IMIGRAN TABLETS 50MG

SUMMARY OF PRODUCT CHARACTERISTICS

1

NAME OF THE MEDICINAL PRODUCT
Imigran Tablets 50mg

2

QUALITATIVE AND QUANTITATIVE COMPOSITION
50mg sumatriptan base as the succinate salt.
For the full list of excipients, see section 6.1.

3

PHARMACEUTICAL FORM
Tablet
50 mg tablet: Pink, film-coated, capsule-shaped, biconvex tablet (nominal
dimensions: 12 mm x 6.5 mm), engraved “GX ES3” on one face and plain on
the other face
or “50” on one face and plain on the other face.

4.

CLINICAL PARTICULARS

4.1

Therapeutic indications
Imigran tablets are indicated for the acute relief of migraine attacks, with
or without aura. Imigran should only be used where there is a clear
diagnosis of migraine.

4.2

Posology and method of administration
Adults
Imigran is indicated for the acute intermittent treatment of migraine. It should not be
used prophylactically. The recommended dose of Imigran should not be exceeded.

It is advisable that Imigran be given as early as possible after the onset of migraine
attack but it is equally effective at whatever stage of the attack it is administered.

The recommended dose of oral Imigran is a 50 mg tablet. Some patients may require
100 mg.
If the patient has responded to the first dose but the symptoms recur a second dose
may be given provided that there is a minimum interval of two hours between the two
doses. No more than 300 mg should be taken in any 24 hour period.
Patients who do not respond to the prescribed dose of Imigran should not take a
second dose for the same attack. In these cases the attack can be treated with
paracetamol, acetylsalicylic acid, or non-steroidal anti-inflammatory drugs. Imigran
may be taken for subsequent attacks.
Imigran 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).

The tablets should be swallowed whole with water.

Paediatric population
The efficacy and safety of Imigran 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 Imigran 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
Imigran in children 10 to 17 years of age is not recommended (see section 5.1).

Elderly (Over 65 years of age)
Experience of the use of Imigran 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 Imigran in patients aged over 65 years is
not recommended.

4.3

Contraindications
Hypersensitivity to sumatriptan or to any of the excipients listed in section 6.1.
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 patients who have symptoms or sign consistent with ischaemic
heart disease.
Sumatriptan should not be administered to patients with a history of cerebovascular
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 with sumatriptan is contraindicated. (see section 4.5)
Concurrent administration of monoamine oxidase inhibitors and sumatriptan is
contraindicated.
Imigran Tablets must not be used within two weeks of discontinuation of therapy with
monoamine oxidase inhibitors.

4.4

Special warnings and precautions for use
Imigran 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 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 (see
section 4.8). Where such symptoms are thought to indicate ischaemic heart disease,
no further doses of sumatriptan should be given and 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 (see section 4.3).
Special consideration should be given 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.
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 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).

Sumatriptan should be administered with caution to patients with conditions which
may affect significantly the absorption, metabolism or excretion of drugs, e.g.
impaired hepatic (Child Pugh grade A or B; see section 5.2) or renal function (see
section 5.2). A 50 mg 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 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.
Patients with rare hereditary problems of galactose intolerance, the Lapp lactase
deficiency or glucose-galactose malabsorption should not take this medicine as it
contains lactose.

4.5

Interaction with other medicinal products and other forms of Interaction
Studies in healthy subjects show that sumatriptan does not interact with
propranolol, flunarizine, pizotifen or alcohol.
There are limited data on an interaction with preparations containing
ergotamine or another triptan/5-HT1 receptor agonist. 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 types of 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 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.
An interaction may occur between sumatriptan and monoamine oxidase
inhibitors (MAOIs) and concomitant 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).

4.6

Fertility, pregnancy and lactation
Pregnancy
Post-marketing data from 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.
Lactation
It has been demonstrated that following subcutaneous administration, sumatriptan is
excreted 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 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.

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 to <1/10),
uncommon (≥1/1000 to <1/100), rare (≥1/10000 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.
Clinical Trial Data
Nervous System Disorders

Common:

Vascular Disorders
Common:

Dizziness, drowsiness, sensory disturbance
including paraesthesia and hypoaesthesia.

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 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.
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.

Post-Marketing Data
Immune System Disorders
Not known:
Hypersensitivity reactions ranging from
cutaneous hypersensitivity to anaphylaxis.
Nervous System Disorders
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:

Cardiac Disorders
Not known:

Vascular 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.

Bradycardia, tachycardia, palpitations, cardiac
arrhythmias, transient ischaemic ECG changes,
coronary artery vasospasm, angina, myocardial
infarction (see sections 4.3 and 4.4).

Hypotension, Raynaud’s phenomenon.

Gastrointestinal Disorders
Not known:
Ischaemic colitis
Diarrhoea.
Musculoskeletal, Connective Tissue and Bone Disorders
Not known:
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
Doses in excess of 400 mg orally were not associated with side effects other
than those mentioned.
If overdose occurs, the patient should be monitored for at least ten hours and
standard supportive treatment applied as required.
It is unknown what effect haemodialysis or peritoneal dialysis has on the
plasma concentrations of Imigran

5

PHARMACOLOGICAL PROPERTIES

5.1

Pharmacodynamic properties
Pharmacotherapeutic group: Analgesics: Selective 5-HT1 receptor agonists.
ATC code: N02CC01
Sumatriptan has been demonstrated to be a specific and selective 5Hydroxytryptamine1 (5HT1D) receptor agonist with no effect on other 5HT
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 but
does not alter cerebral blood flow. The carotid arterial circulation supplies
blood to the extracranial and intracranial tissues such as the meninges and
dilatation of and/or oedema formation 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 these actions (cranial vasoconstriction and
inhibition of trigeminal nerve activity) may contribute to the anti-migraine
action of sumatriptan in humans.
Sumatriptan remains effective in treating menstrual migraine i.e. migraine
without aura that occurs between 3 days prior and up to 5 days post onset of
menstruation. Sumatriptan should be taken as soon as possible in an attack.
Clinical response begins around 30 minutes following a 100 mg oral dose.
Although the recommended dose of oral sumatriptan is 50 mg, migraine
attacks vary in severity both within and between patients. Doses of 25-100 mg
have shown greater efficacy than placebo in clinical trials, but 25 mg is
statistically significantly less effective than 50 and 100 mg.
A number of placebo-controlled clinical studies assessed the safety and
efficacy of oral sumatriptan standard tablets in over 650 child and adolescent
migraineurs aged 10 - 17 years. These studies failed to demonstrate a
statistically significant difference in headache relief at 2 hours between
placebo and any sumatriptan dose. The undesirable effects profile of oral
sumatriptan in children and 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, 70% of
maximum concentration occurring at 45 minutes. After 100 mg dose, the

maximum plasma concentration is 54 ng/ml. Mean absolute oral
bioavailability is 14% partly due to presystemic metabolism and partly due to
incomplete absorption. The elimination phase half-life is approximately 2
hours, although there is an indication of a longer terminal phase. Plasma
protein binding is low (14-21%), 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. Non-renal clearance accounts
for about 80% of the total clearance. Sumatriptan is eliminated primarily by
oxidative metabolism mediated by monoamine oxidase A.
Special patient populations
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 systemic exposure is almost
doubled.
The pharmacokinetics in patients with severe hepatic impairment have not
been studied (see Section 4.3 Contraindications and Section 4.4 Warnings and
Precautions).
The major metabolite, the indole acetic acid analogue of Sumatriptan is mainly
excreted in the urine, where it is present as a free acid and the glucuronide
conjugate. It has no known 5HT1 or 5HT2 activity. Minor metabolites have
not been identified. The pharmacokinetics of oral Sumatriptan do not appear
to be significantly affected by migraine attacks.
In a pilot study, no significant differences were found in the pharmacokinetic
parameters between the elderly and young healthy volunteers.

5.3
Preclinical Safety Data
Sumatriptan was devoid of genotoxic and carcinogenic activity in in-vitro
systems and animal studies.
In a rat fertility study 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.

This effect did not occur during a subcutaneous study where maximum plasma levels
achieved approximately 150 times those in man by the oral route.
In rabbits embryolethality, without marked teratogenic defects, was seen. The
relevance for humans of these findings is unknown.

6.

PHARMACEUTICAL PARTICULARS

6.1

List of excipients
Lactose
Microcrystalline cellulose
Croscarmellose sodium
Magnesium stearate
Methylhydroxypropylcellulose
Titanium dioxide
Triacetin
Iron oxide

6.2

Incompatibilities
None stated.

6.3

Shelf life
36 months.

6.4

Special precautions for storage
Store below 30˚C

6.5

Nature and Contents of Container
Aluminium double foil blister pack or child-resistant foil blister pack in a
cardboard carton, containing either 2, 3, 6, 12, 18 or 24 tablets.

6.6

Instruction for use, handling and disposal
None stated.

7

MARKETING AUTHORISATION HOLDER
Glaxo Wellcome UK Ltd. trading as GlaxoSmithKline UK.
Stockley Park West
Uxbridge
Middlesex. UB11 1BT

8.
MARKETING AUTHORISATION NUMBER(S)
PL 10949/0222

9

DATE OF FIRST AUTHORISATION/RENEWAL OF THE
AUTHORISATION
29/12/2005

10

DATE OF REVISION OF THE TEXT
30/03/2016