Is Repatha (evolocumab) safe in an adult patient with a history of high cholesterol or cardiovascular disease?

Is Repatha (Evolocumab) Safe in Adult Patients?

Yes, Repatha (evolocumab) is safe and well-tolerated in adult patients with high cholesterol or cardiovascular disease, with an excellent safety profile demonstrated in trials up to 78 weeks and cardiovascular outcomes trials extending several years. 1, 2

Safety Profile from Clinical Trials

The most common adverse effects are mild and include nasopharyngitis, upper respiratory tract infection, influenza, back pain, and injection site reactions, occurring in >5% of patients but only slightly more frequently than placebo. 2

• In patients with established cardiovascular disease, the most common adverse reactions were diabetes mellitus, nasopharyngitis, and upper respiratory tract infection 2
• Injection site reactions are relatively infrequent and mild 1
• Myalgia was slightly more frequent with the related PCSK9 inhibitor alirocumab compared to placebo, though evolocumab appears similarly well-tolerated 1

Serious Adverse Events and Long-Term Safety

No excess of adverse events has emerged in patients achieving very low LDL cholesterol levels (<25 mg/dL or even <15 mg/dL) over 78 weeks of treatment, addressing concerns about extremely low cholesterol levels. 1

• A small, nonsignificant increase in neurocognitive events was initially reported, but there is no evidence of increased cognitive adverse effects in the FOURIER or EBBINGHAUS trials 1, 3
• A small nonsignificant increase in ophthalmologic events was noted with alirocumab, though this has not been a prominent concern with evolocumab 1
• The FOURIER trial demonstrated cardiovascular benefit (HR 0.85; 95% CI 0.79-0.92; P<0.001) without significant safety concerns over median follow-up 3

Specific Safety Considerations

The only absolute contraindication is a history of serious hypersensitivity reaction to evolocumab or any excipients. 1, 2

• Angioedema has occurred; if signs or symptoms of serious hypersensitivity reactions occur, discontinue Repatha immediately, treat according to standard of care, and monitor until symptoms resolve 2
• Latex-sensitive patients should be aware that some presentations contain dry natural rubber (a derivative of latex) in the needle cover, though latex-free presentations are available 3, 2

Safety in Special Populations

Evolocumab is well-accepted by statin-intolerant patients, with muscle-related adverse events comparable to those seen with ezetimibe. 1

• In patients with heterozygous familial hypercholesterolemia, evolocumab demonstrated similar safety and efficacy profiles 1
• In homozygous familial hypercholesterolemia patients on maximal lipid-lowering therapy, evolocumab was well-tolerated with efficacy related to residual LDL receptor activity 1
• Safety data in pregnancy are limited; there is a pregnancy safety study monitoring outcomes, and patients should report pregnancies to Amgen 2

Common Pitfalls to Avoid

• Do not prescribe latex-containing presentations to latex-sensitive patients—the carton and Instructions for Use clearly state whether the product contains dry natural rubber 3, 2
• Do not discontinue evolocumab due to concerns about very low LDL cholesterol levels—extensive trial data support safety even at LDL-C <25 mg/dL 1
• Do not withhold evolocumab due to cognitive concerns—dedicated neurocognitive testing in trials showed no increased risk 3

Monitoring Recommendations

• Assess LDL-C when clinically appropriate; the LDL-lowering effect may be measured as early as 4 weeks after initiation 2
• No specific laboratory monitoring for hepatic or muscle toxicity is required, unlike with statins 1
• Monitor for hypersensitivity reactions, particularly after initial doses 2