SUMMARY OF PRODUCT CHARACTERISTICS

1.    NAME OF THE MEDICINAL PRODUCT

Sumatriptan 50 mg Film-coated Tablets

2    QUALITATIVE AND QUANTITATIVE COMPOSITION

50 mg: Each film-coated tablet contains 50 mg of sumatriptan (as sumatriptan succinate).

Excipient(s) with known effect:

50 mg: Each film-coated tablet contains 67.5 mg of lactose (as dry substance) as lactose monohydrate.

For the full list of excipients, see section 6.1.

3    PHARMACEUTICAL FORM

Film-coated tablet.

50 mg: Peach to pink, oblong shaped film-coated tablet debossed “5” and “0” on one side and scoreline on each side.

The tablet can be divided into equal doses.

4    CLINICAL PARTICULARS

4.1    Therapeutic indications

Acute treatment of migraine attacks with or without aura.

4.2    Posology and method of administration

Sumatriptan should not be used prophylactically.

Sumatriptan 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).

Sumatriptan should be taken as early as possible after the onset of a migraine headache. Sumatriptan is equally effective at whatever stage of attack it is administered.

The following recommended dosages should not be exceeded.

Adults

The recommended dose for adults is a single dose of 50 mg. Some patients may require 100 mg..

If the patient does not respond to the first dose of sumatriptan, a second dose should not be taken for the same attack. In these cases the attack can be treated with paracetamol, acetylsalicylic acid, or non-steroidal anti-inflammatory drugs. Sumatriptan film-coated tablets may be taken for subsequent attacks.

If the patient has responded to the first dose, but the symptoms recur a second dose may be given in the next 24 hours, provided that there is a minimum interval of 2 hours between the two doses. No more than 300 mg should be taken in any 24-hour period.

Paediatric population

The efficacy and safety of sumatriptan film-coated tablets 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 sumatriptan film-coated tablets in children 10 to 17 years of age have not been demonstrated in the clinical trials performed in this age group. Therefore, use of sumatriptan film-coated tablets 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 sumatriptan tablets 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 sumatriptan in patients aged over 65 years is not recommended.

Hepatic insufficiency

Patients with mild to moderate liver insufficiency: low doses of 25-50 mg should be considered for patients with mild to moderate liver impairment.

Renal insufficiency See section 4.4.

4.3 Contraindications

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

Sumatriptan should not be given to patients who have had myocardial infarction or who have ischaemic heart disease, Prinzmetal’s variant angina/spasms of the coronary artery or 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 cerebovascular accident (CVA) or transient ischaemic attack (TIA).

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

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

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

Concurrent administration of monoamine oxidase inhibitors (MAOIs) 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

Sumatriptan should only be used when there is a clear diagnosis of migraine.

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

As with other acute migraine therapies, before treating headaches in patients not previously diagnosed as migraineurs, and in migraineurs who present with atypical symptoms, care should be taken to exclude other potentially serious neurological conditions.

It should be noted that migraineurs may be at increased risk of certain cerebrovascular events (e.g. CVA, TIA).

Following administration, sumatriptan can be associated with transient symptoms such as 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 an 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 post-menopausal women and to men over the age of 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.

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 re-uptake inhibitors (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 a 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 the medicine, such as impaired hepatic or renal function.

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

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 amount of patients (see section 4.3).

The recommended dosage should not be exceeded.

Sumatriptan Film-coated Tablets contain lactose. Patients with rare hereditary problems of galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicinal product.

4.5 Interaction with other medicinal products and other forms of interaction

There is no evidence of interactions with propranolol, flunarizine, pizotifen or alcohol.

There are limited data on an interaction with ergotamine-containing preparations or another triptan/5-HT1. 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 type of ergotamine-containing 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 six 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 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 on 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 onperi- and postnatal development. However, embryofetal 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.

Breast-feeding

It has been demonstrated that following subcutaneous administration sumatriptan is secreted into breast milk. Infant exposure can be minimised by avoiding breastfeeding for 12 hours after treatment, during which time any breast milk expressed should be discarded.

4.7 Effects on ability to drive and use machines

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

Drowsiness may occur as a result of migraine or its treatment with sumatriptan. This may influence the ability to drive and to 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, <1/10), uncommon (>1/1000, <1/100), rare (>1/10,000, <1/1000) and very rare (<1/10,000 including isolated reports), not known (cannot be estimated from the avaible data).

Some of the symptoms reported as undesirable effects may be associated symptoms of migraine.

Immune system disorders

Not known: Hypersensitivity reactions ranging from cutaneous hypersensitivity (such as urticaria) to anaphylaxis.

Psychiatric disorders

Not known: Anxiety

Nervous system disorders

Common:    dizziness, drowsiness, sensory disturbance including

paraesthesia and hypoaesthesia

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

Common:    Transient increases in blood pressure arising soon after

treatment. Flushing.

Not known: Hypotension, Raynaud’s phenomenon

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.

Not known: Ischaemic colitis, diarrhoea

Skin and subcutaneous tissue disorders

Not known: Hyperhidrosis

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.

Not known: Neck stiffness, arthralgia

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

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: www.mhra.gov.uk/yellowcard

4.9 Overdose

Symptoms

Doses in excess of 400 mg orally and 16 mg subcutaneously were not associated with side effects other than those mentioned. Patients have received single injections of up to 12 mg subcutaneously without significant adverse effects.

Management

If overdosage occurs, the patient should be monitored for at least 10 hours and standard supportive treatment applied as required. It is unknown what effect haemodialysis or peritoneal dialysis has on the plasma concentrations of sumatriptan.

5 PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Analgesics: antimigraine preparations: selective serotonin (5-HTi) receptor agonists ATC code: N02CC01

Sumatriptan is a specific and selective agonist of the vascular 5-hydroxytryptamine1 receptor, with no effect on other 5-HT receptor sub-types. Receptors of this type have mainly been found in cranial blood vessels. In animals, sumatriptan selectively causes vasoconstriction in the circulation of the carotid artery, which supplies blood to extracranial and intracranial tissues such as the meninges. The dilatation of these vessels is thought to be the underlying mechanism of migraine in humans. The results of tests on animalsindicate that sumatriptan also inhibits the activity of the trigeminal nerve. Both effects (cranial vasoconstriction and inhibition of the activity of the trigeminal nerve) may explain the migraine-inhibiting effect of sumatriptan in humans.

The clinical response begins about 30 minutes after oral administration of a 100 mg dose.

Doses of 25 mg-100 mg have been shown to be more effective than placebo in clinical trials but 25 mg is statistically significantly less effective than 50 mg and 100 mg.

Sumatriptan is effective for the acute treatment of migraine attacks that occur during menstruation in women, i.e. in the period from 3 days before to 5 days after the beginning of menstruation.

A number of placebo-controlled clinical studies assessed the safety and efficacy of oral sumatriptan in approximately 800 children and adolescent migraineurs aged 10 to 17 years. These studies failed to demonstrate relevant differences in headache relief at 2 hours between placebo and any sumatriptan dose. The undesirable effects profile of oral sumatriptan in adolescents aged 10-17 years was similar to that reported from studies in the adult population.

5.2 Pharmacokinetic properties

Following oral administration, sumatriptan is rapidly absorbed, 70 % of maximum concentration is achieved after 45 minutes. The mean peak concentration in plasma after a dose of 100 mg is 54 ng/ml. The mean absolute oral bioavailability after oral administration is 14 % partly due to presystemic metabolism and partly due to incomplete absorption. The elimination half-life is approximately 2 hours.

Binding to plasma protein is low (14 - 21 %) and the mean volume of distribution is 170 litres. The mean total clearance is approximately 1160 ml/min and the mean renal clearance is approximately 260 ml/min. The non-renal clearance accounts for about 80 % of the total clearance, which indicates that sumatriptan is primarily eliminated by metabolism. In patients with hepatic insufficiency, pre-systemic clearance after oral administration is reduced, resulting in an increase in the plasma levels of sumatriptan. The main metabolite, the indole acetic acid analogue of sumatriptan, is mainly excreted in the urine as free acid and glucuronide conjugate. It possesses no known 5-HT₁ or 5-HT₂ activity. Minor metabolites have not been identified. Migraine attacks do not appear to have a significant effect on the pharmacokinetics of orally administered sumatriptan.

5.3 Preclinical safety data

Experimental studies on acute and chronic toxicity gave no evidence on toxic effects in range of human therapeutic doses.

In a rat ferfility study, a reduction in the success of insemination was seen at exposures sufficiently in excess of the maximum human exposure.

In rabbits, embryolethality, without marked teratogenic defects, was seen. The significanceof these findings for humans is unknown.

Sumatriptan was devoid of genotoxic and carcinogenic activity in in vitro systems and animal studies.

6 PHARMACEUTICAL PARTICULARS

6.1 List of excipients

50 mg Core

Lactose monohydrate

Croscarmellose sodium

Cellulose, microcrystalline

Silica colloidal anhydrous

Magnesium stearate

Coating - Opadry II 33G23092 peach

Hypromellose E464

Titanium dioxide E171

Lactose monohydrate

Macrogol 3000

Glycerol triacetate

Iron oxide red E172

Iron oxide yellow E172

Iron oxide black E172

6.2 Incompatibilities

Not applicable

10 DATE OF REVISION OF THE TEXT

22/11/2013