Lamivudine + Zidovudine

Usage

• Lamivudine + Zidovudine is prescribed for the treatment of HIV-1 infection in combination with other antiretroviral agents. It is not a cure for HIV/AIDS but helps manage the disease and slow its progression.
• Pharmacological Classification: Nucleoside Reverse Transcriptase Inhibitor (NRTI) - a type of antiretroviral medication.
• Mechanism of Action: Lamivudine and Zidovudine inhibit the action of reverse transcriptase, a viral enzyme crucial for HIV replication. They are nucleoside analogs that are phosphorylated intracellularly to their active triphosphate forms. These active forms compete with natural nucleosides and are incorporated into the viral DNA, causing chain termination.

Alternate Names

• Combivir (brand name)

How It Works

• Pharmacodynamics: Both lamivudine and zidovudine act intracellularly to inhibit viral reverse transcriptase, preventing viral DNA synthesis and replication. This leads to a decrease in the viral load in the body, improving the immune system’s function and slowing the progression of HIV disease.

• Pharmacokinetics:

  • Absorption: Both drugs are well-absorbed orally.
  • Metabolism: Lamivudine is minimally metabolized, while zidovudine undergoes hepatic metabolism.
  • Elimination: Lamivudine is primarily renally excreted, while zidovudine and its metabolites are excreted both renally and through biliary routes.

• Mode of Action: After entering the cell, both are converted to their active triphosphate forms, which then act as competitive inhibitors and alternate substrates of the viral reverse transcriptase, causing DNA chain termination and interrupting HIV replication.

• Receptor Binding/Enzyme Inhibition: Lamivudine and Zidovudine act as competitive inhibitors of HIV reverse transcriptase.

• Elimination Pathways: Lamivudine is primarily eliminated through renal excretion. Zidovudine undergoes hepatic metabolism and is eliminated renally and in the bile.

Dosage

Standard Dosage

Adults:

• One tablet (150 mg lamivudine/300 mg zidovudine) twice daily.

Children:

• 14-21 kg: One-half tablet twice daily.
• 21-30 kg: One-half tablet in the morning and one whole tablet in the evening.
• ≥30 kg: One tablet twice daily.
• Safety and efficacy in children less than 3 months of age have not been established.

Special Cases:

• Elderly Patients: No specific dosage adjustments, but caution is advised due to potential age-related decreases in renal function.
• Patients with Renal Impairment: Not recommended for patients with creatinine clearance <50 mL/min; individual components should be used with dose adjustment.
• Patients with Hepatic Dysfunction: Not recommended for patients with severe hepatic impairment; individual components should be used with dose adjustment.
• Patients with Comorbid Conditions: Exercise caution in patients with pre-existing bone marrow suppression, liver disease, or pancreatitis.

Clinical Use Cases Dosage recommendations are not specifically provided in the sources for intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations. Dosage adjustments are based primarily on renal/hepatic function.

Dosage Adjustments

• Dose reductions for zidovudine are recommended in patients with renal impairment. However, as a fixed-dose combination, individual components should be used for these patients.

Side Effects

Common Side Effects

• Headache, nausea, diarrhea, fatigue, nasal symptoms, cough, insomnia, loss of body fat.

Rare but Serious Side Effects

• Lactic acidosis, severe hepatomegaly with steatosis, pancreatitis, myopathy, bone marrow suppression, anemia, neutropenia, immune reconstitution inflammatory syndrome.

Long-Term Effects

• Lipodystrophy, metabolic abnormalities, mitochondrial dysfunction, osteonecrosis.

Adverse Drug Reactions (ADR)

• Lactic acidosis, hepatotoxicity, blood dyscrasias.

Contraindications

• Hypersensitivity to lamivudine or zidovudine.
• Abnormally low neutrophil counts (<0.75 x 10⁹/L) or hemoglobin levels (<7.5 g/dL or 4.65 mmol/L).

Drug Interactions

• Co-administration with interferon alfa with or without ribavirin.
• Other drugs that are nephrotoxic or metabolized by the liver may increase the risk of side effects.
• Consult a drug interaction database for a complete list of potential interactions.

Pregnancy and Breastfeeding

• Pregnancy Safety Category: C (FDA classification)
• Fetal risks are considered low based on available data, but caution is advised.
• Both drugs are excreted in breast milk; breastfeeding is not recommended.

Drug Profile Summary As per formatting request, see the individual sections above.

Popular Combinations Lamivudine and zidovudine are typically used in combination with other antiretroviral agents for the treatment of HIV-1. Specific combinations will depend on the patient’s individual circumstances and resistance patterns.

Precautions As per formatting request, see the individual sections above.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Lamivudine + Zidovudine?

A: For adults and adolescents ≥30 kg: one tablet (150 mg lamivudine/300 mg zidovudine) twice daily. Pediatric dosing varies based on weight. Refer to the Dosage section above for details.

Q2: What are the common side effects of this medication?

A: Common side effects include headache, nausea, diarrhea, fatigue, nasal congestion, cough, and insomnia.

Q3: What are the serious side effects of this medication?

A: Serious side effects include lactic acidosis, liver problems (hepatotoxicity), muscle pain or weakness (myopathy), and blood disorders.

Q4: Can Lamivudine + Zidovudine be used during pregnancy?

A: It can be used during pregnancy if clinically needed and the potential benefit outweighs the risk to the fetus. Close monitoring of the mother and fetus is essential.

Q5: Can I breastfeed while taking this medication?

A: Breastfeeding is not recommended while taking Lamivudine + Zidovudine, as both drugs are excreted in breast milk and can pose risks to the infant.

Q6: What should I do if I miss a dose?

A: Take the missed dose as soon as you remember. If it is almost time for the next dose, skip the missed dose and continue your regular dosing schedule. Do not take a double dose.

Q7: What are the contraindications to using this medication?

A: It’s contraindicated in patients with hypersensitivity to either drug and in patients with abnormally low neutrophil or hemoglobin levels.

Q8: Does this drug cure HIV/AIDS?

A: No, Lamivudine + Zidovudine does not cure HIV/AIDS. It helps manage the disease, reduce viral load, and improve immune function, slowing disease progression.

Q9: Are there any dietary restrictions while taking this medication?

A: No specific dietary restrictions are associated with this medication. However, it’s always recommended to maintain a healthy, balanced diet for overall well-being.