Imigran FDT

Sumatriptan succinate.

Tablets containing 50 of sumatriptan base as the succinate salt.
Excipients/Inactive Ingredients: Calcium hydrogen phosphate, Microcrystalline cellulose, Sodium hydrogen carbonate, Croscarmellose sodium, Magnesium Stearate, Purified Water, Hypromellose, Titanium dioxide, Triacetin, Iron oxide red.

Pharmacotherapeutic group: Selective 5-HT₁ receptor agonists. ATC Code: N02CC01.
Pharmacology: Pharmacodynamics: Mechanism of Action: Sumatriptan has been demonstrated to be a selective vascular 5-hydroxytryptamine-1 (5-HT₁D) receptor agonist with no effect at other 5HT-receptor (5-HT_2-7) 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 meninges and dilatation and/or oedema formation in these vessels is thought to be the underlying mechanism of migraine in man. In addition, experimental evidence suggests that sumatriptan inhibits trigeminal nerve activity. Both these actions may contribute to the antimigraine action of sumatriptan in 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 intranasal administration and around 30 minutes following a 100 mg conventional tablet oral dose or 25 mg rectal dose.
Following administration of a 50 mg and 100 mg FDT, onset of pain relief began as early as 30 minutes and 20 minutes, respectively, in a small proportion of subjects and the percentage of responders continued to increase until 67% and 72% of subjects achieved pain relief over two hours, compared to 42% of placebo subjects. Onset of pain-free began as early as 33 minutes and 26 minutes, respectively, in a small proportion of subjects and the percentage of responders continued to increase until 40% and 47% of subjects achieved pain-free response over two hours, compared to 15% of placebo subjects (see Clinical Studies as follows).
Although the recommended dose of oral sumatriptan is 50 mg, migraine attacks vary in severity both within and between patients. Doses of 25 to 100 mg have shown greater efficacy than placebo in clinical trials, but 25 mg is statistically significantly less effective than 50 and 100 mg.
Sumatriptan is effective in the acute treatment of migraine including menstrually-associated migraine.
Clinical Studies: The time to onset of efficacy of sumatriptan 50 mg and 100 mg FDT was demonstrated in adults in two randomised, double-blind, placebo-controlled studies that were identical in design. The data from these studies were combined to obtain single results for each endpoint. Overall, 2696 subjects experiencing moderate to severe migraine pain reported time to pain relief and time to freedom from pain in the sumatriptan 50 mg, 100 mg and placebo groups. Time to pain relief (defined as a reduction in pain severity from moderate or severe to mild or no pain) curves were generated for sumatriptan and placebo for the two hour period after treatment. The time to onset of pain relief was defined as the earliest time point at which statistical significance was first achieved, compared with placebo, and maintained at all subsequent time points on the 0 to 2 hour curve. Freedom from pain (defined as a reduction in pain severity from severe or moderate to no pain) was evaluated using similar methods (see Pharmacodynamic Effects as previously mentioned).
The percentage of subjects achieving pain relief (Figure 1) or freedom from pain (Figure 2) within two hours after treatment was significantly higher among subjects receiving sumatriptan (FDT 50 mg or 100 mg) compared with those receiving placebo (p<0.001). (See Figure 1.)

Click on icon to see table/diagram/image

The time to onset of pain relief for sumatriptan FDT 50 and 100 mg was 30 minutes and 20 minutes, respectively, based on the combined data. From this initial point onwards, the percentage of responders continued to increase until 67% and 72% of subjects achieved pain relief two hours after treatment for 50 and 100 mg, respectively, compared to 42% of subjects in the placebo group (Figure 1). (See Figure 2.)

Click on icon to see table/diagram/image

The time to onset of the pain-free response for sumatriptan FDT 50 and 100 mg was 33 minutes and 26 minutes, respectively, based on the combined data. From this initial point onwards, the percentage of responders continued to increase until 40% and 47% of subjects achieved freedom from pain two hours after treatment for 50 and 100 mg, respectively, compared to 15% of subjects in the placebo group (Figure 2).
IMIGRAN FDT tablets have not been studied in adolescents, however, 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 to 17 years. These studies failed to demonstrate a statistically significant difference in headache relief at two hours between placebo and any sumatriptan dose. The undesirable effects profile of oral sumatriptan in children and adolescents aged 10 to 17 years was similar to that reported from studies in the adult population.
Pharmacokinetics: The pharmacokinetics of sumatriptan do not appear to be significantly affected by migraine attacks.
Absorption: After a 100 mg dose, the mean maximum plasma concentration is 54 nanograms/mL. Mean absolute oral bioavailability is 14% partly due to pre-systemic metabolism and partly due to incomplete absorption.
The C_max of sumatriptan is increased by 15% following oral administration of the fast-disintegrating tablet with a high-fat meal.
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 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.
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 (see Precautions).
Toxicology: Preclinical Safety Data: Carcinogenesis, mutagenesis: Sumatriptan was devoid of genotoxic and carcinogenic activity in in-vitro systems and animal studies.
Pregnancy and lactation: No teratogenic effects have been seen in rats or rabbits, and sumatriptan had no effect on 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.

IMIGRAN FDT are indicated for the acute relief of migraine attacks with or without aura, including acute migraine attacks associated with menstrual period in women.

IMIGRAN 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 a migraine headache. It is equally effective at whatever stage of the attack it is administered.
Populations: Adults: The recommended dose of oral IMIGRAN FDT is a single 50 mg tablet. Some patients may require 100 mg.
If the patient does not respond to the first dose of IMIGRAN, a second dose should not be taken for the same attack. IMIGRAN FDT 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, provided that there is a minimum interval of two hours between doses and not more than 300 mg is taken in any 24-hour period.
The tablets should be swallowed whole with water. Patients with swallowing difficulties may choose to disperse a tablet in a small amount of water before administration. IMIGRAN FDT dispersed in water have a bitter taste.
Children and Adolescents (under 18 years of age): IMIGRAN FDT have not been studied in adolescents or children (see Pharmacology: Pharmacodynamics: Clinical Studies under Actions).
Elderly (over 65 years of age): Experience of the use of standard sumatriptan tablets 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 FDT in patients aged over 65 years is not recommended.

Symptoms and Signs: Doses up to 100 mg orally were not associated with side effects other than those mentioned.
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.

Hypersensitivity to any component of the preparation.
IMIGRAN should not be given to patients who have had a myocardial infarction or have ischaemic heart disease (IHD), Prinzmetal's angina/coronary vasospasm, peripheral vascular disease or patients who have symptoms or signs consistent with 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 2 weeks of discontinuation of therapy with MAOIs.

IMIGRAN should only be used where there is clear diagnosis of migraine.
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 symptoms or if they have not received an appropriate diagnosis for IMIGRAN use.
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 postmenopausal women, males over 40 and patients with risk factors for coronary artery disease. However, these evaluations 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.
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 clinically warranted, appropriate observation of the patient is advised (see Interactions).
The concomitant administration of any triptan/5-HT₁ agonist with sumatriptan is not recommended.
IMIGRAN should be administered with caution to patients with conditions that may affect significantly the absorption, metabolism or excretion of sumatriptan e.g. impaired hepatic (Child Pugh grade A or B; see Pharmacology: Pharmacokinetics: Special Patient Populations under Actions) or renal function.
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.
Effects on the Ability to Drive and Use Machines: Drowsiness may occur as a result of migraine or its treatment with IMIGRAN.
Caution is recommended in patients performing skilled tasks e.g. driving or operating machinery.

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 avoiding breast-feeding for 12 hours after treatment.

Adverse events are listed as follows by system organ class and frequency. Frequencies are defined as: Very common (≥1/10), common (≥1/100, <1/10), uncommon (≥1/1000, <1/100), rare (≥1/10,000, <1/1000) and very rare (<1/10,000) including isolated reports. 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 reporting rate 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.
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 and transient: 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 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 Contraindications and Precautions).
Vascular Disorders: Very Rare: Hypotension, Raynaud's phenomenon.
Gastrointestinal Disorders: Very Rare: Ischaemic colitis.

There is no evidence of interactions with propranolol, 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 6 hours have elapsed following sumatriptan 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 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 Precautions).

Incompatibilities: None reported.
Instructions for Use/Handling: To be swallowed whole with water. Patients with swallowing difficulties may choose to disperse a tablet in a small amount of water before administration. IMIGRAN FDT dispersed in water have a bitter taste.

IMIGRAN FDT tablets should be stored below 30°C.

Antimigraine Preparations

N02CC01 - sumatriptan ; Belongs to the class of selective serotonin (5HT1) agonists preparations. Used to relieve migraine.

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