Common Side Effects of Repatha (Evolocumab)
Repatha is generally well-tolerated with most side effects being mild and self-limiting, including nasopharyngitis, upper respiratory infections, influenza, back pain, and injection site reactions occurring in more than 5% of patients. 1
Most Common Side Effects (>5% incidence)
Respiratory Symptoms
- Nasopharyngitis is the most frequently reported side effect, occurring in 7.8% of patients versus 7.4% with placebo 2
- Upper respiratory tract infections occur in 5.1% of patients versus 4.8% with placebo 2
- Influenza or flu-like symptoms are common, reported in more than 5% of patients 1
Musculoskeletal Effects
- Back pain occurs in more than 5% of patients treated with Repatha 1
Injection Site Reactions
- Local injection site reactions (redness, pain, or bruising) occur in 3.2% of Repatha-treated patients versus 3.0% with placebo 2
- Approximately 2.1% experience injection site reactions versus 1.6% with placebo, with 90% of cases being mild 3, 4
- These reactions are generally mild and self-limiting according to the American College of Cardiology 3
Metabolic Effects
- Diabetes mellitus occurred in 8.8% of Repatha patients versus 8.2% with placebo in the cardiovascular outcomes trial 2
- Among patients without baseline diabetes, new-onset diabetes occurred in 8.1% versus 7.7% with placebo 2
Less Common Side Effects (1-5% incidence)
Hypersensitivity Reactions
- Overall hypersensitivity reactions occurred in 5.1% versus 4.7% with placebo 2
- Specific reactions include:
Do Side Effects Resolve on Their Own?
Self-Limiting Nature
- Most injection site reactions are mild and self-limiting according to the American College of Cardiology 3
- Only 0.1% of patients discontinued treatment due to local injection site reactions 2
- The FDA label advises patients to "tell your healthcare provider if you have any side effect that bothers you or that does not go away" 2, suggesting most effects do resolve spontaneously
Serious Reactions Requiring Discontinuation
- Serious hypersensitivity reactions (trouble breathing, swallowing, hives, swelling) require immediate discontinuation and emergency care 2
- If a serious hypersensitivity reaction occurs, discontinue therapy immediately and treat according to standard of care until symptoms resolve 1
Important Safety Considerations
Neurocognitive Concerns
- Neurocognitive events occurred at rates <1% but were reported slightly more frequently in the evolocumab group 3
- However, no evidence of increased cognitive adverse effects was observed in the FOURIER or EBBINGHAUS trials 1
- Neurocognitive events did not correlate with achieved LDL cholesterol levels 3
Very Low LDL-C Levels
- No excess adverse events have been observed in patients achieving very low LDL-C levels (<25 mg/dL) 3
- No signal of harm was found among patients with LDL-C levels <10 mg/dL during clinical studies 3
Overall Safety Profile
- The overall serious adverse event rate was 7.5% in both evolocumab and standard-therapy groups, showing no increased risk 3
- Overall adverse events occurred in 69.2% of evolocumab patients versus 64.8% in standard-therapy groups 3
Special Populations
Pediatric Patients (10-17 years)
- Common side effects in pediatric patients with HeFH include nasopharyngitis (12% vs 11% placebo), headache (11% vs 2%), and oropharyngeal pain (7% vs 0%) 2
Latex Sensitivity
- Latex-sensitive patients should be advised that needle covers on Repatha products contain latex 1
Clinical Pitfalls to Avoid
- Do not confuse mild injection site reactions with serious hypersensitivity—90% of injection site reactions are mild and do not require discontinuation 3
- Monitor for hypersensitivity reactions, but recognize that discontinuation rates are extremely low (0.1%) 2
- Reassure patients about neurocognitive concerns, as no evidence of increased cognitive effects was found in major trials 1