At what time of day should Abacavir (nucleoside reverse transcriptase inhibitors) Lamivudine (nucleoside reverse transcriptase inhibitors) be taken?

Timing of Abacavir/Lamivudine Administration

Abacavir/lamivudine should be taken twice daily (every 12 hours), and can be administered at any time of day with or without food, as the timing relative to meals does not affect drug absorption or efficacy. 1

Standard Dosing Schedule

The recommended dosing for abacavir/lamivudine is:

• Abacavir 300 mg twice daily 1
• Lamivudine 150 mg twice daily 1, 2
• These can be administered as separate tablets or as the fixed-dose combination (Combivir contains zidovudine/lamivudine, or other combinations) 3

The twice-daily dosing schedule is critical because zidovudine has a relatively short half-life requiring multiple daily doses to maintain therapeutic drug levels 3. While lamivudine can be given once daily in some contexts (300 mg once daily for adults) 2, when combined with abacavir in standard regimens, the twice-daily schedule is maintained for optimal efficacy.

Food and Timing Flexibility

• Both abacavir and lamivudine can be taken with or without food, as coadministration with food has no significant effect on drug exposure 4
• No specific time of day is required - patients can choose morning/evening or any 12-hour interval that fits their schedule 1
• This flexibility differs from drugs like efavirenz, which should be taken at bedtime to minimize neuropsychiatric side effects 1

Once-Daily Dosing Evidence

While once-daily abacavir (600 mg) plus lamivudine (300 mg) has been studied and shown to be noninferior to twice-daily dosing in some populations 5, 6, 7, the standard recommendation remains twice-daily dosing:

• In African children, once-daily abacavir/lamivudine was noninferior to twice daily at week 48 (73% vs 72% with viral load <80 copies/mL) 5
• In treatment-naive adults, once-daily abacavir (600 mg) combined with lamivudine and efavirenz was noninferior to twice-daily abacavir (66% vs 68% achieving <50 copies/mL) 6
• Pharmacokinetic studies show bioequivalent AUC₀₋₂₄ for once versus twice-daily dosing, with the intracellular active metabolite (CBV-TP) having a half-life >20 hours supporting once-daily use 4, 7

However, guidelines consistently recommend twice-daily dosing 1, 3, and attempting once-daily dosing with standard twice-daily formulations would lead to subtherapeutic drug levels, increasing risk of virologic failure and resistance mutations 3.

Clinical Pitfalls to Avoid

• Never modify the dosing frequency of twice-daily formulations to once daily - this creates subtherapeutic levels and promotes resistance 3
• If once-daily dosing is needed for adherence, switch to regimens specifically approved for once-daily use (such as integrase inhibitor-based regimens like bictegravir/TAF/emtricitabine) 1, 3
• For pregnant women or post-exposure prophylaxis, the twice-daily schedule with zidovudine/lamivudine (Combivir) remains the preferred safe regimen 1, 8
• In patients with hepatitis B co-infection, both tenofovir and lamivudine have anti-HBV activity, and discontinuation can cause hepatitis flares 1

Special Populations

For pediatric patients aged 3 months and older:

• Dose should be calculated based on body weight and not exceed 300 mg daily of lamivudine 2
• Can be administered once or twice daily depending on the specific formulation and weight band 2

For patients with renal impairment:

• Doses must be adjusted according to creatinine clearance 2
• Abacavir pharmacokinetics are unchanged in end-stage renal disease, but lamivudine requires dose reduction 4