Dosing and uses of Repatha (evolocumab)
Adult dosage forms and strengths
solution for SC injection
- 140mg/mL in a single-use prefilled syringe or single-use SureClick autoinjector
- 420mg/3.5mL in a single-use Pushtronex system (on-body infusor with prefilled cartridge)
Primary Hyperlipidemia
Indicated as an adjunct to diet and maximally tolerated statin therapy for the treatment of adults with heterozygous familial hypercholesterolemia (HeFH) or clinical atherosclerotic CVD, who require additional lowering of LDL-C
140 mg SC q2weeks or 420 mg SC once monthly (see Administration for instructions regarding single or 3 injections)
When switching dosage regimens, administer the first dose of the new regimen on the next scheduled date of the prior regimen
Homozygous Familial Hypercholesterolemia
Indicated as an adjunct to diet and other LDL-lowering therapies (eg, statins, ezetimibe, LDL apheresis) for the treatment of patients with homozygous familial hypercholesterolemia (HoFH) who require additional lowering of LDL-C
420 mg SC once monthly (see Administration for instructions regarding single or 3 injections)
Measure LDL-C levels 4-8 wk after initiating, since response to therapy depends on the degree of LDL-receptor function
Dosage modifications
Renal impairment
- Mild or moderate: No dose adjustment required
- Severe: Not studied
Hepatic impairment
- Mild or moderate: No dose adjustment required
- Severe: Not studied
Pediatric dosage forms and strengths
SC injection
- 140mg/mL
Primary Hyperlipidemia
Safety and efficacy not established in children with heterozygous familial hypercholesterolemia (HeFH)
Homozygous Familial Hypercholesterolemia
Indicated as an adjunct to diet and other LDL-lowering therapies (eg, statins, ezetimibe, LDL apheresis) for the treatment of patients with homozygous familial hypercholesterolemia (HoFH) who require additional lowering of LDL-C
<13 years: Safety and efficacy not established
13-17 years: 420 mg SC once monthly (see Administration for instructions regarding 1 or 3 injections)
Measure LDL-C levels 4-8 wk after initiating, since response to therapy depends on the degree of LDL-receptor function
Repatha (evolocumab) adverse (side) effects
>10%
Nasopharyngitis (4-10.5%)
1-10%
Upper respiratory tract infection (2.1-9.3%)
Influenza (1.2-7.5%)
Back pain (2.3-6.2%)
Injection site reactions (3.2-5.7%)
Allergic reaction (5.1%)
Cough (1.2-4.5%)
Urinary tract infection (1.3-4.5%)
Sinusitis (4.2%)
Headache (4%)
Myalgia (4%)
Dizziness (3.7%)
Musculoskeletal pain (3.3%)
Hypertension (3.2%)
Diarrhea (3%)
Gastroenteritis (3%)
Arthralgia (1.8%)
Nausea (1.8%)
Fatigue (1.6%)
Muscle spasms (1.3%)
Contusion (1%)
Warnings
Contraindications
History of serious hypersensitivity to evolocumaB
Cautions
Hypersensitivity reactions (eg, rash, urticaria) reported, including some that led to discontinuation of therapy
Pregnancy
Pregnancy
No available data on use in pregnant women
Monoclonal antibodies in humans indicate 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 trimesters
Animal studies
- 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 dosage
- 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
Lactation
Unknown if distributed in human breast milk
The development and health benefits of breastfeeding should be considered along with the mother’s clinical need for the drug and any potential adverse effects on the breastfed infant
Human IgG is present in human milk, but published data suggest that breastmilk IgG antibodies do not enter the neonatal and infant circulation in substantial amounts
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Repatha (evolocumab)
Mechanism of action
Monoclonal antibody that binds to PCSK9 (proprotein convertase subtilisin/kexin type 9)
LDL-C is cleared from the circulation preferentially through the LDL receptor (LDLR) pathway
PCSK9 is a serine protease that destroys LDLR in the liver, resulting in decreased LDL-C clearance and increased plasma LDL-C
PCSK9 inhibitors decrease LDLR degradation by PCSK9, and thereby improve LDL-C clearance and lower plasma LDL-C
Absorption
Bioavailability: 72%
Peak plasma time: 3-4 days
Peak plasma concentration: 18.6 mcg/mL (140 mg); 59 mcg/mL (420 mg)
AUC (last): 188 day·mcg/mL (140 mg); 924 day·mcg/mL (420 mg)
Distribution
Vd: 3.3 L (420 mg)
Elimination
Half-life: 11-17 days
Administration
SC Preparation
Remove prescribed dose from refrigerator at least 30 minutes before administration; this helps administer the entire dose and minimizes injection discomfort
Do not heat syringe, autoinjector, or on-body infuser (eg, microwave or hot water); let them warm to room temperature on their own
Do not leave in direct sunlight; keep in original carton until administered
Do not use autoinjector or on-body infusor if
- Drug appears cloudy or discolored, or contains particles
- Device appears cracked or broken
- The device has been dropped
- The orange cap is missing or not securely attached
SC Administration
Available as 140-mg/mL prefilled syringe or autoinjector; also available as 420-mg/3.5-mL on-body infusor
420 mg dose: Give three 140-mg SC injections consecutively within 30 minutes OR over 9 minutes using the single-use on-body infusor with refilled cartridge
Clean injection site with alcohol wipe and let dry
Do not inject in areas of skin that are bruised, red, tender, or hard
Avoid injecting in scars or stretch marks
Rotate administration sites
See prescribing information for images depicting injection technique for the various devices
Administration sites
- Self-injection: Thigh or abdomen (except for a 2-inch area around the naval)
- Caregiver: Thigh, abdomen, or outer area of upper arm
Missed Dose
For either the q2week or once monthly regimen, administer as soon as possible if there are >7 days until the next scheduled dose, Or
Omit the missed dose and administer the next dose according to the original schedule
Storage
Refrigerate at 2-8°C (36-46°F) in the original carton
Alternatively, may store at room temperature (20-25°C [68-77°F]) in the original carton; however, under these conditions, drug must be used within 30 days; if not used within the 30 days, discard
Protect from direct light
Do not expose to temperatures >25°C (77°F)
Do not shake
