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Repatha® (Evolocumab) Brief Prescribing Information
This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions. Please refer to the Summary of Product Characteristics before prescribing Repatha®. PHARMACEUTICAL FORM Solution for injection (injection) in pre-filled pen (SureClick).The solution is clear to opalescent, colourless to yellowish, and practically free from particles. CLINICAL PARTICULARS Therapeutic indications Hypercholesterolaemia and mixed dyslipidaemia Repatha is indicated in adults with primary hypercholesterolaemia (heterozygous familial and non‑familial) or mixed dyslipidaemia, 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 hypercholesterolaemia Repatha is indicated in adults and adolescents aged 12 years and over with homozygous familial hypercholesterolaemia in combination with other lipid-lowering therapies.Established atherosclerotic cardiovascular disease Repatha 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. For study results with respect to effects on LDL-C, cardiovascular events and populations studied Posology and method of administration Prior to initiating evolocumab, secondary causes of hyperlipidaemia or mixed dyslipidaemia (e.g., nephrotic syndrome, hypothyroidism) should be excluded. Posology Primary hypercholesterolaemia and mixed dyslipidaemia in adults The recommended dose of evolocumab is either 140 mg every two weeks or 420 mg once monthly; both doses are clinically equivalent. Homozygous familial hypercholesterolaemia in adults and adolescents aged 12 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 (see section 5.2). Patients with hepatic impairment No dose adjustment is necessary in patients with mild hepatic impairment, see section 4.4 for patients with moderate and severe hepatic impairment. Paediatric population The safety and efficacy of Repatha in children aged less than 18 years has not been established in the indication for primary hypercholesterolaemia and mixed dyslipidaemia. No data are available. The safety and efficacy of Repatha in children aged less than 12 years has not been established in the indication for homozygous familial hypercholesterolaemia. No data are available. 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. 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. Repatha 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. Contraindications Hypersensitivity to the active substance or to any of the excipients listed in section 6.1 Special warnings and precautions for Use 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. 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‑ reduction. Therefore, close monitoring may be warranted in these patients. Patients with severe hepatic impairment (Child-Pugh class C) have not been studied (see section 5.2). Evolocumab should be used with caution in patients with severe hepatic impairment. Dry natural rubber 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’. Interaction with other medicinal products and other forms of interaction No interaction studies have been performed. The pharmacokinetic interaction between statins and evolocumab was evaluated in the 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 evolocumab. No studies on pharmacokinetic and pharmacodynamics interaction between evolocumab and lipid‑lowering medicinal products other than statins and ezetimibe have been conducted. Fertility, pregnancy and lactation Pregnancy 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. 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. Fertility 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).Effects on ability to drive and use machines Repatha has no or negligible influence on the ability to drive and use machines. Undesirable effects Summary of the safety profile The most commonly reported adverse reactions at the recommended doses are 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. Tabulated list of adverse reactions 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). Description of selected adverse reactions Injection site reactions The most frequent injection site reactions were injection site bruising, erythema, haemorrhage, injection site pain and swelling. Paediatric population There is limited experience with evolocumab 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 evolocumab in paediatric patients with primary hypercholesterolaemia and mixed dyslipidaemia has not been established. Elderly population Of the 18,546 patients treated with evolocumab 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. Immunogenicity In clinical studies, 0.3% of patients (48 out of 17,992 patients) treated with at least one dose of evolocumab 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 evolocumab. Reporting of suspected adverse reactions 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 to their local representative. Special precautions for storage Store in a refrigerator (2°C – 8°C). Do not freeze. Store in the original carton in order to protect from light. If removed from the refrigerator, Repatha may be stored at room temperature (up to 25°C) in the original carton and must be used within 1 month. Special precautions for disposal and other handling Before administration, the solution should be inspected. The solution should not be injected if it contains particles, or is cloudy or discoloured. To avoid discomfort at the site of injection, the medicinal product should be allowed to reach room temperature (up to 25ºC) before injecting. The entire contents should be injected. Any unused medicinal product or waste material should be disposed of in accordance with local requirements. Legal Category: POM. Administrative information: Date of PI: April 2021. Marketing Authorisation Holder: Amgen Europe B.V. Minervum 7061-4817 ZK Breda, the Netherlands. Product License Numbers: Repatha 140mg/ml pre-filled pen pack of 2; 21-475-17 . Local representative in Saudi Arabia: Salehiya Trading Est. Address: P.O.Box 991, Riyadh 11421, Kingdom of Saudi Arabia. Tel: 00966 1 464 6955 Ext. 127.
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Any suspected adverse reactions should be reported immediately to Amgen in accordance with local spontaneous reporting requirements. Amgen Global Fax: +44 2071361046 or send to AGS mailbox: svc-ags-in-uk@amgen.com and Safety-MEA@amgen.com and/or National Pharmacovigilance Centre (NPC), Email: npc.drug@sfda.gov.sa, Fax: +966-11-2057662 |