Avilam

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

Adults and adolescents over 12 years of age

: The recommended dose for HIV infection is 300 mg daily. This is administered as 150 mg twice daily.

Children

Three months to 12 years of age

: The recommended dose for HIV infection is 4 mg/kg twice daily up to a maximum of 300 mg daily.

Less than three months of age

: The limited data available are insufficient to propose specific dosage recommendations.

Lamivudine may be administered with or without food.

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 following adverse events have been reported during therapy for HIV disease with Avilam.

• 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.

Hypersensitivity to Lamivudine or to any of the excipients.

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, Avilam should be used with caution. Treatment with Avilam should be stopped immediately if clinical signs, symptoms, or laboratory abnormalities suggestive of pancreatitis occur

Lactic 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 Avilam 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 Avilam 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

: Avilam 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 Avilam 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.

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.

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 Avilam exposure. Avilam and zalcitabine may inhibit the intracellular phosphorylation of one another. Therefore, use of Avilam in combination with zalcitabine is not recommended.

Tablet

: Store in a cool and dry place, protect from light and moisture.

Oral Solution

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