Repatha

/ Amgen

Prior to initiating evolocumab, secondary causes of hyperlipidemia or mixed dyslipidemia (e.g., nephrotic syndrome, hypothyroidism) should be excluded.
Primary hypercholesterolemia and mixed dyslipidemia (including heterozygous familial hypercholesterolemia):
Adults and pediatric patients (aged 10 years and over): The recommended dose of evolocumab is either 140 mg every two weeks or 420 mg once monthly; both doses are clinically equivalent.
Homozygous familial hypercholesterolemia in adults and pediatric patients aged 10 years and over: The initial recommended dose is 420 mg once monthly. After 12 weeks of treatment, dose frequency can be up-titrated to 420 mg once every 2 weeks if a clinically meaningful response is not achieved. Patients on apheresis may initiate treatment with 420 mg every two weeks to correspond with their apheresis schedule.
Established atherosclerotic cardiovascular disease in adults: The recommended dose of evolocumab is either 140 mg every two weeks or 420 mg once monthly; both doses are clinically equivalent.
Special populations:
Elderly patients (age ≥ 65 years): No dose adjustment is necessary in elderly patients.
Patients with renal impairment: No dose adjustment is necessary in patients with renal impairment.
Patients with hepatic impairment: No dose adjustment is necessary in patients with mild hepatic impairment.
Pediatric population: The safety and effectiveness have not been established in pediatric patients with heterozygous familial hypercholesterolemia (HeFH) or homozygous familial hypercholesterolemia (HoFH) who are younger than 10 years old or in pediatric patients with other types of hyperlipidemia.
Method of administration:
Subcutaneous use.
Evolocumab is for subcutaneous injection into the abdomen, thigh or upper arm region. Injection sites should be rotated and injections should not be given into areas where the skin is tender, bruised, red, or hard.
Evolocumab must not be administered intravenously or intramuscularly.
140 mg solution for injection in pre-filled syringe: The 140 mg dose should be delivered using a single pre-filled syringe. The 420 mg dose should be delivered using three pre-filled syringes administered consecutively within 30 minutes.
140 mg solution for injection in pre-filled pen: The 140 mg dose should be delivered using a single pre-filled pen. The 420 mg dose should be delivered using three pre-filled pens administered consecutively within 30 minutes.
This medicinal product is intended for patient self-administration after proper training. Administration of evolocumab can also be performed by an individual who has been trained to administer the product.
For single use only.

Hypercholesterolemia and mixed dyslipidemia:
This medicinal product is indicated in adults with primary hypercholesterolemia (heterozygous familial and non-familial) or mixed dyslipidemia, and in pediatric patients aged 10 years and over with heterozygous familial hypercholesterolemia, as an adjunct to diet:
• in combination with a statin or statin with other lipid-lowering therapies in patients unable to reach LDL-C goals with the maximum tolerated dose of a statin or,
• alone or in combination with other lipid-lowering therapies in patients who are statin-intolerant, or for whom a statin is contraindicated.
Homozygous familial hypercholesterolemia:
This medicinal product is indicated in adults and pediatric patients aged 10 years and over with homozygous familial hypercholesterolemia in combination with other lipid-lowering therapies.
Established atherosclerotic cardiovascular disease:
This medicinal product is indicated in adults with established atherosclerotic cardiovascular disease (myocardial infarction, stroke or peripheral arterial disease) to reduce cardiovascular risk by lowering LDL-C levels, as an adjunct to correction of other risk factors:
• in combination with the maximum tolerated dose of a statin with or without other lipid-lowering therapies or,
• alone or in combination with other lipid-lowering therapies in patients who are statin-intolerant, or for whom a statin is contraindicated.

Hypersensitivity to the active substance or to any of the excipients.

Traceability:
In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded.
Renal impairment:
This medicinal product should be used with caution in patients with severe renal impairment.
Hepatic impairment:
In patients with moderate hepatic impairment, a reduction in total evolocumab exposure was observed that may lead to a reduced effect on LDL-C reduction. Therefore, close monitoring may be warranted in these patients.
Patients with severe hepatic impairment (Child-Pugh class C) have not been studied. Evolocumab should be used with caution in patients with severe hepatic impairment.
Dry natural rubber:
140 mg solution for injection in pre-filled syringe: The needle cover of the glass pre-filled syringe is made from dry natural rubber (a derivative of latex), which may cause severe allergic reactions.
140 mg solution for injection in pre-filled pen: The needle cover of the pre-filled pen is made from dry natural rubber (a derivative of latex), which may cause severe allergic reactions.
Sodium content:
This medicinal product contains less than 1 mmol sodium (23 mg) per dose, that is to say essentially ‘sodium-free’.

The most commonly reported adverse reactions during pivotal trials, at the recommended doses, were nasopharyngitis (7.4%), upper respiratory tract infection (4.6%), back pain (4.4%), arthralgia (3.9%), influenza (3.2%), and injection site reactions (2.2%). The safety profile in the homozygous familial
hypercholesterolemia population was consistent with that demonstrated in the primary hypercholesterolemia and mixed dyslipidemia population.
See prescribing information for full details.

No formal drug-drug interaction studies have been conducted for Repatha.
The pharmacokinetic interaction between statins and evolocumab was evaluated in the Repatha clinical trials. An approximately 20% increase in the clearance of evolocumab was observed in patients co-administered statins. This increased clearance is in part mediated by statins increasing the concentration of Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) which did not adversely impact the pharmacodynamic effect of evolocumab on lipids. No statin dose adjustments are necessary when used in combination with Repatha.
No studies on pharmacokinetic and pharmacodynamics interaction between Repatha and lipid-lowering drugs other than statins and ezetimibe have been conducted.

Pregnancy: There are no or limited amount of data from the use of Repatha in pregnant women. Repatha should not be used during pregnancy unless the clinical condition of the woman requires treatment with evolocumab.
Breast-feeding: It is unknown whether evolocumab is excreted in human milk.
A risk to breastfed newborns/infants cannot be excluded. A decision must be made whether to discontinue breast-feeding or discontinue/abstain from Repatha therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.
See prescribing information for full details.

No adverse effects were observed in animal studies at exposures up to 300-fold higher than those in patients treated with Repatha at 420 mg once monthly.
There is no specific treatment for Repatha overdose. In the event of an overdose, the patient should be treated symptomatically, and supportive measures instituted as required.

Storage: Store in a refrigerator (2°C – 8°C). Do not freeze. Keep in the original carton in order to protect from light. If removed from the refrigerator, Evolocumab may be stored at room temperature (up to 25°C) in the original carton and must be used within 30 days.
Compatibility: In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.