Source: European Medicines Agency (EU) Revision Year: 2019 Publisher: Amgen Europe B.V., Minervum 7061, 4817 ZK Breda, The Netherlands
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
There is limited experience with Repatha in patients with severe renal impairment (defined as eGFR <30 mL/min/1.73 m²) (see section 5.2). Repatha should be used with caution in patients with severe renal 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 C) have not been studied (see section 5.2). Repatha should be used with caution in patients with severe hepatic impairment.
Repatha 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 allergic reactions.
Repatha 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 allergic reactions.
This medicinal product contains less than 1 mmol sodium (23 mg) per dose, i.e. it is essentially ‘sodium-free’.
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 lipidlowering drugs other than statins and ezetimibe have been conducted.
There are no or limited amount of data from the use of Repatha in pregnant women.
Animal studies do not indicate direct or indirect effects with respect to reproductive toxicity (see section 5.3).
Repatha should not be used during pregnancy unless the clinical condition of the woman requires treatment with evolocumab.
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.
No data on the effect of evolocumab on human fertility are available. Animal studies did not show any effects on fertility endpoints at area under the concentration time curve (AUC) exposure levels much higher than in patients receiving evolocumab at 420 mg once monthly (see section 5.3).
Repatha has no known influence on the ability to drive and use machines.
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 hypercholesterolaemia population was consistent with that demonstrated in the primary hypercholesterolaemia and mixed dyslipidaemia population.
Adverse reactions reported in pivotal, controlled clinical studies, and spontaneous reporting, are displayed by system organ class and frequency in table 1 below using the following convention: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100), rare (≥1/10,000 to <1/1,000) and very rare (<1/10,000).
Table 1. Adverse reactions with Repatha:
Common: Influenza, Nasopharyngitis, Upper respiratory tract infection
Common: Hypersensitivity, Rash
Uncommon: Urticaria
Common: Nausea
Rare: Angioedema
Common: Back pain, Arthralgia
Common: Injection site reactions^1^
Uncommon: Influenza-like illness
1 See section Description of selected adverse reactions
The most frequent injection site reactions were injection site bruising, erythema, haemorrhage, injection site pain, and swelling.
There is limited experience with Repatha in paediatric patients. Fourteen patients aged ≥12 to <18 years with homozygous familial hypercholesterolaemia were included in clinical studies. No difference in safety was observed between adolescent and adult patients with homozygous familial hypercholesterolaemia.
The safety and effectiveness of Repatha in paediatric patients with primary hypercholesterolaemia and mixed dyslipidaemia has not been established.
Of the 18,546 patients treated with Repatha in double-blind clinical studies 7,656 (41.3%) were ≥65 years old, while 1,500 (8.1%) were ≥75 years old. No overall differences in safety or efficacy were observed between these patients and younger patients.
In clinical studies, 0.3% of patients (48 out of 17,992 patients) treated with at least one dose of Repatha tested positive for binding antibody development. The patients whose sera tested positive for binding antibodies were further evaluated for neutralising antibodies and none of the patients tested positive for neutralising antibodies. The presence of anti-evolocumab binding antibodies did not impact the pharmacokinetic profile, clinical response, or safety of Repatha.
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system listed in Appendix V.
In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.
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