Sumatriptan 50mg Tablets
SUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Sumatriptan 50mg tablets
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each tablet contains 50mg sumatriptan as sumatriptan succinate.
Excipients with known effect: Each tablet contains 185.48mg lactose (as lactose monohydrate)
For the full list of excipients, see 6.1.
3 PHARMACEUTICAL FORM
Tablet
Pink, with partly pink dots, oblong tablet of width 6.8-7.2mm and length of 11.8-12.2mm with a break-line on both sides.
The score line is only to facilitate breaking for the ease of swallowing and not to divide into equal doses
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
Sumatriptan is indicated for the acute treatment of migraine attacks with or without aura.
4.2
Posology and method of administration
Posology
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.
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 these cases the attack can be treated with paracetamol, acetylsalicyclic acid or non-steroidal anti-inflammatory drugs. 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 two hours between the doses and not more than 300 mg sumatriptan is taken during this period.
Paediatric population:
The efficacy and safety of sumatriptan 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 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 tablets in children 10 to 17 years of age is not recommended (see section 5.1).
Patients over 65 years of age:
Experience of the use of sumatriptan in patients over 65 years is limited. The pharmacokinetics do not differ significantly from a younger population However, the kinetics in elderly subjects have not been sufficiently investigated. Therefore, until more data are available, the use sumatriptan in elderly patients aged over 65 years is not recommended.
Patients with hepatic insufficiency:
In patients with mild to moderate hepatic insufficiency low doses of 25-50 mg sumatriptan should be considered.
Method of administration
The tablets should be swallowed whole with water. The sumatriptan substance has a bitter taste. The bitter taste is masked with the aid of grapefruit flavour.
4.3 Contraindications
• Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. (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
• The use of sumatriptan in patient with moderate to severe hypertension, mild uncontrolled hypertension is contraindicated
• Concomitant administration of preparations containing ergotamine or ergotamine derivatives (including methysergide) or any triptan/5-hydroxytryptaminel (5-HT1) receptor agonist is contraindicated (see section 4.5)
• Concomitant use of monoamine oxidase inhibitors and the use of sumatriptan within 2 weeks after discontinuation of therapy with monoamine oxidase inhibitors.
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 opthalmoplegic 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 higher risk of certain cerebrovascular symptoms
such as stroke (CVA (cerebrovascular accident)) and TIA (transient ischarmic 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 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 postmenopausal women and
men over 40 years of age who have 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.
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 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 (SNRls). If concomitant administration of sumatriptan and SSRIs is clinically justified, appropriate observation of the patient is advised (see section 4.5).
Caution must also be exercised in patients with conditions that influence absorption, metabolism or excretion of medicinal products, such as hepatic or renal insufficiency. 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 after use of sumatriptan. The 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).
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
The recommended dosage should not be exceeded.
This medicinal product contains lactose. Patients with rare hereditary conditions such as galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption should not uses this medicinal product.
4.5 Interaction with other medicinal products and other forms of interaction
Study in healthy subjects show that sumatriptan does not interact with propranolol, flunarizine, pizotifen or alcohol.
Data on the interaction with ergotamine-containing preparations or another triptan/5-HT1 receptor agonist are limited. In theory, an increased risk of coronary vasospasms is possible, and concomitant administration is contraindicated (See section 4.3).
It is not known how long one must wait between the use of sumatriptan and ergotamine-containing preparations or another triptan /5-HTj receptor agonist. 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 or another triptan/5-HT1 receptor agonist 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 and at least 24 hours before administering another triptan/5-HT1 receptor agonist (see section 4.3).
Since an interaction can occur between sumatriptan and monoamine oxidase inhibitors, concomitant use 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 sumatriptan and SSRIs.
There may be a risk of serotonergic syndrome also if sumatriptan is used concomitantly with lithium, triptans and SNRIs see section (see section 4.4).
4.6 Fertility, pregnancy and lactation
Pregnancy
Post-marketing data on the use of sumatriptan during the first trimester are available from more than 1000 women. Although these data do not contain sufficient information for a definite 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 direct 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 risk to the unborn child.
Breast-feeding
It has been demonstrated that following subcutaneous administration, Sumatriptan is excreted into breast milk. Exposure of the infant can be minimised by avoiding breast-feeding for 12 hours after administration of sumatriptan during which any breast milk expressed should be discarded.
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 drowsiness, 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) and rare (> 1/10,000, <1/1000) and very rare (</10,000) including isolated reports
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, 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). 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, somnolence
(all events are mostly mild to moderate in intensity and
transient).
Investigations
Very rare: Minor disturbances in liver function tests have been
observed.
Post-Marketing Data
Immune System Disorders
Hypersensitivity reactions of all degrees of severity, ranging from cutaneous hypersensitivity (such as urticaria) to rare cases of anaphylaxis.
Very rare:
Nervous System 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. Tremor, dystonia, nystagmus, scotoma.
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, angina, myocardial infarction (see section 4.3 and 4.4).
Vascular disorders
Very rare: Hypotension, Raynaud’s phenomenon.
Gastrointestinal disorders
Very rare: Ischaemic colitis, diarrhoea
Musculoskeletal, connective tissue and bone disorders Very rare: Neck stiffness, arthralgia
Psychiatric disorders
Not known: Anxiety.
Skin and subcutaneous tissue 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 www.mhra.gov.uk/yellowcard.
4.9 Overdose
Symptoms of overdose
Doses in excess of 400mg were not associated with side effect other than those mentioned
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 overdose with sumatriptan occurs, the patient should be monitored for at least 10 hours and standard supportive treatment applied.. 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: Analgesics: selective serotonin (5-HT1 receptor) agonists
ATC code: N02CC01
Sumatriptan is a specific and selective 5-hydroxytryptamine-1d receptor agonist, and has not demonstrated activity on the other 5HT (5HT2 - 5HT7) receptors. The vascular 5HTJd receptor 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 dilatation 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 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.
A clinical response occurs approx. 30 minutes after oral administration of a dose of 100 mg.
Although the recommended dose of oral sumatriptan is 50mg, migraine attacks vary in severity both within and between patients. Doses of 25-100mg have shown greater efficacy than placebo in clinical trials, but 25mg is statistically significantly less effective than 50 and 100mg.
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 approx. 2 hours. Mean total clearance is 1160 ml/minute and mean renal clearance is approx. 260ml/minute. Non-renal clearance is approx. 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 glucuronide conjugate. This metabolite has no known 5HT1 or 5HT2 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 a rat, oral doses of sumatriptan resulting in plasma levels approximately 200 times those seen in man after a 100 mg oral dose were associated. with 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.
This effect did not occur during a subcutaneous study where maximum plasma levels achieved approximately 150 times those in man by the oral route.
Sumatriptan was devoid of genotoxic and carcinogenic activity in in-vitro systems and animal studies.
6 PHARMACEUTICAL PARTICULARS
List of excipients
6.1
Ammonium methacrylate copolymer type A
carmellose sodium (E466)
microcrystalline cellulose (E450)
croscarmellose sodium (E468)
lactose monohydrate
magnesium stearate (E470b)
flavouring (grapefruit)
red iron oxide (E172)
yellow iron oxide (E172)
6.2 Incompatibilities
Not applicable.
6.3 Shelf life
5 years
6.4 Special precautions for storage
This medicinal product does not require any special storage conditions.
6.5 Nature and contents of container
Aluminium/aluminium blister strips in a cardboard carton 2, 3, 4, 6, 8, 12, 18, 20, 30, 50 and 100 tablets Not all pack sizes may be marketed.
6.6 Special precautions for disposal and other handling
No special requirements for disposal.
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Any unused medicinal product or waste material should be disposed of in accordance with local requirements
Tillomed Laboratories Ltd. 3 Howard Road,
Eaton Socon, St. Neots, Cambridgeshire PE19 8ET United Kingdom
MARKETING AUTHORISATION NUMBER(S)
PL11311/0439
DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
Date of first authorisation: 30/11/2009
10/09/2015