Switching to or from Repatha (Evolocumab): Protocols, Timing, and What the Evidence Shows

What the Repatha label says about switching

The label's one explicit switching instruction concerns evolocumab's own dosing schedules. If the dosage regimen is switched, the first dose of the new regimen is given on the next scheduled date of the prior regimen [1].

A 420 mg dose is given as three consecutive 140 mg injections within 30 minutes, so each monthly dose is three injections [1]. In homozygous familial hypercholesterolemia, treatment starts at 420 mg once monthly and may increase to 420 mg every 2 weeks if the response is not clinically meaningful by 12 weeks [1]. LDL-C can be measured as early as 4 weeks after starting, and on the monthly schedule the sample is taken just before the next dose [1].

If a dose is missed

The Repatha label says that a dose missed by 7 days or less should be administered and the original schedule resumed. If a dose is more than 7 days late, the next scheduled dose is used for the every-2-week regimen; for the monthly regimen, the missed dose is administered and a new monthly schedule begins on that date [1].

Switching to or from another lipid-lowering drug

The Repatha label's switching instruction covers only evolocumab's own two schedules. It gives no timing rule for moving between evolocumab and another PCSK9 antibody, inclisiran, bempedoic acid, ezetimibe or a statin [1].

The label has no drug interactions section. It reports about 20% lower evolocumab Cmax and AUC in adults on a high-intensity statin, which it calls not clinically meaningful [1]. In FOURIER, 27,564 patients with atherosclerotic cardiovascular disease and LDL-C of 70 mg/dL or higher on a statin received evolocumab or placebo; at 48 weeks LDL-C was 59% lower than with placebo, from a median of 92 to 30 mg/dL, over a median follow-up of 2.2 years [2].

Safety points from the label

Hypersensitivity reactions including angioedema are the label's only Warning and Precaution; the label says to stop treatment and treat the reaction if symptoms are serious, and a history of a serious hypersensitivity reaction to evolocumab or any excipient is a contraindication [1]. Some autoinjector and syringe needle covers contain dry natural rubber, and latex-free presentations exist [1]. In a 52-week placebo-controlled trial of 420 mg monthly, injection site reactions occurred in 5.7% of the 599 people on Repatha versus 5.0% of the 302 on placebo [1].