Uses of Lamicudine & Zidovudin: - HIV infection HIV infection Neutrophil count <0.75 x 109/l; haemoglobin levels <7.5 g/dl or 4.65 mmol/l. Lactation.

Drugs for HIV / Anti-retroviral drugs

Lamivudine and Zidovudine are synthetic nucleoside analogues with activity against human immunodeficiency virus (HIV).Lamivudine: Intracellularly, Lamivudine is phosphorylated to its active 5’-triphosphate metabolite, Lamivudine triphosphate (L-TP). The principal mode of action of L-TP is inhibition of reverse transcription (RT) via DNA chain termination after incorporation of the nucleoside analogue. Following oral administration, Lamivudine is rapidly absorbed and extensively distributed. Binding to plasma protein is low.Zidovudine: Intracellularly, Zidovudine is phosphorylated to its active 5’-triphosphate metabolite, Zidovudine triphosphate (ZDV-TP). The principal mode of action of ZDV-TP is inhibition of RT via DNA chain termination after incorporation of the nucleoside analogue. Following oral administration, Zidovudine is rapidly absorbed and extensively distributed. Binding to plasma protein is low. Zidovudine is eliminated primarily by hepatic metabolism.

How to use Lamivudine + Zidovudine: Take this medicine in the dose and duration as advised by your doctor. Swallow it as a whole. Do not chew, crush or break it. Lamivudine + Zidovudine may be taken with or without food, but it is better to take it at a fixed time. Administration: May be taken with or without food. Adult Dose: Oral HIV infection Adult: Each tab contains lamivudine 150 mg and zidovudine 300 mg: >30 kg: 1 tab bid. Avoid administering to patients < 30 kg Hepatic impairment: Severe: Not recommended, use separate preparations. Child Dose: HIV Infection <12 years: Not recommended; fixed-dose combination cannot be adjusted for children > 12 years and < 30 kg: Not recommended >12 years and >30 kg: As adults; 150 mg/300 mg (1 tablet) PO q12hr Renal Dose: Renal impairment: CrCl (ml/min) Dosage Recommendation <50 Not recommended, use separate preparations

Zidovudine: acyclovir and valacyclovir may increase CNS depression. Increased risk of haematologic toxicity with ganciclovir, valganciclovir, dapsone, doxorubicin, vincristine and vinblastine. Doxorubicin may reduce phophorylation; fluconazole may increase levels/effects; increased risk of hepatic decompensation or haematologic toxicities with interferon-? and ribavirin (also increases risk of pancreatitis and lactic acidosis). Methadone may increase effects/levels. Increased risk of myalgia, malaise and/or fever, maculopapular rash and effects/levels with probenecid. Stavudine may decrease antiviral activity; valproic acid may increase plasma levels (AUC increased by 80%). Lamivudine: Increased risk of hepatic decompensation or haematologic toxicities with interferon-? and ribavirin (also increases risk of mitochondrial toxicity, pancreatitis and lactic acidosis). Ganciclovir and valganciclovir may increase effects and toxicity; sulfamethoxazole/trimethoprim may increase AUC and decrease clearance (increasing levels and effects).

Neutrophil count <0.75 x 109/l; haemoglobin levels <7.5 g/dl or 4.65 mmol/l. Lactation.

Common - Nausea - Headache - Diarrhea - Fatigue - Cough - Feeling of discomfort - Nasal congestion (stuffy nose) >10% Headache (35%),Nausea (33%),Malaise & fatigue (27%),Cough (18%),Diarrhea (18%),Vomiting (13%),Musculoskeletal pain (12%),Neuropathy (12%),Insomnia & other sleep disorders (11%) 1-10% Anorexia &/or decreased appetite (10%),Dizziness (10%),Fever or chills (10%),Abdominal pain (9%),Depressive disorders (9%),Skin rashes (9%),Myalgia (8%),Neutropenia (7.2% ),Abdominal cramps (6%),Arthralgia (5%),Dyspepsia (5%),Anemia (2.9% ) Frequency Not Defined (serious) Erythema multiforme,Stevens-Johnson syndrome,Lactic acidosis,Pancreatitis,Hepatomegaly (Severe),Steatosis of liver (Severe),Anaphylaxis,Immune hypersensitivity reaction,Rhabdomyolysis Potentially Fatal: Lactic acidosis associated with liver failure and pancreatitis (normally after several mth of treatment); haematological toxicity (eg neutropenia and severe anaemia).

Pregnancy Category C. There arc no adequate and well controlled studies of this drug in pregnant women. This drug should be used during pregnancy only if the potential benefits outweigh the risks. The Centers for Disease Control and Prevention recommend that HIV-infected mothers should not breast-feed their infants to avoid risking postnatal transmission of HIV. Because of the potential for HIV transmission and the potential for serious adverse effects in nursing infants, mothers should be instructed not to breast feed if they are receiving efavirenz.

Precaution: Renal and hepatic impairment; poor bone marrow reserve prior to treatment; risk of opportunistic infection; patients (especially obese women) with risk factors for or active liver disease. Patients with low body wt should avoid the combined formulation. Separate formulations of lamivudine or zidovudine should not be given at the same time as the combined formulation. If dose adjustment is necessary for either component, separate formulations should be used. Monitor haematological parameters (advanced disease: 2 wkly for 1st 3 mth of treatment, then monthly; early disease: 1-3 mthly), LFTs, mean cell volume, serum creatinine kinase, viral load, CD4 counts and blood lactate levels. Patient to report any sore throat, nausea, vomiting, unexplained bruising or bleeding. Maintain adequate hydration (2-3 L/day) unless fluid restricted. Withdraw treatment if symptomatic hyperlactaemia, metabolic/lactic acidosis, progressive heptomegaly or rapidly elevating aminotransferase levels occur. Cases of lactic acidosis and hepatic steatosis syndrome have been reported in pregnancy. Monitor hepatic enzymes and electrolytes regularly during 3rd trimester. Lactation: not recommended

Stored at a cool and dry place, protected from light and moisture. Keep the medicine out of the reach of children.

Drugs for HIV / Anti-retroviral drugs

Lamivudine: NRTI; following phosphorylation, inhibits HIV reverse transcriptase by viral DNA chain termination; cytosine analog Zidovudine: NRTI; interferes with HIV viral RNA-dependent DNA polymerase (inhibits viral replication); thymidine analog

Pregnancy Category C. There arc no adequate and well controlled studies of this drug in pregnant women. This drug should be used during pregnancy only if the potential benefits outweigh the risks. The Centers for Disease Control and Prevention recommend that HIV-infected mothers should not breast-feed their infants to avoid risking postnatal transmission of HIV. Because of the potential for HIV transmission and the potential for serious adverse effects in nursing infants, mothers should be instructed not to breast feed if they are receiving efavirenz.