ANTIRETROVIRAL DRUGS BACK Lamivir S Lamivir-S 30 Tablets Lamivir-S 40 Tablets Warning LACTIC ACIDOSIS AND SEVERE HEPATOMEGALY WITH STEATOSIS, INCLUDING FATAL CASES, HAVE BEEN REPORTED WITH THE USE OF NUCLEOSIDE ANALOGUES ALONE OR IN COMBINATION, INCLUDING LAMIVUDINE AND STAVUDINE (See "Warnings and Precautions" Section). Composition Lamivir-S 30 Tablets Each tablet contains Lamivudine 150 mg Stavudine 30 mg Lamivir-S 40 Tablets Each tablet contains Lamivudine 150 mg Stavudine 40 mg Description Lamivir-S is a combination of two drugs commonly used in the management of Human Immunodeficiency Virus (HIV) infection. Both stavudine and lamivudine belong to the nucleoside analogue class of antiretroviral drugs. Both drugs act by inhibiting the reverse transcriptase of HIV, and by terminating the growth of the DNA chain. Stavudine in combination with lamivudine has been shown to have synergistic antiretroviral activity. Each tablet of Lamivir-S contains half of the commonly prescribed daily doses of both stavudine and lamivudine. With the availability of this combination tablet patients may be better able to adhere to complex drug treatment regimens, thereby enhancing compliance. Indications Lamivir-S is indicated for the treatment of HIV infection. Dosage and Administration Adults Lamivir-S 30 1 tablet twice daily for patients weighing < 60 kg Lamivir-S 40 1 tablet twice daily for patients weighing > 60 kg Dose Adjustment: Because it is a fixed-dose combination, Lamivir-S should not be prescribed for patients requiring dosage adjustment, such as those with reduced renal function (creatinine clearance < 50 ml/min), those with low body weight (< 50 kg or 110 lbs), or those experiencing dose-limiting adverse events. Contraindications Lamivir-S is contraindicated in patients with clinically significant hypersensitivity to any of the components contained in the formulation. Warnings and Precautions LACTIC ACIDOSIS/SEVERE HEPATOMEGALY WITH STEATOSIS Lactic acidosis/severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of antiretroviral nucleoside analogues alone or in combination, including stavudine and lamivudine. A majority of these cases have been in women. Obesity and prolonged nucleoside exposure may be risk factors. Caution should be exercised when administering stavudine to any patient, and particularly to those with known risk factors for liver disease. Cases have also been reported in patients with no known risk factors. Treatment should be discontinued in any patient who develops clinical or laboratory findings suggestive of lactic acidosis or hepatotoxicity (which may include hepatomegaly and steatosis even in the absence of marked aminotransferase elevations). PERIPHERAL NEUROPATHY Stavudine therapy can be associated with severe peripheral neuropathy, which is dose-related. It has occurred more frequently in patients with advanced HIV infection, a history of neuropathy, or concurrent neurotoxic drug therapy, including didanosine. Patients should be monitored for the development of neuropathy that is usually characterized by numbness, tingling or pain in the feet or hands. Stavudine-related peripheral neuropathy may resolve if therapy is withdrawn promptly. In some cases, symptoms may worsen temporarily following discontinuation of therapy. If symptoms resolve completely, resumption of treatment with stavudine may be considered using the following dosage schedule for adults: 20 mg twice daily for patients > 60 kg 15 mg twice daily for patients < 60 kg IMPAIRED RENAL FUNCTION Reduction of the dosage of both stavudine and lamivudine is required in patients with a creatinine clearance of 50 ml/min or less. Hence, Lamivir-S cannot be used in this patient population. PATIENTS WITH HIV AND HEPATITIS B VIRUS COINFECTION In clinical trials, some patients with HIV infection who have chronic liver disease due to hepatitis B virus infection experienced clinical or laboratory evidence of recurrent hepatitis upon discontinuation of lamivudine. Consequences may be more severe in patients with decompensated liver disease. DRUG INTERACTIONS Trimethoprim 160 mg/sulphamethoxazole 800 mg once daily has been shown to increase lamivudine exposure (AUC). PREGNANCY Both lamivudine and stavudine are classified under category C. There are no adequate and well-controlled studies in pregnant women. Lamivir-S should be used during pregnancy only if the potential benefits outweigh the potential risk. LACTATION It is recommended that HIV-infected mothers do not breast-feed their infants to avoid risking postnatal transmission of HIV infection. It is not known whether stavudine or lamivudine are excreted in human milk. PAEDIATRICS Lamivir-S is not intended for use in paediatric patients. Side Effects Lamivudine Pancreatitis has been reported with the use of lamivudine. Lactic acidosis and hepatic steatosis, hepatitis and liver failure have been reported with the use of antiretroviral nucleoside analogs, alone or in combination. Other side effects associated with the use of lamivudine are diarrhea, malaise and fatigue, headache, nausea and vomiting, abdominal pain and discomfort, peripheral neuropathy, arthralgias, myalgias, skin rash, pruritus, transient neutropenia and thrombocytopenia and rarely, pancreatitis. Transiently elevated levels of hepatic enzymes and bilirubin (> 5 times the normal level) have also been observed occasionally during treatment with the drug. Resolution of transient neutropenia and raised hepatic and bilirubin levels occurred without dosage modification or discontinuation of therapy. Stavudine Therapy with stavudine can be associated with severe peripheral neuropathy, which is dose related and occurs more frequently in patients with advanced HIV infection or who have previously experienced peripheral neuropathy. Lactic acidosis and hepatic steatosis, hepatitis and liver failure have been reported with the use of antiretroviral nucleoside analogues, alone or in combination. Rash, diarrhoea, nausea/vomiting, pancreatitis, dementia and other peripheral neurologic symptoms have also been associated with the use of stavudine. Overdosage Lamivudine There is no known antidote for lamivudine. It is not known whether lamivudine can be removed by peritoneal dialysis or hemodialysis. Stavudine Stavudine can be removed by hemodialysis. Experience with adults treated with 12 to 24 times the recommended daily dosage revealed no acute toxicity. Complications of chronic overdosage include peripheral neuropathy and hepatic toxicity. Presentation Lamivir-S 30 Container of 60 tablets Lamivir-S 40 Container of 60 tablets TOP