Läkemedelsverket 2013-07-12
SUMMARY OF PRODUCT CHARACTERISTICS
1.
NAME OF THE MEDICINAL PRODUCT
Sumatriptan Actavis 50 mg coated tablets
Sumatriptan Actavis 100 mg coated tablets
2.
QUALITATIVE AND QUANTITATIVE COMPOSITION
One tablet contains 50 mg or 100 mg sumatriptan (as sumatriptan succinate).
Excipient with known effect:
50 mg:
Lactose monohydrate and anhydrous lactose corresponding to 176 mg anhydrous lactose.
100 mg:
Lactose monohydrate and anhydrous lactose corresponding to 352 mg anhydrous lactose.
For the full list of excipients, see section 6.1.
3.
PHARMACEUTICAL FORM
Coated tablet (tablet).
50 mg: white, oval, biconvex tablets with scoring on both sides and on the edges, imprinted with "SN" on
one side and "50" on the other.
100 mg: white, oval, biconvex tablets, imprinted with "SN" on one side and "100" on the other.
50 mg: the tablet can be divided into equal doses
4.
CLINICAL PARTICULARS
4.1
Therapeutic indications
Acute treatment of migraine 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 migraine pain has appeared. However, sumatriptan is
equally effective when administered at a later time during the attack.
The following recommended dosages should not be exceeded.
Posology
Adults
The recommended dose for adults is a single dose of 50 mg. For some patients, 100 mg may be necessary.
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.
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If the patient does not respond to the first dose of sumatriptan, another dose should not be taken for the same
attack.
Sumatriptan may be used to treat 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 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 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 in children 10 to 17 years of age
is not recommended (see section 5.1).
Elderly
There is limited experience of the use of sumatriptan in patients over the age of 65 years. The
pharmacokinetics of the medicinal product in elderly patients has not been studied enough. The use of
sumatriptan in patients over 65 years is not recommended until more clinical data are available.
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.
Method of administration
The tablets should be swallowed whole with water.
The tablets may be crushed and suspended in liquid.
4.3
Contraindications
Hypersensitivity to the active substance, or to any of the excipients listed in section 6.1.
A history of myocardial infarction or diagnosed coronary artery disease, Prinzmetal's angina/coronary artery
spasm, peripheral vascular disease, or symptoms or signs of ischemic heart disease.
A history of cerebrovascular accident (CVA) or transient ischemic attacks (TIA).
Severe hepatic impairment.
Moderate or severe hypertension and mild, uncontrolled hypertension.
Concomitant use of ergotamine or ergotamine derivatives (including methysergide) or any triptan/5hydroxytryptamine1 (5-HT1) receptor agonist and sumatriptan is contraindicated (see section 4.5).
Concomitant treatment with reversible (e.g. moclobemide) or irreversible (e.g. selegiline) monoamine
oxidase inhibitors (MAOI's) and sumatriptan is contraindicated.
Sumatriptan must not be used within 2 weeks of discontinuation of treatment with MAOI.
4.4
Special warnings and precautions for use
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Sumatriptan Actavis tablets should only be used in cases where the diagnosis of migraine is definite.
Sumatriptan Actavis is not indicated in hemiplegic, basilar or ophthalmoplegic migraine.
As with other acute migraine therapies, serious neurological conditions should be excluded before treating a
patient with newly diagnosed migraine or migraine patients who have atypical symptoms.
It should be noted that migraineurs may be at increased risk of certain cerebrovascular events (e.g. CVA,
TIA).
After intake of sumatriptan, transient symptoms may occur, especially chest pain and tightness, which may
be intense and radiate to the throat (see section 4.8). If there is any suspicion that these symptoms indicate
ischaemic heart disease, treatment with sumatriptan should be discontinued and appropriate investigations
carried out.
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 (see section 4.3).
Sumatriptan should not be administered to patients at risk of developing ischemic heart disease, including
heavy smokers and heavy consumers of nicotine substitutes, until an evaluation excluding cardiovascular
disease has been carried out (see section 4.3). This should be especially noted when prescribing to
postmenopausal women and men over 40 years of age who have these risk factors. Such investigation will,
however, not identify all patients with heart disease. In very rare cases, severe cardiovascular conditions
have occurred even in patients without underlying heart 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 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 (see section 4.5).
Caution should be exercised when administering sumatriptan to patients with conditions which may affect
absorption, metabolism or excretion of sumatriptan, e.g. hepatic or renal impairment.
Sumatriptan should be given with caution to patients with a history of seizures or other risk factors, which
reduce the seizure threshold, as seizures have been reported in association with sumatriptan (see section
4.8).
Patients with known hypersensitivity to sulphonamides may react to sumatriptan with allergic reactions
ranging from cutaneous hypersensitivity reactions to anaphylaxis.
Evidence of cross allergy is limited. However, caution should be exercised when administering sumatriptan
to these patients.
With co-administration of triptans and herbal remedies containing St. John's Wort (Hypericum perforatum),
the incidence of undesirable effects may increase.
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.
The recommended dose of Sumatriptan Actavis should not be exceeded.
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The tablet contains lactose monohydrate. Patients with any of the following rare hereditary disorders
should not use this medicine: galactose intolerance, Lapp lactase deficiency or glucose-galactose
malabsorption.
4.5
Interaction with other medicinal products and other forms of interaction
There is no evidence of interactions with propranolol, flunarizine, pizotifen or alcohol.
Information is limited regarding interaction with medicinal products containing ergotamine or another
triptan/5-HT1 receptor agonist. Co-administration is contraindicated as, theoretically, there is an increased
risk of coronary artery spasm.
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. It depends on both the dose and the
type of products used. The effects may be additive. At least 24 hours should elapse after the patient has
taken a product containing ergotamine or another triptan/5-HT1 receptor agonist before sumatriptan is given.
Conversely, it is advised to wait at least 6 hours following use of sumatriptan before administering an
ergotamine-containing product and at least 24 hours before administering another triptan/5-HT1 receptor
agonist (see section 4.3).
Interactions may occur between sumatriptan and MAOI's and co-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).
There may also be a risk of serotonin syndrome if sumatriptan and lithium are given concomitantly.
4.6
Fertility, pregnancy and lactation
Pregnancy
Post-marketing data are available from over 1000 pregnancies in which exposure to sumatriptan occurred
during the first trimester. Although there is insufficient information for definite conclusions, there is no
indication of an increased risk of congenital defects. Experience of treatment with sumatriptan during the
second and third trimester is limited.
Animal studies give no indications of direct teratogenic effects or harmful effects to the peri- and postnatal
development. However, survival in rabbit foetuses may be affected (see section 5.3).
Pregnant women should only be treated with sumatriptan if the anticipated benefit to the mother outweighs
the possible risk to the foetus.
Breastfeeding
Sumatriptan is excreted in breast milk after subcutaneous administration. To reduce the effect on the child,
breast feeding should be avoided for 12 hours after treatment with sumatriptan, during which time any
breast milk expressed should be discarded.
4.7
Effects on ability to drive and use machines
No studies on the effects of sumatriptan on the ability to drive and use machines have been performed.
Drowsiness may occur in a migraine patient due to the migraine attack or the treatment with sumatriptan.
This may affect the ability to drive and use machines.
4.8
Undesirable effects
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Undesirable effects are listed below according to organ system and frequency.
Frequency is defined as: very common (≥1/10), common (≥1/100, <1/10), uncommon (≥1/1000, <1/100),
rare (≥1/10,000, <1/1000), very rare (<1/10,000), 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 varying from cutaneous hypersensitivity reactions (such as urticaria) to
anaphylaxis.
Nervous system disorders
Common: Sensory disturbance including paraesthesia and hypoaesthesia, dizziness, drowsiness.
Very rare: Seizures. Although some of these patients have a history of seizure or concurrent conditions
predisposing to seizures. There are also reports in patients without any clearly predisposing factors.
Nystagmus, scotoma, tremor, dystonia.
Eye disorders
Very rare: Flickering, diplopia, amblyopia, impaired vision. Loss of vision including reports of permanent
sight reduction. However, the migraine attack itself may cause disturbances in vision.
Cardiac disorders
Very rare: Bradycardia, tachycardia, palpitations, cardiac arrhythmias, transient ischemic ECG changes,
coronary artery vasospasm, angina or myocardial infarction (see section 4.3 and 4.4).
Vascular disorders
Common: Transient increase 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; however, relationship to sumatriptan has not been established.
Very rare: Ischemic colitis.
Not known: Diarrhoea.
Musculoskeletal and connective tissue disorders
Common: Feeling of heaviness (usually transient, may be intensive and of varying location including chest
and throat). Myalgia.
Very rare: Neck stiffness.
Not known: Arthralgia.
General disorders and administration site conditions
Common: Pain, feeling of heat or cold, pressure or tightness (these symptoms are normally transient, and
may be intensive and of varying location including chest and throat). Feelings of weakness and fatigue (both
symptoms are normally mild to moderate in intensity and transient)
Investigations
Very rare: Minor disturbances in liver function tests.
Psychiatric disorders
Not known: Anxiety.
Skin and subcutaneous tissue disorders
Not known: Hyperhidrosis.
4.9
Overdose
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Symptoms
Patients have received up to 12 mg sumatriptan as a subcutaneous single injection with no significant
undesirable effects. Occasional doses of sumatriptan of more than 16 mg subcutaneously and 400 mg orally,
have caused no other side effects than those given in section 4.8.
Treatment
On overdose, the patient should be monitored for at least ten hours and given suitable symptomatic
treatment.
There is no documentation on the effect of haemodialysis or peritoneal dialysis on plasma concentrations of
sumatriptan.
5.
PHARMACOLOGICAL PROPERTIES
5.1
Pharmacodynamic properties
Pharmacotherapeutic group: Antimigraine preparations, Selective serotonin (5-HT1) agonists
ATC code: N02CC01
Sumatriptan is a selective agonist of vascular 5-hydroxytryptamine-1 receptors with no effect on other 5HT
receptors. This type of receptor is mainly found in cranial blood vessels. In animals, sumatriptan selectively
constricts the carotid arterial circulation which supplies the extra- and intracranial tissues such as the
meninges. Dilatation of these blood vessels is thought to be the underlying cause of migraine in humans.
Animal studies also suggest that sumatriptan inhibits trigeminal nerve activity. Both of these mechanisms
(cranial artery constriction and inhibition of trigeminal nerve activity) may contribute to the effect of
sumatriptan in humans. The clinical response begins about 30 minutes after an oral dose of 100 mg.
Paediatric population
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 and 70% of the maximum plasma
concentration is reached within 45 minutes. After an oral dose of 100 mg, the mean maximum plasma
concentration is 54 ng/ml. Mean oral bioavailability is 14%, partly due to presystemic metabolism and partly
due to incomplete absorption.
The elimination phase half-life is approximately 2 hours.
Plasma protein binding is low (14-21%) and mean volume of distribution is 170 litres. Mean total plasma
clearance is approximately 1160 ml/min and the mean renal plasma clearance is approximately 260 ml/min.
Extra-renal clearance accounts for about 80% of the total clearance, indicating that sumatriptan is mainly
eliminated through metabolism. The major metabolite, the indole acetic acid analogue of sumatriptan, is
mainly excreted in the urine, as a free acid and the glucuronide conjugate. The metabolite has no known
5HT1 or 5HT2 activity. The other metabolites have not been identified. The pharmacokinetics of oral
sumatriptan do not appear to be significantly affected by migraine attacks.
5.3
Preclinical safety data
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In a rat fertility study with doses well above the maximum doses used in humans, a reduction in successful
inseminations was seen. In rabbits, embryolethality without marked teratogenic defects was seen. The
relevance for humans of these findings 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
Tablet core:
Lactose monohydrate
Croscarmellose sodium
Lactose, anhydrous
Cellulose, microcrystalline
Magnesium stearate
Tablet coating:
Lactose monohydrate
Mannitol
Titanium dioxide (E 171)
Talc
Triacetin
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
Blister packs of PVC/Aluminium or PVC/PVDC/Aluminium: 2, 3, 4, 6, 12, 18 and 24 tablets
HDPE tablet containers with tamper evident LDPE lids: 2, 3, 4, 6, 12, 18 and 24 tablets
Not all pack sizes may be marketed.
6.6
Special precautions for disposal
No special requirements.
7.
MARKETING AUTHORISATION HOLDER
<[To be completed nationally]>
8.
MARKETING AUTHORISATION NUMBER(S)
7
<[To be completed nationally]>
9.
DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
29-05-2007
10.
DATE OF REVISION OF THE TEXT
2013-07-12
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