4.1. Therapeutic indications

Imigran Radis tablets are indicated for the acute relief of migraine attacks, with or without aura. Imigran should only be used where there is a clear diagnosis of migraine.

4.2. Posology and method of administration

Adults

Imigran Radis is indicated for the acute intermittent treatment of migraine. It should not be used prophylactically. The recommended dose of Imigran should not be exceeded.

It is advisable that Imigran be given as early as possible after the onset of migraine attack but it is equally effective at whatever stage of the attack it is administered.

The recommended dose of oral Imigran is a 50mg tablet. Some patients may require 100mg.

If the patient has responded to the first dose but the symptoms recur a second dose may be given provided that there is a minimum interval of two hours between the two doses. No more than 300mg should be taken in any 24 hour period.

Patients who do not respond to the prescribed dose of Imigran Radis should not take a second dose for the same attack. In these cases the attack can be treated with paracetamol, acetylsalicylic acid, or non-steroidal anti-inflammatory drugs. Imigran Radis may be taken for subsequent attacks.

Imigran Radis is recommended as monotherapy for the acute treatment of migraine and should not be given concomitantly with ergotamine or derivatives of ergotamine (including methysergide) (see section 4.3).

The tablets should be swallowed whole with water. Patients with swallowing difficulties may choose to disperse a tablet in a small amount of water before administration. Sumatriptan dispersed in water has a bitter taste.

Paediatric population

The efficacy and safety of Imigran Radis in children aged less than 10 years have not been established. No clinical data are available in this age group.

The efficacy and safety of Imigran Radis in children 10 to 17 years of age have not been demonstrated in the clinical trials performed in this age group. Therefore the use of Imigran Radis in children 10 to 17 years of age is not recommended (see section 5.1).

Elderly (Over 65 years of age)

Experience of the use of Imigran Radis in patients aged over 65 years is limited. The pharmacokinetics do not differ significantly from a younger population but until further clinical data are available, the use of Imigran Radis in patients aged over 65 years is not recommended.

4.3. Contraindications

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

Sumatriptan should not be given to patients who have had myocardial infarction or have ischaemic heart disease, coronary vasospasm (Prinzmetal's angina), peripheral vascular disease or patients who have symptoms or signs consistent with ischaemic heart disease.

Sumatriptan should not be administered to patients with a history of cerebrovascular accident (CVA) or transient ischaemic attack (TIA).

Sumatriptan should not be administered to patients with severe hepatic impairment.

The use of sumatriptan in patients with moderate and severe hypertension and mild uncontrolled hypertension is contraindicated.

The concomitant administration of ergotamine or derivatives of ergotamine (including methysergide) or any triptan/5-hydroxytryptamine1 (5-HT1) receptor agonist with sumatriptan is contraindicated. (see section 4.5)

Concurrent administration of monoamine oxidase inhibitors and sumatriptan is contraindicated. Sumatriptan must not be used within two weeks of discontinuation of therapy with monoamine oxidase inhibitors.

4.4. Special warnings and precautions for use

Imigran Radis should only be used where there is a clear diagnosis of migraine.

Sumatriptan is not indicated for use in the management of hemiplegic, basilar or ophthalmoplegic migraine.

Before treating with Sumatriptan care should be taken to exclude potentially serious neurological conditions (e.g. CVA, TIA) if the patient presents with atypical symptoms or if they have not received an appropriate diagnosis for sumatriptan use.

Following administration, sumatriptan can be associated with transient symptoms including chest pain and 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 sumatriptan should be given and appropriate evaluation should be carried out.

Sumatriptan should not be given to patients with risk factors for ischaemic heart disease, including those patients who are heavy smokers or users of nicotine substitution therapies, without prior cardiovascular evaluation (see section 4.3). Special consideration should be given to postmenopausal women and males over 40 with these risk factors. These evaluations however, may not identify every patient who has cardiac disease and, in very rare cases, serious cardiac events have occurred in patients without underlying cardiovascular disease.

Sumatriptan should be administered with caution to patients with mild controlled hypertension, since transient increases in blood pressure and peripheral vascular resistance have been observed in a small proportion of patients (see section 4.3).

There have been rare post-marketing reports describing patients with serotonin syndrome (including altered mental status, autonomic instability and neuromuscular abnormalities) following the use of a selective serotonin reuptake inhibitor (SSRI) and sumatriptan. Serotonin syndrome has been reported following concomitant treatment with triptans and serotonin noradrenaline reuptake inhibitors (SNRIs).

If concomitant treatment with sumatriptan and an SSRI/SNRI is clinically warranted, appropriate observation of the patient is advised (see section 4.5).

Sumatriptan should be administered with caution to patients with conditions which may affect significantly the absorption, metabolism or excretion of drugs, e.g. impaired hepatic (Child Pugh grade A or B; see section 5.2) or renal function (see section 5.2). A 50mg dose should be considered in patients with hepatic impairment.

Sumatriptan should be used with caution in patients with a history of seizures or other risk factors which lower the seizure threshold, as seizures have been reported in association with sumatriptan (see section 4.8).

Patients with known hypersensitivity to sulphonamides may exhibit an allergic reaction following administration of sumatriptan. Reactions may range from cutaneous hypersensitivity to anaphylaxis. Evidence of cross-sensitivity is limited, however, caution should be exercised before using sumatriptan in these patients.

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

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

This medicine contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially 'sodium-free'.

4.5. Interaction with other medicinal products and other forms of interaction

Studies in healthy subjects show that sumatriptan does not interact with propranolol, flunarizine, pizotifen or alcohol.

There are limited data on an interaction with preparations containing ergotamine or another triptan/5-HT1 receptor agonist. The increased risk of coronary vasospasm is a theoretical possibility and concomitant administration is contraindicated (see section 4.3).

The period of time that should elapse between the use of sumatriptan and ergotamine-containing preparations or another triptan/5-HT1 receptor agonist is not known. This will also depend on the doses and types of products used. The effects may be additive. It is advised to wait at least 24 hours following the use of ergotamine-containing preparations or another triptan/5-HT1 receptor agonist before administering sumatriptan. Conversely, it is advised to wait at least 6 hours following use of sumatriptan before administering an ergotamine-containing product and at least 24 hours before administering another triptan/5-HT1 receptor agonist.

An interaction may occur between sumatriptan and monoamine oxidase inhibitors (MAOIs) and concomitant administration is contraindicated (see section 4.3).

There have been rare post-marketing reports describing patients with serotonin syndrome (including altered mental status, autonomic instability and neuromuscular abnormalities) following the use of SSRIs and sumatriptan. Serotonin syndrome has also been reported following concomitant treatment with triptans and SNRIs (see section 4.4).

4.6. Fertility, pregnancy and lactation

Pregnancy

Post-marketing data from the use of sumatriptan during the first trimester in over 1,000 women are available. Although these data contain insufficient information to draw definitive conclusions, they do not point to an increased risk of congenital defects. Experience with the use of sumatriptan in the second and third trimester is limited.

Evaluation of experimental animal studies does not indicate direct teratogenic effects or harmful effects on peri- and postnatal development. However, embryofoetal viability might be affected in the rabbit (see section 5.3). Administration of sumatriptan should only be considered if the expected benefit to the mother is greater than any possible risk to the foetus.

Lactation

Sumatriptan is excreted into breast milk, with average relative infant doses of < 4% following administration of a single dose of sumatriptan. Infant exposure can be minimised by avoiding breast feeding for 12 hours after treatment, during which time any breast milk expressed should be discarded.

There have been reports of breast pain and/or nipple pain following sumatriptan intake in breastfeeding women (see section 4.8). The pain was usually transient and disappeared in 3 to 12 hours.

4.7. Effects on ability to drive and use machines

No studies on the effects on the ability to drive and use machines have been performed. Drowsiness may occur as a result of migraine or treatment with sumatriptan. This may influence the ability to drive and operate machinery.

4.8. Undesirable effects

Adverse events are listed below by system organ class and 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 <1/1000), very rare (<1/10000), not known (cannot be estimated from the available data). Some of the symptoms reported as undesirable effects may be associated symptoms of migraine.

Clinical Trial Data

Nervous System Disorders

Common:

Dizziness, drowsiness, sensory disturbance including paraesthesia and hypoaesthesia.

Vascular Disorders

Common:

Transient increases in blood pressure arising soon after treatment. Flushing.

Respiratory, Thoracic and Mediastinal Disorders

Common

Dyspnoea.

Gastrointestinal Disorders

Common:

Nausea and vomiting occurred in some patients but it is unclear if this is related to sumatriptan or the underlying condition.

Musculoskeletal and Connective Tissue Disorders

Common:

Sensations of heaviness (usually transient and may be intense and can affect any part of the body including the chest and throat). Myalgia.

General Disorders and Administration Site Conditions

Common:

Pain, sensations of heat or cold, pressure or tightness (these events are usually transient and may be intense and can affect any part of the body including the chest and throat).

Feelings of weakness, fatigue (both events are mostly mild to moderate in intensity and transient).

Investigations

Very rare:

Minor disturbances in liver function tests have occasionally been observed.

Post-Marketing Data

Immune System Disorders

Not known:

Hypersensitivity reactions ranging from cutaneous hypersensitivity to anaphylaxis.

Nervous System Disorders

Not known:

Seizures, although some have occurred in patients with either a history of seizures or concurrent conditions predisposing to seizures there are also reports in patients where no such predisposing factors are apparent.

Tremor, dystonia, nystagmus, scotoma.

Eye Disorders

Not known:

Flickering, diplopia, reduced vision. Loss of vision including reports of permanent defects. However, visual disorders may also occur during a migraine attack itself.

Cardiac Disorders

Not known:

Bradycardia, tachycardia, palpitations, cardiac arrhythmias, transient ischaemic ECG changes, coronary artery vasospasm, angina, myocardial infarction (see sections 4.3 and 4.4).

Vascular Disorders

Not known:

Hypotension, Raynaud's phenomenon.

Gastrointestinal Disorders

Not known:

Ischaemic colitis, diarrhoea, dysphagia.

Musculoskeletal, Connective Tissue and Bone Disorders

Not known:

Neck stiffness.

Arthralgia.

Reproductive system and breast disorders

Rare:

Breast pain.

General Disorders and Administration Site Conditions

Not known:

Pain trauma activated, pain inflammation activated.

Psychiatric disorders

Not known:

Anxiety.

Skin and subcutaneous disorders

Not known:

Hyperhidrosis.

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 at Website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

4.9. Overdose

Doses up to 100 mg orally were not associated with side effects other than those mentioned.

If overdosage occurs, the patient should be monitored for at least ten hours and standard supportive treatment applied as required.

It is unknown what effect haemodialysis or peritoneal dialysis has on the plasma concentrations of Imigran.