Avilam

• HIV infection

Lamivudine in combination with other antiretroviral agents is indicated for the treatment of HIV infection.

N/A

Hypersensitivity to Lamivudine or to any of the excipients.

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 possibility of interactions with other medicinal products administered concurrently should be considered, particularly when the main route of elimination is active renal secretion. Administration of trimethoprim/sulfamethoxazole 160 mg/800 mg results in a 40% increase in Lamivudine exposure. Lamivudine and zalcitabine may inhibit the intracellular phosphorylation of one another. Therefore, use of Lamivudine in combination with zalcitabine is not recommended.

The following adverse events have been reported during therapy for HIV disease with Lamivudine.Blood and lymphatic systems disorders- Uncommon: Neutropenia, anaemia and thrombocytopenia Very rare: Pure red cell aplasia Nervous system disorders- Common: Headache, insomnia Very rare: Cases of peripheral neuropathy (or paraesthesia). Respiratory, thoracic and mediastinal disorders Common: Cough, nasal symptoms- Gastrointestinal disorders- Common: Nausea, vomiting, abdominal pain or cramps, diarrhea Rare: Rises in serum amylase. Cases of pancreatitis have been reported. Hepatobiliary disorders- Uncommon: Transient rises in liver enzymes (AST, ALT). Rare: Hepatitis Skin and subcutaneous tissue disorders- Common: Rash, alopecia Musculoskeletal and connective tissue disorders- Common: Arthralgia, muscle disorders Rare: Rhabdomyolysis, Lipodystrophy General disorders and administration site conditions- Common: Fatigue, malaise, fever. Cases of lactic acidosis, usually associated with severe hepatomegaly and hepatic steatosis, have been reported with the use of nucleoside analogues.

Pregnancy Category C. The safety of Lamivudine in human pregnancy has not been established.Lactation: Following oral administration Lamivudine excreted in breast milk at similar concentrations to those found in serum. That’s why it is recommended that mothers taking Lamivudine do not breast-feed their infants.

Lamivudin is not recommended for use as monotherapy. In pediatric patients with a history of prior antiretroviral nucleoside exposure, a history of pancreatitis, or other significant risk factors for the development of pancreatitis, Lamivudine should be used with caution. Treatment with Lamivudine should be stopped immediately if clinical signs, symptoms, or laboratory abnormalities suggestive of pancreatitis occurLactic Acidosis/Severe Hepatomegaly with Steatosis: 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 other antiretrovirals. A majority of these cases have been in women. Obesity and prolonged nucleoside exposure may be risk factors. Particular caution should be exercised when administering Lamivudine to any patient with known risk factors for liver disease.In patients with moderate to severe renal impairment, the dose should be adjusted. Patients receiving Lamivudin or any other antiretroviral therapy may continue to develop opportunistic infections and other complications of HIV infection, and therefore should remain under close clinical observation by physicians experienced in the treatment of patients with associated HIV diseases.

Renal impairment: Lamivudine concentrations are increased in patients with moderate to severe renal impairment due to decreased clearance. The dose should therefore be adjusted.Adults and adolescents over 12 years: CrCl 50 ml/min: first dose 150 mg & maintenance dose 150 mg twice daily CrCl 30 to <50 ml/min: first dose 150 mg & maintenance dose 150 mg once daily CrCl 15 to 29 ml/min: first dose 150 mg & maintenance dose 100 mg once daily CrCl 5 to 14 ml/min: first dose 150 mg & maintenance dose 50 mg once daily CrCl <5 ml/min: first dose 50 mg & maintenance dose 25 mg once daily Hepatic Impairment: Data obtained in patients with moderate to severe hepatic impairment shows that Lamivudine pharmacokinetics are not significantly affected by hepatic dysfunction. Based on these data, no dose adjustment is necessary in patients with moderate or severe hepatic impairment unless accompanied by renal impairment.