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Silymarin (Milk thistle) is indicated for the treatment and prevention of-

• Liver disease, (non-alcoholic & alcoholic)
• Liver cirrhosis, (non-alcoholic & alcoholic)
• Infectious hepatitis
• Drug-induced hepatitis
• Liver disease secondary to diabetes mellitus
• Toxicity of narcotics
• Fatty liver
• Jaundice

Cholagogues, Cholelitholytics & Hepatic Protectors, Herbal and Nutraceuticals

Silymarin, a flavonoid complex of Silybum marianum or Milk thistle, is the biologically active component. It provides hepatocellular protection through toxin blockade at the membrane level, enhances protein synthesis, antioxidant activity, anti-fibrotic activity and possible anti-inflammatory or immunomodulating effects.

1 capsule 2 to 3 times daily or as directed by a physician.

Well tolerated in the recommended dose. Occasionally a mild laxative effect may observe.

Contraindicated in patient with a known hypersensitivity to silymarin.

Concomitant use of silymarin and butyrophenones or phenothiazines has resulted in the reduction of lipid peroxidation.

No experience is available about the use of Silymarin 70 mg or 140 mg during pregnancy and lactation. Therefore, if needed Silymarin 70 mg or 140 mg should be taken with caution according to the physician’s advice.

Store in a cool & dry place, away from light & moisture. Keep out of reach of children.

Hepatocellular Carcinoma: Sorafenib is indicated for the treatment of patients with unresectablehepatocellular carcinoma (HCC).

Renal Cell Carcinoma: Sorafenib is indicated for the treatment of patients with advanced renal cell carcinoma (RCC).

Targeted Cancer Therapy

Sorafenib is a kinase inhibitor that decreases tumor cell proliferation in vitro. Sorafenib was shown to inhibit multiple intracellular (CRAF, BRAF and mutant BRAF) and cell surface kinases (KIT, FLT-3, RET, VEGFR-1, VEGFR-2, VEGFR-3, and PDGFR-ß). Several of these kinases are thought to be involved in tumor cell signaling, angiogenesis, and apoptosis. Sorafenib inhibited tumor growth and angiogenesis of human hepatocellular carcinoma and renal cell carcinoma, and several other human tumor xenografts in immunocompromised mice.

Advanced renal cell carcinoma: 400 mg bid. May continue until patient is no longer responding or unacceptable toxicity occurs.

Hepatic Impairment: No safety data is available for use in patients with Child-Pugh C hepatic impairment.

Should be taken on an empty stomach. May be taken with a low or moderate fat meal. If the patient intends to have a high fat meal, sorafenib should be taken on an empty stomach at least 1 hr before or 2 hr after meals. Swallow whole, do not chew/crush.

Rash and hand-foot skin reactions. Hypophosphataemia, hypertension, bleeding, tinnitus, depression and erectile dysfunction. Alopecia, pruritus, dry skin, erythema, acne, flushing, exfoliative dermatitis, hoarseness, GI disturbances, arthralgia, myalgia, asthenia, pain and peripheral neuropathy.

Sorafenib is contraindicated in patients with known severe hypersensitivity to sorafenib or any other component of Sorafenib. Sorafenib in combination with carboplatin and paclitaxel is contraindicated in patients with squamous cell lung cancer

Interrupt teatment if patient develops cardiac infarction, ischaemia and/or bleeding fatalities. Regular monitoring of BP, CBC and platelet is recommended. Monitor INR in patients who are on treatment with warfarin. Adequate contraception should be used during and for at least 2 wk after stopping treatment. May need to discontinue treatment if severe or persistent hypertension occurs.

Inducers of isoenzyme CYP3A4 e.g. carbamazepine, dexamethasone, phenobarbital, phenytoin, rifampicin may decrease sorafenib plasma concentration. Coadmin with sorafenib may increase the plasma concentration of doxorubicin and irinotecan.

Pregnancy category D There is positive evidence of human foetal risk, but the benefits from use in pregnant women may be acceptable despite the risk (e.g., if the drug is needed in a life-threatening situation or for a serious disease for which safer drugs cannot be used or are ineffective).

There is no specific treatment for Sorafenib overdose. The highest dose of Sorafenib studied clinically is 800 mg twice daily. The adverse reactions observed at this dose were primarily diarrhea and dermatologic. No information is available on symptoms of acute overdose in animals because of the saturation of absorption in oral acute toxicity studies conducted in animals. In cases of suspected overdose, Sorafenib should be withheld and supportive care instituted.

Store at 25° C.

Silymarin (Milk thistle) is indicated for the treatment and prevention of-

• Liver disease, (non-alcoholic & alcoholic)
• Liver cirrhosis, (non-alcoholic & alcoholic)
• Infectious hepatitis
• Drug-induced hepatitis
• Liver disease secondary to diabetes mellitus
• Toxicity of narcotics
• Fatty liver
• Jaundice

Cholagogues, Cholelitholytics & Hepatic Protectors, Herbal and Nutraceuticals

Silymarin, a flavonoid complex of Silybum marianum or Milk thistle, is the biologically active component. It provides hepatocellular protection through toxin blockade at the membrane level, enhances protein synthesis, antioxidant activity, anti-fibrotic activity and possible anti-inflammatory or immunomodulating effects.

1 capsule 2 to 3 times daily or as directed by a physician.

Well tolerated in the recommended dose. Occasionally a mild laxative effect may observe.

Contraindicated in patient with a known hypersensitivity to silymarin.

Concomitant use of silymarin and butyrophenones or phenothiazines has resulted in the reduction of lipid peroxidation.

No experience is available about the use of Silymarin 70 mg or 140 mg during pregnancy and lactation. Therefore, if needed Silymarin 70 mg or 140 mg should be taken with caution according to the physician’s advice.

Store in a cool & dry place, away from light & moisture. Keep out of reach of children.

Silymarin (Milk thistle) is indicated for the treatment and prevention of-

• Liver disease, (non-alcoholic & alcoholic)
• Liver cirrhosis, (non-alcoholic & alcoholic)
• Infectious hepatitis
• Drug-induced hepatitis
• Liver disease secondary to diabetes mellitus
• Toxicity of narcotics
• Fatty liver
• Jaundice

Cholagogues, Cholelitholytics & Hepatic Protectors, Herbal and Nutraceuticals

Silymarin, a flavonoid complex of Silybum marianum or Milk thistle, is the biologically active component. It provides hepatocellular protection through toxin blockade at the membrane level, enhances protein synthesis, antioxidant activity, anti-fibrotic activity and possible anti-inflammatory or immunomodulating effects.

1 capsule 2 to 3 times daily or as directed by a physician.

Well tolerated in the recommended dose. Occasionally a mild laxative effect may observe.

Contraindicated in patient with a known hypersensitivity to silymarin.

Concomitant use of silymarin and butyrophenones or phenothiazines has resulted in the reduction of lipid peroxidation.

No experience is available about the use of Silymarin 70 mg or 140 mg during pregnancy and lactation. Therefore, if needed Silymarin 70 mg or 140 mg should be taken with caution according to the physician’s advice.

Store in a cool & dry place, away from light & moisture. Keep out of reach of children.

Parenteral anti-coagulants

Heparin inhibits reactions that lead to the clotting of blood and the formation of fibrin clots both in vitro and in vivo. Heparin acts at multiple sites in the normal coagulation system. Small amounts of heparin in combination with antithrombin III (heparin cofactor) can inhibit thrombosis by inactivating activated Factor X and inhibiting the conversion of prothrombin to thrombin. Once active thrombosis has developed, larger amounts of heparin can inhibit further coagulation by inactivating thrombin and preventing the conversion of fibrinogen to fibrin. Heparin also prevents the formation of a stable fibrin clot in inhibiting the activation of the fibrin stabilizing factor.

Bleeding time is usually unaffected by heparin. Clotting time is prolonged by full therapeutic doses of heparin; in most cases, it is not measurably affected by low doses of heparin.

Intravenous-
Prophylaxis of re-occlusion of the coronary arteries following thrombolytic therapy in myocardial infarction

• Adult: 60 U/kg (max: 4,000 U) or a bolus of 5,000 U if streptokinase was used, followed by 12 U/kg/hr (max: 1,000 U/hr) w/ a treatment duration of 48 hr.

Intravenous-
Peripheral arterial embolism, Unstable angina, Venous thromboembolism

• Adult: 75-80 U/kg or 5,000 U (10,000 U in severe pulmonary embolism) IV loading dose followed by 18 U/kg or 1,000-2,000 U/hr continuous infusion. Alternatively, intermittent inj of 5,000-10,000 U 4-6 hrly.
• Child: 50 U/kg loading dose, followed by an infusion of 15-25 U/kg/hr.
• Elderly: Lower dosages may be required.

Subcutaneous-
Prophylaxis of postoperative venous thromboembolism

• Adult: 5,000 U given 2 hr before surgery then 8-12 hrly for 7 days or until the patient is ambulant.

Subcutaneous-
Venous thromboembolism

• Adult: 15,000-20,000 U 12 hrly or 8,000-10,000 U 8 hrly.
• Child: 250 U/kg bid.
• Elderly: Lower dosages may be required.

Hypersensitivity reactions (e.g. chills, fever, urticaria, asthma, rhinitis); painful, ischaemic and cyanosed limbs; osteoporosis (in long-term admin), suppression of aldosterone synthesis leading to hyperkalaemia, cutaneous necrosis, delayed transient alopecia, priapism, rebound hyperlipaemia; increased serum concentrations of AST and ALT, prolonged prothrombin time; local irritation, erythema, mild pain, haematoma or ulceration on inj site.

Current or history of heparin-induced thrombocytopenia; generalised or local haemorrhagic tendency, including uncontrolled severe HTN, severe liver insufficiency, active peptic ulcer, acute or subacute septic endocarditis, intracranial haemorrhage or injuries and operations on the CNS, eyes and ears, and in women with abortus imminens; epidural anaesth during birth; locoregional anaesth in elective surgical procedures (in patients receiving heparin for treatment rather than prophylaxis).

Patient with increased risk of bleeding complications, HTN, DM, pre-existing metabolic acidosis. Do not use in catheter lock flushing. Hepatic and renal impairment. Elderly. Pregnancy and lactation.

Enhanced anticoagulant effect with other drugs affecting platelet function or the coagulation system (e.g. platelet aggregation inhibitors, thrombolytic agents, salicylates, NSAIDs, vit K antagonists, dextrans, activated protein C). Decreased anticoagulant effect with gyceryl trinitrate infusion. Increased risk of hyperkalaemia with ACE inhibitors or angiotensin II antagonists.

Pregnancy Category C. Either studies in animals have revealed adverse effects on the foetus (teratogenic or embryocidal or other) and there are no controlled studies in women or studies in women and animals are not available. Drugs should be given only if the potential benefit justifies the potential risk to the foetus.

Nursing Mothers: Due to its large molecular weight, heparin is not likely to be excreted in human milk, and any heparin in milk would not be orally absorbed by a nursing infant. Benzyl alcohol present in maternal serum is likely to cross into human milk and may be orally absorbed by a nursing infant. Exercise caution when administering Heparin Sodium Injection to a nursing mother.

Pediatric Use: There are no adequate and well controlled studies on heparin use in pediatric patients. Pediatric dosing recommendations are based on clinical experience. Carefully examine all Heparin Sodium Injection vials to confirm choice of the correct strength prior to administration of the drug. Pediatric patients, including neonates, have died as a result of medication errors in which vials have been confused with “catheter lock flush” vials

Symptoms: Bleeding (nose bleeds, blood in urine or tarry stools may be noted as the 1st sign of bleeding).

Management: May give protamine sulfate by slow IV infusion over 10 min to treat severe bleeding (1 mg of protamine sulfate neutralises approx 100 U of heparin). Max: 50 mg as a single dose.

Store between 20-25° C. Protect from freezing.

Parenteral anti-coagulants

Heparin inhibits reactions that lead to the clotting of blood and the formation of fibrin clots both in vitro and in vivo. Heparin acts at multiple sites in the normal coagulation system. Small amounts of heparin in combination with antithrombin III (heparin cofactor) can inhibit thrombosis by inactivating activated Factor X and inhibiting the conversion of prothrombin to thrombin. Once active thrombosis has developed, larger amounts of heparin can inhibit further coagulation by inactivating thrombin and preventing the conversion of fibrinogen to fibrin. Heparin also prevents the formation of a stable fibrin clot in inhibiting the activation of the fibrin stabilizing factor.

Bleeding time is usually unaffected by heparin. Clotting time is prolonged by full therapeutic doses of heparin; in most cases, it is not measurably affected by low doses of heparin.

Intravenous-
Prophylaxis of re-occlusion of the coronary arteries following thrombolytic therapy in myocardial infarction

• Adult: 60 U/kg (max: 4,000 U) or a bolus of 5,000 U if streptokinase was used, followed by 12 U/kg/hr (max: 1,000 U/hr) w/ a treatment duration of 48 hr.

Intravenous-
Peripheral arterial embolism, Unstable angina, Venous thromboembolism

• Adult: 75-80 U/kg or 5,000 U (10,000 U in severe pulmonary embolism) IV loading dose followed by 18 U/kg or 1,000-2,000 U/hr continuous infusion. Alternatively, intermittent inj of 5,000-10,000 U 4-6 hrly.
• Child: 50 U/kg loading dose, followed by an infusion of 15-25 U/kg/hr.
• Elderly: Lower dosages may be required.

Subcutaneous-
Prophylaxis of postoperative venous thromboembolism

• Adult: 5,000 U given 2 hr before surgery then 8-12 hrly for 7 days or until the patient is ambulant.

Subcutaneous-
Venous thromboembolism

• Adult: 15,000-20,000 U 12 hrly or 8,000-10,000 U 8 hrly.
• Child: 250 U/kg bid.
• Elderly: Lower dosages may be required.

Hypersensitivity reactions (e.g. chills, fever, urticaria, asthma, rhinitis); painful, ischaemic and cyanosed limbs; osteoporosis (in long-term admin), suppression of aldosterone synthesis leading to hyperkalaemia, cutaneous necrosis, delayed transient alopecia, priapism, rebound hyperlipaemia; increased serum concentrations of AST and ALT, prolonged prothrombin time; local irritation, erythema, mild pain, haematoma or ulceration on inj site.

Current or history of heparin-induced thrombocytopenia; generalised or local haemorrhagic tendency, including uncontrolled severe HTN, severe liver insufficiency, active peptic ulcer, acute or subacute septic endocarditis, intracranial haemorrhage or injuries and operations on the CNS, eyes and ears, and in women with abortus imminens; epidural anaesth during birth; locoregional anaesth in elective surgical procedures (in patients receiving heparin for treatment rather than prophylaxis).

Patient with increased risk of bleeding complications, HTN, DM, pre-existing metabolic acidosis. Do not use in catheter lock flushing. Hepatic and renal impairment. Elderly. Pregnancy and lactation.

Enhanced anticoagulant effect with other drugs affecting platelet function or the coagulation system (e.g. platelet aggregation inhibitors, thrombolytic agents, salicylates, NSAIDs, vit K antagonists, dextrans, activated protein C). Decreased anticoagulant effect with gyceryl trinitrate infusion. Increased risk of hyperkalaemia with ACE inhibitors or angiotensin II antagonists.

Pregnancy Category C. Either studies in animals have revealed adverse effects on the foetus (teratogenic or embryocidal or other) and there are no controlled studies in women or studies in women and animals are not available. Drugs should be given only if the potential benefit justifies the potential risk to the foetus.

Nursing Mothers: Due to its large molecular weight, heparin is not likely to be excreted in human milk, and any heparin in milk would not be orally absorbed by a nursing infant. Benzyl alcohol present in maternal serum is likely to cross into human milk and may be orally absorbed by a nursing infant. Exercise caution when administering Heparin Sodium Injection to a nursing mother.

Pediatric Use: There are no adequate and well controlled studies on heparin use in pediatric patients. Pediatric dosing recommendations are based on clinical experience. Carefully examine all Heparin Sodium Injection vials to confirm choice of the correct strength prior to administration of the drug. Pediatric patients, including neonates, have died as a result of medication errors in which vials have been confused with “catheter lock flush” vials

Symptoms: Bleeding (nose bleeds, blood in urine or tarry stools may be noted as the 1st sign of bleeding).

Management: May give protamine sulfate by slow IV infusion over 10 min to treat severe bleeding (1 mg of protamine sulfate neutralises approx 100 U of heparin). Max: 50 mg as a single dose.

Store between 20-25° C. Protect from freezing.

Parenteral anti-coagulants

Heparin inhibits reactions that lead to the clotting of blood and the formation of fibrin clots both in vitro and in vivo. Heparin acts at multiple sites in the normal coagulation system. Small amounts of heparin in combination with antithrombin III (heparin cofactor) can inhibit thrombosis by inactivating activated Factor X and inhibiting the conversion of prothrombin to thrombin. Once active thrombosis has developed, larger amounts of heparin can inhibit further coagulation by inactivating thrombin and preventing the conversion of fibrinogen to fibrin. Heparin also prevents the formation of a stable fibrin clot in inhibiting the activation of the fibrin stabilizing factor.

Bleeding time is usually unaffected by heparin. Clotting time is prolonged by full therapeutic doses of heparin; in most cases, it is not measurably affected by low doses of heparin.

Intravenous-
Prophylaxis of re-occlusion of the coronary arteries following thrombolytic therapy in myocardial infarction

• Adult: 60 U/kg (max: 4,000 U) or a bolus of 5,000 U if streptokinase was used, followed by 12 U/kg/hr (max: 1,000 U/hr) w/ a treatment duration of 48 hr.

Intravenous-
Peripheral arterial embolism, Unstable angina, Venous thromboembolism

• Adult: 75-80 U/kg or 5,000 U (10,000 U in severe pulmonary embolism) IV loading dose followed by 18 U/kg or 1,000-2,000 U/hr continuous infusion. Alternatively, intermittent inj of 5,000-10,000 U 4-6 hrly.
• Child: 50 U/kg loading dose, followed by an infusion of 15-25 U/kg/hr.
• Elderly: Lower dosages may be required.

Subcutaneous-
Prophylaxis of postoperative venous thromboembolism

• Adult: 5,000 U given 2 hr before surgery then 8-12 hrly for 7 days or until the patient is ambulant.

Subcutaneous-
Venous thromboembolism

• Adult: 15,000-20,000 U 12 hrly or 8,000-10,000 U 8 hrly.
• Child: 250 U/kg bid.
• Elderly: Lower dosages may be required.

Hypersensitivity reactions (e.g. chills, fever, urticaria, asthma, rhinitis); painful, ischaemic and cyanosed limbs; osteoporosis (in long-term admin), suppression of aldosterone synthesis leading to hyperkalaemia, cutaneous necrosis, delayed transient alopecia, priapism, rebound hyperlipaemia; increased serum concentrations of AST and ALT, prolonged prothrombin time; local irritation, erythema, mild pain, haematoma or ulceration on inj site.

Current or history of heparin-induced thrombocytopenia; generalised or local haemorrhagic tendency, including uncontrolled severe HTN, severe liver insufficiency, active peptic ulcer, acute or subacute septic endocarditis, intracranial haemorrhage or injuries and operations on the CNS, eyes and ears, and in women with abortus imminens; epidural anaesth during birth; locoregional anaesth in elective surgical procedures (in patients receiving heparin for treatment rather than prophylaxis).

Patient with increased risk of bleeding complications, HTN, DM, pre-existing metabolic acidosis. Do not use in catheter lock flushing. Hepatic and renal impairment. Elderly. Pregnancy and lactation.

Enhanced anticoagulant effect with other drugs affecting platelet function or the coagulation system (e.g. platelet aggregation inhibitors, thrombolytic agents, salicylates, NSAIDs, vit K antagonists, dextrans, activated protein C). Decreased anticoagulant effect with gyceryl trinitrate infusion. Increased risk of hyperkalaemia with ACE inhibitors or angiotensin II antagonists.

Pregnancy Category C. Either studies in animals have revealed adverse effects on the foetus (teratogenic or embryocidal or other) and there are no controlled studies in women or studies in women and animals are not available. Drugs should be given only if the potential benefit justifies the potential risk to the foetus.

Nursing Mothers: Due to its large molecular weight, heparin is not likely to be excreted in human milk, and any heparin in milk would not be orally absorbed by a nursing infant. Benzyl alcohol present in maternal serum is likely to cross into human milk and may be orally absorbed by a nursing infant. Exercise caution when administering Heparin Sodium Injection to a nursing mother.

Pediatric Use: There are no adequate and well controlled studies on heparin use in pediatric patients. Pediatric dosing recommendations are based on clinical experience. Carefully examine all Heparin Sodium Injection vials to confirm choice of the correct strength prior to administration of the drug. Pediatric patients, including neonates, have died as a result of medication errors in which vials have been confused with “catheter lock flush” vials

Symptoms: Bleeding (nose bleeds, blood in urine or tarry stools may be noted as the 1st sign of bleeding).

Management: May give protamine sulfate by slow IV infusion over 10 min to treat severe bleeding (1 mg of protamine sulfate neutralises approx 100 U of heparin). Max: 50 mg as a single dose.

Store between 20-25° C. Protect from freezing.

Rifaximin is indicaed in-

• Treatment of traveler's diarrhea by noninvasive strains of E. coli
• reduction in risk of overt hepatic encephalopathy
• bacterial overgrowth of irritable bowel syndrome.

4-Quinolone preparations

Rifaximin is a semisynthetic, rifamycin-based non-systemic antibiotic. Very little of the drug will pass the gastrointestinal wall into the circulation as is common for other types of orally administered antibiotics. Rifaximin inhibits bacterial RNA synthesis by its action on the beta-subunit of the DNA-dependent RNA polymerase. It shows the same broad spectrum activity as rifamycin which exerts bactericidal action against many species of Gram-positive and Gram-negative, aerobic and anaerobic bacteria.

Traveler's Diarrhea: For patients ≥12 years of age: 200 mg 3 times daily for 3 days.
Hepatic Encephalopathy: For patients ≥18 years of age: 550 mg 2 times daily.
Bacterial overgrowth of irritable bowel syndrome: 400 mg 3 times daily for 10 days or 550 mg 3 times daily for 14 days. Can be taken with or without food

Side effects include flatulence, headache, abdominal pain, rectal tenesmus, defecation urgency, nausea, constipation, pyrexia, vomiting. Reactions have been reported, including anaphylaxis, angioneurotic edema, and exfoliative dermatitis.

Contraindicated in patients with a hypersensitivity to Rifaximin or to any of the rifamycin antimicrobial agents, or any components of this product

Rifaximin is not found to be effective in patients with diarrhea complicated by fever and/or blood in the stools. Rifaximin therapy should be discontinued if diarrhea symptoms get worse or persist for more than 24-48 hours and alternative antibiotic therapy should be considered. Pseudomembranous colitis has been reported with nearly all antibacterial agents and may range in severity from mild to life-threatening. Therefore, it is important to consider this diagnosis in patients who present with diarrhea subsequent to the administration of antibacterial agents.

In an in vitro study has suggested that Rifaximin induces CYP3A4. However, in patients with normal liver function, Rifaximin at the recommended dosing regimen is not expected to induce CYP3A4.

Pregnancy category C. It is not known whether Rifaximin is excreted in human milk or not.

Renal Impairment: The pharmacokinetics of Rifaximin in patients with impaired renal function has not been studied.
Hepatic Impairment: The systemic exposure of Rifaximin was markedly elevated in patients with hepatic impairment compared to healthy subjects.

No specific information is available on the treatment of over dosage with Rifaximin. In case of over dosage, discontinue Rifaximin, treat symptomatically and institute supportive measures as required.

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

Rifaximin is indicaed in-

• Treatment of traveler's diarrhea by noninvasive strains of E. coli
• reduction in risk of overt hepatic encephalopathy
• bacterial overgrowth of irritable bowel syndrome.

4-Quinolone preparations

Rifaximin is a semisynthetic, rifamycin-based non-systemic antibiotic. Very little of the drug will pass the gastrointestinal wall into the circulation as is common for other types of orally administered antibiotics. Rifaximin inhibits bacterial RNA synthesis by its action on the beta-subunit of the DNA-dependent RNA polymerase. It shows the same broad spectrum activity as rifamycin which exerts bactericidal action against many species of Gram-positive and Gram-negative, aerobic and anaerobic bacteria.

Traveler's Diarrhea: For patients ≥12 years of age: 200 mg 3 times daily for 3 days.
Hepatic Encephalopathy: For patients ≥18 years of age: 550 mg 2 times daily.
Bacterial overgrowth of irritable bowel syndrome: 400 mg 3 times daily for 10 days or 550 mg 3 times daily for 14 days. Can be taken with or without food

Side effects include flatulence, headache, abdominal pain, rectal tenesmus, defecation urgency, nausea, constipation, pyrexia, vomiting. Reactions have been reported, including anaphylaxis, angioneurotic edema, and exfoliative dermatitis.

Contraindicated in patients with a hypersensitivity to Rifaximin or to any of the rifamycin antimicrobial agents, or any components of this product

Rifaximin is not found to be effective in patients with diarrhea complicated by fever and/or blood in the stools. Rifaximin therapy should be discontinued if diarrhea symptoms get worse or persist for more than 24-48 hours and alternative antibiotic therapy should be considered. Pseudomembranous colitis has been reported with nearly all antibacterial agents and may range in severity from mild to life-threatening. Therefore, it is important to consider this diagnosis in patients who present with diarrhea subsequent to the administration of antibacterial agents.

In an in vitro study has suggested that Rifaximin induces CYP3A4. However, in patients with normal liver function, Rifaximin at the recommended dosing regimen is not expected to induce CYP3A4.

Pregnancy category C. It is not known whether Rifaximin is excreted in human milk or not.

Renal Impairment: The pharmacokinetics of Rifaximin in patients with impaired renal function has not been studied.
Hepatic Impairment: The systemic exposure of Rifaximin was markedly elevated in patients with hepatic impairment compared to healthy subjects.

No specific information is available on the treatment of over dosage with Rifaximin. In case of over dosage, discontinue Rifaximin, treat symptomatically and institute supportive measures as required.

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

This is indicated in Jaundice, Toxic liver injury, Hepatitis, Chronic indigestion, Anorexia.

Herbal and Nutraceuticals

Aphanamixis polystachya: It contains aphanamixin, amoorin, flindissol, melianone, rohitukin that have hepatoprotective, antiviral and antibacterial activities.

Woodfordia fructicosa: It has octacosanol, ß- sitosterol, polystachoside, ellagic acid and polyphenols, which are used in the treatment of liver diseases and bowel complaints.

Emblica officinalis: It is a rich source of vitamin C, which acts as an anti-oxidant. It also contains ellagic & phyllenbic acids, phyllantidine & phyllantine that are used in the treatment of jaundice, dyspepsia, and peptic ulcer. It decreases SGOT, SGPT and LDH. It reduces serum cholesterol, triglycerides, phospholipid & LDL levels. It also decreases glutathione depletion and prevents cytochrome P-450 stimulation.

Terminalia chebula: It contains anthraquinone glycoside, chebulinic acid, tannic acid, gallic acid that are used in enlarged spleen & liver. It promotes digestive power.

Terminalia belerica: It contains tannin, ß-sitosterol, gallic acid, ellagic acid. It has significant hepatoprotective activity and prevents the development of fatty liver. It increases the biliary secretion.

Zingiber officinale: It increases bile secretion & enhances gastrointestinal motility. It has anti-vomiting, anti flatulent and digestive activities.

Piper longum (Root & fruit): It facilitates the regeneration of hepatocytes following toxic liver damage. It has piperine alkaloid that stimulates digestive enzyme activity including that of pancreatic lipase, amylase, trypsin and chymotrypsin.

Elettaria cardamomum: It increases the flow of bile from gall bladder in to the intestine. It has also anti vomiting, anti-flatulent and digestive activities.

Cinnamomum tamala: It contains essential oil, eugenol, terpin and cinnamic aldehyde that has anti-flatulent & digestive activities.

Cinnamomum zeylanicum: It is a very efficient carminative & antispasmodic. It has also hepatoprotective and digestives activities.

Adult: 2-4 tea-spoonful 2-3 times daily after meal.
Child: 1-2 tea-spoonful 2-3 times daily after meal.

Not yet known.

There is no absolute contraindication.

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

Vaccines, Anti-sera & Immunoglobulin

Neonates, infants and children upto 19 years of age: The recommended dose of Hepatitis B vaccine (rDNA) is >10 mcg of antigen protein in 0.5 ml.

Adults 19 years of age and older: The recommended dose of Hepatitis B vaccine (rDNA) is >20 mcg of antigen in 1 ml.

Primary immunization schedule for all ages:
The usual immunization schedule consists of 3 doses of vaccine-

• First dose: at elected date
• Second dose: 1 month after first dose
• Third dose: 6 months after first dose

or accelerated schedule consists of 4 doses of vaccine-

• First dose: at elected date
• Second dose: 1 month after first dose
• Third dose: 2 months after first dose
• Fourth dose: 12 months after first dose

Accelerated schedule confer protection more quickly and is expected to provide better patient compliance.

Neonate born to hepatitis B surface antigen-positive mother, 4 doses of 10 micrograms:

• First dose: at birth with Hepatitis B immunoglobulin injection (separate site)
• Second dose: 1 month after first dose
• Third dose: 2 months after first dose
• Fourth dose: 12 months after first dose

For travellers departing within 1 month, adult over 18 years,

• First dose: at elected date
• Second dose: 7 days after first dose
• Third dose: 21 days after first dose
• Fourth dose: 12 months after first dose

Renal insufficiency (including haemodialysis patients), adult and child over 16 years 4 doses of 40 micrograms-

• First dose: at the appropriate date
• Second dose: 1 month after first dose
• Third dose: 2 months after first dose
• Fourth dose: 6 months after first dose

Immunization schedule and booster doses may need to be adjusted in those with low antibody concentration.

Booster vaccinations: For persons with normal immune status who have been vaccinated, booster doses of
Hepatitis B vaccine has not been established. However, booster doses are recommended for hemodialysis patients or other immunocompromised persons.

Method of administration: Hepatitis B Vaccine is for intramuscular injection only. Do not inject intravenously. Hepatitis B Vaccine should be given intramuscularly in the deltoid muscle of adult and children or in the anterolateral aspect of thigh in children under 1 year.

Preparation for administration: The vaccine should be shaken well before use to obtain a homogenous turbid white suspension. Do not shake vigorously. The vaccine should be inspected visually for particulate matter and discoloration prior to administration. If either of these conditions exists, the vaccine should not be administered. The vaccine should be used as supplied; no dilution is necessary

Co-administration: Hepatitis B vaccine can be given at the same time with other vaccine as Diphtheria, Tetanus, Pertussis (DTP), Polio (OPV), Measles, Mumps and Rubella (MMR), Haemophilus influenzae b, Hepatitis A and BCG vaccines at separate sites and with separate syringes. It should not be mixed with other vaccines or medicinal products in the same syringe.

Hepatitis B vaccine is generally well tolerated. Most recipients of Hepatitis B vaccine experience some reactions upon vaccination. These are generally moderate and short. They mainly consist of local reactions at the injection site (erythema, induration and tenderness). Systemic reactions (malaise, headache, diarrhea, vomiting, myalgia and elevated temperature) are reported less commonly. In very rare cases allergic type reactions (pruritus, rash, urticaria) may be observed.

Hypersensitivity to any component of the vaccine, including yeast, is a contraindication. This vaccine is contraindicated in patients with previous hypersensitivity to any Hepatitis B virus containing vaccine.

The effect of Hepatitis B on fetal development or reproduction capacity has not been evaluated. However, it should only be used during pregnancy when there is a high risk of infection. Adequate human data on use during lactation and adequate animal reproduction studies are not available. It may be administered to nursing mothers only if clearly needed.

Keep out of the reach and sight of children. Store at +2°C to +8°C. Transportation should also be at +2°C to +8°C. Protect from light. Do not freeze.

Lamivudine is indicated for the treatment of chronic hepatitis B associated with evidence of hepatitis B viral replication and active liver inflammation.

Hepatic viral infections (Hepatitis B)

Lamivudine is a synthetic nucleoside analogue. Lamivudine is phosphorylated intracellularly to lamivudine triphosphate. Incorporation of the monophosphate form into viral DNA occurs by hepatitis B virus (HBV) polymerase. As a result DNA chain is terminated. Lamivudine triphosphate also inhibits the RNA and DNA-dependent DNA polymerase activities of HIV-1 reverse transcriptase (RT). Lamivudine triphosphate is a very weak inhibitor of mammalian alpha, beta, and gamma-DNA polymerases.

The recommended oral dose of Lamivudine for the treatment of chronic hepatitis B in adults is 100 mg once daily.

Several serious adverse events reported with lamivudine (lactic acidosis and severe hepatomegaly with steatosis, post treatment exacerbations of hepatitis B, pancreatitis, and emergence of viral mutants associated with reduced drug susceptibility and diminished treatment response). Malaise, fatigue, fever, ENT infections, sore throat, nausea, vomiting, abdominal discomfort, pain, diarrhea, myalgia, arthralgia, headache, skin rashes may occur. Lactic acidosis and severe hepatomegaly with steatosis, have been reported.

Lamivudine is contraindicated in patients hypersensitive to any of the components of the product.

Patients should be assessed before beginning treatment and during treatment with lamivudine by a physician experienced in the management of chronic hepatitis B.

Trimethoprim 160 mg / Sulfamethoxazole 800 mg once daily has been shown to increase lamivudine exposure (AUC). The effect of higher doses of trimethoprim /sulfamethoxazole on lamivudine pharmacokinetics has not been investigated.

There is no adequate and well-controlled study in pregnant women. Lamivudine should be used during pregnancy only if the potential benefits outweigh the risks. Although it is not known if lamivudine is excreted in human milk, there is the potential for adverse effects from lamivudine in nursing infants. Mothers should be instructed not to breast feed if they are receiving lamivudine.

It is recommended that doses of Lamivudine should be adjusted in accordance with renal function. Dosage adjustment of Lamivudine in accordance with creatinine clearance is as follows:

• CrCl 50 ml/min: 100 mg once daily
• CrCl 30-49 ml/min: 100 mg first dose, then 50 mg once daily
• CrCl 15-29 ml/min: 100 mg first dose, then 25 mg once daily
• CrCl 5-14 ml/min: 35 mg first dose, then 15 mg once daily
• CrCl <5 ml/min: 35 mg first dose, then 10 mg once daily

Use in children: Safety and efficacy of lamivudine for the treatment of chronic hepatitis B in children have not been established.

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

Rifaximin is indicaed in-

• Treatment of traveler's diarrhea by noninvasive strains of E. coli
• reduction in risk of overt hepatic encephalopathy
• bacterial overgrowth of irritable bowel syndrome.

4-Quinolone preparations

Rifaximin is a semisynthetic, rifamycin-based non-systemic antibiotic. Very little of the drug will pass the gastrointestinal wall into the circulation as is common for other types of orally administered antibiotics. Rifaximin inhibits bacterial RNA synthesis by its action on the beta-subunit of the DNA-dependent RNA polymerase. It shows the same broad spectrum activity as rifamycin which exerts bactericidal action against many species of Gram-positive and Gram-negative, aerobic and anaerobic bacteria.

Traveler's Diarrhea: For patients ≥12 years of age: 200 mg 3 times daily for 3 days.
Hepatic Encephalopathy: For patients ≥18 years of age: 550 mg 2 times daily.
Bacterial overgrowth of irritable bowel syndrome: 400 mg 3 times daily for 10 days or 550 mg 3 times daily for 14 days. Can be taken with or without food

Side effects include flatulence, headache, abdominal pain, rectal tenesmus, defecation urgency, nausea, constipation, pyrexia, vomiting. Reactions have been reported, including anaphylaxis, angioneurotic edema, and exfoliative dermatitis.

Contraindicated in patients with a hypersensitivity to Rifaximin or to any of the rifamycin antimicrobial agents, or any components of this product

Rifaximin is not found to be effective in patients with diarrhea complicated by fever and/or blood in the stools. Rifaximin therapy should be discontinued if diarrhea symptoms get worse or persist for more than 24-48 hours and alternative antibiotic therapy should be considered. Pseudomembranous colitis has been reported with nearly all antibacterial agents and may range in severity from mild to life-threatening. Therefore, it is important to consider this diagnosis in patients who present with diarrhea subsequent to the administration of antibacterial agents.

In an in vitro study has suggested that Rifaximin induces CYP3A4. However, in patients with normal liver function, Rifaximin at the recommended dosing regimen is not expected to induce CYP3A4.

Pregnancy category C. It is not known whether Rifaximin is excreted in human milk or not.

Renal Impairment: The pharmacokinetics of Rifaximin in patients with impaired renal function has not been studied.
Hepatic Impairment: The systemic exposure of Rifaximin was markedly elevated in patients with hepatic impairment compared to healthy subjects.

No specific information is available on the treatment of over dosage with Rifaximin. In case of over dosage, discontinue Rifaximin, treat symptomatically and institute supportive measures as required.

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

Rifaximin is indicaed in-

• Treatment of traveler's diarrhea by noninvasive strains of E. coli
• reduction in risk of overt hepatic encephalopathy
• bacterial overgrowth of irritable bowel syndrome.

4-Quinolone preparations

Rifaximin is a semisynthetic, rifamycin-based non-systemic antibiotic. Very little of the drug will pass the gastrointestinal wall into the circulation as is common for other types of orally administered antibiotics. Rifaximin inhibits bacterial RNA synthesis by its action on the beta-subunit of the DNA-dependent RNA polymerase. It shows the same broad spectrum activity as rifamycin which exerts bactericidal action against many species of Gram-positive and Gram-negative, aerobic and anaerobic bacteria.

Traveler's Diarrhea: For patients ≥12 years of age: 200 mg 3 times daily for 3 days.
Hepatic Encephalopathy: For patients ≥18 years of age: 550 mg 2 times daily.
Bacterial overgrowth of irritable bowel syndrome: 400 mg 3 times daily for 10 days or 550 mg 3 times daily for 14 days. Can be taken with or without food

Side effects include flatulence, headache, abdominal pain, rectal tenesmus, defecation urgency, nausea, constipation, pyrexia, vomiting. Reactions have been reported, including anaphylaxis, angioneurotic edema, and exfoliative dermatitis.

Contraindicated in patients with a hypersensitivity to Rifaximin or to any of the rifamycin antimicrobial agents, or any components of this product

Rifaximin is not found to be effective in patients with diarrhea complicated by fever and/or blood in the stools. Rifaximin therapy should be discontinued if diarrhea symptoms get worse or persist for more than 24-48 hours and alternative antibiotic therapy should be considered. Pseudomembranous colitis has been reported with nearly all antibacterial agents and may range in severity from mild to life-threatening. Therefore, it is important to consider this diagnosis in patients who present with diarrhea subsequent to the administration of antibacterial agents.

In an in vitro study has suggested that Rifaximin induces CYP3A4. However, in patients with normal liver function, Rifaximin at the recommended dosing regimen is not expected to induce CYP3A4.

Pregnancy category C. It is not known whether Rifaximin is excreted in human milk or not.

Renal Impairment: The pharmacokinetics of Rifaximin in patients with impaired renal function has not been studied.
Hepatic Impairment: The systemic exposure of Rifaximin was markedly elevated in patients with hepatic impairment compared to healthy subjects.

No specific information is available on the treatment of over dosage with Rifaximin. In case of over dosage, discontinue Rifaximin, treat symptomatically and institute supportive measures as required.

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

Hepatic viral infections (Hepatitis C)

Sofosbuvir is nucleotide analog inhibitor, which specifically inhibits HCV NS5B (non-structural protein 5B) RNA-dependent RNA polymerase. Following intracellular metabolism to form the pharmacologically active uridine analog triphosphate (GS-461203), sofosbuvir incorporates into HCV RNA by the NS5B polymerase and acts as a chain terminator. More specifically, Sofosbuvir prevents HCV viral replication by binding to the two Mg2+ ions present in HCV NS5B polymerase's GDD active site motif and preventing further replication of HCV genetic material

One 400 mg tablet taken once daily with or without food. Should be used in combination with Ribavirin or in combination with Pegylated Interferon and Ribavirin for the treatment of CHC.

Recommended combination therapy: (HCV Mono-infected and HCV/HIV-1 Co-infected)-

• Genotype 1 or 4: Sofosbuvir + Peginterferon alfa + Ribavirin for 12 weeks
• Genotype 2: Sofosbuvir + Ribavirin for 12 weeks
• Genotype 3: Sofosbuvir + Ribavirin for 24 weeks

Sofosbuvir in combination with Ribavirin for 24 weeks can be considered for CHC patients with genotype 1 infection who are Interferon ineligible

Should be used in combination with Ribavirin for treatment of CHC in patients with hepatocellular carcinoma awaiting liver transplantation for up to 48 weeks or until liver transplantation whichever occurs first

A dose recommendation cannot be made for patients with severe renal impairment or end stage renal disease

The most common adverse events (incidence greater than or equal to 20%, all grades) observed with Sofosbuvir in combination with Ribavirin were fatigue and headache. The most common adverse events observed with Sofosbuvir in combination with Peginterferon alfa and Ribavirin were fatigue, headache, nausea, insomnia, anemia, pruritus, asthenia, rash, decreased appetite, chills, influenza like illness, pyrexia, diarrhea, neutropenia, myalgia, irritability.

When Sofosbivur is used in combination with Ribavirin or Peginterferon alfa/ Ribavirin, the contraindications applicable to those agents are applicable to combination therapies. Sofosbuvir combination treatment with Ribavirin or Peginterferon alfa/Ribavirin is contraindicated in women who are pregnant or may become pregnant and men whose female partners are pregnant, because of the risks for birth defects and fetal death associated with Ribavirin.

Bradycardia with amiodarone co-administration: Serious symptomatic bradycardia may occur in patients taking amiodarone and Sofosbuvir in combination with another direct acting antiviral (DAA), particularly in patients also receiving beta blockers, or those with underlying cardiac comorbidities and/or advanced liver disease. Co-administration of amiodarone with Sofosbuvir in combination with another DAA is not recommended. In patients without alternative, viable treatment options, cardiac monitoring is recommended.

Reduced therapeutic effect with drugs that are potent P-gp inducers in the intestine (eg rifampicin, St. John's wort, carbamazepine & phenytoin), modafinil, phenobarb/ oxcarbazepine, rifabutin/ rifapentine. P-gp &/or BCRP inhibitors. May result in serious symptomatic bradycardia when co-administered with amiodarone in combination with another direct acting antiviral.

Pregnancy Category B: Sofosbuvir There are no adequate and well-controlled studies with Sofosbuvir in pregnant women.

Nursing Mothers: It is not known whether Sofosbuvir and its metabolites are present in human breast milk.

Pediatric Use: Safety and effectiveness of Sofosbuvir in children less than 18 years of age have not been established.

Geriatric Use: Sofosbuvir was administered to 90 subjects aged 65 and over. The response rates observed for subjects over 65 years of age were similar to that of younger subjects across treatment groups. No dose adjustment of Sofosbuvir is warranted in geriatric patients.

The highest dose of Sofosbuvir is a single dose of Sofosbuvir 1200 mg. No specific antidote is available for overdose treatment. Treatment of overdose with Sofosbuvir consists of general supportive measures including monitoring of vital signs as well as observation of the clinical status of the patient.

Keep out of the reach of children. Keep in a cool & dry place. Protect from light.

This is indicated for the treatment of Hepatic Encephalopathy, Acute Liver Failure, Hyperammonemia due to Acute and Chronic Hepatitis, Fatty Liver, Alcoholic Liver damage, Adjunct to hepatotoxic drugs, Liver Cirrhosis, Post hepatitis convalescence etc.

Digestive Enzyme

L-Ornithine L-Aspartate is a stable combination of two important endogenous Amino Acids, L-Ornithine and L-Aspartate. After administration, it quickly breaks down into L-Ornithine and L-Aspartate. L-Ornithine being a substrate of urea cycle, converts toxic ammonia into non-toxic urea which is eliminated via kidneys, helping the diseased liver to carry out its normal function smoothly (detoxification). The process lowers the elevated level of ammonia in blood (hyperammonemia) which is a common problem in most of the liver diseases. L-Aspartate is an essential component of citric acid cycle which liberates energy (ATP), and thus helps in regeneration of damaged liver cells.

Sachet: 1-2 sachets granules is dissolved in a large amount of fluid (e.g. in a glass of water or juice) and is taken orally 3 times a day during or after meals.

Injection (Infusion Concentrate): The recommended dose is up to 20 gm (4 ampoules daily). In case of loss of consciousness (pre-coma) and clouding of consciousness (coma) up to 8 ampoules within 24 hours, depending on the severity of the condition.

Very rarely side effects like nausea and vomiting occur. These side effects are usually transient and do not necessitate the withdrawal of the drug.

Monitoring of serum and urinary urea levels at regular intervals should be done.

No data regarding the interactions of L-Ornithine L-Aspartate was found.

The administration in pregnancy and lactation should be avoided.

Store in a cool and dry place, keep away from light.

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

For prevention and treatment of vitamin deficiency in children and infants.

Specific combined vitamin preparations

Vitamin A plays an essential role in the function of retina and is essential for growh and differentiation of epithelial tissue.

Vitamin B: Plays a role in the synthesis and maintenance of coenzyme A. Necessary for lipid metabolism, carbohydrate metabolism, tissue respiration, glycogenolysis, inhibition of very low-density lipoprotein (VLDL) synthesis. May increaase chylomicron triglyceride removal from plasma.

Vitamin B12 (cyanocobalamin): Required for the maintenance of normal erthropoiesis, nucleprotein and myelin synthesis, cell reproduction and normal growth; intrinsic factor, a glycoprotein secreted by the gastric mucosa, is required for active absorption of Vitamin B12 from the Gl tract. Necessary for normal tissue respiration; plays a role in activation of pyridoxine and conversion of tryptophan to niacin.

Vitamin E is an antioxidant which preserves essential cellular constituents.

Vitamin C: Necessary for collagen formation and tissue repair; plays a role in oxidation/reduction reactions as well as other metabolic pathways including synthesis of catecholamines, carnitine, and steroids; also plays a role in conversion of folic acid to folinic acid.

Vitamin D3 is a fat-soluble sterol. It is necessary for the regulation and regulation of calcium and phosphate homoeostasis and bone mineralisation. Vitamin D is also essential for healthy bones as it aids in Calcium absorption from the Gl tract. In addition to this it stimulates bone formation. Clinical studies also show that Calcium and Vitamin D has synergistic effects on bone growth as well as in Osteoporosis and fracture prevention.

Below 1 year: 9-10 drops (0.3 ml)
1 year and above: 23-25 drops (1.0 ml) once daily or as advised by the physicians.

Multivitamin preparation with ordinary doses of component are usually nontoxic

Supplemental vitamins should not be prescribed for patients with haemochromatosis or Wilson’s disease. Hypersensitivity to any of the ingredients is contraindicated. Excessive doses of vitamin A and D can lead to hypervitaminosis. When multivitamin preparations are prescribed allowance must be made for vitamins from other sources.

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

The HER2 (or c-erbB2) proto-oncogene encodes a transmembrane receptor protein of 185 kDa, which is structurally related to the epidermal growth factor receptor. Trastuzumab has been shown, in both in vitro assays and in animals, to inhibit the proliferation of human tumor cells that overexpress HER2. Trastuzumab is a mediator of antibody-dependent cellular cytotoxicity (ADCC). In vitro, Trastuzumab-mediated ADCC has been shown to be preferentially exerted on HER2 overexpressing cancer cells compared with cancer cells that do not overexpress HER2.

Recommended Doses and Schedules: Do not administer as an intravenous push or bolus. Do not mix Trastuzumab with other drugs.

Adjuvant Treatment, Breast Cancer: Administer according to one of the following doses and schedules for a total of 52 weeks of Trastuzumab therapy:

During and following paclitaxel, docetaxel, or docetaxel/carboplatin:

• Initial dose of 4 mg/kg as an intravenous infusion over 90 minutes then at 2 mg/kg as an intravenous infusion over 30 minutes weekly during chemotherapy for the first 12 weeks (paclitaxel or docetaxel) or 18 weeks (docetaxel/carboplatin).
• One week following the last weekly dose of Trastuzumab, administer Trastuzumab at 6 mg/kg as an intravenous infusion over 30−90 minutes every three weeks.

As a single agent within three weeks following completion of multi-modality, anthracycline-based chemotherapy regimens:

• Initial dose at 8 mg/kg as an intravenous infusion over 90 minutes
• Subsequent doses at 6 mg/kg as an intravenous infusion over 30−90 minutes every three weeks.
• Extending adjuvant treatment beyond one year is not recommended

Metastatic Treatment, Breast Cancer: Administer Trastuzumab, alone or in combination with paclitaxel, at an initial dose of 4 mg/kg as a 90 minute intravenous infusion followed by subsequent once-weekly doses of 2 mg/kg as 30-minute intravenous infusions until disease progression.

Metastatic Gastric Cancer: Administer Trastuzumab at an initial dose of 8 mg/kg as a 90-minute intravenous infusion followed by subsequent doses of 6 mg/kg as an intravenous infusion over 30–90 minutes every three weeks until disease progression. Or, as directed by the registered physician.

The most serious adverse reactions caused by Trastuzumab includes Cardiomyopathy, Infusion Reactions, Embryo-Fetal Toxicity, Pulmonary Toxicity, Exacerbation of Chemotherapy-Induced Neutropenia. The most common adverse reactions in patients receiving Trastuzumab in the adjuvant and metastatic breast cancer setting are fever, nausea, vomiting, infusion reactions, diarrhea, infections, increased cough, headache, fatigue, dyspnea, rash, neutropenia, anemia, and myalgia.

Cardiomyopathy: Trastuzumab can cause left ventricular cardiac dysfunction, arrhythmias, hypertension, disabling cardiac failure, cardiomyopathy, and cardiac death. Trastuzumab can also cause asymptomatic decline in left ventricular ejection fraction (LVEF). There is a 4-6 fold increase in the incidence of symptomatic myocardial dysfunction among patients receiving Trastuzumab as a single agent or in combination therapy compared with those not receiving Trastuzumab. The highest absolute incidence occurs when Trastuzumab is administered with an anthracycline. Withhold Trastuzumab for ≥ 16% absolute decrease in LVEF from pre treatment values or an LVEF value below institutional limits of normal and ≥ 10% absolute decrease in LVEF from pretreatment values. The safety of continuation or resumption of Trastuzumab in patients with Trastuzumab-induced left ventricular cardiac dysfunction has not been studied.

Cardiac Monitoring: Conduct thorough cardiac assessment, including history, physical examination, and determination of LVEF by echocardiogram or MUGA scan. The following schedule is recommended:

• Baseline LVEF measurement immediately prior to initiation of Trastuzumab
• LVEF measurements every 3 months during and upon completion of Trastuzumab
• Repeat LVEF measurement at 4 week intervals if Trastuzumab is withheld for significant left ventricular cardiac dysfunction.
• LVEF measurements every 6 months for at least 2 years following completion of Trastuzumab as a component of adjuvant therapy.

Infusion Reactions: Infusion reactions consist of a symptom complex characterized by fever and chills, and on occasion included nausea, vomiting, pain (in some cases at tumor sites), headache, dizziness, dyspnea, hypotension, rash, and asthenia. Serious and fatal infusion reactions have been reported. Severe reactions, which include bronchospasm, anaphylaxis, angioedema, hypoxia, and severe hypotension, were usually reported during or immediately following the initial infusion. However, the onset and clinical course were variable, including progressive worsening, initial improvement followed by clinical deterioration, or delayed post-infusion events with rapid clinical deterioration. For fatal events, death occurred within hours to days following a serious infusion reaction. Interrupt Trastuzumab infusion in all patients experiencing dyspnea, clinically significant hypotension, and intervention of medical therapy administered (which may include epinephrine, corticosteroids, diphenhydramine, bronchodilators, and oxygen). Patients should be evaluated and carefully monitored until complete resolution of signs and symptoms. Permanent discontinuation should be strongly considered in all patients with severe infusion reactions. There are no data regarding the most appropriate method of identification of patients who may safely be retreated with Trastuzumab after experiencing a severe infusion reaction. Prior to resumption of Trastuzumab infusion, the majority of patients who experienced a severe infusion reaction were pre-medicated with antihistamines and/or corticosteroids. While some patients tolerated Trastuzumab infusions, others had recurrent severe infusion reactions despite pre-medications.

Embryo-Fetal Toxicity: Trastuzumab can cause fetal harm when administered to a pregnant woman. Use of Trastuzumab during pregnancy resulted in cases of oligohydramnios and oligohydramnios sequence manifesting as pulmonary hypoplasia, skeletal abnormalities, and neonatal death. Advise females of reproductive potential to use effective contraception during treatment and for 7 months following the last dose of Trastuzumab.

Pulmonary Toxicity: Trastuzumab use can result in serious and fatal pulmonary toxicity. Pulmonary toxicity includes dyspnea, interstitial pneumonitis, pulmonary infiltrates, pleural effusions, non-cardiogenic pulmonary edema, pulmonary insufficiency and hypoxia, acute respiratory distress syndrome, and pulmonary fibrosis. Such events can occur as sequelae of infusion reactions. Patients with symptomatic intrinsic lung disease or with extensive tumor involvement of the lungs, resulting in dyspnea at rest, appear to have more severe toxicity.

Exacerbation of Chemotherapy-Induced Neutropenia: In randomized, controlled clinical trials, the per-patient incidences of NCI-CTC Grade 3-4 neutropenia and of febrile neutropenia were higher in patients receiving Trastuzumab in combination with myelosuppressive chemotherapy as compared to those who received chemotherapy alone. The incidence of septic death was similar among patients who received Trastuzumab and those who did not.

Patients who receive anthracycline after stopping Trastuzumab may be at increased risk of cardiac dysfunction because of Trastuzumab’s long washout period based on population PK analysis. If possible, physicians should avoid anthracycline-based therapy for up to 7 months after stopping Trastuzumab. If anthracyclines are used, the patient’s cardiac function should be monitored carefully.

It can cause fetal harm when administered to a pregnant woman. Verify the pregnancy status of females of reproductive potential prior to the initiation of Trastuzumab. Advise pregnant women and females of reproductive potential that exposure to Trastuzumab during pregnancy or within 7 months prior to conception can result in fetal harm. Advise females of reproductive potential to use effective contraception during treatment and for 7 months following the last dose of Trastuzumab. There is no information regarding the presence of Trastuzumab in human milk, the effects on the breastfed infant, or the effects on milk production.

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

Reconstitute each 440 mg vial of Trastuzumab with 20 ml of Bacteriostatic Water for Injection (BWFI), USP, containing 1.1% benzyl alcohol as a preservative to yield a multi-dose solution containing 21 mg/ml Trastuzumab. In patients with known hypersensitivity to benzyl alcohol, reconstitute with 20 ml of Sterille Water for Injection (SWFI) without preservative to yield a single use solution.

Store the vial in original carton at 2 o -8 o C. Protect from light. Keep out of the reach of children. Store reconstituted Trastuzumab in the refrigerator at 2°C to 8°C, discard unused Trastuzumab after 28 days. If Trastuzumab is reconstituted with SWFI without preservative, use immediately and discard any unused portion. Do not freeze. The solution of Trastuzumab for infusion diluted in 0.9% Sodium Chloride Injection, USP, should be stored at 2°C to 8°C for no more than 24 hours prior to use. Do not freeze.

The HER2 (or c-erbB2) proto-oncogene encodes a transmembrane receptor protein of 185 kDa, which is structurally related to the epidermal growth factor receptor. Trastuzumab has been shown, in both in vitro assays and in animals, to inhibit the proliferation of human tumor cells that overexpress HER2. Trastuzumab is a mediator of antibody-dependent cellular cytotoxicity (ADCC). In vitro, Trastuzumab-mediated ADCC has been shown to be preferentially exerted on HER2 overexpressing cancer cells compared with cancer cells that do not overexpress HER2.

Recommended Doses and Schedules: Do not administer as an intravenous push or bolus. Do not mix Trastuzumab with other drugs.

Adjuvant Treatment, Breast Cancer: Administer according to one of the following doses and schedules for a total of 52 weeks of Trastuzumab therapy:

During and following paclitaxel, docetaxel, or docetaxel/carboplatin:

• Initial dose of 4 mg/kg as an intravenous infusion over 90 minutes then at 2 mg/kg as an intravenous infusion over 30 minutes weekly during chemotherapy for the first 12 weeks (paclitaxel or docetaxel) or 18 weeks (docetaxel/carboplatin).
• One week following the last weekly dose of Trastuzumab, administer Trastuzumab at 6 mg/kg as an intravenous infusion over 30−90 minutes every three weeks.

As a single agent within three weeks following completion of multi-modality, anthracycline-based chemotherapy regimens:

• Initial dose at 8 mg/kg as an intravenous infusion over 90 minutes
• Subsequent doses at 6 mg/kg as an intravenous infusion over 30−90 minutes every three weeks.
• Extending adjuvant treatment beyond one year is not recommended

Metastatic Treatment, Breast Cancer: Administer Trastuzumab, alone or in combination with paclitaxel, at an initial dose of 4 mg/kg as a 90 minute intravenous infusion followed by subsequent once-weekly doses of 2 mg/kg as 30-minute intravenous infusions until disease progression.

Metastatic Gastric Cancer: Administer Trastuzumab at an initial dose of 8 mg/kg as a 90-minute intravenous infusion followed by subsequent doses of 6 mg/kg as an intravenous infusion over 30–90 minutes every three weeks until disease progression. Or, as directed by the registered physician.

The most serious adverse reactions caused by Trastuzumab includes Cardiomyopathy, Infusion Reactions, Embryo-Fetal Toxicity, Pulmonary Toxicity, Exacerbation of Chemotherapy-Induced Neutropenia. The most common adverse reactions in patients receiving Trastuzumab in the adjuvant and metastatic breast cancer setting are fever, nausea, vomiting, infusion reactions, diarrhea, infections, increased cough, headache, fatigue, dyspnea, rash, neutropenia, anemia, and myalgia.

Cardiomyopathy: Trastuzumab can cause left ventricular cardiac dysfunction, arrhythmias, hypertension, disabling cardiac failure, cardiomyopathy, and cardiac death. Trastuzumab can also cause asymptomatic decline in left ventricular ejection fraction (LVEF). There is a 4-6 fold increase in the incidence of symptomatic myocardial dysfunction among patients receiving Trastuzumab as a single agent or in combination therapy compared with those not receiving Trastuzumab. The highest absolute incidence occurs when Trastuzumab is administered with an anthracycline. Withhold Trastuzumab for ≥ 16% absolute decrease in LVEF from pre treatment values or an LVEF value below institutional limits of normal and ≥ 10% absolute decrease in LVEF from pretreatment values. The safety of continuation or resumption of Trastuzumab in patients with Trastuzumab-induced left ventricular cardiac dysfunction has not been studied.

Cardiac Monitoring: Conduct thorough cardiac assessment, including history, physical examination, and determination of LVEF by echocardiogram or MUGA scan. The following schedule is recommended:

• Baseline LVEF measurement immediately prior to initiation of Trastuzumab
• LVEF measurements every 3 months during and upon completion of Trastuzumab
• Repeat LVEF measurement at 4 week intervals if Trastuzumab is withheld for significant left ventricular cardiac dysfunction.
• LVEF measurements every 6 months for at least 2 years following completion of Trastuzumab as a component of adjuvant therapy.

Infusion Reactions: Infusion reactions consist of a symptom complex characterized by fever and chills, and on occasion included nausea, vomiting, pain (in some cases at tumor sites), headache, dizziness, dyspnea, hypotension, rash, and asthenia. Serious and fatal infusion reactions have been reported. Severe reactions, which include bronchospasm, anaphylaxis, angioedema, hypoxia, and severe hypotension, were usually reported during or immediately following the initial infusion. However, the onset and clinical course were variable, including progressive worsening, initial improvement followed by clinical deterioration, or delayed post-infusion events with rapid clinical deterioration. For fatal events, death occurred within hours to days following a serious infusion reaction. Interrupt Trastuzumab infusion in all patients experiencing dyspnea, clinically significant hypotension, and intervention of medical therapy administered (which may include epinephrine, corticosteroids, diphenhydramine, bronchodilators, and oxygen). Patients should be evaluated and carefully monitored until complete resolution of signs and symptoms. Permanent discontinuation should be strongly considered in all patients with severe infusion reactions. There are no data regarding the most appropriate method of identification of patients who may safely be retreated with Trastuzumab after experiencing a severe infusion reaction. Prior to resumption of Trastuzumab infusion, the majority of patients who experienced a severe infusion reaction were pre-medicated with antihistamines and/or corticosteroids. While some patients tolerated Trastuzumab infusions, others had recurrent severe infusion reactions despite pre-medications.

Embryo-Fetal Toxicity: Trastuzumab can cause fetal harm when administered to a pregnant woman. Use of Trastuzumab during pregnancy resulted in cases of oligohydramnios and oligohydramnios sequence manifesting as pulmonary hypoplasia, skeletal abnormalities, and neonatal death. Advise females of reproductive potential to use effective contraception during treatment and for 7 months following the last dose of Trastuzumab.

Pulmonary Toxicity: Trastuzumab use can result in serious and fatal pulmonary toxicity. Pulmonary toxicity includes dyspnea, interstitial pneumonitis, pulmonary infiltrates, pleural effusions, non-cardiogenic pulmonary edema, pulmonary insufficiency and hypoxia, acute respiratory distress syndrome, and pulmonary fibrosis. Such events can occur as sequelae of infusion reactions. Patients with symptomatic intrinsic lung disease or with extensive tumor involvement of the lungs, resulting in dyspnea at rest, appear to have more severe toxicity.

Exacerbation of Chemotherapy-Induced Neutropenia: In randomized, controlled clinical trials, the per-patient incidences of NCI-CTC Grade 3-4 neutropenia and of febrile neutropenia were higher in patients receiving Trastuzumab in combination with myelosuppressive chemotherapy as compared to those who received chemotherapy alone. The incidence of septic death was similar among patients who received Trastuzumab and those who did not.

Patients who receive anthracycline after stopping Trastuzumab may be at increased risk of cardiac dysfunction because of Trastuzumab’s long washout period based on population PK analysis. If possible, physicians should avoid anthracycline-based therapy for up to 7 months after stopping Trastuzumab. If anthracyclines are used, the patient’s cardiac function should be monitored carefully.

It can cause fetal harm when administered to a pregnant woman. Verify the pregnancy status of females of reproductive potential prior to the initiation of Trastuzumab. Advise pregnant women and females of reproductive potential that exposure to Trastuzumab during pregnancy or within 7 months prior to conception can result in fetal harm. Advise females of reproductive potential to use effective contraception during treatment and for 7 months following the last dose of Trastuzumab. There is no information regarding the presence of Trastuzumab in human milk, the effects on the breastfed infant, or the effects on milk production.

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

Reconstitute each 440 mg vial of Trastuzumab with 20 ml of Bacteriostatic Water for Injection (BWFI), USP, containing 1.1% benzyl alcohol as a preservative to yield a multi-dose solution containing 21 mg/ml Trastuzumab. In patients with known hypersensitivity to benzyl alcohol, reconstitute with 20 ml of Sterille Water for Injection (SWFI) without preservative to yield a single use solution.

Store the vial in original carton at 2 o -8 o C. Protect from light. Keep out of the reach of children. Store reconstituted Trastuzumab in the refrigerator at 2°C to 8°C, discard unused Trastuzumab after 28 days. If Trastuzumab is reconstituted with SWFI without preservative, use immediately and discard any unused portion. Do not freeze. The solution of Trastuzumab for infusion diluted in 0.9% Sodium Chloride Injection, USP, should be stored at 2°C to 8°C for no more than 24 hours prior to use. Do not freeze.