ALT, alanine aminotransferase; AST, aspartate transferase; ULN, upper limit of normal

• More than 3,800 unique subjects have received rimegepant 75 mg in Phase II and Phase III studies⁶
• The most common adverse reaction was nausea for acute treatment (1.2%) and for migraine prophylaxis (1.4%)⁵
• Most adverse reactions were mild or moderate in severity⁵
• Hypersensitivity reactions, including dyspnoea and severe rash, have occurred in less than 1% of patients treated with rimegepant in clinical studies⁵
• Hypersensitivity reactions, including serious hypersensitivity, can occur days after administration⁵

common (≥1/100 to <1/10) and uncommon (≥1/1,000 to <1/100)

• Hypersensitivity to the active substance or to any of contained excipients (gelatin, mannitol (E421), mint flavour, sucralose).

• Hypersensitivity reactions, including serious hypersensitivity, can occur days after administration.
• If a hypersensitivity reaction occurs, VYDURA should be discontinued and appropriate therapy should be initiated.
• Hypersensitivity reactions, including dyspnoea and rash, have occurred in <1% of patients treated with VYDURA in clinical studies.

• In patients with severe hepatic impairment or those with end-stage renal disease (CLcr <15 mL/min).
• For concomitant use with strong inhibitors of CYP3A4  (e.g., clarithromycin, itraconazole, ritonavir) or strong inducers of CYP3A4 (e.g., phenobarbital, rifampicin, St John’s wort (Hypericum perforatum)) or moderate inducers of CYP3A4 (e.g., bosentan, efavirenz, modafinil).

• Overuse of any type of medicinal products for headaches can make them worse. If this situation is experienced or suspected, medical advice should be obtained, and treatment should be discontinued.
• The diagnosis of MOH should be suspected in patients who have frequent or daily headaches despite (or because of) the regular use of medicinal products for acute headache.

• There is limited experience with VYDURA in patients aged 65 and older. No dose adjustment is required as the pharmacokinetics of VYDURA are not affected by age.
• The safety and efficacy of VYDURA in paediatric patients (<18 years of age) have not been established.

• Inhibitors of CYP3A4 increase plasma concentrations of rimegepant.
• Concomitant administration of rimegepant with strong CYP3A4 inhibitors (e.g., clarithromycin, itraconazole, ritonavir) is not recommended.
• 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).

• 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.
• 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% Cmax and by 64%) in rimegepant exposure, which may lead to loss of efficacy.

• 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).
• 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).

• 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.
• As a precautionary measure, it is preferable to avoid the use of VYDURA during pregnancy.

• 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.

• Animal studies showed no clinically relevant impact on female and male fertility.