PRODUCT MONOGRAPH IMITREX DF IMITREX ... - GlaxoSmithKline
PRODUCT MONOGRAPH IMITREX DF IMITREX ... - GlaxoSmithKline PRODUCT MONOGRAPH IMITREX DF IMITREX ... - GlaxoSmithKline
Adults with Severe Hepatic ImpairmentTablets, Nasal Spray and InjectionAll formulations of sumatriptan are contraindicated in patients with severe hepaticimpairment (see CONTRAINDICATIONS).AdministrationTabletsThe tablet should be swallowed whole with water, not crushed, chewed or split.InjectionPatients should be advised to read the patient instruction leaflet regarding the safedisposal of syringes and needles.Nasal SprayThe nasal spray should be administered into one nostril only. The device is a ready-tousesingle-dose unit and must not be primed before administration. Patients should beadvised to read the patient instruction leaflet regarding the use of the nasal spray devicebefore administration.OVERDOSAGEThere have been some reports of overdosage with IMITREX ® . Patients have receivedsingle injections of up to 12 mg subcutaneously without significant adverse effects.Doses up to 16 mg subcutaneously and up to 400 mg orally were not associated with sideeffects other than those mentioned. The highest dose of IMITREX ® Nasal Sprayadministered without significant adverse effects was 20 mg given three times daily for4 days.If overdosage with sumatriptan occurs, the patient should be monitored and standardsupportive treatment applied as required. Toxicokinetic data are not available.The effect of hemodialysis or peritoneal dialysis on the serum concentration ofsumatriptan is unknown.For management of a suspected drug overdose, contact your regional Poison ControlCentre.October 21, 2014Page 20 of 58
ACTION AND CLINICAL PHARMACOLOGYMechanism of ActionIMITREX DF ® and IMITREX ® have been shown to be effective in relieving migraineheadache. Sumatriptan is an agonist for a vascular 5-hydroxytryptamine 1D (5-HT 1D )receptor subtype (a member of the 5-HT 1 family), and has only weak affinity for 5-HT 1Areceptors and no significant activity (as measured using standard radioligand bindingassays) or pharmacological activity at 5-HT 2 , 5-HT 3 , 5-HT 4 , 5-HT 5A , or 5-HT 7 receptorsubtypes, or at alpha 1 -, alpha 2 -, or beta-adrenergic; dopamine 1 or dopamine 2 ; muscarinic;or benzodiazepine receptors.The therapeutic activity of IMITREX DF ® and IMITREX ® in migraine is generallyattributed to its agonist activity at 5-HT 1B /5-HT 1D receptors. Two current theories havebeen proposed to explain the efficacy of 5-HT 1 receptor agonists in migraine. One theorysuggests that activation of 5-HT 1 receptors located on intracranial blood vessels,including those on the arteriovenous anastomoses, leads to vasoconstriction, which isbelieved to be correlated with the relief of migraine headache. The other hypothesissuggests that activation of 5-HT 1 receptors on perivascular fibres of the trigeminal systemresults in the inhibition of pro-inflammatory neuropeptide release. These theories are notmutually exclusive.Experimental data from animal studies show that sumatriptan also activates 5-HT 1receptors on peripheral terminals of the trigeminal nerve, which innervates cranial bloodvessels. This causes the inhibition of neuropeptide release. It is thought that such anaction may contribute to the anti-migraine action of sumatriptan in humans.Cardiovascular EffectsIn vitro studies in human isolated epicardial coronary arteries suggest that thepredominant contractile effect of 5-HT is mediated via 5-HT 2 receptors. However, 5-HT 1receptors also contribute to some degree to the contractile effect seen. Transientincreases in systolic and diastolic blood pressure (up to 20 mmHg) of rapid onset (withinminutes), have occurred after intravenous administration of up to 64 μg/kg (3.2 mg for50 kg subject) to healthy volunteers. These changes were not dose related and returned tonormal within 10-15 minutes. Following oral administration of 200 mg or intranasaladministration of 40 mg, however, mean peak increases in blood pressure were smallerand of slower onset than after intravenous or subcutaneous administration.PharmacodynamicsSignificant relief begins about 10-15 minutes following subcutaneous injection,15 minutes following intranasal administration and 30 minutes following oraladministration.October 21, 2014Page 21 of 58
- Page 3 and 4: IMITREX DF ®(sumatriptan succinate
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Adults with Severe Hepatic ImpairmentTablets, Nasal Spray and InjectionAll formulations of sumatriptan are contraindicated in patients with severe hepaticimpairment (see CONTRAINDICATIONS).AdministrationTabletsThe tablet should be swallowed whole with water, not crushed, chewed or split.InjectionPatients should be advised to read the patient instruction leaflet regarding the safedisposal of syringes and needles.Nasal SprayThe nasal spray should be administered into one nostril only. The device is a ready-tousesingle-dose unit and must not be primed before administration. Patients should beadvised to read the patient instruction leaflet regarding the use of the nasal spray devicebefore administration.OVERDOSAGEThere have been some reports of overdosage with <strong>IMITREX</strong> ® . Patients have receivedsingle injections of up to 12 mg subcutaneously without significant adverse effects.Doses up to 16 mg subcutaneously and up to 400 mg orally were not associated with sideeffects other than those mentioned. The highest dose of <strong>IMITREX</strong> ® Nasal Sprayadministered without significant adverse effects was 20 mg given three times daily for4 days.If overdosage with sumatriptan occurs, the patient should be monitored and standardsupportive treatment applied as required. Toxicokinetic data are not available.The effect of hemodialysis or peritoneal dialysis on the serum concentration ofsumatriptan is unknown.For management of a suspected drug overdose, contact your regional Poison ControlCentre.October 21, 2014Page 20 of 58
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