evolocumab [SC]

Adult Dosing

HeFH or primary hyperlipidemia with established clinical atherosclerotic CVD

Recommended dose: 140 mg SC q2wks or 420 mg SC once monthly

Note:

When switching dosage regimens, administer the first dose of the new regimen on the next scheduled date of the prior regimen.

Homozygous Familial Hypercholesterolemia (HoFH)

Recommended dose: 420 mg SC once monthly

Note:

Measure LDL-C levels 4-8 wks after initiating therapy, since response to therapy depends on the degree of LDL-receptor function.

For both dosage regimens

Missed dose: Administer evolocumab 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
Give 3 injections consecutively within 30 minutes to administer the dose of 420 mg.
Refer package insert for administration instructions

Pediatric Dosing

Primary Hyperlipidemia (HeFH)

Safety and effectiveness of evolocumab have not been established in children with heterozygous familial hypercholesterolemia (HeFH)

Homozygous Familial Hypercholesterolemia (HoFH)

Child <13 years: Safety and effectiveness have not been established
Child 13-17 years: 420 mg SC once monthly

Note:

Measure LDL-C levels 4-8 wks after initiating therapy, since response to therapy depends on the degree of LDL-receptor function
Missed dose: Administer evolocumab 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
Give 3 injections consecutively within 30 minutes to administer the dose of 420 mg
Refer package insert for administration instructions

[Outline]

Adult Dosing
Pediatric Dosing

Indications ⬆ ⬇

Treatment of adults with heterozygous familial hypercholesterolemia (HeFH) or clinical atherosclerotic CVD requiring additional lowering of LDL-C; indicated as an adjunct to diet and maximally tolerated statin therapy
Treatment of patients with homozygous familial hypercholesterolemia (HoFH) requiring additional lowering of LDL-C; indicated as an adjunct to diet and other LDL-lowering therapies such as statins, ezetimibe, LDL apheresis

Contraindications ⬆ ⬇

Hypersensitivity to any of the ingredients of the product

Black Box Warnings ⬆ ⬇

Dosing Adjustment ⬆ ⬇

Renal Dose Adjustment

Mild to moderate impairment: No dose adjustments
Severe impairment: Dose adjustments not defined

Hepatic Dose Adjustment

Mild to moderate impairment: No dose adjustments
Severe impairment: Dose adjustments not defined

Warnings/Precautions ⬆ ⬇

Hypersensitivity reactions such as rash and urticaria have occurred with evolocumab treatment
If signs or symptoms of serious allergic reactions occur, discontinue treatment with evolocumab, treat according to the standard of care, and monitor until signs and symptoms resolve

Pregnancy/Breast Feeding ⬆ ⬇

Pregnancy category: Not Rated; however, though monoclonal antibodies in humans are unlikely to cross the placenta in the first trimester, they are likely to cross the placenta in increasing amounts in the second and third trimester. Therefore, weigh the benefits and risks of evolocumab therapy and possible risks to the fetus before prescribing it to pregnant women.

Breastfeeding: Safety unknown.

Adverse Reactions ⬆ ⬇

CNS: Headache, dizziness
CV: Hypertension
GI: Diarrhea, gastroenteritis, nausea
EENT: Nasopharyngitis, sinusitis
RESP: Upper respiratory tract infection, bronchitis, cough
MUSC: Back pain, myalgia, musculoskeletal pain, arthralgia, muscle spasms
LOCAL: Injection site reactions
GU: Urinary tract infection
DERM: Contusion
MISC: Influenza, fatigue

Clinical Pharmacology ⬆ ⬇

PCSK9 inhibitors (monoclonal antibodies); binds to PCSK9 (human proprotein convertase subtilisin kexin 9) and inhibits binding of circulating PCSK9 to LDLR (low density lipoprotein receptor) and prevents PCSK9-mediated LDLR degradation. LDLR are sent back to liver cell surface. Thus PCSK9 inhibitors increase the number of LDRLs available to remove LDL from circulation thereby lowering LDL-C levels.

Absolute bioavailability: 72%
Metabolism: Unknown; CYP450: Unknown
Half-life: 11-17 days

Brands and Availability ⬆ ⬇