Aquipta · 4.3 Contraindications · 1

HOS-100203 · has-adverse-reaction-information · PDF-Seite 5

Summary of the safety profile Safety was evaluated in 3 852 patients with migraine who received at least one dose of atogepant in clinical studies. Of these, 1 225 patients were exposed to atogepant for prophylaxis daily for at least 6 months and 826 patients were exposed for 12 months. 895 patients were exposed during 24 weeks on an as-needed basis for treatment of acute migraine attacks. In 12-week, placebo-controlled prophylaxis clinical studies, 678 patients received at least one dose of atogepant 60 mg once daily, and 663 patients received placebo. In the placebo-controlled clinical study for acute treatment of migraine, 1 195 patients received at least one dose of atogepant 60 mg, and 1 177 patients received placebo; patients received both atogepant and placebo to treat qualifying migraines. In placebo-controlled prophylaxis studies, the most commonly reported adverse reactions were nausea (9%), constipation (8%), and fatigue/somnolence (5%). Most of the reactions were mild or moderate in severity. The adverse reaction that most commonly led to discontinuation for prophylaxis was nausea (0.4%). Nausea (1.3%) was the most commonly reported adverse reaction for acute treatment. Tabulated list of adverse reactions Adverse reactions reported in clinical trials and from post-marketing experience are listed below by system organ class and frequency, most frequent reactions first. Frequencies are defined as follows: 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), or not known (cannot be estimated from the available data). Within each frequency grouping, adverse reactions are presented in the order of decreasing seriousness. 5 Table 2: Adverse reactions identified with atogepant System organ class Frequency Adverse reaction Acute treatment of migraine Gastrointestinal disorders Common Nausea Investigations Uncommon ALT/AST increased** Prophylaxis of migraine Immune system disorders Not known Hypersensitivity (e.g., anaphylaxis, dyspnoea, rash, pruritus, urticaria, facial oedema) Metabolism and nutrition disorders

Auszug; vollständigen Abschnitt im Original lesen.

HOS-100199 · has-contraindication-information · PDF-Seite 3

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1 (see section 4.4). 3

HOS-100198 · has-indication-information · PDF-Seite 2

AQUIPTA is indicated for: • Acute treatment of migraine with or without aura in adults • Prophylaxis of migraine in adults who have at least 4 migraine days per month.

HOS-100201 · has-interaction-information · PDF-Seite 4

CYP3A4 inhibitors Strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, clarithromycin, ritonavir) can significantly increase systemic exposure to atogepant. Co-administration of atogepant with itraconazole resulted in increased exposure (Cmax by 2.15-fold and AUC by 5.5-fold) of atogepant in healthy subjects (see section 4.2). Changes in atogepant exposure when co-administered with weak or moderate CYP3A4 inhibitors are not expected to be clinically significant. Transporter inhibitors Organic anion transporting polypeptide (OATP) inhibitors (e.g., rifampicin, ciclosporin, ritonavir) can significantly increase systemic exposure to atogepant. Co-administration of atogepant with single dose rifampicin resulted in increased exposure (Cmax by 2.23-fold and AUC by 2.85-fold) of atogepant in healthy subjects (see section 4.2). Frequently co-administered medicinal products Co-administration of atogepant with oral contraceptive components ethinyl estradiol and levonorgestrel, paracetamol, naproxen, sumatriptan, or ubrogepant did not result in significant pharmacokinetic interactions for either atogepant or co-administered medicinal products. Co- administration with famotidine or esomeprazole did not result in clinically relevant changes of atogepant exposure.

HOS-100202 · has-pregnancy-information · PDF-Seite 4

Pregnancy There are limited data from the use of atogepant in pregnant women. Studies in animals have shown reproductive toxicity (see section 5.3). Atogepant is not recommended during pregnancy and in women of childbearing potential not using contraception. 4 Breast-feeding Pharmacokinetic data after single-dose administration showed minimal transfer of atogepant into breast milk (see section 5.2). There are no data on the effects of atogepant on the breastfed infant or the effects of atogepant on milk production. The developmental and health benefits of breast-feeding should be considered along with the mother’s clinical need for atogepant and any potential adverse effects on the breastfed infant from atogepant or from the underlying maternal condition. Fertility No human data on the effect of atogepant on fertility are available. Animal studies showed no impact on female and male fertility with atogepant treatment (see section 5.3).

HOS-100200 · has-warning-information · PDF-Seite 4

Serious hypersensitivity reactions Serious hypersensitivity reactions, including anaphylaxis, dyspnoea, rash, pruritus, urticaria, and facial oedema, have been reported with use of AQUIPTA (see section 4.8). Most serious reactions have occurred within 24 hours of first use, however, some hypersensitivity reactions can occur days after administration. Patients should be warned about the symptoms associated with hypersensitivity. If a hypersensitivity reaction occurs, discontinue AQUIPTA and institute appropriate therapy. Hepatic impairment Atogepant is not recommended in patients with severe hepatic impairment (see section 4.2). Excipients with known effect AQUIPTA 10 mg tablets contain less than 1 mmol sodium (23 mg) per tablet, that is to say essentially ‘sodium-free’. AQUIPTA 60 mg tablets contain 31.5 mg sodium per tablet, equivalent to 1.6% of the WHO recommended maximum daily intake of 2 g sodium for an adult.