IMIGRAN nasal spray is indicated for the acute relief of migraine attacks with orwithout aura.
It is particularly suitable for patients who suffer with nausea and vomiting or who require a rapid onset of effect during an attack.

IMIGRAN should not be used prophylactically. The recommended dose ofIMIGRAN
should not be exceeded.
It is advisable that IMIGRAN be given as early as possible after the onset of amigraine headache. It is equally effective at whatever stage of the attack it isadministered.
Populations
• Adults (18 years of age and over)
The optimal dose of IMIGRAN nasal spray is 20 mg for administration into one nostril. Due to inter-/intra-patient variability of both the migraine attacks and the absorption of sumatriptan, 10 mg may be effective in some patients and attacks.
If the patient does not respond to the first dose of IMIGRAN, a second dose should not be taken for the same attack. IMIGRAN nasal spraymay be taken for subsequent attacks.
If the patient has responded to the first dose, but the symptoms recur a second dosemay be given in the next 24 hours, provided that there is a minimum interval of 2 hours between the doses.

No more than two sumatriptan 20 mg nasal sprays should be used in any 24-hour period.
• Adolescents (12 to 17 years of age)
The recommended dose of IMIGRAN nasal spray is 10 mg for administration into one nostril. Due to inter-/intra-patient variability of migraine attacks and the exposure to IMIGRAN, a dose of 20 mg may be required in some patients.
If a patient does not respond to the first dose of IMIGRAN, a second dose should not be taken for the same attack. IMIGRAN nasal spraymay be taken for subsequent attacks.
If the patient has responded to the first dose of IMIGRAN nasal spray, 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 two sumatriptan 20 mg nasal sprays to be used in any 24-hour period.
• Children (under 12 years of age)
The safety and effectiveness of IMIGRAN nasal spray in children has not yetbeen established.
• Elderly (over 65 years of age)
There is no clinical experience of the use of IMIGRAN nasal spray in patients over65 years of age.

− Hypersensitivity to any component of the preparation. − IMIGRAN should not be given to patients who have had myocardial infarction or have ischaemic heart disease (IHD), Prinzmetal's angina/coronary vasospasm, peripheral vascular disease or patients who have symptoms or signs consistentwith IHD. − IMIGRAN should not be administered to patients with a history of previous cerebrovascular accident (CVA) or transient ischaemic attack (TIA). − The use of IMIGRAN in patients with uncontrolled hypertension is contraindicated. − IMIGRAN should not be administered to patients with severe hepatic impairment. − The concomitant use of ergotamine or derivatives of ergotamine (including methysergide) is contraindicated (see Interactions). − Concurrent administration of monoamine oxidase inhibitors (MAOIs) and IMIGRAN is contraindicated. IMIGRAN must not be used within two weeks of discontinuation of therapy with MAOIs.

IMIGRAN should only be used where there is a clear diagnosis ofmigraine.
IMIGRAN is not indicated for use in the management of hemiplegic, basilar or ophthalmoplegic migraine.

Before treating with IMIGRAN, care should be taken to exclude potentially serious neurological conditions (e.g. CVA, TIA) if the patient presents with atypical symptomsor if they have not received an appropriate diagnosis for IMIGRANuse.
Following administration, IMIGRAN can be associated with transient symptoms including chest pain and tightness which may be intense and involve the throat (see Adverse Reactions). Where such symptoms are thought to indicate IHD appropriate evaluation should be carried out.

IMIGRAN should not be given to patients in whom unrecognised cardiac disease is likely without a prior evaluation for underlying cardiovascular disease. Such patients include post-menopausal women, males over 40 and patients with risk factors for coronaryartery disease. However, these evaluations may not identify every patient who hascardiac disease and, in very rare cases, serious cardiac events have occurred in patientswithout underlying cardiovascular disease.
IMIGRAN should be administered with caution to patients with controlled hypertension as 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 IMIGRAN and an SSRI/SNRI is clinicallywarranted, appropriate observation of the patient is advised (see Interactions).
The concomitant administration of any triptan/5-HT1 agonist with IMIGRAN is not recommended.

IMIGRAN should be administered with caution to patients with conditions that mayaffect significantly the absorption, metabolism or excretion of the drug, e.g. impaired hepatic (Child Pugh grade A or B; see Pharmacokinetics – Special Patient Populations) or renal function (see Pharmacokinetics).

IMIGRAN should be used with caution in patients with a history of seizures or other risk factors which lower the seizure threshold. Patients with known hypersensitivity to sulphonamides may exhibit an allergic reaction following administration of IMIGRAN. Reactions may range from cutaneous hypersensitivity to anaphylaxis. Evidence of cross-sensitivity is limited, however, caution should be exercised before using IMIGRAN in these patients. Overuse of acute headache treatments has been associated with the exacerbation of headache (medication overuse headache, MOH) in susceptible patients. Withdrawal of the treatment may be necessary. Undesirable effects may be more common during concomitant use of triptans and herbal preparations containing St John's Wort (Hypericum perforatum).

There is no evidence of interactions with propanolol, flunarizine, pizotifen or alcohol. Prolonged vasospastic reactions have been reported with ergotamine. As these effects may be additive, 24 hours should elapse before IMIGRAN can be taken following any ergotamine containing preparation. Conversely, ergotamine containing preparations should not be taken until six hours have elapsed following IMIGRAN administration. An interaction may occur between IMIGRAN and MAOIs and concomitant administration is contraindicated (see Contraindications). There have been rare post-marketing reports describing patients with serotoninsyndrome (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 Warnings and Precautions).

Pregnancy

Caution should be exercised by considering the expected benefit to the mother against possible risk to the foetus. Post-marketing data from multiple prospective pregnancy registries have documented the pregnancy outcomes in over 1,000 women exposed to sumatriptan. Although there is insufficient information to draw definitive conclusions, the findings have not detected an increase in the frequency of birth defects nor a consistent pattern of birth defects, amongst women exposed to sumatriptan compared with the general population.

 

Lactation
It has been demonstrated that following subcutaneous administration sumatriptan is excreted into breast milk. Infant exposure can be minimised by avoidingbreast-feeding for 12 hours after treatment.

Drowsiness may occur as a result of migraine or treatment with IMIGRAN.
Caution is recommended in patients performing skilled tasks, e.g. driving or operating machinery.

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) and very rare (<1/10000) including isolatedreports. The data from clinical trials are estimates. It should be noted that the background rate in comparator groups was not taken into account. Post-marketing data refer to reportingrate rather than true frequency.
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; following administration of IMIGRAN nasal spraymild, transient irritation or burning sensation in the nose or throat or epistaxis have been reported.
 

Gastrointestinal Disorders
Common: Nausea and vomiting occurred in some patients but the relationship to sumatriptan is not clear.

Musculoskeletal and Connective Tissue Disorders
The following symptom is usually transient and may be intense and can affect any part of the body including the chest and throat:
Common: Sensations of heaviness.
General Disorders and Administration Site Conditions
The following symptoms are usually transient and may be intense and can affect any part of the body including the chest and throat:
Common: Pain, sensations of heat or cold, pressure or tightness.
The following symptoms are mostly mild to moderate in intensity andtransient: Common: Feelings of weakness, fatigue.
Investigations
Very rare: Minor disturbances in liver function tests have occasionally been observed.
 

Post-Marketing Data
Immune System Disorders
Very rare: Hypersensitivity reactions ranging from cutaneous hypersensitivity to anaphylaxis.
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 (usually transient). However, visual disorders may also occur duringa migraine attack itself.

Cardiac disorders
Very rare: Bradycardia, tachycardia, palpitations, cardiac arrhythmias, transient ischaemic ECG changes, coronary artery vasospasm, angina, myocardial infarction (see Contraindications, Warnings and Precautions).
Vascular disorders
Very rare: Hypotension, Raynaud’s phenomenon.
Gastrointestinal Disorders
Very rare: Ischaemic colitis.

 

To report any side effect(s):

Kingdom of Saudi Arabia
-National Pharmacovigilance and Drug Safety Centre (NPC)
• Fax: +966-11-205-7662
• Call NPC at +966-11-2038222, Ext: 2353-2356-2317-2354-2334-2340
• Toll-free: 8002490000
• E-mail: npc.drug@sfda.gov.sa
• Website: www.sfda.gov.sa/npc
-GlaxoSmithKline - Head Office, Jeddah
• Tel: 00966(012)6536666
• Fax: 00966(012)6536660
• P.O Box 55850, Jeddah 21544, Saudi Arabia

Symptoms and Signs
Single doses of IMIGRAN, up to 40 mg intra-nasally have not been associated withside effects other than those mentioned.
In clinical studies volunteers have received 20 mg of IMIGRAN by the intra-nasal route three times a day for a period of four days without significant adverse effects.
Treatment
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.

ATC Code
N02CC01.
Mechanism of Action
Pharmacotherapeutic group: Selective 5-HT1 receptor agonists.
Sumatriptan has been demonstrated to be a selective vascular 5-hydroxytryptamine-1-(5- HT1D) receptor agonist with no effect at other 5-HT receptor (5-HT2–7) subtypes.The vascular 5-HT1D receptor is found predominantly in cranial blood vessels andmediates 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 and/or oedema formation in these vessels is thought to be the underlying mechanism of migraine inman. In addition, experimental evidence suggests that sumatriptan inhibits trigeminal nerve activity. Both these actions may contribute to the anti-migraine action of sumatriptanin humans.
Pharmacodynamic Effects
Clinical response begins 10 to 15 minutes following a 6 mg subcutaneous injection, 15 minutes following a 20 mg dose given by intra-nasal administration and around 30 minutes following a 100 mg oral dose or 25 mg rectal dose.

The pharmacokinetics of sumatriptan do not appear to be significantly affectedby migraine attacks.
Absorption
After intra-nasal administration, sumatriptan is rapidly absorbed, with maximumplasma concentration occurring in 1 to 1.5 hours. After a 20 mg dose, the mean maximum concentration is 12.9 nanograms/mL. Mean intra-nasal bioavailability, relative to subcutaneous administration is 15.8%, partly due to pre-systemicmetabolism.

Distribution
Plasma protein binding is low (14 to 21%); the mean total volume of distribution is 170 litres.
Metabolism
The major metabolite, the indole acetic acid analogue of sumatriptan is mainlyexcreted 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.
Elimination
The elimination half-life is approximately two hours. The mean total plasma clearance is approximately 1,160 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
Following oral administration, pre-systemic clearance is reduced in patients with hepatic impairment resulting in increased plasma levels of sumatriptan. A similar increasewould be expected following intra-nasal administration (see Warnings andPrecautions).
• Adolescents (12 to 17 years of age)
A pharmacokinetic study in adolescent subjects (12 to 17 years) indicated that themean maximum plasma concentration was 13.9 nanograms/mL and mean elimination half-life was approximately two hours following a 20 mg intra-nasal dose. Population pharmacokinetic modelling indicated that clearance and volume of distribution both increase with body size in the adolescent population resulting in higher exposure inlower body weight adolescents.

Carcinogenesis, mutagenesis
Sumatriptan was devoid of genotoxic and carcinogenic activity in in-vitro systemsand animal studies.
Reproductive toxicology
In a rat fertility study oral doses of sumatriptan resulting in plasma levels approximately 750 times those seen in man after a 20 mg intra-nasal dose were associated with a reduction in the success of insemination.

This effect did not occur during a subcutaneous study where maximum plasma levels in rats achieved approximately 500 times those seen in man by the intra-nasal route.
Pregnancy and lactation
No teratogenic effects have been seen in rats or rabbits, and sumatriptan had no effecton the post-natal development of rats.
When administered to pregnant rabbits throughout the period of organogenesis sumatriptan has occasionally caused embryolethality at doses that were sufficiently high to produce maternal toxicity.
Animal toxicology and/or pharmacology
In 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.

Potassium dihydrogen phosphate. Dibasic sodium phosphate anhydrous. Sulphuric acid.
Sodium hydroxide. Purified water.

Not applicable

The expiry date is indicated on the packaging.

Store IMIGRAN Nasal Spray below 30°C, don’t freeze.
It should be kept in the sealed blister, preferably in the box, to protect from light.

Unit dose disposable nasal spray device.

The nasal Spray consists of the following parts:

The Nozzle: This is the part that you put into your nostril. The spray comes out of a tiny hole in the top.
The Finger grip: this is the part that you hold when you use the spray.
The Blue plunger: When you press the plunger the whole dose sprays into your nostril in one go.

The plunger only works once so do not press it until you have put the nozzle into your nostril or you will waste the dose.

 

 

ONE SPRAY PER DEVICE –DO NOT TEST BEFORE USE

HOW TO USE THE NASAL SPRAY

The nasal spraymust only be removed from the blister packaging immediately before use.
• First get into a comfortable position. You may like to sit down if there is a seat close-by.
• Blow your nose if it feels blocked, or if you have a cold.

 

 

•Peel open a blister pack and take out a nasal spray.
• Hold the nasal spray gently with your fingers and thumb as shown in the picture.
• Do not press the blue plunger yet.

 

• Block one nostril by pressing a finger firmly on the side of your nose.
• Breathe out gently through your mouth.

 

 

• Put the nozzle of the nasal spray into the other nostril, as far as feels comfortable (about 1 cm or ½ inch).
• Hold your head in upright position and close your mouth.
• Start to breathe in gently through your nose and at the same time press the blue plunger firmly with your thumb.
• The plunger may feel a bit stiff and you may hear it click.
• Keep your head upright and breathe gently through your mouth for 10- 20 seconds. This helps the medicine stay in your nose. You can remove the spray and your finger from the other side of your nose whilst you do this.
• Your nose may feel wet inside and you may notice a slight taste after using the spray– this is normal and will soon pass.
• After being use once, your nasal spray is now empty. It should be disposed of safely and hygienically.

 

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