Repatha (evolocumab)

Repatha (evolocumab) Injection, an antibody cholesterol medication, is a human monoclonal immunoglobulin G2 (IgG2) as an adjunct to diet and maximally tolerated statin therapy for the treatment of adults with heterozygous familial hypercholesterolemia (HeFH) or clinical atherosclerotic cardiovascular disease (CVD), who require additional lowering of low density lipoprotein cholesterol (LDL-C). Repatha is also indicated as an adjunct to diet and other LDL-lowering therapies (e.g., statins, ezetimibe, LDL apheresis) for the treatment of patients with homozygous familial hypercholesterolemia (HoFH) who require additional lowering of LDL-C.

The safety and effectiveness of REPATHA have not been established in pediatric patients with HoFH who are younger than 13 years old.

Common side effects of Repatha include:

• runny or stuffy nose,
• upper respiratory tract infection,
• influenza,
• back pain,
• injection site reactions (redness, pain, and bruising),
• allergic reactions (rash and hives),
• cough,
• urinary tract infection,
• sinus infection,
• headache,
• muscle pain,
• dizziness,
• high blood pressure,
• diarrhea, and
• stomach upset.

The recommended subcutaneous dosage of Repatha in adults with established cardiovascular disease or in adults with primary hyperlipidemia (including heterozygous familial hypercholesterolemia [HeFH]) is either 140 mg every 2 weeks OR 420 mg once monthly, based on patient preference for dosing frequency and injection volume. When switching dosage regimens, administer the first dose of the new regimen on the next scheduled date of the prior regimen.

The recommended subcutaneous dosage of Repatha in patients with HoFH is 420 mg once monthly. In patients with HoFH, measure LDL-C levels 4 to 8 weeks after starting Repatha, since response to therapy will depend on the degree of LDL-receptor function.

When monitoring LDL-C for patients receiving Repatha 420 mg once monthly, note that LDL-C can vary considerably during the dosing interval in some patients.

• If a dose is missed, instruct the patient to administer Repatha within 7 days from the missed dose and resume the patient's original schedule.
• If an every-2-week dose is not administered within 7 days, instruct the patient to wait until the next dose on the original schedule.
• If a once-monthly dose is not administered within 7 days, instruct the patient to administer the dose and start a new schedule based on this date.

No information provided

There are no data available on use of Repatha in pregnant women to inform a drug-associated risk.

In animal reproduction studies, there were no effects on pregnancy or neonatal/infant development when monkeys were subcutaneously administered evolocumab from organogenesis through parturition at dose exposures up to 12 times the exposure at the maximum recommended human dose of 420 mg every month.

In a similar study with another drug in the PCSK9 inhibitor antibody class, humoral immune suppression was observed in infant monkeys exposed to that drug in utero at all doses. The exposures where immune suppression occurred in infant monkeys were greater than those expected clinically.

No assessment for immune suppression was conducted with evolocumab in infant monkeys. Measurable evolocumab serum concentrations were observed in the infant monkeys at birth at comparable levels to maternal serum, indicating that evolocumab, like other IgG antibodies, crosses the placental barrier.

FDA’s experience with monoclonal antibodies in humans indicates that they are unlikely to cross the placenta in the first trimester; however, they are likely to cross the placenta in increasing amounts in the second and third trimester. Consider the benefits and risks of Repatha and possible risks to the fetus before prescribing Repatha to pregnant women.

In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.

There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to Repatha during pregnancy.

Please contact 1-877-311-8972 or https://mothertobaby.org/ongoing-study/repatha/ to enroll in or to obtain information about the registry.

There is no information regarding the presence of evolocumab in human milk, the effects on the breastfed infant, or the effects on milk production. The development and health benefits of breastfeeding should be considered along with the mother's clinical need for Repatha and any potential adverse effects on the breastfed infant from Repatha or from the underlying maternal condition. Human IgG is present in human milk, but published data suggest that breast milk antibodies do not enter the neonatal and infant circulation in substantial amounts.