Sumatriptan 50mg Tablets
Out of date information, search anotherSUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Sumatriptan 50mg Tablets
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
One tablet contains sumatriptan succinate, corresponding to 50 mg sumatriptan.
Excipient(s) with known effect:
One tablet contains 199 mg of lactose.
For the full list of excipients, see section 6.1.
3 PHARMACEUTICAL FORM
Tablet.
Pink, oval-shaped, biconvex tablets with a scoreline on one side.
The score line is not intended for breaking the tablet.
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
Acute treatment of migraine attacks with or without aura.
4.2 Posology and method of administration
Sumatriptan tablets 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. 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.
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.
The tablets should be swallowed whole with water.
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 the use of sumatriptan film-coated tablets in children 10 to 17 years of age is not recommended (see section 5.1 ).
Elderly patients (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.
4.3 Contraindications
Hypersensitivity to the active substance or to any of the excipients
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 cerebrovascular 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 (see section 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 tablets 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 increased risk of certain cerebrovascular events (e.g. CVA, TIA).
Following administration, sumatriptan can be associated with transient symptoms such as chest pain and sensations of 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 patient who are diabetics, heavy smokers or users of nicotine substitution therapies without a 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 postmarketing 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 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 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 a know hypersensitivity to sulphonamides may exhibit an allergic reaction to 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 doses of sumatriptan should not be exceeded.
This medicinal product contains lactose. Patients with rare hereditary problems of galactose intolerance, the 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 postmarketing 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)
There may be a risk of serotonergic syndrome also if sumatriptan is used concomitantly with lithium.
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 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.
Breast-feeding
It has been demonstrated that following subcutaneous administration sumatriptan is secreted into breast milk. Infant exposure can be minimised by avoiding breast feeding 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 use 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), not known (cannot be estimated from the available data).
Some of the symptoms reported as undesirable effects may be associated symptoms of migraine.
Immune system disorders:
Very rare: Hypersensitivity reactions ranging from cutaneous hypersensitivity to rare cases of anaphylaxis.
Psychiatric disorder Not known: Anxiety
Nervous system disorders:
Common: Dizziness, drowsiness. sensory disturbance including paraesthesia and hypoaesthesia.
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, tremor, dystonia.
Eye disorders:
Very rare: 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:
Very rare: Bradycardia, tachycardia, palpitations, cardiac arrhythmias, transient ischaemic ECG changes, coronary artery vasospasm, myocardial infarction (see section 4.3 and 4.4).
Vascular disorders:
Common: Transient increased in blood pressure arising soon after treatment. Flushing.
Very rare: 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.
Very rare: Ischaemic colitis Not known: 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
Very rare: Neck stiffness Not known: 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
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 ten hours and, , standard supportive treatment applied as required. It is unknown what effect hemodialysis or peritoneal dialysis has on plasma concentrations of sumatriptan.
5 PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Analgesics: antimigraine preparations; selective serotonin (5HT1) agonists.
ATC code: N02CC01.
Sumatriptan is a specific and selective agonist of the vascular 5-hydroxytryptamine1 receptor, with no effect on other 5HT receptor sub-types. Receptors of this type have mainly been found in cranial blood vessels. In animals, sumatriptan causes selectively 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 for migraine in humans. The results of tests on animals indicate 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 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.
A number of placebo-controlled clinical studies assessed the safety and efficacy of oral sumatriptan in approximately 800 children and adolescent migrainerus 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 and 70% of the 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 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 proteins is low (14 - 21%) and the mean distribution volume 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, presystemic 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 5HTj or 5HT2 activity. Minor metabolites have not been identified. Migraine attacks do not seem 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 fertility study, a reduction in 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 significance of these findings for humans is unknown.
Sumatriptan was devoid of genotoxic and carcinogenic effects in in vitro systems and animal studies.
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
lactose monohydrate microcrystalline cellulose croscarmellose sodium magnesium stearate red iron oxide (E172)
6.2 Incompatibilities
Not applicable.
6.3 Shelf life
4 years.
6.4 Special precautions for storage
This medicinal product does not require any special storage conditions.
6.5 Nature and contents of container
OPA/Al/PVC aluminium blister pack. Pack sizes: 1, 2, 4, 6 and 12 tablets.
Not all pack sizes may be marketed.
6.6 Special precautions for disposal
No special requirements.
MARKETING AUTHORISATION HOLDER
PLIVA Pharma Ltd Vision House Bedford Road Petersfield
Hampshire GU32 3QB UK
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MARKETING AUTHORISATION NUMBER(S)
PL 10622/0286
DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
06/02/2012
DATE OF REVISION OF THE TEXT
24/03/2014