Vydura · 4.6 Fertility, pregnancy and lactation · 1

HOS-099971 · has-adverse-reaction-information · PDF-Seite 5

Summary of the safety profile The most common adverse reaction for acute treatment of migraine was nausea (1.2%). Most of the reactions were mild or moderate in severity. Hypersensitivity, including dyspnoea and severe rash, occurred in less than 1% of patients treated. For migraine prophylaxis, the most common adverse reactions were nausea (3.3% for every other day dosing regimen; 3.5% for every day dosing regimen) and constipation (1.0% for every other day dosing regimen; 3.5% for every day dosing regimen). Most of the reactions were mild or moderate in severity. Tabulated list of adverse reactions Adverse reaction frequencies for migraine prophylaxis are derived from pooled data from 831 participants, of whom 229 participants received rimegepant every day for 12 weeks and 602 participants received rimegepant every other day for 12 weeks. Adverse reactions are listed by MedDRA system organ class in Table 1. The corresponding frequency category for each drug reaction is based on the following convention (CIOMS III): 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). Table 1 : List of Adverse Reactions System Organ Class Adverse Reaction Frequency Acute Treatment Immune system disorders Anaphylactic reactiona Uncommon Hypersensitivity, including dyspnoea and severe Uncommon rash Gastrointestinal disorders Nausea Common Prophylaxis Immune system disorders Anaphylactic reactiona Not known Hypersensitivitya Not known Gastrointestinal disorders Nausea, Constipation Common a Adverse Drug Reactions (ADR) identified post-marketing. Long-term safety Long-term safety of rimegepant was assessed in two one year, open-label extensions; 1662 patients received rimegepant for at least 6 months and 740 received rimegepant for 12 months for acute or prophylactic (every other day plus as needed dosing) treatment. An additional open-label safety study of prophylactic treatment with every day dosing was conducted in 250 patients receiving rimegepant for up to 24 weeks. Description of selected adverse reactions Hypersensitivity reaction

Auszug; vollständigen Abschnitt im Original lesen.

HOS-099967 · has-contraindication-information · PDF-Seite 3

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

HOS-099966 · has-indication-information · PDF-Seite 2

VYDURA is indicated for the • Acute treatment of migraine with or without aura in adults; • Preventive treatment of episodic migraine in adults who have at least 4 migraine attacks per month.

HOS-099969 · has-interaction-information · PDF-Seite 3

Rimegepant is a substrate of CYP3A4, P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) efflux transporters (see section 5.2). CYP3A4 inhibitors Inhibitors of CYP3A4 increase plasma concentrations of rimegepant. Concomitant administration of rimegepant with strong CYP3A4 inhibitors (e.g., clarithromycin, itraconazole, ritonavir) is not 3 recommended (see section 4.4). Concomitant administration of rimegepant with itraconazole resulted in a significant increase in rimegepant exposure (AUC by 4-fold and Cmax 1.5-fold). Concomitant administration of rimegepant with medicinal products that moderately inhibit CYP3A4 (e.g., diltiazem, erythromycin, fluconazole) may increase exposure to rimegepant. Concomitant administration of rimegepant with fluconazole resulted in increased exposures of rimegepant (AUC by 1.8-fold) with no relevant effect on Cmax. Another dose of rimegepant within 48 hours should be avoided when it is concomitantly administered with moderate inhibitors of CYP3A4 (e.g., fluconazole) (see section 4.2). CYP3A4 inducers Inducers of CYP3A4 decrease plasma concentrations of rimegepant. Concomitant administration of VYDURA with strong CYP3A4 inducers (e.g., phenobarbital, rifampicin, St John’s wort (Hypericum perforatum)) or moderate CYP3A4 inducers (e.g., bosentan, efavirenz, modafinil) is not recommended (see section 4.4). The effect of CYP3A4 induction may last for up to 2 weeks after discontinuation of the strong or moderate CYP3A4 inducer. Concomitant administration of rimegepant with rifampicin resulted in a significant decrease (AUC reduced by 80% and Cmax by 64%) in rimegepant exposure, which may lead to loss of efficacy. P-gp and BCRP only inhibitors Inhibitors of P-gp and BCRP efflux transporters may increase plasma concentrations of rimegepant. Another dose of VYDURA within 48 hours should be avoided when it is concomitantly administered with strong inhibitors of P-gp (e.g., cyclosporine, verapamil, quinidine) (see section 4.2). Concomitant administration of rimegepant with cyclosporine (a potent P-gp and BCRP inhibitor) or with quinidine (a selective P-gp inhibitor) resulted in a significant increase of similar magnitude in rimegepant exposure (AUC and Cmax by > 50%, but less than two-fold).

HOS-099970 · has-pregnancy-information · PDF-Seite 4

Pregnancy There are limited data from the use of rimegepant in pregnant women. Animal studies demonstrate that rimegepant is not embryocidal, and no teratogenic potential has been observed at clinically relevant exposures. Adverse effects on embryo-foetal development (decreased foetal body weight and increased skeletal variations in rats) were only observed at exposure levels associated with maternal toxicity (approximately 200 times greater than clinical exposures) following administration of rimegepant during pregnancy (see section 5.3). As a precautionary measure, it is preferable to avoid the use of VYDURA during pregnancy. Breast-feeding In a single center study of 12 breast-feeding women treated with a single dose of rimegepant 75 mg, minimal concentrations of rimegepant were observed in breast milk. The relative percentage of a maternal dose estimated to reach the infant is less than 1%. There are no data on the effects on milk production. The developmental and health benefits of breast-feeding should be considered along with the mother’s clinical need for VYDURA and any potential adverse reactions on the breastfed infant from rimegepant or from the underlying maternal condition. Fertility Animal studies showed no clinically relevant impact on female and male fertility (see section 5.3)

HOS-099968 · has-warning-information · PDF-Seite 3

Hypersensitivity reactions, including dyspnoea and rash, have occurred in less than 1% of patients treated with rimegepant in clinical studies (see section 4.8). Hypersensitivity reactions, including serious hypersensitivity such as anaphylactic reaction, have been reported in the clinical and post-marketing settings (see section 4.8). Some hypersensitivity reactions can occur days after administration. If a hypersensitivity reaction occurs, rimegepant should be discontinued and appropriate therapy should be initiated. VYDURA is not recommended: - in patients with severe hepatic impairment (see section 4.2); - in patients with end-stage renal disease (CLcr < 15 ml/min) (see section 4.2); - for concomitant use with strong inhibitors of CYP3A4 (see section 4.5); - for concomitant use with strong or moderate inducers of CYP3A4 (see section 4.5).