Single doses of sumatriptan up to 40 mg intranasally, in excess of 16 mg subcutaneously and 400 mg orally have not been associated with side effects other than those mentioned.
In clinical studies volunteers have received 20 mg of sumatriptan by the intranasal route three times a day for a period of 4 days without significant adverse effects.
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.
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 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 is contraindicated.
Concurrent administration of monoamine oxidase inhibitors (MAOIs) and sumatriptan is contraindicated.
Sumatriptano Generis 50 mg Comprimidos must not be used within 2 weeks of discontinuation of therapy with monoamine oxidase inhibitors.
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.
Adverse events reported in adults have also been observed in adolescents. These include very rare reports of coronary artery vasospasm and myocardial infarction.
| Immune system disorders | |
| Not known: | Hypersensitivity reactions ranging from cutaneous hypersensitivity (such as urticaria) to anaphylaxis. |
| Nervous system disorders | |
| Very common: | Dysgeusia/unpleasant taste. |
| Common: | Dizziness, drowsiness, sensory disturbance including paraesthesia andhypoaesthesia. |
| 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. |
| 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: | Following administration of sumatriptan nasal spray mild, transient irritation or burning sensation in the nose or throat or epistaxis have been reported. 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. |
| 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. |
| 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
In non-clinical studies carried out to test for local and ocular irritancy, following administration of sumatriptan nasal spray, there was no nasal irritancy seen in laboratory animals and no ocular irritancy observed when the spray was applied directly to the eyes of rabbits.
Experimental studies of acute and chronic toxicity showed no evidence of toxic effects within the human therapeutic dose range. 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, embryo-lethality without marked teratogenic defects was seen.
Sumatriptan was devoid of genotoxic and carcinogenic activity in in-vitro systems and animal studies.
Sumatriptano Generis 50 mg Comprimidos Nasal Spray is indicated for the acute treatment of migraine attacks with or without aura.
Pharmacotherapeutic group: Selective 5-HT1 receptor agonists.
ATC code: N02CC01.
Sumatriptan is a selective vascular 5-hydroxytryptamine-1-(5-HT1d) receptor agonist with no effect on other 5-HT receptor (5-HT2-5-HT7) subtypes. The vascular 5-HT1d receptor is found predominantly in cranial blood vessels and mediates vasoconstriction. In animals, sumatriptan selectively constricts the carotid arterial circulation, which supplies blood to the extracranial and intracranial tissues such as the meninges. Dilatation and/or oedema in these vessels is thought to be the underlying mechanism of migraine in man. In addition, evidence from animal studies suggests that sumatriptan inhibits trigeminal nerve activity. Both cranial vasoconstriction and inhibition of trigeminal nerve activity may contribute to the anti-migraine action of sumatriptan in humans.
Clinical response begins 15 minutes following a 20 mg dose given by intranasal administration.
Because of its route of administration, Sumatriptano Generis 50 mg Comprimidos Nasal Spray may be particularly suitable for patients who suffer nausea and vomiting during a migraine attack.
The magnitude of treatment effect is smaller in adolescents compared with adults.
After intranasal administration, sumatriptan is rapidly absorbed, median times to maximum plasma concentrations being 1.5 (range: 0.25-3) hours in adults and 2 (range: 0.5-3) hours in adolescents. After a 20 mg dose, the mean maximum concentration is 13ng/mL. Mean intranasal bioavailability, relative to subcutaneous administration is about 16%, partly due to pre-systemic metabolism.
Plasma protein binding is low (14-21%) and the mean volume of distribution is 170L. The elimination half-life is approximately 2 hours. The mean total plasma clearance is approximately 1160mL/min and the mean renal plasma clearance is approximately 260mL/min.
A pharmacokinetic study in adolescent subjects (12-17 years) indicated that the mean maximum plasma concentration was 13.9ng/mL and mean elimination half-life was approximately 2 hours following a 20 mg intranasal dose. Population pharmacokinetic modelling indicated that clearance and volume of distribution both increase with body size in the adolescent population resulting in higher exposure in lower bodyweight adolescents.
Non-renal clearance accounts for about 80% of the total clearance. Sumatriptan is eliminated primarily by oxidative metabolism mediated by monoamine oxidase A. The major metabolite, the indole acetic acid analogue of sumatriptan, is mainly excreted in urine, where it is present as a free acid and the glucuronide conjugate. It has no known 5-HT1 or 5-HT2 activity. Minor metabolites have not been identified. The pharmacokinetic profile of intranasal sumatriptan does not appear to be significantly affected by migraine attacks.
Special Patient Populations
Elderly (over 65)
The kinetics in the elderly have been insufficiently studied to justify a statement on possible differences in kinetics between elderly and young volunteers.
Hepatic impairment
Sumatriptan pharmacokinetics after an oral dose (50 mg) and a subcutaneous dose (6 mg) were studied in 8 patients with mild to moderate hepatic impairment matched for sex, age, and weight with 8 healthy subjects. Following an oral dose, sumatriptan plasma exposure (AUC and Cmax) almost doubled (increased approximately 80%) in patients with mild to moderate hepatic impairment compared to the control subjects with normal hepatic function. There was no difference between the patients with hepatic impairment and control subjects after the s.c. dose. This indicates that mild to moderate hepatic impairment reduces presystemic clearance and increases the bioavailability and exposure to sumatriptan compared to healthy subjects.
Following oral administration, pre-systemic clearance is reduced in patients with mild to moderate hepatic impairment and plasma exposure, measured by Cmax and AUC, almost doubled.).
Sumatriptano Generis 50 mg Comprimidos Nasal Spray 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 other 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. 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.Special consideration should be give 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 and in adolescents.
Sumatriptan should be given with caution in patients with mild controlled hypertension, since transient increases in blood pressure and peripheral vascular resistance have been observed in a small proportion of patients.
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
Sumatriptan should be administered with caution to patients with conditions that may affect significantly the absorption, metabolism, or excretion of the drug, e.g. impaired hepatic (mild to moderate impairment) 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.
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.
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 to operate machinery.
Sumatriptano Generis 50 mg Comprimidos Nasal Spray should not be used prophylactically.
The recommended dose of Sumatriptano Generis 50 mg Comprimidos should not be exceeded.
Sumatriptano Generis 50 mg Comprimidos is recommended as monotherapy for the acute treatment of a migraine attack and should not be given concomitantly with ergotamine or derivatives of ergotamine (including methysergide).
It is advisable that Sumatriptano Generis 50 mg Comprimidos be given as early as possible after the onset of a migraine headache. It is equally effective at whatever stage of the attack it is administered.
Adults (18 years of age and over)
The optimal dose of Sumatriptano Generis 50 mg Comprimidos Nasal Spray is 20 mg for administration into one nostril. However, due to inter/intra patient variability of both the migraine attacks and the absorption of sumatriptan, 10 mg may be effective in some patients.
If a patient does not respond to the first dose of Sumatriptano Generis 50 mg Comprimidos, 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. Sumatriptano Generis 50 mg Comprimidos 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 following 24 hours, provided that there is a minimum interval of 2 hours between the two doses.
No more than two doses of Sumatriptano Generis 50 mg Comprimidos 20 mg Nasal Spray should be taken in any 24-hour period.
Adolescents (12-17 years of age)
Use of sumatriptan in adolescents should be on the recommendation of a specialist or physician who has significant experience in treating migraine, taking into account local guidance.
The recommended dose of Sumatriptano Generis 50 mg Comprimidos Nasal Spray is 10 mg for administration into one nostril.
If a patient does not respond to the first dose of Sumatriptano Generis 50 mg Comprimidos, 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.
Sumatriptano Generis 50 mg Comprimidos 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 following 24 hours, provided that there is a minimum interval of 2 hours between the two doses.
No more than two doses of Sumatriptano Generis 50 mg Comprimidos 10 mg Nasal Spray should be taken in any 24-hour period.
Children (under 12 years of age)
Sumatriptano Generis 50 mg Comprimidos Nasal Spray is not recommended for use in children under 12 years of age due to insufficient data on safety and efficacy.
Elderly (over 65)
There is no experience of the use of Sumatriptano Generis 50 mg Comprimidos Nasal Spray in patients over 65. The pharmacokinetics in elderly patients have not been sufficiently studied. Therefore the use of sumatriptan is not recommended until further data are available.
No special requirements.
