What are the side effects of Repatha (evolocumab)?

Repatha (Evolocumab) Side Effects

Repatha is generally well-tolerated with common side effects including nasopharyngitis, upper respiratory tract infections, influenza, back pain, and injection site reactions occurring in more than 5% of patients, while serious adverse events are rare and comparable to placebo. 1, 2

Common Side Effects (>5% of patients)

Respiratory symptoms are the most frequently reported adverse effects:

• Nasopharyngitis (common cold symptoms) 1, 2
• Upper respiratory tract infections 1, 2
• Influenza or flu-like symptoms 1, 2

Musculoskeletal complaints:

• Back pain occurs commonly 1, 2
• Myalgia (muscle pain) has been reported 3
• Arthralgia (joint pain) 3

Injection site reactions:

• Occur in approximately 2.1% of patients versus 1.6% with placebo 1
• Manifestations include redness, pain, or bruising at the injection site 1, 2
• Approximately 90% of injection site reactions are mild and self-limiting 1

Metabolic effects:

• High blood sugar levels (diabetes mellitus) reported in patients with established cardiovascular disease 2

Serious Adverse Events

Hypersensitivity reactions are the primary serious concern:

• Angioedema has been reported 2
• If serious hypersensitivity reactions occur (trouble breathing/swallowing, hives, rash, itching, swelling of face/lips/tongue/throat/arms), immediately discontinue Repatha and seek emergency medical care 2

Overall serious adverse event rate:

• Serious adverse events occurred in 7.5% of evolocumab patients versus 7.5% in standard-therapy groups, showing no increased risk 4

Neurocognitive Concerns

A small increase in neurocognitive events was initially noted but has not been confirmed in rigorous testing:

• Neurocognitive adverse events occurred at rates <1%, but were reported slightly more frequently in the evolocumab group 4
• No evidence of increased cognitive adverse effects was observed in the FOURIER or EBBINGHAUS trials 1
• Importantly, neurocognitive events did not correlate with achieved LDL cholesterol levels during treatment 4

Laboratory Abnormalities

Liver and muscle enzyme elevations are uncommon:

• Aminotransferase elevations: 1.0% with evolocumab versus 1.2% with standard therapy 4
• Creatine kinase elevations: 0.6% with evolocumab versus 1.1% with standard therapy 4

Safety at Very Low LDL-C Levels

No excess adverse events have been observed even with extremely low LDL cholesterol levels:

• No signal of harm among patients achieving LDL-C levels <25 mg/dL 1
• No safety concerns identified in patients with LDL-C levels <10 mg/dL during clinical studies 1
• This finding from the FOURIER trial demonstrated that patients benefit from LDL lowering below traditional targets without additional safety concerns 5

Special Populations and Considerations

Latex sensitivity:

• Some Repatha presentations contain dry natural rubber (latex derivative) in the needle cover 2
• Latex-sensitive patients should be prescribed presentations without natural rubber latex 1, 2

Drug interactions:

• No clinically significant drug-drug interactions have been identified 1, 6
• Evolocumab can be safely combined with statins and other lipid-lowering therapies 6

Monitoring Recommendations

Routine monitoring should include:

• Observation for signs and symptoms of hypersensitivity reactions 1
• Assessment of injection site reactions, though most are mild and self-limiting 1
• LDL-C levels can be measured as early as 4 weeks after initiation to assess response 2

Overall Safety Profile

The adverse event profile is reassuring:

• Overall adverse events occurred in 69.2% of evolocumab patients versus 64.8% in standard-therapy groups 4
• The incidence of side effects is low and mainly limited to mild symptoms 3
• Long-term safety data from the FOURIER trial (median 2.2 years follow-up) showed no unexpected adverse events with the exception of slightly more injection-site reactions 5