Evolocumab

C10A - Cholesterol and triglyceride regulating preparations ATC C10AX13 Antibody approved 2015 Parenteral

JFDA label: Repatha 140 mg/ml

Mechanism of Action

Inhibitor of Proprotein convertase subtilisin/kexin type 9 — Subtilisin/kexin type 9 inhibitor

Target	Action	Gene / class
Proprotein convertase subtilisin/kexin type 9 efficacy	INHIBITOR	PCSK9

Indications

Approved

Homozygous familial hypercholesterolemia
Hyperlipidemia, primary (including heterozygous familial hyperlipidemia)
Prevention of cardiovascular events in patients with established cardiovascular disease

Contraindications

Source: Lexicomp

Serious hypersensitivity to evolocumab or any component of the formulation. Documentation of allergenic cross-reactivity for PCSK9 inhibitors is limited. However, because of similarities in chemical structure and/or pharmacologic actions, the possibility of cross-sensitivity cannot be ruled out with certainty Absolute

Adverse Reactions

Very Common >10%Common 1–10%Uncommon 0.1–1% Rare 0.01–0.1%Very Rare <0.01%Not Known

Cardiac disorders (1)

Common Hypertension

Nervous system disorders (2)

Common Dizziness · fatigue

Renal and urinary disorders (1)

Common Urinary tract infection

Blood and lymphatic system disorders (1)

Common Bruise

Gastrointestinal disorders (2)

Common Gastroenteritis · nausea

Skin and subcutaneous tissue disorders (1)

Common Skin rash

Musculoskeletal and connective tissue disorders (1)

Common Myalgia

Infections and infestations (1)

Common Influenza

General disorders and administration site conditions (1)

Common Injection site reaction

Other (1)

Very Common Respiratory: Nasopharyngitis

Respiratory, thoracic and mediastinal disorders (3)

Common cough · sinusitis · Upper respiratory tract infection

Dosing

Source: Lexicomp

Homozygous familial hypercholesterolemia (HoFH): SubQ: 420 mg once monthly. Note: Use in combination with diet and other lipid-lowering therapies (eg, statin, ezetimibe, LDL apheresis). Off-label dosing: 420 mg once every 2 weeks (after 12 weeks, may decrease to 420 mg once a month) in conjunction with lipid apheresis has been studied in a limited number of patients (Bruckert 2014). The European Atherosclerosis Society recommends administration directly after lipid apheresis (EAS [France 2016]). Hyperlipidemia, primary (including heterozygous familial hyperlipidemia [HeFH]): SubQ: 140 mg every 2 weeks or 420 mg once monthly. Note: Use in combination with diet and an optimized regimen of lipid-lowering therapy (eg, maximum tolerated dose of statin) (Sabatine 2015). Switching regimens: Administer the first dose of the new regimen on the next scheduled day of the prior regimen. Prevention of cardiovascular events in patients with established CVD: SubQ: 140 mg every 2 weeks or 420 mg once monthly. Note: Use in combination with an optimized regimen of lipid-lowering therapy (eg, high-intensity statin) (Sabatine 2017). Switching regimens: Administer the first dose of the new regimen on the next scheduled day of the prior regimen. Missed dose: Administer within 7 days from the missed dose and resume original schedule. If an every-2-week dose is not administered within 7 days, wait until the next dose on the original schedule. If a once-monthly dose is not administered within 7 days, administer the dose and start a new schedule based on this date.

Homozygous familial hypercholesterolemia: Adolescents 13 to 17 years: SubQ: Refer to adult dosing Missed dose: Refer to adult dosing.

Refer to adult dosing.

No dosage adjustment necessary.

Mild to moderate impairment (Child Pugh classes A and B): No dosage adjustment necessary. Severe impairment (Child Pugh class C): There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).

Warnings & Precautions

Source: Lexicomp

Hypersensitivity reactions

Hypersensitivity reactions (eg, rash, urticaria) have been reported, some requiring discontinuation. Discontinue treatment and initiate supportive treatment in patients who develop signs/symptoms of serious allergic reaction; monitor until symptoms resolve. Concurrent drug therapy issues:

Drug-drug interactions

Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information. Dosage form specific issues:

Latex

The packaging (needle cap of prefilled syringe and autoinjector) may contain dry natural rubber, which is a derivative of latex.

Pregnancy & Lactation

Pregnancy

Adverse events were not observed in animal reproduction studies. IgG antibodies are known to cross the placenta in increasing amounts during the second and third trimesters; exposure of the fetus to evolocumab is expected.

Lactation

It is not known if evolocumab is present in breast milk. However, IgG antibodies are present in human milk; available data suggest that concentrations do not reach the neonatal circulation in substantial amounts. According to the manufacturer, the decision to continue or discontinue breastfeeding during therapy should take into account the risk of exposure to the infant and the benefits of treatment to the mother.

Monitoring

Clinical pearl	Lipid profile; in patients with homozygous familial hypercholesterolemia, measure LDL-C levels 4 to 8 weeks after initiation (response to evolocumab will depend on degree of LDL-receptor function); signs/symptoms of hypersensitivity reactions.

Biology & Pharmacokinetics

Pharmacokinetics

Bioavailability	72.0%
Half-life	11 to 17 days

Registered Products (2)

Brand	Form / strength	Pack	Agent	Citizen (JOD)
Repatha	Pre-filled Pen 140 mg/ml	2 PFP pack varies	Adatco Drug Store	—
Repatha	Pre-filled Pen 140 mg/ml	1 PFP pack varies	Adatco Drug Store	—