Praluent · 4.8 Undesirable effects · 1

HOS-097289 · has-adverse-reaction-information · PDF-Seite 6

Summary of the safety profile The most common adverse reactions, at recommended doses, are local injection site reactions (6.1%), upper respiratory tract signs and symptoms (2.0%), and pruritus (1.1%). Most common adverse reactions leading to treatment discontinuation in patients treated with alirocumab were local injection site reactions. The safety profile in ODYSSEY OUTCOMES was consistent with the overall safety profile described in the Phase 3 controlled trials. No difference in the safety profile was observed between the two doses (75 mg and 150 mg) used in the Phase 3 program. Tabulated list of adverse reactions The following adverse reactions were reported in patients treated with alirocumab in pooled controlled studies and/or post-marketing use (see Table 1). Frequencies for all adverse reactions identified from clinical trials have been calculated based on their incidence in pooled Phase 3 clinical trials. Adverse reactions are presented by system organ class. Frequency categories are defined as: 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); very rare (<1/10,000) and not known (cannot be estimated from the available data). The frequency of adverse reactions reported during post-marketing use cannot be determined as they are derived from spontaneous reports. Consequently, the frequency of these adverse reactions is qualified as "not known". Table 1 – Adverse reactions System organ class Common Rare Not known Immune system disorders Hypersensitivity, hypersensitivity vasculitis Respiratory, thoracic and Upper respiratory mediastinal disorders tract signs and symptoms* Skin and subcutaneous tissue Pruritus Urticaria, Angioedema disorders eczema nummular 6 System organ class Common Rare Not known General disorders and Injection site Flu-like illness administration site conditions reactions** * including mainly oropharyngeal pain, rhinorrhea, sneezing ** including erythema/r

Auszug; vollständigen Abschnitt im Original lesen.

HOS-097285 · has-contraindication-information · PDF-Seite 4

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

HOS-097284 · has-indication-information · PDF-Seite 3

Primary hypercholesterolaemia and mixed dyslipidaemia Praluent is indicated in adults with primary hypercholesterolaemia (heterozygous familial and non-familial) or mixed dyslipidaemia, and in paediatric patients 8 years of age and older with heterozygous familial hypercholesterolaemia (HeFH) 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. Established atherosclerotic cardiovascular disease Praluent is indicated in adults with established atherosclerotic cardiovascular 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 see section 5.1.

HOS-097287 · has-interaction-information · PDF-Seite 5

Effects of alirocumab on other medicinal products Since alirocumab is a biological medicinal product, no pharmacokinetic effects of alirocumab on other medicinal products and no effect on cytochrome P450 enzymes are anticipated. Effects of other medicinal products on alirocumab Statins and other lipid-modifying therapy are known to increase production of PCSK9, the protein targeted by alirocumab. This leads to the increased target-mediated clearance and reduced systemic exposure of alirocumab. Compared to alirocumab monotherapy, the exposure to alirocumab is about 40%, 15%, and 35% lower when used concomitantly with statins, ezetimibe, and fenofibrate, respectively. However, reduction of LDL-C is maintained during the dosing interval when alirocumab is administered every two weeks.

HOS-097288 · has-pregnancy-information · PDF-Seite 5

Pregnancy There are no data from the use of Praluent in pregnant women. Alirocumab is a recombinant IgG1 antibody, therefore it is expected to cross the placental barrier (see section 5.3). Animal studies do not indicate direct or indirect harmful effects with respect to maintenance of pregnancy or embryo-foetal development; maternal toxicity was noted in rats, but not in monkeys at doses in excess of the human dose, and a weaker secondary immune response to antigen challenge was observed in the offspring of monkeys (see section 5.3). The use of Praluent is not recommended during pregnancy unless the clinical condition of the woman requires treatment with alirocumab. Breast-feeding It is not known whether alirocumab is excreted in human milk. Human immunoglobulin G (IgG) is excreted in human milk, in particular in colostrum; the use of Praluent is not recommended in breast-feeding women during this period. For the remaining duration of breast-feeding, exposure is expected to be low. 5 Since the effects of alirocumab on the breast-fed infant are unknown, a decision should be made whether to discontinue nursing or to discontinue Praluent during this period. Fertility In animal studies, there were no adverse effects on surrogate markers of fertility (see section 5.3). There are no data on adverse effects on fertility in humans.

HOS-097286 · has-warning-information · PDF-Seite 4

Traceability 4 In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded. Allergic reactions General allergic reactions, including pruritus, as well as rare and sometimes serious allergic reactions such as hypersensitivity, nummular eczema, urticaria, and hypersensitivity vasculitis have been reported in clinical studies. Angioedema has been reported in the postmarketing setting (see section 4.8). If signs or symptoms of serious allergic reactions occur, treatment with alirocumab must be discontinued and appropriate symptomatic treatment initiated (see section 4.3). Renal impairment In clinical studies, there was limited representation of patients with severe renal impairment (defined as eGFR < 30 mL/min/1.73 m2) (see section 5.2). Alirocumab should be used with caution in patients with severe renal impairment. Hepatic impairment Patients with severe hepatic impairment (Child-Pugh C) have not been studied (see section 5.2). Alirocumab should be used with caution in patients with severe hepatic impairment.