Makindo Medical Notes

⚠️ Warning: Lactic acidosis and severe hepatomegaly with steatosis (including fatal cases) have been reported with nucleoside analogues and other antiretrovirals. 🩸 Discontinue Lamivudine (EPIVIR) immediately if there are clinical or laboratory signs of lactic acidosis or pronounced hepatotoxicity. Monitor LFTs and lactate closely in at-risk patients.

🧠 About

• Lamivudine is a nucleoside reverse transcriptase inhibitor (NRTI) used in the management of HIV infection and chronic hepatitis B.
• It is almost always used as part of a combination antiretroviral therapy (cART) regimen to prevent resistance.
• For prescribing, always refer to the BNF Lamivudine monograph and local HIV or HBV protocols.

⚙️ Mode of Action

• Lamivudine is a cytosine analogue that inhibits reverse transcriptase (HIV) and DNA polymerase (HBV).
• After intracellular phosphorylation to lamivudine triphosphate, it competes with natural nucleotides for incorporation into viral DNA, leading to chain termination.
• By blocking viral DNA synthesis, it reduces viral replication and viral load.

💊 Indications and Dosing

• HIV infection: 300 mg once daily or 150 mg twice daily (in combination therapy).
• Chronic hepatitis B: 100 mg once daily as monotherapy or in combination regimens.
• Post-exposure prophylaxis (PEP): As part of a triple-drug regimen; dosing per HIV guidelines.
• Prevention of mother-to-child transmission: Used with zidovudine and nevirapine in antenatal and perinatal protocols.

📊 Dose Adjustments

• Reduce dose in renal impairment — primarily excreted unchanged in urine.
• Standard adult dose (300 mg OD) may be reduced to 150 mg daily when eGFR < 50 mL/min/1.73 m².

⚠️ Interactions

• Caution with nephrotoxic drugs (e.g. aminoglycosides, amphotericin B, NSAIDs) – increased risk of accumulation.
• Use cautiously with myelosuppressive drugs (e.g. zidovudine, ganciclovir) – risk of additive haematological toxicity.
• Generally few clinically significant CYP450 interactions (cleared renally, not hepatically).

⚕️ Cautions

• Adjust dose in renal failure and monitor for toxicity.
• In patients co-infected with HIV and hepatitis B, discontinuation can trigger severe hepatitis flares due to HBV reactivation.
• Monitor for features of lactic acidosis (unexplained fatigue, myalgia, breathlessness, abdominal pain).

🚫 Contraindications

• Known hypersensitivity to lamivudine or excipients.
• Relative: significant hepatic impairment with active lactic acidosis – specialist review required.

💥 Side Effects

• Generally well tolerated. Common: fatigue, nausea, diarrhoea, headache, insomnia, myalgia.
• Uncommon: peripheral neuropathy, pancreatitis, anaemia, lactic acidosis.
• Severe HBV exacerbations may occur upon discontinuation in HIV/HBV co-infected individuals — requires post-treatment monitoring.
• Rare: elevated liver enzymes, hepatic steatosis, hypersensitivity reactions.

📖 Educational Summary

Lamivudine was one of the earliest and safest NRTIs, forming the backbone of many combination regimens (e.g. with abacavir or zidovudine). Its dual activity against both HIV and hepatitis B makes it invaluable in coinfection. However, resistance develops rapidly if used as monotherapy, hence the importance of combination therapy. Pathophysiologically, its link with lactic acidosis and steatosis stems from mitochondrial DNA polymerase inhibition, leading to impaired oxidative phosphorylation and fat accumulation in hepatocytes. In the UK, treatment decisions are usually guided by specialist infectious disease or hepatology teams.

📚 References

• Lamivudine – British National Formulary
• HIV Treatment Guidelines (BHIVA, 2023)
• NICE NG93: HIV testing and management
• European Association for the Study of the Liver (EASL) Hepatitis B Guidelines, 2023