Summary of Product Characteristics

Transcription

1 Summary of Product Characteristics 1. Name of the Medicinal Product Sumatriptan Merck 50 mg film-coated tablet Sumatriptan Merck 100 mg film-coated tablet 2. Qualitative and Quantitative Composition Each tablet contains 50 mg sumatriptan as sumatriptan succinate Each tablet contains 100 mg sumatriptan as sumatriptan succinate For a full list of excipients, see section Pharmaceutical Form Film-coated tablet. Sumatriptan 50 mg: Pink, round film-coated tablets with the inscription SU50 on one side and G on the other. Sumatriptan 100 mg: White, round film-coated tablets with the inscription SU100 on one side and G on the other. 4. Clinical Particulars 4.1 Indications Sumatriptan is indicated for the acute treatment of migraine attacks with or without aura. 4.2 Posology and Method of Administration General recommendations with regard to use and administration: Sumatriptan should not be used prophylactically. Sumatriptan is intended as monotherapy for the acute treatment of a migraine attack, and must not be administered concomitantly with ergotamine or derivatives of ergotamine (including methysergide) (see section 4.3). Sumatriptan should be used as soon as possible after the onset of the migraine headache. However, sumatriptan is equally effective when used at a later time during the migraine attack. The following recommended dosages of Sumatriptan should not be exceeded.

2 Adults: The recommended dosage for adults is 50 mg sumatriptan. Some patients require 100 mg sumatriptan. Although the recommended oral dose of sumatriptan is 50 mg, it must be taken into account that the severity of migraine attacks varies both within and between patients. Doses of 25 mg 100 mg have shown to be more effective than placebo in clinical trials but 25 mg is statistically significantly less effective than 50 mg and 100 mg. Patients who do not respond to the first dose of sumatriptan should not use a second dose for the same attack. In a subsequent attack, Sumatriptan may be used again. If the patient has responded to the first dose, but the symptoms recur later, 1 or 2 additional doses can be taken during the next 24 hours, provided that there is a minimum interval of 2 hours between the doses and not more than 300 mg sumatriptan is taken during this period. Children and adolescents (under 18 years): The safety and efficacy of sumatriptan tablets has not been established in children and adolescents. Patients over 65 years of age: Experience of the use of sumatriptan in patients over 65 years is limited. However, the kinetics in elderly subjects have not been sufficiently investigated. Therefore, until more data are available, the use of sumatriptan in elderly patients is not recommended. Patients with hepatic insufficiency: In patients with mild to moderate hepatic insufficiency low doses of mg sumatriptan should be considered. Method of administration: The tablets must be taken with water. 4.3 Contraindications Hypersensitivity to sumatriptan or to any of the excipients (see also section 4.4 with regard to the use in patients with known hypersensitivity to sulphonamides). A history of myocardial infarction, ischaemic heart disease, or coronary vasospasm (Prinzmetal s angina). Peripheral vascular disease. Symptoms or signs suggesting ischaemic heart disease. A history of stroke (cerebrovascular accident (CVA)) or transient ischaemic attack (TIA) Severe disturbances of hepatic function. Moderate to severe hypertension, mild uncontrolled hypertension. Concomitant administration of preparations containing ergotamine or ergotamine derivatives (including methysergide) (see section 4.5). Concomitant use of monoamine oxidase inhibitors and the use of sumatriptan within two weeks after discontinuation of therapy with monoamine oxidase inhibitors.

3 4.4 Special Warnings and Precautions for Use Sumatriptan should only be prescribed when there is a clear diagnosis of migraine. Sumatriptan is not indicated for the treatment of basilar, hemiplegic or ophthalmoplegic migraine. Just as with other acute migraine therapy, in patients who have not been diagnosed earlier as migraine patients and in migraine patients who have atypical symptoms, it should be ensured that other, possibly serious, neurological conditions have first been excluded. It should be noted that migraine patients are at a higher risk of certain cerebrovascular symptoms such as stroke (CVA (cerebrovascular accident)) and TIA (transient ischaemic attack). The use of sumatriptan may be followed by complaints in the chest and throat, including pain and/or a sensation of tightness in the thorax (see section 4.8). These disorders may be intense and involve the throat. If symptoms suggesting ischaemic heart disease occur, sumatriptan should be discontinued, and appropriate evaluation should be carried out. Sumatriptan should not be prescribed for patients with risk factors for ischaemic heart disease, such as e.g. diabetics, heavy smokers or patients on nicotine substitution therapy without prior cardiovascular examination (see section 4.3). Special consideration should be given to post-menopausal women and men over 40 years of age who have these these risk factors. However, not every patient with cardiac disease may be identified by prior examination. In very rare cases, serious cardiac complications have occurred in patients without underlying cardiovascular disease. In rare cases, asthenia, hyperreflexia and incoordination have been described in postmarketing reports following use of a selective serotonin reuptake inhibitor (SSRIs) and sumatriptan. If concomitant administration of sumatriptan and SSRIs is clinically justified, appropriate observation of the patient is advised. Caution must also be exercised in patients with conditions that influence absorption, metabolism or excretion of medicinal products, such as hepatic or renal insufficiency. 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. Patients with known hypersensitivity to sulphonamides may exhibit an allergic reaction after use of sumatriptan. These reactions can vary from cutaneous hypersensitivity to anaphylaxis. Evidence of cross sensitivity is limited, however, caution should be exercised before using sumatriptan in these patients. Undesirable effects can occur more frequently in cases of concomitant use of triptans and herbal preparations containing St. John s wort (Hypericum perforatum). As with other treatments for acute migraine attacks, chronic daily headache /exacerbation of headache has been reported in cases of excessive use of sumatriptan. It may then be necessary to discontinue the treatment. The recommended dosage should not be exceeded.

4 This product contains lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine. 4.5 Interactions with Other Medicinal Products and Other Forms of Interaction No evidence of interactions with propranalol, flunarizine, pizotifen or alcohol has been found. Data on the interaction with ergotamine-containing preparations are limited. In theory, an increased risk of coronary vasospasms is possible, and concomitant administration is contraindicated. It is not known how long one must wait between the use of sumatriptan and ergotamine-containing preparations. This depends on the level of the dosage and the selected ergotamine-containing agent. The effects may be additive. It is advised that an interval of at least 24 hours be observed after the use of ergotamine-containing preparations before administering sumatriptan. Conversely, it is advised that one should wait at least 6 hours after the use of sumatriptan before administering ergotamine-containing preparations (see section 4.3). Since an interaction can occur between sumatriptan and monoamine oxidase inhibitors, concomitant use is contraindicated (see section 4.3). Interactions between sumatriptan and SSRIs occur rarely. There may be a risk of serotonergic syndrome also if sumatriptan is used concomitantly with lithium. 4.6 Pregnancy and Lactation Post-marketing data on the use of sumatriptan during the first trimester are available from more than 1,000 women. Although these data do not contain sufficient information for a definitive conclusion to be reached, they do not indicate an increased risk of congenital defects. Experience of the use of sumatriptan in the second and third trimesters is limited. Up to now, animal studies do not indicate teratogenicity or harmful effects during peri- and post-natal development. However, in rabbits embryofoetal viability may be influenced (see section 5.3). Administration of sumatriptan should only be considered if the expected benefits for the mother outweigh any possible risks for the unborn child. Lactation: Sumatriptan is excreted into breast milk. Exposure of the child can be minimised by avoiding breast-feeding for 12 hours after administration of sumatriptan, during which time the breast milk should be expressed and discarded.

5 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. Account should be taken of the fact that symptoms such as dizziness and weakness caused by a migraine attack itself or by treatment with sumatriptan may affect ability to drive or operate machines. 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 Clinical Trial Data Nervous System Disorders Common: Tingling, dizziness, drowsiness. Vascular disorders Common: Transient increases in blood pressure arising soon after treatment. Flushing. 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, connective tissue and bone disorders Common: Sensations of heaviness (usually transient and may be intense and can affect any part of the body including the chest and throat). General Disorders and Administration Site Conditions Common: Pain, sensations of heat, 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). Common: Investigations Very rare: Feelings of weakness, fatigue, somnolence and flushing (all events are mostly mild to moderate in intensity and transient). Minor disturbances in liver function tests have been observed. Post-Marketing Data Immune System Disorders Very rare: Hypersensitivity reactions of all degrees of severity, ranging from cutaneous hypersensitivity to rare cases of anaphylaxis. Nervous System Disorders

6 Very rare: Eye disorders Very rare: Cardiac disorders Very rare: Vascular disorders Very rare: 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. Nystagmus, scotoma. Flickering, diplopia, reduced vision. Loss of vision including reports of permanent defects. However, visual disorders may also occur during a migraine attack itself. Bradycardia, tachycardia, palpitations, cardiac arrhythmias, transient ischaemic ECG changes, coronary artery vasospasm, myocardial infarction (see section 4.3 and 4.4). Hypotension, Raynaud s phenomenon. Gastrointestinal disorders Very rare: Ischaemic colitis. Musculoskeletal, connective tissue and bone disorders Very rare: Neck stiffness. 4.9 Overdose Symptoms of Overdose Isolated cases of overdose with sumatriptan tablets have been described. Patients have received up to 12 mg of sumatriptan, as a single subcutaneous injection without significant undesirable effects. With single doses up to 200 mg rectally or 40 mg nasally and more than 16 mg subcutaneously and 400 mg orally, no adverse reactions other than those mentioned in the relevant section were found. There is no experience to date of higher doses. Therapy of Overdose If an overdose with sumatriptan occurs, the patient should be monitored for at least 10 hours. No clinically relevant antagonist of sumatriptan is known. Therefore, in the event of overdose, symptomatic treatment is advised. The effect of haemodialysis or peritoneal dialysis on the plasma levels of sumatriptan is unknown. 5. Pharmacological Properties 5.1 Pharmacodynamic Properties Pharmacotherapeutic group: selective serotonin agonist. ATC code: N02CC01 Sumatriptan is a specific and selective 5-hydroxytryptamine-1d receptor agonist and has not demonstrated activity on the other 5HT (5HT 2-5HT 7 ) receptors. The vascular 5-HT 1d receptor

7 is found predominantly in the cranial blood vessels and has a vasoconstrictor effect. In experimental animals, it has been shown that sumatriptan causes vasoconstriction of the arterioles and the arteriovenous anastomata of the carotid vascular bed. This vascular bed provides the blood supply to the extracranial and intracranial tissues, such as the meninges. It has been proposed that dilation of these arterial vessels, and the formation of oedema here, is the underlying cause of a migraine attack in humans. There is also evidence from animal experiments to suggest that sumatriptan inhibits the activity of the trigeminal nerve. Both effects (cranial vasoconstriction and inhibition of the activity of the trigeminal nerve) might contribute to the anti-migraine effect of sumatriptan in humans. A clinical response occurs approx. 30 minutes after oral administration of a dose of 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. 5.2 Pharmacokinetic Properties Following oral administration sumatriptan is rapidly absorbed, 70% of the maximum concentration being reached after approx. 45 minutes. After oral administration of 100 mg, the peak plasma concentration is on average 54 ng/ml. Absolute bioavailability after oral administration is on average 14%. This is partly due to presystemic metabolism and partly to incomplete absorption. In patients with hepatic insufficiency, presystemic clearance after oral administration is reduced, resulting in an increase in the plasma levels of sumatriptan. Protein binding is low (14-21%) and the mean volume of distribution is 170 litres. The elimination half-life is approximately 2 hours. Mean total clearance is 1160 ml/min and mean renal clearance is approx. 260 ml/min. Non-renal clearance is approximately 80% of total clearance, suggesting that sumatriptan is primarily cleared through oxidative metabolism mediated by monoamine oxidase A. The major metabolite, the indole acetic acid analogue of sumatriptan, is excreted in the urine as the acid or as the glucoronide conjugate. This metabolite has no known 5HT 1 or 5HT 2 activity. Minor metabolites have not been identified. The pharmacokinetics of the oral administration of sumatriptan does not appear to be influenced by a migraine attack. Pharmacokinetics in special groups: Elderly: The kinetics in elderly subjects has not been sufficiently studied to permit a statement on possible differences in the kinetics between elderly and young volunteers. 5.3 Preclinical Safety Data In a fertility study in the rat, a reduction in the success of insemination was seen on exposure to concentrations higher than the maximum exposure in humans. In rabbits embryolethality was observed, without marked teratogenic effects.

8 Sumatriptan was devoid of genotoxic and carcinogenic activity in in-vitro systems and animal studies. 6. Pharmaceutical Particulars 6.1 List of Excipients Tablet interior Lactose monohydrate Microcrystalline cellulose Croscarmellose (E468) Magnesium stearate (E470b) Film coating Titanium dioxide (E171) Polydextrose (E 1200) Hypromellose (E484) Glyceryl triacetate (E1518) Macrogol/ Sumatriptan 50 mg tablets Red iron oxide (E172) Yellow iron oxide (E172). 6.2 Incompatibilities Not applicable. 6.3 Shelf Life 3 years 6.4 Special Precautions for Storage This medicinal product does not require any special storage conditions. 6.5 Nature and Contents of Container Polyamide-aluminium-PVC/aluminium foil blister packs in a cardboard carton Package sizes: 2, 3, 4, 5, 6, 10, 12, 18, 20 and 24 tablets. Not all pack sizes may be marketed. 6.6 Instructions for Use and Handling No special requirements

9 7. Marketing Authorisation Holder 8. Marketing Authorisation Number(s) 9. Date of First Authorisation/renewal of the Authorisation 10. Date of Revision of the Text