Repatha (Evolocumab) Safety in Pregnancy
Repatha should not be used during pregnancy except in rare, exceptional circumstances where severe maternal cardiovascular disease cannot be controlled by other means, as there is insufficient safety data to evaluate drug-associated risks of major birth defects, miscarriage, or adverse maternal-fetal outcomes. 1
FDA Labeling and Available Evidence
The FDA drug label explicitly states that available data from clinical trials and postmarketing reports are insufficient to evaluate for drug-associated risks of major birth defects, miscarriage, or other adverse maternal or fetal outcomes. 1
Key Safety Concerns
Placental Transfer and Fetal Exposure:
- Evolocumab, as an IgG2 monoclonal antibody, crosses the placental barrier like other IgG antibodies, with transport increasing especially near term. 1
- Measurable evolocumab serum concentrations were observed in infant monkeys at birth at comparable levels to maternal serum, confirming placental transmission. 1
Potential Immune Effects:
- In animal studies with another PCSK9 inhibitor antibody in the same class, humoral immune suppression was observed in infant monkeys exposed in utero at all doses tested. 1
- While no assessment for immune suppression was conducted specifically with evolocumab in infant monkeys, this class effect raises theoretical concerns. 1
Animal Reproduction Data
In cynomolgus monkey studies, no effects on embryo-fetal or postnatal development were observed when evolocumab was administered during organogenesis through parturition at exposures 12 times the maximum recommended human dose of 420 mg monthly. 1 However, animal studies do not always predict human outcomes, and the lack of immune testing in exposed offspring is a notable limitation.
Limited Human Case Report
One case report described evolocumab use at 31 and 35 weeks of gestation in a 34-year-old woman with compound heterozygous familial hypercholesterolemia and prior coronary artery bypass surgery, with LDL-C levels reaching 420 mg/dL. 2 Both mother and infant were discharged without notable complications. 2 However, this single case with third-trimester exposure only provides extremely limited safety information and cannot establish safety for broader use.
Clinical Decision Framework
When Repatha Might Be Considered:
- Only in life-threatening maternal cardiovascular situations where LDL-C levels pose immediate risk to maternal survival 2
- When all pregnancy-compatible lipid-lowering therapies have failed or are contraindicated 1
- After thorough discussion of unknown fetal risks versus known maternal risks of uncontrolled severe hypercholesterolemia 1
Mandatory Actions if Used:
- Healthcare providers must report any Repatha exposure during pregnancy to Amgen at 1-800-772-6436 or through their adverse event reporting system. 1
- Document the severe, uncontrolled maternal disease that necessitated use 1
- Plan for neonatal follow-up given potential immune effects from in utero exposure 1
Breastfeeding Considerations
There is no information regarding the presence of evolocumab in human milk or its effects on the breastfed infant. 1 While human IgG is present in breast milk, published data suggest that breast milk antibodies do not enter the neonatal circulation in substantial amounts. 1 The decision to breastfeed should consider the mother's clinical need for Repatha and any potential adverse effects on the infant. 1
Critical Pitfall to Avoid
The greatest pitfall is assuming that the single published case report establishes safety—it does not. 2 The absence of reported complications in one infant does not provide adequate evidence for routine use, and the theoretical risk of immune suppression based on class effects remains unresolved. 1