Are lamivudine, abacavir, and dolutegravir dialyzable in patients undergoing hemodialysis?

Dialyzability of Lamivudine, Abacavir, and Dolutegravir

Lamivudine is dialyzable with approximately 50% extraction during hemodialysis, but dose adjustment after dialysis is not required due to its large volume of distribution; abacavir is not dialyzable and requires no dose adjustment; dolutegravir is not dialyzable due to high protein binding (>98%) and requires no dose adjustment in patients undergoing hemodialysis. 1, 2

Lamivudine

Dialyzability Characteristics

• Lamivudine is removed by hemodialysis with an extraction ratio of approximately 50%, but the clinical impact is minimal due to its large volume of distribution (approximately 100 liters) 2
• A 4-hour hemodialysis session removes approximately 28 mg of lamivudine but does not significantly affect maximum concentration (Cmax) or area under the curve (AUC0-24) 3
• The intradialysis half-life is 5.3 hours compared to 17.2 hours without dialysis 3

Dosing Recommendations for Hemodialysis Patients

• Administer lamivudine after hemodialysis to avoid drug loss during the dialysis process 1
• For patients with creatinine clearance <5 mL/min or on hemodialysis: give 35 mg first dose, then 10 mg every 24 hours 1
• Alternative dosing: 0.05 mg every 24 hours or 0.5 mg every 7 days after hemodialysis 1
• No supplemental dose is needed after hemodialysis sessions because the amount removed does not significantly impact overall drug exposure 2, 3

Peritoneal Dialysis

• Peritoneal dialysis (both CAPD and APD) removes approximately 24 mg of lamivudine over 24 hours 3
• Peritoneal dialysis clearance is only 1/15th to 1/30th of plasma clearance, contributing minimally to overall drug elimination 4
• No supplemental dosing is required for patients on peritoneal dialysis 4

Abacavir

Dialyzability Characteristics

• Abacavir is not significantly removed by hemodialysis due to its pharmacokinetic properties 1
• The drug is primarily metabolized hepatically with minimal renal excretion 1

Dosing Recommendations

• No dose adjustment is required for patients with any degree of renal impairment or those undergoing dialysis 1
• Combination products containing abacavir (Trizivir, Epzicom) should be administered as separate component medications in patients with creatinine clearance <50 mL/min to allow proper dose adjustment of the renally-excreted components 1

Dolutegravir

Dialyzability Characteristics

• Dolutegravir is not dialyzable because it is highly protein-bound (>98%) and primarily metabolized by the liver 1
• As an integrase inhibitor with high molecular weight and extensive protein binding, dialysis is unlikely to result in significant drug removal 1

Dosing Recommendations

• No dose adjustment is required for patients with renal impairment of any severity or those undergoing hemodialysis 1
• Dolutegravir can be safely used in combination with other antiretrovirals in dialysis patients without dose modification 1

Clinical Pitfalls and Caveats

Common Mistakes to Avoid

• Do not give supplemental lamivudine doses after hemodialysis despite its dialyzability—the large volume of distribution prevents clinically significant drug loss 2, 3
• Do not assume all nucleoside reverse transcriptase inhibitors behave similarly in dialysis; lamivudine requires dose reduction while abacavir does not 1
• Avoid using fixed-dose combination products in patients with renal impairment when individual components have different dosing requirements 1

Monitoring Considerations

• Monitor for lamivudine-related side effects even at reduced doses, though the drug is generally well-tolerated in dialysis patients 5
• In kidney transplant recipients on lamivudine, be aware of higher rates of YMDD mutation development (29% vs 0% in hemodialysis patients) 5
• Regular monitoring of renal function is essential when using these agents, particularly in the post-transplant setting 5