Repatha
(evolocumab)Dosage & Administration
In adults with established CVD or with primary hyperlipidemia:
In pediatric patients aged 10 years and older with HeFH:
In adults and pediatric patients aged 10 years and older with HoFH:
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Repatha Prescribing Information
REPATHA is indicated:
- In adults with established cardiovascular disease to reduce the risk of myocardial infarction, stroke, and coronary revascularization
- As an adjunct to diet, alone or in combination with other low-density lipoprotein cholesterol (LDL-C)-lowering therapies, in adults with primary hyperlipidemia, including heterozygous familial hypercholesterolemia (HeFH), to reduce LDL-C
- As an adjunct to diet and other LDL-C-lowering therapies in pediatric patients aged 10 years and older with HeFH, to reduce LDL-C
- As an adjunct to other LDL-C-lowering therapies in adults and pediatric patients aged 10 years and older with homozygous familial hypercholesterolemia (HoFH), to reduce LDL-C
Recommended Dosage
- In adults with established cardiovascular disease or with primary hyperlipidemia:
- The recommended dosage of REPATHA is either 140 mg every 2 weeks OR 420 mg once monthly administered subcutaneously [see Dosage and Administration (2.3)].
- If switching dosage regimens, administer the first dose of the new regimen on the next scheduled date of the prior regimen.
- In pediatric patients aged 10 years and older with HeFH:
- The recommended dosage of REPATHA is either 140 mg every 2 weeks OR 420 mg once monthly administered subcutaneously [see Dosage and Administration (2.3)].
- If switching dosage regimens, administer the first dose of the new regimen on the next scheduled date of the prior regimen.
- In adults and pediatric patients aged 10 years and older with HoFH:
- The initial recommended dosage of REPATHA is 420 mg once monthly administered subcutaneously [see Dosage and Administration (2.3)].
- The dosage can be increased to 420 mg every 2 weeks if a clinically meaningful response is not achieved in 12 weeks.
- Patients on lipid apheresis may initiate treatment with 420 mg every 2 weeks to correspond with their apheresis schedule. Administer REPATHA after the apheresis session is complete.
- Assess LDL-C when clinically appropriate. The LDL-lowering effect of REPATHA may be measured as early as 4 weeks after initiation.
- When monitoring LDL-C for patients receiving REPATHA 420 mg once monthly, note that LDL-C can vary during the dosing interval in some patients; recommend measuring LDL-C just prior to the next scheduled dose [see Clinical Studies (14)].
Missed Doses
If a dose is missed:
- Within 7 days from the missed dose, instruct the patient to administer REPATHA and resume the patient's original schedule.
- More than 7 days after the missed dose:
- For an every 2-week dose, instruct the patient to wait until the next dose on the original schedule.
- For a once-monthly dose, instruct the patient to administer the dose and start a new schedule based on this date.
Important Administration Instructions
- Advise latex-sensitive patients that the needle cover of the glass single-dose prefilled syringe and the single-dose prefilled autoinjector contain dry natural rubber (a derivative of latex) that may cause allergic reactions in individuals sensitive to latex [see Warnings and Precautions (5.1)].
- Train patients and/or caregivers on how to prepare and administer REPATHA, according to the Instructions for Use and instruct them to read and follow the Instructions for Use each time they use REPATHA.
- Prior to use, allow REPATHA to warm to room temperature for at least 30 minutes for the prefilled autoinjector or syringe and for at least 45 minutes for the on-body infusor with prefilled cartridge if REPATHA has been refrigerated [see How Supplied/Storage and Handling (16)].
- Visually inspect REPATHA prior to administration. REPATHA is a clear to opalescent, colorless to pale yellow solution. Do not use if the solution is cloudy, discolored, or contains particles.
- Administer REPATHA subcutaneously into areas of the abdomen, thigh, or upper arm that are not tender, bruised, red, or indurated. Avoid injecting into areas with scars or stretch marks. Rotate injection sites for each administration.
- The 420 mg dose of REPATHA can be administered:
- over 5 minutes by using the single-dose on-body infusor with prefilled cartridge, or
- by giving 3 injections consecutively within 30 minutes using the single-dose prefilled autoinjector or single-dose prefilled syringe.
REPATHA is a clear to opalescent, colorless to pale yellow solution available as follows:
- Injection: 140 mg/mL solution in a single-dose prefilled syringe
- Injection: 140 mg/mL solution in a single-dose prefilled SureClick® autoinjector
- Injection: 420 mg/3.5 mL solution in a single-dose Pushtronex® system (on-body infusor with prefilled cartridge)
Pregnancy
Risk Summary
Available data from clinical trials and postmarketing reports on REPATHA use in pregnant women are insufficient to evaluate for a drug-associated risk of major birth defects, miscarriage or other adverse maternal or fetal outcomes. 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. Monoclonal antibodies are transported across the placenta in increasing amounts especially near term; therefore, evolocumab has the potential to be transmitted from the mother to the developing fetus.
The estimated background risk of major birth defects and miscarriage for the indicated population(s) is unknown. 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 safety study for REPATHA. If REPATHA is administered during pregnancy, healthcare providers should report REPATHA exposure by contacting Amgen at 1-800-77-AMGEN (1-800-772-6436) or https://wwwext.amgen.com/products/global-patient-safety/adverse-event-reporting.
Data
Animal Data
In cynomolgus monkeys, no effects on embryo-fetal or postnatal development (up to 6 months of age) were observed when evolocumab was dosed during organogenesis to parturition at 50 mg/kg once every 2 weeks by the subcutaneous route at exposures 30- and 12-fold the recommended human doses of 140 mg every 2 weeks and 420 mg once monthly, respectively, based on plasma AUC. No test of humoral immunity in infant monkeys was conducted with evolocumab.
Lactation
Risk Summary
There is no information regarding the presence of evolocumab in human milk, the effects on the breastfed infant, or the effects on milk production. 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.
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.
Pediatric Use
The safety and effectiveness of REPATHA in combination with diet and other LDL-C-lowering therapies for the treatment of HoFH have been established in pediatric patients aged 10 years and older. Use of REPATHA for this indication is supported by evidence from an adequate and well-controlled trial in adults and pediatric patients aged 13 years and older with HoFH (including 7 pediatric patients treated with REPATHA) and from open-label studies which included an additional 19 pediatric patients aged 11 years and older with HoFH not previously treated with REPATHA [see Adverse Reactions (6.1) and Clinical Studies (14)].
The safety and effectiveness of REPATHA as an adjunct to diet and other LDL-C-lowering therapies for the treatment of HeFH have been established in pediatric patients aged 10 years and older. Use of REPATHA for this indication is based on data from a 24-week, randomized, placebo-controlled, double-blind trial in pediatric patients with HeFH. In the trial, 104 patients received REPATHA 420 mg subcutaneously once monthly and 53 patients received placebo; 39 patients (25%) were 10 to 11 years of age [see Adverse Reactions (6.1) and Clinical Studies (14)].
The safety and effectiveness of REPATHA have not been established in pediatric patients with HeFH or HoFH who are younger than 10 years old or in pediatric patients with other types of hyperlipidemia.
Geriatric Use
In controlled trials, 7656 (41%) patients treated with REPATHA were ≥ 65 years old and 1500 (8%) were ≥ 75 years old. No overall differences in safety or effectiveness were observed between these patients and younger patients, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.
Renal Impairment
No dose adjustment is needed in patients with renal impairment [see Clinical Pharmacology (12.3)].
Hepatic Impairment
No dose adjustment is needed in patients with mild to moderate hepatic impairment (Child-Pugh A or B). No data are available in patients with severe hepatic impairment [see Clinical Pharmacology (12.3)].
REPATHA is contraindicated in patients with a history of a serious hypersensitivity reaction to evolocumab or any of the excipients in REPATHA. Serious hypersensitivity reactions including angioedema have occurred in patients treated with REPATHA [see Warnings and Precautions (5.1)].
Hypersensitivity Reactions
Hypersensitivity reactions, including angioedema, have been reported in patients treated with REPATHA. If signs or symptoms of serious hypersensitivity reactions occur, discontinue treatment with REPATHA, treat according to the standard of care, and monitor until signs and symptoms resolve. REPATHA is contraindicated in patients with a history of serious hypersensitivity reactions to evolocumab or any excipient in REPATHA [see Contraindications (4)].
The needle cover of the glass single-dose prefilled syringe and the single-dose prefilled autoinjector contain dry natural rubber (a derivative of latex) which may cause an allergic reaction in individuals sensitive to latex.