Real-World Experience With Higher-Than-Recommended Doses of Lamivudine in Patients With Varying Degrees of Renal Impairment

Abstract

BackgroundAlthough nucleoside reverse transcriptase inhibitors have been associated with lactic acidosis, lamivudine (3TC) has not been reported to have an increased risk with elevated concentrations. Therefore, some recommend that the lowest tablet strength of 3TC be considered in patients with kidney disease to avoid the inconvenience of liquid formations. Our institution avoids dose-adjusting 3TC until creatinine clearance (CrCl) <30 mL/min and uses 100–150-mg tablets daily in hemodialysis. The aim of this study was to describe the use of higher-than-recommended doses of 3TC in a real-world setting.MethodsBlood samples were collected before and 0.5–1.5 hours after 3TC administration in HIV+ adults. Predose (Cmin) and postdose (Cmax) samples were measured by high-performance liquid chromatography. Physiologically based pharmacokinetic modeling was utilized to simulate areas under the curve (AUCs) and profiles by CrCl. Lactic acid levels and patient-reported adverse events were obtained to monitor for safety, and viral suppression was assessed for efficacy.ResultsThirty-four patients with varying degrees of renal function were enrolled. Observed 3TC Cmax values were comparable among CrCl cohorts. Simulated 3TC AUC values in patients with CrCl 30–49, 15–29, and 0–15 mL/min were consistent with historical data, and fold-errors were between 0.5 and 2.0. All lactic acid levels were within normal limits, and no adverse effects were reported.ConclusionsThis study is the first to describe the use of higher-than-recommended doses of 3TC in a real-world setting. 3TC was well tolerated across all levels of renal function. These results can guide providers in their selection of higher 3TC dosing in select patients with renal dysfunction to maximize adherence.

A retrospective evaluation of highly active antiretroviral therapy simplification in patients with end-stage renal disease receiving hemodialysis

“…Notably, only a small percentage of lamivudine is removed during HD, and thus, no supplemental dosing is required. 18,19 Limited lamivudine pharmacokinetic data are available for the safe use in PLWH with ESRD on HD. 18 In a recent analysis, 10 patients received lamivudine 100-150 mg daily.…”

“…The lamivudine AUC was 2.74-and 1.83-fold higher in patients on 150 mg and 100 mg daily doses, respectively, with ESRD on HD compared to patients with glomerular filtration rates >50 mL/ min. 18 An additional report utilizing the FDC dolutegravir/ abacavir/lamivudine tablet demonstrated virologic control and safety in 6 patients with ESRD on HD. 20 These reports provide some additional safety data regarding drug accumulation after daily NRTI dosing strategies in ESRD HD patients and may be an option for fixed dose lamivudine formulations.…”

Changes over time in creatinine clearance and comparison of emergent adverse events for HIV-positive adults receiving standard doses (300 mg/day) of lamivudine-containing antiretroviral therapy with baseline creatinine clearance of 30–49 vs ≥50 mL/min

“…There have been two recent publications on the use of higher-than-recommended doses of 3TC in patients with renal impairment. One study enrolled 34 HIV-positive patients with varying degrees of renal function and used physiologically-based pharmacokinetic modeling to simulate drug concentrations over time using areas under the curve (AUCs) and drug profiles by CLcr [12]. The authors noted that at their facility, 3TC is generally not dose-adjusted until CLcr <30 mL/min and that 100–150-mg 3TC tablets daily are used in HIV-positive patients on hemodialysis (HD).…”

An Overview of the Current Hepatitis B Treatment Strategies after Liver Transplantation

“…These limitations can be due to previously existing drug resistance, drug intolerance, contraindications, or their cost. 18,[24][25][26] Current drug treatment protocols Lamivudine Lamivudine, a dideoxynucleoside analogue, is an antiviral drug generally used in the treatment of hepatitis B as well as human immunodeficiency virus (HIV) infections. [27][28][29] Lamivudine is classified as nucleoside analogue reverse transcriptase inhibitors (NRTIs), and its antiviral activity is due to inhibition of reverse transcriptase enzyme in the form of lamivudine triphosphate.…”