What are the potential drug interactions with Repatha (evolocumab)?

Repatha (Evolocumab) Drug Interactions

Repatha (evolocumab) has minimal drug interactions, with only a modest 20-30% decrease in exposure observed when co-administered with high-intensity statins, which is not clinically significant. 1

Pharmacokinetic Profile and Elimination

Repatha is a monoclonal antibody that follows two elimination pathways:

• At low concentrations: elimination occurs through saturable binding to PCSK9
• At higher concentrations: elimination occurs through a non-saturable proteolytic pathway 1

The effective half-life of evolocumab is approximately 11-17 days, which supports its convenient dosing schedule of either 140 mg every 2 weeks or 420 mg once monthly. 1

Documented Drug Interactions

Statins

• A modest 20-30% decrease in Cmax and 40-50% decrease in AUC of evolocumab has been observed when co-administered with high-intensity statin regimens
• This interaction is not considered clinically meaningful and does not require dose adjustment 1

Special Populations

Renal Impairment

• Monoclonal antibodies are not typically eliminated via renal pathways
• While exposure may be decreased in patients with severe renal impairment or ESRD on hemodialysis, the reduction in PCSK9 levels remains similar to those with normal renal function
• No dose adjustment is required for renal impairment 1

Hepatic Impairment

• Patients with mild or moderate hepatic impairment show 20-30% lower Cmax and 40-50% lower AUC compared to healthy patients
• No specific dose adjustments are recommended for hepatic impairment 1

Age, Gender, Race, and Body Weight

• Pharmacokinetics are not significantly affected by age, gender, or race
• Exposure decreases with increasing body weight, but these differences are not clinically meaningful 1

Pediatric Patients

• Pharmacokinetics have been evaluated in pediatric patients aged 10-17 years with HeFH and HoFH
• No specific drug interactions have been identified in this population 1

Administration Considerations

Latex Sensitivity

• Patients with latex sensitivity should be advised that some needle covers contain dry natural rubber
• Alternative administration options should be considered for these patients 2

Clinical Implications

The minimal drug interaction profile of Repatha makes it a favorable option for patients on multiple medications. Unlike many other lipid-lowering therapies, Repatha does not require:

• Dose adjustments when used with other medications
• Specific timing relative to other drug administration
• Additional monitoring for drug-drug interactions

Monitoring Recommendations

• No specific laboratory monitoring is required beyond routine lipid profile assessment
• No requirement for liver function tests, renal function, or complete blood counts specifically due to drug interactions 2

The favorable drug interaction profile of Repatha contributes to its excellent safety profile observed in clinical trials, where rates of adverse events were similar between evolocumab and controls, even when used in combination with statins. 3