients at 38-42 weeks, during labor and delivery. Nitrofurantoin is also contraindicated in those patients with known hypersensitivity to Nitrofurantoin.

If acute, sub-acute or chronic pulmonary reactions occur, Nitrofurantoin should be discontinued. Antacid preparations containing magnesium trisilicate should not be taken while taking Nitrofurantoin.

Antacids containing Magnesium Trisilicate, when administered concomitantly with Nitrofurantoin, reduce both the rate and extent of absorption of Uricosuric drugs, such as Probenecid and Sulfinpyrazone, can inhibit renal tubular secretion of Nitrofurantoin.

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. Nitrofurantoin has been detected in human breast milk in trace amounts. Because of the potential for serious adverse reactions from Nitrofurantoin in nursing infants under one month of age, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

Occasional incidents of acute overdosage of Nitrofurantoin have not resulted in any specific symptoms other than vomiting. Induction of emesis is recommended.

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

Nitrofurantoin is specifically indicated for the treatment & prophylaxis of urinary tract infections caused by susceptible strains of Escherichia coli, Enterococci, Staphylococcus aureus, Staphylococcus saprophyticus and certain susceptible strains of Klebsiella and Enterobacter species.

Systemic Urinary Anti- infective

Nitrofurantoin is an antibacterial agent specific for urinary tract infections. Nitrofurantoin is highly soluble in urine, to which it may impart a brown color. Nitrofurantoin inactivates or alters bacterial ribosomal proteins and other macromolecules. Nitrofurantoin has been shown to be active against the following bacteria: Gram-Positive Aerobes Staphylococcus saprophyticus, Coagulase-negative staphylococci (including Staphylococcus epidermidis), Enterococcus faecalis, Staphylococcus aureus, Streptococcus agalactiae, Group D streptococci, Viridans group streptococci. Gram-Negative Aerobes- Escherichia coli, Citrobacter amalonaticus, Citrobacter diversus, Citrobacter freundii, Klebsiella oxytoca, Klebsiella ozaenae.

Nitrofurantoin tablet (In adults):

• Uncomplicated urinary tract infections: 50-100 mg four times a day- the lower dosage level is recommended. Therapy should be continued for one week or for at least 3 days after sterility of the urine is obtained.
• For long-term suppressive therapy: In adults, a reduction of dosage to 50-100 mg at bedtime may be adequate.

Nitrofurantoin capsule (In adults):

• Acute Uncomplicated Urinary Tract Infections (UTIs): 50 mg four times daily for 7 days.
• Long term suppression: 50-100 mg once a day.
• Prophylaxis: 50 mg four times daily for the duration of procedure and for three days thereafter.

Nitrofurantoin SR capsule:

• Adults and Children over 12 years: One 100 mg capsule every 12 hours for seven days.
• Genito-urinary surgical prophylaxis: One capsule twice daily on day of procedure and for next 3 days.

Nitrofurantoin suspension: Children: 5-7 mg/kg/day in four divided doses (contraindicated under one month of age). The average dose of Nintoin suspension for pediatric patients are as follows-

• 7 to 11 kg: ½ (2.5 ml) teaspoonfuls 4 times daily.
• 12 to 21 kg: 1 (5 ml) teaspoonfuls 4 times daily.
• 22 to 30 kg: 1½ (7.5 ml) teaspoonfuls 4 times daily.
• 31 to 41 kg: 2 (10 ml) teaspoonfuls 4 times daily.

Therapy should be continued for one week or for at least 3 days after sterility of the urine is obtained. For long-term suppressive therapy in children, doses as low as 1 mg/kg per 24 hours, given in a single dose or in two divided doses, may be adequate.

Nitrofurantoin should be taken with food.

The most frequent clinical adverse events are nausea, headache, and flatulence. Other less occurred adverse events are diarrhea, dyspepsia, abdominal pain, constipation, emesis, dizziness and drowsiness.

Anuria, oliguria or significant impairment of renal function are contraindications. This drug is contraindicated in pregnant patients at 38-42 weeks, during labor and delivery. Nitrofurantoin is also contraindicated in those patients with known hypersensitivity to Nitrofurantoin.

If acute, sub-acute or chronic pulmonary reactions occur, Nitrofurantoin should be discontinued. Antacid preparations containing magnesium trisilicate should not be taken while taking Nitrofurantoin.

Antacids containing Magnesium Trisilicate, when administered concomitantly with Nitrofurantoin, reduce both the rate and extent of absorption of Uricosuric drugs, such as Probenecid and Sulfinpyrazone, can inhibit renal tubular secretion of Nitrofurantoin.

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. Nitrofurantoin has been detected in human breast milk in trace amounts. Because of the potential for serious adverse reactions from Nitrofurantoin in nursing infants under one month of age, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

Occasional incidents of acute overdosage of Nitrofurantoin have not resulted in any specific symptoms other than vomiting. Induction of emesis is recommended.

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

Nitrofurantoin is specifically indicated for the treatment & prophylaxis of urinary tract infections caused by susceptible strains of Escherichia coli, Enterococci, Staphylococcus aureus, Staphylococcus saprophyticus and certain susceptible strains of Klebsiella and Enterobacter species.

Systemic Urinary Anti- infective

Nitrofurantoin is an antibacterial agent specific for urinary tract infections. Nitrofurantoin is highly soluble in urine, to which it may impart a brown color. Nitrofurantoin inactivates or alters bacterial ribosomal proteins and other macromolecules. Nitrofurantoin has been shown to be active against the following bacteria: Gram-Positive Aerobes Staphylococcus saprophyticus, Coagulase-negative staphylococci (including Staphylococcus epidermidis), Enterococcus faecalis, Staphylococcus aureus, Streptococcus agalactiae, Group D streptococci, Viridans group streptococci. Gram-Negative Aerobes- Escherichia coli, Citrobacter amalonaticus, Citrobacter diversus, Citrobacter freundii, Klebsiella oxytoca, Klebsiella ozaenae.

Nitrofurantoin tablet (In adults):

• Uncomplicated urinary tract infections: 50-100 mg four times a day- the lower dosage level is recommended. Therapy should be continued for one week or for at least 3 days after sterility of the urine is obtained.
• For long-term suppressive therapy: In adults, a reduction of dosage to 50-100 mg at bedtime may be adequate.

Nitrofurantoin capsule (In adults):

• Acute Uncomplicated Urinary Tract Infections (UTIs): 50 mg four times daily for 7 days.
• Long term suppression: 50-100 mg once a day.
• Prophylaxis: 50 mg four times daily for the duration of procedure and for three days thereafter.

Nitrofurantoin SR capsule:

• Adults and Children over 12 years: One 100 mg capsule every 12 hours for seven days.
• Genito-urinary surgical prophylaxis: One capsule twice daily on day of procedure and for next 3 days.

Nitrofurantoin suspension: Children: 5-7 mg/kg/day in four divided doses (contraindicated under one month of age). The average dose of Nintoin suspension for pediatric patients are as follows-

• 7 to 11 kg: ½ (2.5 ml) teaspoonfuls 4 times daily.
• 12 to 21 kg: 1 (5 ml) teaspoonfuls 4 times daily.
• 22 to 30 kg: 1½ (7.5 ml) teaspoonfuls 4 times daily.
• 31 to 41 kg: 2 (10 ml) teaspoonfuls 4 times daily.

Therapy should be continued for one week or for at least 3 days after sterility of the urine is obtained. For long-term suppressive therapy in children, doses as low as 1 mg/kg per 24 hours, given in a single dose or in two divided doses, may be adequate.

Nitrofurantoin should be taken with food.

The most frequent clinical adverse events are nausea, headache, and flatulence. Other less occurred adverse events are diarrhea, dyspepsia, abdominal pain, constipation, emesis, dizziness and drowsiness.

Anuria, oliguria or significant impairment of renal function are contraindications. This drug is contraindicated in pregnant patients at 38-42 weeks, during labor and delivery. Nitrofurantoin is also contraindicated in those patients with known hypersensitivity to Nitrofurantoin.

If acute, sub-acute or chronic pulmonary reactions occur, Nitrofurantoin should be discontinued. Antacid preparations containing magnesium trisilicate should not be taken while taking Nitrofurantoin.

Antacids containing Magnesium Trisilicate, when administered concomitantly with Nitrofurantoin, reduce both the rate and extent of absorption of Uricosuric drugs, such as Probenecid and Sulfinpyrazone, can inhibit renal tubular secretion of Nitrofurantoin.

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. Nitrofurantoin has been detected in human breast milk in trace amounts. Because of the potential for serious adverse reactions from Nitrofurantoin in nursing infants under one month of age, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

Occasional incidents of acute overdosage of Nitrofurantoin have not resulted in any specific symptoms other than vomiting. Induction of emesis is recommended.

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

Nitrofurantoin is specifically indicated for the treatment & prophylaxis of urinary tract infections caused by susceptible strains of Escherichia coli, Enterococci, Staphylococcus aureus, Staphylococcus saprophyticus and certain susceptible strains of Klebsiella and Enterobacter species.

Systemic Urinary Anti- infective

Nitrofurantoin is an antibacterial agent specific for urinary tract infections. Nitrofurantoin is highly soluble in urine, to which it may impart a brown color. Nitrofurantoin inactivates or alters bacterial ribosomal proteins and other macromolecules. Nitrofurantoin has been shown to be active against the following bacteria: Gram-Positive Aerobes Staphylococcus saprophyticus, Coagulase-negative staphylococci (including Staphylococcus epidermidis), Enterococcus faecalis, Staphylococcus aureus, Streptococcus agalactiae, Group D streptococci, Viridans group streptococci. Gram-Negative Aerobes- Escherichia coli, Citrobacter amalonaticus, Citrobacter diversus, Citrobacter freundii, Klebsiella oxytoca, Klebsiella ozaenae.

Nitrofurantoin tablet (In adults):

• Uncomplicated urinary tract infections: 50-100 mg four times a day- the lower dosage level is recommended. Therapy should be continued for one week or for at least 3 days after sterility of the urine is obtained.
• For long-term suppressive therapy: In adults, a reduction of dosage to 50-100 mg at bedtime may be adequate.

Nitrofurantoin capsule (In adults):

• Acute Uncomplicated Urinary Tract Infections (UTIs): 50 mg four times daily for 7 days.
• Long term suppression: 50-100 mg once a day.
• Prophylaxis: 50 mg four times daily for the duration of procedure and for three days thereafter.

Nitrofurantoin SR capsule:

• Adults and Children over 12 years: One 100 mg capsule every 12 hours for seven days.
• Genito-urinary surgical prophylaxis: One capsule twice daily on day of procedure and for next 3 days.

Nitrofurantoin suspension: Children: 5-7 mg/kg/day in four divided doses (contraindicated under one month of age). The average dose of Nintoin suspension for pediatric patients are as follows-

• 7 to 11 kg: ½ (2.5 ml) teaspoonfuls 4 times daily.
• 12 to 21 kg: 1 (5 ml) teaspoonfuls 4 times daily.
• 22 to 30 kg: 1½ (7.5 ml) teaspoonfuls 4 times daily.
• 31 to 41 kg: 2 (10 ml) teaspoonfuls 4 times daily.

Therapy should be continued for one week or for at least 3 days after sterility of the urine is obtained. For long-term suppressive therapy in children, doses as low as 1 mg/kg per 24 hours, given in a single dose or in two divided doses, may be adequate.

Nitrofurantoin should be taken with food.

The most frequent clinical adverse events are nausea, headache, and flatulence. Other less occurred adverse events are diarrhea, dyspepsia, abdominal pain, constipation, emesis, dizziness and drowsiness.

Anuria, oliguria or significant impairment of renal function are contraindications. This drug is contraindicated in pregnant patients at 38-42 weeks, during labor and delivery. Nitrofurantoin is also contraindicated in those patients with known hypersensitivity to Nitrofurantoin.

If acute, sub-acute or chronic pulmonary reactions occur, Nitrofurantoin should be discontinued. Antacid preparations containing magnesium trisilicate should not be taken while taking Nitrofurantoin.

Antacids containing Magnesium Trisilicate, when administered concomitantly with Nitrofurantoin, reduce both the rate and extent of absorption of Uricosuric drugs, such as Probenecid and Sulfinpyrazone, can inhibit renal tubular secretion of Nitrofurantoin.

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. Nitrofurantoin has been detected in human breast milk in trace amounts. Because of the potential for serious adverse reactions from Nitrofurantoin in nursing infants under one month of age, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

Occasional incidents of acute overdosage of Nitrofurantoin have not resulted in any specific symptoms other than vomiting. Induction of emesis is recommended.

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

Specific combined vitamin preparations

Vitamin-B complex contains the most important members of the vitamin B group in pure form and in therapeutically balanced proportions. The members of the vitamin B group contained in Vitamin-B complex are components of enzyme systems that regulate various stages of carbohydrate, fat and protein metabolism, each of the components playing a specific biological role. Deficiency of B vitamin causes glossitis, stomatitis, cheilosis, polyneuritis, beriberi, pellagra and vascularisation of cornea.

Tablet/ capsule: usual recommended dose is 1-2 tablet/capsule 3 times daily or as directed by the physician.

Syrup: 2-3 teaspoonful daily or as directed by the physician.

Injection: It is for intramuscular and intravenous administration. Usual recommended dose is 2 ml daily or as directed by the physician. In addition with Thiamine, Riboflavin, Nicotinamide, Pyridoxine; injectable dosage from contains D-Panthenol 5 mg.

Adverse reactions have been reported with specific vitamins and minerals, but generally at levels substantially higher than those in Vitamin-B complex. However, allergic and idiosyncratic reactions are possible at lower levels. Iron, even at the usual recommended level has been associated with gastrointestinal intolerance in some patients.

Vitamin-B complex is contraindicated in patients hypersensitive to any of its components.

As little as 5 mg pyridoxine daily can decrease the efficacy of levodopa in the treatment of parkinsonism. Therefore, Vitamin-B complex is not recommended for patients undergoing such therapy

It is safe to use Vitamin-B complex in pregnancy and lactation.

Multi-vitamin & Multi-mineral combined preparations, Specific mineral & vitamin combined preparations

Vitamins and minerals are essential for normal metabolic functions including hematopoiesis. The members of vitamin B-group are components of enzyme system that regulate various stages of carbohydrate, fat and protein metabolism, each of the components playing a specific biological role. Vitamin C is involved in tissue repair and collagen formation. Vitamin A plays an essential role in the function of retina and is essential for growth and differentiation of epithelial tissue. Vitamin E is an antioxidant which preserves essential cellular constituents. Vitamin D is supplemented for prevention and cure of nutritional and metabolic rickets and for treatment of hypoparathyroidism. Iron, Copper, Manganese, Zinc serve as catalysts in enzyme systems which perform vital cellular functions.

Orally one tablet daily for adult and children over 5 years of age or as directed by the physicians.

Side effects have been reported with specific vitamins & minerals, but at level substantially higher than those in this tablet. Iron has been associated with gastrointestinal intolerance in some patients.

This is contraindicated in patients hypersensitive to any of its components. This is not intended for treatment of severe specific deficiencies of vitamins or minerals. It is not recommended for patients undergoing treatment with levodopa as pyridoxine decreases the efficacy of levodopa. During the first trimester of pregnancy, larger doses of vitamin A (more than 10 tablets per day) may be teratogenic.

Not intended for treatment of pernicious anemia or other megaloblastic anemia where vitamin B12 is deficient.

During the first trimester of pregnancy, recommended daily dose should not be exceeded. Because larger doses of Vitamin-A (multiple tablets per day) may be teratogenic.

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

Drugs for Haemolytic Hypoplastic & Renal Anemia

Treatment of anemia in chronic renal failure: Erythropoietin is administered to maintain hemoglobin concentration between 11 to 12 g/dl and hematocrit of 33-36 % in adults.

Starting dose:

• Adult: Usually 50 to 100 lU/kg three times in a week (TIW) by IV or Subcutaneous route.
• Pediatric: 50 lU/kg TIW by IV or Subcutaneous route.

Dose adjustment: Dose should be increased if hematocrit doses not increase by 5 to 6 points after 8 weeks therapy, and hematocrit is below suggested target range. Dose should be reduced when hematocrit approaches 36% or hematocrit increases >4 points in any 2-week period.

Maintenance dose: Maintenance dose must be individualized for each patient. In patients undergoing dialysis, the median maintenance dose is 75 lU/kg TIW, with a range from 12.5 to 525 lU/kg TIW as directed by the physician. In CRF patients not on dialysis, maintenance dose is 75 to 150 lU/kg/week.

Treatment of Anemia in Cancer Patients on Chemotherapy:

Starting dose:

• Adult: 150 lU/kg TIW by Subcutaneous route or 40,000 IU Subcutaneous route weekly.
• Pediatric: 25 to 300 lU/kg 3 to 7 times per week by Subcutaneous or IV route.

Dose adjustment: If the response is not satisfactory, the dose should be increased to 300 lU/kg TIW. If the hematocrit exceeds 40%, the dose should be withheld until the hematocrit falls to 36%.The dose should be reduced to 25% when treatment is resumed and titrated to maintain the desired hematocrit.

Surgery Patients: The recommended dose is 300 lU/kg/day subcutaneously for 10 days before surgery, on the day of surgery, and for 4 days after surgery. An alternate dose schedule is 600 lU/kg subcutaneously in once weekly dose (21, 14, and 7 days before surgery) plus a fourth dose on the day of surgery.

Zidovudine-treated HIV-infected Patients:
Starting dose

• Adult: 100 lU/kg as an IV or Subcutaneous injection TIW for 8 weeks.
• Pediatric: 50 to 400 lU/kg 2 to 3 times per week by Subcutaneous or IV route.

Dose adjustment: If the response is not satisfactory, the dose should be increased by 50-1001U/kg TIW. Response should be evaluated every 4 to 8 weeks thereafter and the dose adjusted accordingly by 50 to 100 lU/kg increments TIW.

Maintenance dose: The dose is titrated to maintain the hematocrit between 33-36%.

General: Headache, dizziness, fever, malaise, arthralgia and occasionally hyperkalemia. Cardiovascular: Hypertension is the most common side effect, palpitations. Gastrointestinal: Nausea, vomiting, anorexia and diarrhea may occur occasionally. Allergic reactions.

Erythropoietin is contraindicated in patients with:

• Uncontrolled hypertension
• Known hypersensitivity to mammalian cell-derived products
• A history of hypersensitivity to Erythropoietin or any component of the preparation.

Erythropoietin should be used with caution in those patients with controlled hypertension, ischaemic vascular disease, history of seizures, or suspected allergy to the product.

Iron evaluation: Prior to and during Erythropoietin therapy, the patient's iron stores, including transferrin saturation and serum ferritin, should be evaluated. Transferrin saturation should be at least 20%, and ferritin should be at least 100 ng/ml. Virtually all patients will require supplemental Iron to increase or maintain transferrin saturation to levels that will adequately support erythropoiesis.

Pregnancy Category C. Since there are no controlled studies of erythropoietin in pregnant women, and because animal reproduction studies are not always predictive of human responses, erythropoietin should be used during pregnancy only if clearly needed. It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when erythropoietin is administered to a nursing woman.

Doses of up to 1500 lU/kg TIW for 3 to 4 weeks have been administered to adults without any direct toxic effects. If the suggested target range is exceeded, drug therapy may be temporarily withheld until the hemoglobin returns to the suggested target range. If polycythemia is of concern, phlebotomy may be indicated to decrease the hemoglobin.

Erythropoietin should be stored at 2°C to 8°C. Protect from light. Do not freeze & avoid shaking.

Drugs for Haemolytic Hypoplastic & Renal Anemia

Treatment of anemia in chronic renal failure: Erythropoietin is administered to maintain hemoglobin concentration between 11 to 12 g/dl and hematocrit of 33-36 % in adults.

Starting dose:

• Adult: Usually 50 to 100 lU/kg three times in a week (TIW) by IV or Subcutaneous route.
• Pediatric: 50 lU/kg TIW by IV or Subcutaneous route.

Dose adjustment: Dose should be increased if hematocrit doses not increase by 5 to 6 points after 8 weeks therapy, and hematocrit is below suggested target range. Dose should be reduced when hematocrit approaches 36% or hematocrit increases >4 points in any 2-week period.

Maintenance dose: Maintenance dose must be individualized for each patient. In patients undergoing dialysis, the median maintenance dose is 75 lU/kg TIW, with a range from 12.5 to 525 lU/kg TIW as directed by the physician. In CRF patients not on dialysis, maintenance dose is 75 to 150 lU/kg/week.

Treatment of Anemia in Cancer Patients on Chemotherapy:

Starting dose:

• Adult: 150 lU/kg TIW by Subcutaneous route or 40,000 IU Subcutaneous route weekly.
• Pediatric: 25 to 300 lU/kg 3 to 7 times per week by Subcutaneous or IV route.

Dose adjustment: If the response is not satisfactory, the dose should be increased to 300 lU/kg TIW. If the hematocrit exceeds 40%, the dose should be withheld until the hematocrit falls to 36%.The dose should be reduced to 25% when treatment is resumed and titrated to maintain the desired hematocrit.

Surgery Patients: The recommended dose is 300 lU/kg/day subcutaneously for 10 days before surgery, on the day of surgery, and for 4 days after surgery. An alternate dose schedule is 600 lU/kg subcutaneously in once weekly dose (21, 14, and 7 days before surgery) plus a fourth dose on the day of surgery.

Zidovudine-treated HIV-infected Patients:
Starting dose

• Adult: 100 lU/kg as an IV or Subcutaneous injection TIW for 8 weeks.
• Pediatric: 50 to 400 lU/kg 2 to 3 times per week by Subcutaneous or IV route.

Dose adjustment: If the response is not satisfactory, the dose should be increased by 50-1001U/kg TIW. Response should be evaluated every 4 to 8 weeks thereafter and the dose adjusted accordingly by 50 to 100 lU/kg increments TIW.

Maintenance dose: The dose is titrated to maintain the hematocrit between 33-36%.

General: Headache, dizziness, fever, malaise, arthralgia and occasionally hyperkalemia. Cardiovascular: Hypertension is the most common side effect, palpitations. Gastrointestinal: Nausea, vomiting, anorexia and diarrhea may occur occasionally. Allergic reactions.

Erythropoietin is contraindicated in patients with:

• Uncontrolled hypertension
• Known hypersensitivity to mammalian cell-derived products
• A history of hypersensitivity to Erythropoietin or any component of the preparation.

Erythropoietin should be used with caution in those patients with controlled hypertension, ischaemic vascular disease, history of seizures, or suspected allergy to the product.

Iron evaluation: Prior to and during Erythropoietin therapy, the patient's iron stores, including transferrin saturation and serum ferritin, should be evaluated. Transferrin saturation should be at least 20%, and ferritin should be at least 100 ng/ml. Virtually all patients will require supplemental Iron to increase or maintain transferrin saturation to levels that will adequately support erythropoiesis.

Pregnancy Category C. Since there are no controlled studies of erythropoietin in pregnant women, and because animal reproduction studies are not always predictive of human responses, erythropoietin should be used during pregnancy only if clearly needed. It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when erythropoietin is administered to a nursing woman.

Doses of up to 1500 lU/kg TIW for 3 to 4 weeks have been administered to adults without any direct toxic effects. If the suggested target range is exceeded, drug therapy may be temporarily withheld until the hemoglobin returns to the suggested target range. If polycythemia is of concern, phlebotomy may be indicated to decrease the hemoglobin.

Erythropoietin should be stored at 2°C to 8°C. Protect from light. Do not freeze & avoid shaking.

Drugs for Haemolytic Hypoplastic & Renal Anemia

Treatment of anemia in chronic renal failure: Erythropoietin is administered to maintain hemoglobin concentration between 11 to 12 g/dl and hematocrit of 33-36 % in adults.

Starting dose:

• Adult: Usually 50 to 100 lU/kg three times in a week (TIW) by IV or Subcutaneous route.
• Pediatric: 50 lU/kg TIW by IV or Subcutaneous route.

Dose adjustment: Dose should be increased if hematocrit doses not increase by 5 to 6 points after 8 weeks therapy, and hematocrit is below suggested target range. Dose should be reduced when hematocrit approaches 36% or hematocrit increases >4 points in any 2-week period.

Maintenance dose: Maintenance dose must be individualized for each patient. In patients undergoing dialysis, the median maintenance dose is 75 lU/kg TIW, with a range from 12.5 to 525 lU/kg TIW as directed by the physician. In CRF patients not on dialysis, maintenance dose is 75 to 150 lU/kg/week.

Treatment of Anemia in Cancer Patients on Chemotherapy:

Starting dose:

• Adult: 150 lU/kg TIW by Subcutaneous route or 40,000 IU Subcutaneous route weekly.
• Pediatric: 25 to 300 lU/kg 3 to 7 times per week by Subcutaneous or IV route.

Dose adjustment: If the response is not satisfactory, the dose should be increased to 300 lU/kg TIW. If the hematocrit exceeds 40%, the dose should be withheld until the hematocrit falls to 36%.The dose should be reduced to 25% when treatment is resumed and titrated to maintain the desired hematocrit.

Surgery Patients: The recommended dose is 300 lU/kg/day subcutaneously for 10 days before surgery, on the day of surgery, and for 4 days after surgery. An alternate dose schedule is 600 lU/kg subcutaneously in once weekly dose (21, 14, and 7 days before surgery) plus a fourth dose on the day of surgery.

Zidovudine-treated HIV-infected Patients:
Starting dose

• Adult: 100 lU/kg as an IV or Subcutaneous injection TIW for 8 weeks.
• Pediatric: 50 to 400 lU/kg 2 to 3 times per week by Subcutaneous or IV route.

Dose adjustment: If the response is not satisfactory, the dose should be increased by 50-1001U/kg TIW. Response should be evaluated every 4 to 8 weeks thereafter and the dose adjusted accordingly by 50 to 100 lU/kg increments TIW.

Maintenance dose: The dose is titrated to maintain the hematocrit between 33-36%.

General: Headache, dizziness, fever, malaise, arthralgia and occasionally hyperkalemia. Cardiovascular: Hypertension is the most common side effect, palpitations. Gastrointestinal: Nausea, vomiting, anorexia and diarrhea may occur occasionally. Allergic reactions.

Erythropoietin is contraindicated in patients with:

• Uncontrolled hypertension
• Known hypersensitivity to mammalian cell-derived products
• A history of hypersensitivity to Erythropoietin or any component of the preparation.

Erythropoietin should be used with caution in those patients with controlled hypertension, ischaemic vascular disease, history of seizures, or suspected allergy to the product.

Iron evaluation: Prior to and during Erythropoietin therapy, the patient's iron stores, including transferrin saturation and serum ferritin, should be evaluated. Transferrin saturation should be at least 20%, and ferritin should be at least 100 ng/ml. Virtually all patients will require supplemental Iron to increase or maintain transferrin saturation to levels that will adequately support erythropoiesis.

Pregnancy Category C. Since there are no controlled studies of erythropoietin in pregnant women, and because animal reproduction studies are not always predictive of human responses, erythropoietin should be used during pregnancy only if clearly needed. It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when erythropoietin is administered to a nursing woman.

Doses of up to 1500 lU/kg TIW for 3 to 4 weeks have been administered to adults without any direct toxic effects. If the suggested target range is exceeded, drug therapy may be temporarily withheld until the hemoglobin returns to the suggested target range. If polycythemia is of concern, phlebotomy may be indicated to decrease the hemoglobin.

Erythropoietin should be stored at 2°C to 8°C. Protect from light. Do not freeze & avoid shaking.

Drugs for Haemolytic Hypoplastic & Renal Anemia

Treatment of anemia in chronic renal failure: Erythropoietin is administered to maintain hemoglobin concentration between 11 to 12 g/dl and hematocrit of 33-36 % in adults.

Starting dose:

• Adult: Usually 50 to 100 lU/kg three times in a week (TIW) by IV or Subcutaneous route.
• Pediatric: 50 lU/kg TIW by IV or Subcutaneous route.

Dose adjustment: Dose should be increased if hematocrit doses not increase by 5 to 6 points after 8 weeks therapy, and hematocrit is below suggested target range. Dose should be reduced when hematocrit approaches 36% or hematocrit increases >4 points in any 2-week period.

Maintenance dose: Maintenance dose must be individualized for each patient. In patients undergoing dialysis, the median maintenance dose is 75 lU/kg TIW, with a range from 12.5 to 525 lU/kg TIW as directed by the physician. In CRF patients not on dialysis, maintenance dose is 75 to 150 lU/kg/week.

Treatment of Anemia in Cancer Patients on Chemotherapy:

Starting dose:

• Adult: 150 lU/kg TIW by Subcutaneous route or 40,000 IU Subcutaneous route weekly.
• Pediatric: 25 to 300 lU/kg 3 to 7 times per week by Subcutaneous or IV route.

Dose adjustment: If the response is not satisfactory, the dose should be increased to 300 lU/kg TIW. If the hematocrit exceeds 40%, the dose should be withheld until the hematocrit falls to 36%.The dose should be reduced to 25% when treatment is resumed and titrated to maintain the desired hematocrit.

Surgery Patients: The recommended dose is 300 lU/kg/day subcutaneously for 10 days before surgery, on the day of surgery, and for 4 days after surgery. An alternate dose schedule is 600 lU/kg subcutaneously in once weekly dose (21, 14, and 7 days before surgery) plus a fourth dose on the day of surgery.

Zidovudine-treated HIV-infected Patients:
Starting dose

• Adult: 100 lU/kg as an IV or Subcutaneous injection TIW for 8 weeks.
• Pediatric: 50 to 400 lU/kg 2 to 3 times per week by Subcutaneous or IV route.

Dose adjustment: If the response is not satisfactory, the dose should be increased by 50-1001U/kg TIW. Response should be evaluated every 4 to 8 weeks thereafter and the dose adjusted accordingly by 50 to 100 lU/kg increments TIW.

Maintenance dose: The dose is titrated to maintain the hematocrit between 33-36%.

General: Headache, dizziness, fever, malaise, arthralgia and occasionally hyperkalemia. Cardiovascular: Hypertension is the most common side effect, palpitations. Gastrointestinal: Nausea, vomiting, anorexia and diarrhea may occur occasionally. Allergic reactions.

Erythropoietin is contraindicated in patients with:

• Uncontrolled hypertension
• Known hypersensitivity to mammalian cell-derived products
• A history of hypersensitivity to Erythropoietin or any component of the preparation.

Erythropoietin should be used with caution in those patients with controlled hypertension, ischaemic vascular disease, history of seizures, or suspected allergy to the product.

Iron evaluation: Prior to and during Erythropoietin therapy, the patient's iron stores, including transferrin saturation and serum ferritin, should be evaluated. Transferrin saturation should be at least 20%, and ferritin should be at least 100 ng/ml. Virtually all patients will require supplemental Iron to increase or maintain transferrin saturation to levels that will adequately support erythropoiesis.

Pregnancy Category C. Since there are no controlled studies of erythropoietin in pregnant women, and because animal reproduction studies are not always predictive of human responses, erythropoietin should be used during pregnancy only if clearly needed. It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when erythropoietin is administered to a nursing woman.

Doses of up to 1500 lU/kg TIW for 3 to 4 weeks have been administered to adults without any direct toxic effects. If the suggested target range is exceeded, drug therapy may be temporarily withheld until the hemoglobin returns to the suggested target range. If polycythemia is of concern, phlebotomy may be indicated to decrease the hemoglobin.

Erythropoietin should be stored at 2°C to 8°C. Protect from light. Do not freeze & avoid shaking.

Drugs for Haemolytic Hypoplastic & Renal Anemia

Treatment of anemia in chronic renal failure: Erythropoietin is administered to maintain hemoglobin concentration between 11 to 12 g/dl and hematocrit of 33-36 % in adults.

Starting dose:

• Adult: Usually 50 to 100 lU/kg three times in a week (TIW) by IV or Subcutaneous route.
• Pediatric: 50 lU/kg TIW by IV or Subcutaneous route.

Dose adjustment: Dose should be increased if hematocrit doses not increase by 5 to 6 points after 8 weeks therapy, and hematocrit is below suggested target range. Dose should be reduced when hematocrit approaches 36% or hematocrit increases >4 points in any 2-week period.

Maintenance dose: Maintenance dose must be individualized for each patient. In patients undergoing dialysis, the median maintenance dose is 75 lU/kg TIW, with a range from 12.5 to 525 lU/kg TIW as directed by the physician. In CRF patients not on dialysis, maintenance dose is 75 to 150 lU/kg/week.

Treatment of Anemia in Cancer Patients on Chemotherapy:

Starting dose:

• Adult: 150 lU/kg TIW by Subcutaneous route or 40,000 IU Subcutaneous route weekly.
• Pediatric: 25 to 300 lU/kg 3 to 7 times per week by Subcutaneous or IV route.

Dose adjustment: If the response is not satisfactory, the dose should be increased to 300 lU/kg TIW. If the hematocrit exceeds 40%, the dose should be withheld until the hematocrit falls to 36%.The dose should be reduced to 25% when treatment is resumed and titrated to maintain the desired hematocrit.

Surgery Patients: The recommended dose is 300 lU/kg/day subcutaneously for 10 days before surgery, on the day of surgery, and for 4 days after surgery. An alternate dose schedule is 600 lU/kg subcutaneously in once weekly dose (21, 14, and 7 days before surgery) plus a fourth dose on the day of surgery.

Zidovudine-treated HIV-infected Patients:
Starting dose

• Adult: 100 lU/kg as an IV or Subcutaneous injection TIW for 8 weeks.
• Pediatric: 50 to 400 lU/kg 2 to 3 times per week by Subcutaneous or IV route.

Dose adjustment: If the response is not satisfactory, the dose should be increased by 50-1001U/kg TIW. Response should be evaluated every 4 to 8 weeks thereafter and the dose adjusted accordingly by 50 to 100 lU/kg increments TIW.

Maintenance dose: The dose is titrated to maintain the hematocrit between 33-36%.

General: Headache, dizziness, fever, malaise, arthralgia and occasionally hyperkalemia. Cardiovascular: Hypertension is the most common side effect, palpitations. Gastrointestinal: Nausea, vomiting, anorexia and diarrhea may occur occasionally. Allergic reactions.

Erythropoietin is contraindicated in patients with:

• Uncontrolled hypertension
• Known hypersensitivity to mammalian cell-derived products
• A history of hypersensitivity to Erythropoietin or any component of the preparation.

Erythropoietin should be used with caution in those patients with controlled hypertension, ischaemic vascular disease, history of seizures, or suspected allergy to the product.

Iron evaluation: Prior to and during Erythropoietin therapy, the patient's iron stores, including transferrin saturation and serum ferritin, should be evaluated. Transferrin saturation should be at least 20%, and ferritin should be at least 100 ng/ml. Virtually all patients will require supplemental Iron to increase or maintain transferrin saturation to levels that will adequately support erythropoiesis.

Pregnancy Category C. Since there are no controlled studies of erythropoietin in pregnant women, and because animal reproduction studies are not always predictive of human responses, erythropoietin should be used during pregnancy only if clearly needed. It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when erythropoietin is administered to a nursing woman.

Doses of up to 1500 lU/kg TIW for 3 to 4 weeks have been administered to adults without any direct toxic effects. If the suggested target range is exceeded, drug therapy may be temporarily withheld until the hemoglobin returns to the suggested target range. If polycythemia is of concern, phlebotomy may be indicated to decrease the hemoglobin.

Erythropoietin should be stored at 2°C to 8°C. Protect from light. Do not freeze & avoid shaking.

Naproxen is indicated for the relief of sign and symptoms of rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, juvenile arthritis, tendonitis, bursitis & acute gout. It is also indicated for the management of primary dysmenorrhea & pain.

Drugs for Osteoarthritis, Drugs used for Rheumatoid Arthritis, Non-steroidal Anti-inflammatory Drugs (NSAIDs)

Naproxen is a non steroidal anti-inflammatory drug (NSAID) with anti-inflammatory, analgesic & antipyretic properties. It is rapidly absorbed from the gastrointestinal tract and achieves 95% bioavailability.

Naproxen Tablet-

• Rheumatoid arthritis, osteoarthritis and ankylosing spondylitis: The usual dose is 500-1000 mg daily in two divided doses after meals.
• Management of pain, primary dysmenorrhea, acute tendonitis & bursitis: Recommended starting dose is 500 mg followed by 500 mg every 12 hours or 250 mg every 6-8 hours. The initial total daily dose should not exceed 1250 mg and thereafter, the total daily dose should not exceed 1000 mg.
• Acute gout: Recommended starting dose is 750 mg followed by 250 mg every 8 hours until the attack has subsided.

Naproxen Suspension-

• For Juvenile rheumatoid arthritis: The usual dose for children over 2 years is 10 mg/kg/day given as two divided doses at 12-hours intervals. Therapy in children under 2 years of age is not recommended.

Naproxen Gel-

• Is to be applied 2-6 times a day as required and is not recommended for use in children.

Most frequently reported side effects include following:

• Gastrointestinal: Heartburn, abdominal pain, nausea, diarrhea, dyspepsia.
• Central Nervous System: Headache, vertigo, drowsiness.
• Dermatological: Pruritus (itching), purpura.
• Cardiovascular: Edema, palpitation.
• Others: Visual disturbances, hearing disturbances.

Naproxen is contraindicated in patients with known hypersensitivity to Naproxen. It should not be given to patients who have experienced asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs. It is contraindicated for the treatment of perioperative pain in the setting of coronary artery bypass graft (CABG) surgery.

ACE inhibitors: diminish the antihypertensive effect of ACE inhibitors.
Antacids & Sucralfate: delay the absorption of Naproxen.
Aspirin: increase adverse effects.
Diuretics: reduce the natriuretic effect of Furosemide and Thiazides.
Methotrexate: enhance the toxicity of Methotrexate.
Warfarin: increase the risk of GI bleeding.
Selective Serotonin Reuptake Inhibitors (SSRI): increase the risk of GI bleeding.

US FDA pregnancy category of Naproxen is C. So, Naproxen should be avoided in pregnancy & lactation unless the potential benefits to the other outweigh the possible risks to the fetus.

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