AVOCOMB KID TABLETS 30MG/60MG

Indications

• HIV infection in combination with other antiretroviral drugs
• Chronic hepatitis B infection with evidence of viral replication and active liver inflammation or fibrosis

Dosage

Children: For children aged 3 months to

Adults: For HIV infection, the adult dose is 150 mg every 12 hours or alternatively 300 mg once daily. For chronic hepatitis B, the recommended dose is 300 mg once daily.

Mechanism of action

Lamivudine is phosphorylated intracellularly to its active form, lamivudine triphosphate (L-TP). This active metabolite is incorporated into viral DNA by HIV reverse transcriptase and HBV polymerase, leading to DNA chain termination. Lamivudine competes with deoxycytidine triphosphate for binding to reverse transcriptase, and its incorporation into DNA results in the disruption of DNA synthesis due to the absence of a 3'-OH group necessary for chain elongation.

Pharmacodynamics

As a nucleoside reverse transcriptase inhibitor (NRTI), lamivudine disrupts the viral DNA synthesis pathway, particularly for HIV-1 and HBV. The active metabolite formed competes with natural nucleotides and incorporates into the growing viral DNA chain, ultimately leading to chain termination. This action inhibits the replication of the virus, thereby reducing viral load in infected individuals.

Pharmacokinetics

Lamivudine is absorbed via passive diffusion and is rapidly phosphorylated to its active triphosphate form within cells. Its bioavailability is approximately 80-85% when taken orally. The drug has a half-life of about 5-7 hours in plasma and is primarily eliminated via the kidneys through glomerular filtration and active tubular secretion. Renal impairment necessitates dose adjustments, particularly in patients with creatinine clearance below 50 mL/min.

Contra-indications

• Severe hypersensitivity to lamivudine or any of its excipients
• Patients with decompensated liver disease when used for chronic hepatitis B

Adverse effects

• Peripheral neuropathy
• Headache
• Nausea
• Diarrhea
• Fatigue
• Insomnia
• Malaise
• Cough
• Pharyngitis
• Respiratory tract infections
• Alopecia
• Arthralgia

Interactions

• Trimethoprim may increase exposure to lamivudine
• Concomitant use with other antiretroviral drugs should be evaluated for cross-resistance

Precautions

• Monitor liver function tests every 3 months in patients with chronic hepatitis B
• Recurrent hepatitis may occur upon discontinuation in chronic hepatitis B patients
• Use with caution in renal impairment; dose adjustments may be necessary if creatinine clearance is less than 50 mL/min

Pregnancy

Lamivudine is classified as category B, indicating that there are no known risks in humans, but caution should be exercised. It may be used during pregnancy if deemed necessary by the healthcare provider.

Breast-feeding

Lamivudine can be used with caution while breastfeeding, provided adequate measures are taken to prevent hepatitis B infection in infants.

Storage

Store in a cool, dry place away from direct sunlight. Keep out of reach of children.

Formulations

• Lamivudine 150 mg tablets
• Lamivudine 300 mg tablets
• Epivir oral solution

Indications

• HIV infection
• Prevention of maternal-to-child transmission of HIV
• Post-exposure prophylaxis in HIV-exposed individuals

Dosage

Children: For paediatric patients, dosing varies based on weight and age. It is generally based on

Adults: For adults, the typical initial dosage is 300 mg orally twice daily, or 200 mg three times daily. Dosing may be adjusted based on clinical response and tolerability.

Mechanism of action

Zidovudine is phosphorylated intracellularly to its active form, zidovudine triphosphate. This active metabolite competes with the natural nucleoside thymidine for incorporation into viral DNA by reverse transcriptase. Once incorporated, it causes chain termination, thereby preventing the completion of viral DNA synthesis. This effectively halts the replication of the virus, reducing the viral load in the body.

Pharmacodynamics

Zidovudine exhibits dose-dependent antiviral activity against HIV. The drug is effective against both HIV-1 and HIV-2. Its efficacy is influenced by the presence of viral resistance, which can develop through mutations in the reverse transcriptase enzyme. Zidovudine has been shown to improve immunological parameters, reduce the incidence of opportunistic infections, and prolong survival in HIV-infected individuals.

Pharmacokinetics

Zidovudine is rapidly absorbed following oral administration, with peak plasma concentrations occurring within 30 to 90 minutes. It undergoes extensive first-pass metabolism in the liver, leading to a bioavailability of approximately 60-70%. The drug has a half-life of about 1 hour, but its active form has a longer half-life. Zidovudine is primarily eliminated by renal excretion, with both unchanged drug and metabolites found in urine. Dosing adjustments may be necessary in patients with renal impairment.

Contra-indications

• Hypersensitivity to zidovudine or any of its components
• Severe bone marrow suppression

Adverse effects

• Nausea
• Headache
• Fatigue
• Anemia
• Neutropenia
• Lactic acidosis
• Myopathy
• Hepatotoxicity

Interactions

• Other myelosuppressive agents
• Ribavirin
• Probenecid
• Acetaminophen
• Skeletal muscle relaxants
• Antiretroviral agents

Precautions

• Monitor blood counts regularly due to risk of hematological toxicity
• Use with caution in patients with liver impairment
• Caution in elderly patients and those with renal impairment

Pregnancy

Zidovudine is classified as Category C. It should only be used if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

Zidovudine is excreted in breast milk. Caution should be exercised when administering to breastfeeding mothers.

Storage

Store at room temperature, away from moisture and light. Keep out of reach of children.

Formulations

• Tablets
• Oral solution
• Injection

Mechanism of action

Lamivudine is a synthetic nucleoside analogue and is phosphorylated intracellularly to its active 5'-triphosphate metabolite, lamivudine triphosphate (L-TP). This nucleoside analogue is incorporated into viral DNA by HIV reverse transcriptase and HBV polymerase, resulting in DNA chain termination. Lamivudine enters cells by passive diffusion and is phosphorylated to its active metabolite, lamivudine triphosphate. Lamivudine triphosphate competes with deoxycytidine triphosphate for binding to reverse transcriptase, and incorporation into DNA results in chain termination. Lamivudine has very low affinity for human alpha and omega DNA polymerases, moderate affinity for beta DNA polymerase, and higher affinity for gamma DNA polymerase.

Pharmacodynamics

Lamivudine is a nucleoside reverse transcriptase inhibitor (NRTI) with activity against Human Immunodeficiency Virus Type 1 (HIV-1) and hepatitis B (HBV) to disrupt viral DNA synthesis. When phosphorylated, lamivudine can form active metabolites that compete for incorporation into viral DNA. Via DNA incorporation, lamivudine metabolites competitively inhibit the activity of the HIV reverse transcriptase enzyme and act as a chain terminator of DNA synthesis. Due to the lack of a 3'-OH group, incorporated nucleoside analogues prevent the formation of a 5' to 3' phosphodiester linkage that is essential for DNA chain elongation.