AQUIPTA Tablet Ref.[51145] Active ingredients: Atogepant

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.

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 (C_max 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 (C_max 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. Coadministration with famotidine or esomeprazole did not result in clinically relevant changes of atogepant exposure.

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.

Breast-feeding

It is unknown whether atogepant is excreted in human milk. Available toxicological data in animals have shown excretion of atogepant in milk (see section 5.3). A risk to the newborns/infants cannot be excluded. A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from atogepant therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.

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).

Atogepant has no or negligible influence on the ability to drive and use machines. However, it may cause somnolence in some patients. Patients should exercise caution before driving or using machinery until they are reasonably certain that atogepant does not adversely affect performance.

Summary of the safety profile

Safety was evaluated in 2 657 patients with migraine who received at least one dose of atogepant in clinical studies. Of these, 1 225 patients were exposed to atogepant for at least 6 months and 826 patients were exposed for 12 months.

In 12-week, placebo-controlled clinical studies, 678 patients received at least one dose of atogepant 60 mg once daily, and 663 patients received placebo.

The most commonly reported adverse drug 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 was nausea (0.4%).

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.

^* Defined in clinical trials as weight decrease of at least 7% at any point.
^** Cases of ALT/AST elevations (defined as ≥3× upper limit of normal) temporally associated with atogepant were observed in clinical trials, including cases with a potential positive dechallenge history that resolved within 8 weeks of discontinuation. However, the overall frequency of liver enzyme elevations was similar in the atogepant and placebo groups.

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 via the national reporting system listed in Appendix V.

Not applicable.