ALMOGRAN Film-coated tablet Ref.[6137] Active ingredients: Almotriptan

Almotriptan should only be used where there is a clear diagnosis of migraine. It should not be used to treat basilar, hemiplegic or ophthalmoplegic migraine.

As with other acute migraine therapies, before treating headaches in patients not previously diagnosed as migraine sufferers and in migraine sufferers who present atypical symptoms, care should be taken to exclude other potentially serious neurological conditions. Cerebrovascular accidents have been reported in patients treated with 5-HT_1B/1D agonists. It should be noted that migraineurs may be at increased risk of certain cerebrovascular events (e.g. cerebrovascular accident, transient ischemic attack).

In very rare cases, as with other 5-HT_1B/1D receptor agonists, coronary vasospasm and myocardial infarction have been reported. Therefore almotriptan should not be administered to patients who could have an undiagnosed coronary condition without prior evaluation of potential underlying cardiovascular disease. Such patients include postmenopausal women, males over 40 and patients with other risk factors for coronary disease such as uncontrolled hypertension, hypercholesterolaemia, obesity, diabetes, smoking or a clear family history of cardiovascular disease. These evaluations however, may not identify every patient who has cardiac disease and in very rare case, serious cardiac events have occurred in patients without underlying cardiovascular disease when 5-HT₁ agonists have been administered.

Following administration, almotriptan can be associated with transient symptoms including chest pain and tightness which may be intense and involve the throat (see Section 4.8 Undesirable effects). Where such symptoms are thought to indicate ischaemic heart disease, no further dose should be taken and appropriate evaluation should be carried out.

Caution should be exercised when prescribing almotriptan to patients with known hypersensitivity to sulphonamides.

Serotonin syndrome (including altered mental status, autonomic instability and neuromuscular abnormalities) has been reported following concomitant treatment with triptans and selective serotonin reuptake inhibitors (SSRIs) or serotonin noradrenaline reuptake inhibitors (SNRIs). These reactions can be severe. If concomitant treatment with almotriptan and a SSRI or SNRI is clinically warranted, appropriate observation of the patient is advised, particularly during treatment initiation, with dose increases, or with addition of another serotoninergic medication (See Section 4.5).

It is advised to wait at least 6 hours following use of almotriptan before administering ergotamine. At least 24 hours should elapse after the administration of an ergotamine-containing preparation before almotriptan is given. Although additive vasospastic effects were not observed in a clinical trial in which 12 healthy subjects received oral almotriptan and ergotamine, such additive effects are theoretically possible (see Section 4.3 Contraindications).

Patients with severe renal impairment should not take more than one 12.5 mg tablet in a 24 hour period.

Caution is recommended in patients with mild to moderate hepatic disease and treatment is contraindicated in patients with severe hepatic disease (see section 5.2 Pharmacokinetic properties).

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

As with other 5-HT_1B/1D receptor agonists, almotriptan may cause mild, transient increases in blood pressure, which may be more pronounced in the elderly.

Medication overuse headache (MOH)

Prolonged use of any 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 diagnosis of MOH should be suspected in patients who have frequent or daily headaches despite (or because of) the regular use of headache medications.

The maximum recommended dose of almotriptan should not be exceeded.

Interaction studies were performed with monoamine oxidase A inhibitors, beta-blockers, selective serotonin re-uptake inhibitors, calcium channel blockers or inhibitors of Cytochrome P450 isoenzymes 3A4 and 2D6. There are no in vivo interaction studies assessing the effect of almotriptan on other drugs.

As with other 5-HT₁ agonists, the potential risk of a serotoninergic syndrome due to a pharmacodynamic interaction in case of concomitant treatment with MAOIs cannot be ruled out.

There have been reports describing patients with symptoms compatible with serotonin syndrome (including altered mental status, autonomic instability and neuromuscular abnormalities) following the use of selective serotonin reuptake inhibitors (SSRIs) or serotonin noradrenaline reuptake inhibitors (SNRIs) and triptans (see Section 4.4).

Multiple dosing with the calcium channel blocker verapamil, a substrate of CYP3A4, resulted in a 20% increase in C_max and AUC of almotriptan. The increase is not considered clinically relevant. No clinically significant interactions were observed.

Multiple dosing with propranolol did not alter the pharmacokinetics of almotriptan. No clinically significant interactions were observed.

In vitro studies performed to evaluate the ability of almotriptan to inhibit the major CYP enzymes in human liver microsomes and human monoamine oxidase (MAO) showed that almotriptan would not be expected to alter the metabolism of drugs metabolised by CYP or MAO-A and MAO-B enzymes.

Pregnancy

For almotriptan, very limited data on pregnant patients are available. Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonal/foetal development, parturition or postnatal development (see section 5.3).

Caution should be exercised when prescribing almotriptan to pregnant women.

Breast-feeding

There are no data regarding excretion of almotriptan in human milk. Studies in rats have shown that almotriptan and/or its metabolites are excreted in milk.

Caution should therefore be exercised when prescribing during lactation. Infant exposure may be minimised by avoiding breast feeding for 24 hours after treatment.

There are no studies on the effect of almotriptan on the ability to drive or operate machinery. However, since somnolence may occur during a migraine attack and has been reported as a side effect of treatment with almotriptan, caution is recommended in patients performing skilled tasks.

Almogran/Amignul was evaluated in over 2700 patients for up to one year in clinical trials. The most common adverse reactions at the therapeutic dose were dizziness, somnolence, nausea, vomiting and fatigue. None of the adverse reactions had an incidence superior to 1.5%.

The following adverse reactions have been evaluated in clinical studies and/or reported in post-marketing experience. They have been listed by System Organ Class (SOC) and in descending order of frequency. Frequencies are defined as: very common (>1/10), common (≥1/100 to <1/10), uncommon (≥1/1000 to <1/100), rare (≥1/10,000 to <1/1,000), very rare (<1/10,000) and not known (cannot be estimated from the available data).

Immune system disorders

Not known: Hypersensitivity reactions (including angioedema), Anaphylactic reactions

Nervous system disorders

Common: Dizziness, Somnolence

Uncommon: Paraesthesia, Headache

Not known: Seizures

Eye disorders

Not known: Visual impairment*, Vision blurred*

Ear and labyrinth disorders

Uncommon: Tinnitus

Cardiac disorders

Uncommon: Palpitations

Very rare: Coronary vasospasm, Myocardial infarction, Tachycardia

Respiratory, thoracic and mediastinal disorders

Uncommon: Throat tightness

Gastrointestinal Disorders

Common: Nausea, Vomiting

Uncommon: Diarrhoea, Dyspepsia, Dry mouth

Not known: Intestinal ischemia

Musculoskeletal, connective tissue and bone disorders

Uncommon: Myalgia, Bone pain

General Disorders

Common: Fatigue

Uncommon: Chest pain, Asthenia

* However visual disorders may also occur during a migraine attack itself.

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.