MIGARD Film-coated tablet Ref.[8338] Active ingredients: Frovatriptan

Frovatriptan should only be used where a clear diagnosis of migraine has been established.

Frovatriptan is not indicated for the management of hemiplegic, basilar or ophthalmoplegic migraine.

As with other treatments of migraine attack, it is necessary to exclude other, potentially serious, neurological conditions before treating the headache of patients without a previous diagnosis of migraine, or migraine patients presenting with atypical symptoms. It should be noted that migraineurs present an increased risk of certain cerebral vascular events (eg CVA or TIA).

The safety and efficacy of frovatriptan administered during the aura phase, before the headache phase of migraine, has not been established.

As for other 5-HT₁ receptor agonists, frovatriptan must not be administered to patients at risk of coronary artery disease (CAD), including heavy smokers or users of nicotine substitution therapy without a prior cardiovascular evaluation (see section 4.3). Specific attention should be given to post-menopausal women and men over 40 years of age presenting with these risk factors.

However, cardiac evaluations may not identify every patient who has cardiac disease. In very rare cases serious cardiac events have occurred in patients with no underlying cardio-vascular disease when taking 5-HT₁ receptor agonists.

Frovatriptan administration can be associated with transient symptoms including chest pain or tightness which may be intense and involve the throat. (see section 4.8).

Where such symptoms are thought to indicate ischaemic heart disease no further doses of frovatriptan should be taken and additional investigations should be carried out.

Patients should be informed of the early signs and symptoms of hypersensitivity reactions including cutaneous disorders, angioedema and anaphylaxis (see section 4.8). In case of serious allergic/hypersensitivity reactions, frovatriptan treatment should be discontinued immediately and it should not be administered again.

It is advised to wait 24 hours following the use of frovatriptan before administering an ergotamine-type medication. At least 24 hours should be elapse after administration of an ergotamine-containing preparation before frovatriptan is given (see sections 4.3 and 4.5).

In case of too frequent use (repeated administration several days in a row corresponding to a misuse of the product), the active substance can accumulate leading to an increase of the side-effects.

Prolonged use of any type of painkiller for headaches can make them worse. If this situation is experienced or suspected, medical advice should be obtained and treatment should be discontinued. The possibility of MOH should be taken into consideration in patients who have frequent or daily headaches despite (or because of) the regular use of headache medications.

Do not exceed the recommended dose of frovatriptan.

Undesirable effects may be more common during concomitant use of triptans (5HT agonists) and herbal preparations containing St John’s Wort (Hypericum perforatum).

This medicinal product contains lactose, therefore patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicine.

This medicine contains less than 1 mmol sodium (23 mg) per dosage unit, that is to say essentially ‘sodium-free’.

Contraindications of concomitant use

Ergotamine and ergotamine derivatives (including méthysergide) and other 5-HT₁ agonists

Risks of hypertension and coronary artery constriction due to additive vasospastic effects when used concomitantly for the same migraine attack (see section 4.3).

Effects can be additive. It is recommended to wait at least 24 hours after administration of ergotamine-type medication before administering frovatriptan. Conversely it is recommended to wait 24 hours after frovatriptan administration before administering an ergotamine-type medication (see section 4.4).

Concomitant use not recommended

Monoamine Oxidase Inhibitors

Frovatriptan is not a substrate for MAO-A, however a potential risk of serotonin syndrome or hypertension cannot be excluded (see section 5.2).

Concomitant use requiring caution

Selective serotonin-reuptake inhibitors (citalopram, fluoxetine, fluvoxamine, paroxetine, sertraline)

Potential risk of hypertension, coronary vasoconstriction or serotonin syndrome.

Strict adherence to the recommended dose is an essential factor to prevent this syndrome.

Methylergometrine

Risks of hypertension, coronary artery constriction.

Fluvoxamine

Fluvoxamine is a potent inhibitor of cytochrome CYP1A2 and has been shown to increase the blood levels of frovatriptan by 27-49%.

Oral contraceptives

In female subjects taking oral contraceptives, concentrations of frovatriptan were 30% higher than in females not taking oral contraceptives. No increased incidence in the adverse event profile was reported.

Hypericum perforatum (St. John wort) (oral route)

As with other triptans the risk of the occurence of serotonin syndrome may be increased.

Pregnancy

There are no or limited amount of data from the use of frovatriptan in pregnant women. Studies in animals have shown reproductive toxicity (see section 5.3). The potential risk for humans is unknown. MIGARD is not recommended during pregnancy and in women of childbearing potential not using contraception, unless clearly necessary.

Breast-feeding

It is unknown whether Frovatriptan/metabolites are excreted in human milk. Frovatriptan and/or its metabolites are excreted in the milk of lactating rats with the maximum concentration in milk being four-fold higher than maximum blood levels. A risk to the breastfeeding newborns/infants cannot be excluded.

MIGARD is not recommended during breast-feeding, unless is clearly needed. In this case, a 24 hours interval must be observed.

No studies on the effects on the ability to drive and use machines have been performed.

Migraine or treatment with frovatriptan may cause somnolence. Patients should be advised to evaluate their ability to perform complex tasks such as driving during migraine attacks and following administration of frovatriptan.

Frovatriptan has been administered to over 2700 patients at the recommended dose of 2.5 mg and the most common side effects (<10%) include dizziness, fatigue, paraesthesia, headache and vascular flushing. The undesirable effects reported in clinical trials with frovatriptan were transient, generally mild to moderate and resolved spontaneously. Some of the symptoms reported as undesirable effects may be associated symptoms of migraine.

The table below shows all the adverse reactions that are considered to be related to treatment with 2.5 mg frovatriptan and showed a greater incidence than with placebo in the 4 placebo controlled trials. They are listed in decreasing incidence by body-system. Adverse reactions collected in the post-marketing experience are noted with an asterisk*.

In two open long-term clinical studies the observed effects were not different from those listed above.

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 Yellow Card Scheme Website: www.mhra.gov.uk/yellowcard.

Not applicable.