Usage
Lamivudine is an antiviral medication primarily used to treat chronic hepatitis B and HIV-1 infection. It belongs to the nucleoside reverse transcriptase inhibitor (NRTI) class of antiretrovirals. For HIV, it is always used in combination with other antiretroviral drugs. For Hepatitis B, it can be used alone or in combination. Lamivudine works by inhibiting the reverse transcriptase enzyme, which is essential for viral replication. This action prevents the virus from making copies of itself, thereby reducing the viral load in the body.
Alternate Names
The International Nonproprietary Name (INN) is lamivudine. It is also known as 3TC. Popular brand names include Epivir and Epivir-HBV.
How It Works
Pharmacodynamics: Lamivudine is intracellularly phosphorylated to its active form, lamivudine triphosphate. This active metabolite competes with natural substrates for incorporation into viral DNA by the reverse transcriptase of HIV and hepatitis B virus, thus acting as a chain terminator of DNA synthesis.
Pharmacokinetics:
- Absorption: Lamivudine is rapidly and well-absorbed after oral administration, with a bioavailability of approximately 80-85%.
- Metabolism: Lamivudine is minimally metabolized by the liver.
- Elimination: Primarily eliminated by renal excretion, both as unchanged drug and minor metabolites. The elimination half-life is 5-7 hours.
Mode of Action: Lamivudine triphosphate inhibits the activity of the viral reverse transcriptase by competing with the natural substrate, deoxycytidine triphosphate. It gets incorporated into the viral DNA chain, causing chain termination and preventing further DNA synthesis. This ultimately inhibits viral replication.
Dosage
Standard Dosage
Adults:
- HIV Infection: 300 mg daily (either as 150 mg twice daily or 300 mg once daily) in combination with other antiretrovirals.
- Chronic Hepatitis B: 100 mg once daily.
Children:
- HIV Infection (3 months and older): Dosage is based on body weight, typically 4 mg/kg twice daily or 8 mg/kg once daily, up to a maximum of 300 mg/day. For specific weight band recommendations, consult pediatric HIV treatment guidelines. The scored tablet is preferred over the oral solution in children who can swallow tablets. Once-daily dosing of the oral solution is not recommended when initiating therapy in infants and young children.
- Chronic Hepatitis B (2-17 years): 3 mg/kg once daily, up to a maximum of 100 mg/day.
Special Cases:
- Elderly Patients: Dosage adjustments are generally not needed unless significant renal impairment is present.
- Patients with Renal Impairment: Dosage adjustments are necessary. Specific recommendations vary depending on creatinine clearance and should be based on current guidelines.
- Patients with Hepatic Dysfunction: Dosage adjustments are generally not necessary for moderate to severe hepatic impairment. However, caution is advised in patients with decompensated liver disease.
- Patients with Comorbid Conditions: Consider individual patient factors and potential drug interactions.
Clinical Use Cases
Lamivudine’s dosage recommendations are generally for continuous chronic administration for the treatment of HIV and Hepatitis B. It is not specifically dosed for clinical scenarios like:
- Intubation
- Surgical Procedures
- Mechanical Ventilation
- Intensive Care Unit (ICU) Use
- Emergency Situations
If a patient undergoing one of these procedures is already on lamivudine, standard dosing should be continued if possible or adjusted based on renal/hepatic function.
Dosage Adjustments
Dosage adjustments are required for renal impairment. Specific recommendations vary depending on creatinine clearance and should be based on current guidelines.
Side Effects
Common Side Effects:
Nausea, diarrhea, headache, fatigue, nasal symptoms, cough, sore throat.
Rare but Serious Side Effects:
Pancreatitis (particularly in children), lactic acidosis, severe hepatomegaly with steatosis, peripheral neuropathy, muscle pain or weakness, aplastic anemia, Stevens-Johnson syndrome, immune reconstitution inflammatory syndrome.
Long-Term Effects:
Lipodystrophy, metabolic abnormalities (e.g., hypertriglyceridemia, hypercholesterolemia, insulin resistance, hyperglycemia), osteonecrosis.
Adverse Drug Reactions (ADR):
Any of the rare but serious side effects listed above would be considered an ADR and necessitates immediate intervention.
Contraindications
Hypersensitivity to lamivudine.
Drug Interactions
Clinically significant interactions with other antiretrovirals should be checked. Trimethoprim increases lamivudine concentrations. Sorbitol can decrease lamivudine absorption. Consult a comprehensive drug interaction resource for a complete list. Coadministration with zalcitabine or emtricitabine is not recommended.
Pregnancy and Breastfeeding
Data suggest lamivudine is generally safe during pregnancy. Although the drug labels for lamivudine and tenofovir recommend against their use during breastfeeding, the amount of drug transferred through breast milk appears to be negligible and some clinical guidelines support their continued use in breastfeeding mothers on antiretroviral therapy with an undetectable viral load. However, a decision to breastfeed should be made in consultation with a healthcare provider after carefully considering the risks and benefits.
Drug Profile Summary
- Mechanism of Action: Nucleoside reverse transcriptase inhibitor, inhibits viral DNA synthesis.
- Side Effects: Nausea, diarrhea, headache, fatigue; rarely, pancreatitis, lactic acidosis, and liver toxicity.
- Contraindications: Hypersensitivity to lamivudine.
- Drug Interactions: Trimethoprim, sorbitol, zalcitabine, emtricitabine; check resources for others.
- Pregnancy & Breastfeeding: Generally considered safe during pregnancy; Can be used during breastfeeding when the mother has an undetectable viral load but should be carefully considered with the patient and provider.
- Dosage: HIV: 300mg daily, HBV: 100mg daily. Pediatric and renal dosing requires adjustments.
- Monitoring Parameters: Liver function tests, renal function tests, complete blood counts, HIV viral load (if applicable), HBV viral load (if applicable).
Popular Combinations
For HIV, lamivudine is commonly used in combination with other antiretrovirals as part of a highly active antiretroviral therapy (HAART) regimen. Specific combinations vary and should be determined based on current guidelines. For Hepatitis B, it is often used in combination with other antiviral medications, such as tenofovir or entecavir.
Precautions
- Screen for hepatitis B before starting treatment. Close monitoring of patients coinfected with HBV and HIV is needed during and after lamivudine therapy.
- Assess renal function before and during treatment.
- Monitor for signs and symptoms of lactic acidosis and pancreatitis.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Lamivudine?
A: For adults with HIV, 300 mg daily. For adults with chronic hepatitis B, 100 mg daily. Pediatric and renal dosing requires adjustments.
Q2: What is the mechanism of action of lamivudine?
A: Lamivudine is a nucleoside reverse transcriptase inhibitor. It acts by inhibiting viral DNA synthesis.
Q3: What are the common side effects of lamivudine?
A: Common side effects include nausea, diarrhea, headache, and fatigue.
Q4: What are the serious side effects of lamivudine?
A: Rare but serious side effects include pancreatitis, lactic acidosis, and liver toxicity.
Q5: What are the contraindications to lamivudine use?
A: Hypersensitivity to the drug.
Q6: Does lamivudine interact with other medications?
A: Yes, clinically significant interactions exist. Consult a drug interaction resource or the latest guidelines. Trimethoprim increases lamivudine levels, and sorbitol can decrease absorption. Zalcitabine and emtricitabine should not be co-administered with lamivudine.
Q7: Can lamivudine be used during pregnancy and breastfeeding?
A: Generally considered safe during pregnancy, but the decision should be made on a case-by-case basis in consultation with a doctor. Can be used during breastfeeding in mothers with suppressed viral load but requires discussion with healthcare providers.
Q8: How should lamivudine be administered?
A: Orally, with or without food. Tablets can be crushed and mixed with food or liquid if needed.
A: Lamivudine undergoes minimal hepatic metabolism and is primarily eliminated renally.
Q10: What should be monitored in patients taking lamivudine?
A: Monitor for signs and symptoms of lactic acidosis, pancreatitis, liver damage, renal function, and blood counts.
