Siagran

Each tablet contains Sumatriptan succinate is equivalent to Sumatriptan 50 mg.

Pharmacology: Pharmacodynamics: Sumatriptan is a selective 5-hydroxytryptamine₁ serotonin (5-HT₁ or serotonin) receptors agonist, particularly the 5-HT_1D (also called 5HT_1Dα) and 5-HT_1B (also called 5HT_1Dβ) subtypes on intracranial blood vessels that become dilated during a migraine attack and on sensory nerves of the trigeminal system. Sumatriptan has the highest affinity for the 5-HT_1D receptor, the most common serotonin receptor subtype in the brain, and a 2- to 17-fold lower affinity for 5-HT_1A receptors. Sumatriptan has essentially no affinity at other serotonin receptors (eg. 5-HT_2-4) or at receptors of the dopamine1, dopamine2, muscarinic, histamine, benzodiazepine, alpha-adrenergic and beta-adrenergic receptors.
Sumatriptan activates 5-HT_1D and 5-HT_1B to result in cranial vessel constriction, inhibition of neuropeptide release, and reduced transmission in trigeminal pain pathway correlating with relief of migraine.
Pharmacokinetics: Absorption: Sumatriptan is rapidly absorbed. The bioavailability is about 14-15% because of incomplete absorption and presystemic metabolism. After a single 50 mg oral dose, peak plasma Sumatriptan concentrations averaged 31 ng/mL at 0.5-3 hours, while a single 100 mg oral dose of Sumatriptan produced peak plasma drug concentrations averaging 51 ng/mL approximately 2-2.5 hours. The onset of action of Sumatriptan in patients with migraine headaches correlates well with peak plasma drug concentrations. Plasma Sumatriptan concentrations associated with therapeutic effects in patients with migraine have ranged from 18-60 ng/mL. Onset of relief of migraine symptoms occurs about 30 minutes, maximum pain relief attained within 3-6 hours.
Food has no significant effect on oral 5-HT₁ agonist bioavailability, but delays Sumatriptan's T_max by approximately 30 minutes.
Distribution: Sumatriptan is approximately 14-21% bound to plasma proteins. The volume of distribution is 2.4 L/kg.
Metabolism: Sumatriptan is metabolized in the liver via monoamine oxidase (MAO) isoenzyme, principally the A isoenzyme (MAO-A); extensive first-pass metabolism following oral administration. The major metabolite of Sumatriptan is its inactive indole acetic acid analog eliminated in urine.
Elimination: The elimination half-life is approximately 2 hours. Sumatriptan is excreted in urine via glomerular filtration and tubular secretion about 57-60% of total dose; mostly as indole acetic acid metabolite and 3% of total dose as unchanged drug. Renal plasma clearance accounts for only 22% of the systemic clearance of 1,176-1,200 mL/min. Furthermore Sumatriptan is excreted in feces about 37-40%.

Sumatriptan is indicated for the acute treatment of migraine attacks with or without aura.

The tablets should be swallowed whole with water. Administer as soon as symptoms appear.
Adults: Maximum oral dose of Sumatriptan is 300 mg daily.
Single oral Sumatriptan doses of 50 or 100 mg are recommended for management of acute migraine pain. If the headache returns or the patient has a partial response to the initial dose, the dose may be repeated after 2 hours, a second oral dose of up to 100 mg may be given.
If the first attack of migraine treated with Sumatriptan fails to respond to the drug, the diagnosis of migraine should be reconsidered before Sumatriptan is administered to treat subsequent attacks.
Children and Adolescents (under 18 years of age): There are insufficient data to make a recommendation for the use of Sumatriptan in this population.
Elderly (over 65 years of age): Use is not recommended because of the risk of adverse reactions in elderly patients who have reduced renal function, hepatic function and/or cardiac function and of concomitant disease. Moreover, the experience of the use of Sumatriptan in patients aged over 65 years is limited.
Hepatic impairment: Oral Sumatriptan therapy is considered in patients with mild to moderate hepatic impairment. The maximum single dose generally should not exceed 50 mg because the bioavailability of Sumatriptan following oral administration may be increased markedly in patients with liver disease. Severe hepatic impairment is contraindication.
Renal impairment: It has not been evaluated in renal impairment patient so there are no dosage adjustments. However, dosage adjustment not expected due to extensive metabolism to inactive agents.

Overdose and 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.

1. Hypersensitivity to Sumatriptan or any component of the formulation.
2. Because Sumatriptan has the potential to cause vasospasm, it is contraindicated in patients who have ischemic heart disease or signs or symptoms of ischemic heart disease; including Prinzmetal's angina, angina pectoris, myocardial infarction, silent myocardial ischemia, coronary artery vasospasm and peripheral vascular disease; including ischemic bowel disease.
3. Sumatriptan is contraindicated in patients who have cerebrovascular syndromes; including strokes, transient ischemic attacks.
4. Sumatriptan is contraindicated in patients with uncontrolled hypertension.
5. Sumatriptan is contraindicated in patients with Wolff-Parkinson-White syndrome (symptoms: palpitations, dizziness, lightheadedness, fainting) or arrhythmias associated with other cardiac accessory conduction pathway disorders.
6. Sumatriptan is contraindicated in patients with hemiplegic or basilar migraine.
7. Sumatriptan also is contraindicated in patients with severe hepatic impairment.
8. Concomitant use of Sumatriptan and monoamine oxidase inhibitors (MAOIs) especially, isoenzyme A (MAO-A inhibitors: e.g. moclobemide) therapy or within 2 weeks of discontinuing MAOIs is contraindicated because these drug can increase systemic exposure to Sumatriptan. 9. The use of Sumatriptan within 24 hours of treatment with ergot alkaloids.
10. Coadministration of two 5-HT₁ agonist within 24 hours of each other is contraindicated.

Use Sumatriptan only when a clear diagnosis of migraine has been established. In patients not previously diagnosed with migraine attacks in those with a history of migraine presenting with atypical symptoms, care should be taken to exclude other potentially serious neurologic conditions before initiation of Sumatriptan therapy.
Sumatriptan should not be used for prophylaxis.
Excessive use of drugs for the management of acute migraine attacks; for 10 or more days per month, may result in migraine-like daily headaches or a marked increase in the frequency of migraine attacks. Withdrawal of the overused drugs, treatment of withdrawal symptoms and consideration of prophylactic therapy for migraine attacks may be necessary.
Patients with multiple cardiovascular risk factors (e.g. postmenopausal women, men older than 40 years, patients with risk factors such as hypertension, hypercholesterolemia, obesity, diabetes, smoking, or history of coronary artery disease) who have not previously received therapy with a 5-HT₁ receptor agonist should undergo cardiovascular evaluation prior to initiation of Sumatriptan therapy. Moreover, patients who experience sensations of chest pain/pressure/tightness or symptoms suggestive of angina following dosing should be evaluated for coronary artery disease or Prinzmetal's angina before receiving additional doses. And it's recommended that patients who are intermittent long-term to use 5-HT₁ agonist, undergo periodic interval cardiovascular evaluation.
Anaphylactic, anaphylactoid and hypersensitivity reactions have been reported. Particularly, patients with known hypersensitivity to sulphonamides may exhibit an allergic reaction following Sumatriptan administration. Even though evidence of cross-sensitivity is limited.
Sumatriptan should be used with caution in patients with controlled hypertension, and blood pressure should be monitored in all patients receiving the drug.
Sumatriptan can caused drowsiness. Also, patients should be advised to avoid performing hazardous activities that require mental alertness (e.g. Operating machinery, driving a motor vehicle).
There have been rare reports of seizure after use of Sumatriptan and it should be used with caution in patients with a history of epilepsy or other conditions predisposing to seizures.
Sumatriptan should be used with caution in patients with diseases that may alter the absorption, metabolism, or excretion of the drug, e.g. impaired renal or hepatic function. Use the oral formulation with caution (and with dosage limitations) in patients with mild to moderate hepatic impairment.
Concurrent use Sumatriptan with selective serotonin-reuptake inhibitors (SSRIs: e.g. fluoxetine, fluvoxamine, paroxetine, sertraline) or norepinephrine-reuptake inhibitors (SNRIs: e.g. duloxetine) can cause serotonin syndrome. If concomitant treatment is clinically warranted, the patients should be observed carefully particularly, during initiation of therapy, when dosage is increase, or when another serotonergic agent is initiated. In addition, patients should be advised of potential drug interaction symptoms; mental status changes including weakness, progressive agitation, tingling, incoordination, chest pain, dyspnea and be instructed to report such symptoms to their clinician immediately.

Pregnancy category: C.
A very small quantity of Sumatriptan crosses the placenta to the fetus. There are no adequate and well-controlled studies evaluating the use of Sumatriptan in pregnant women. Sumatriptan should be used during pregnancy only if the potential benefit justifies the risk to the fetus.
Sumatriptan is distributed into breast milk following administration of the drug to lactating animals or nursing woman. It is recommended to avoid breast-feeding for 12 hours after receiving Sumatriptan.

Sumatriptan generally is well tolerated when given in recommended dosage.
Common adverse effects reported in patients receiving oral Sumatriptan for the treatment of migraine include malaise or fatigue, nausea or vomiting (however, nausea and vomiting also are symptoms associated with migraine attacks and/or the postdromal period, and it may be difficult to distinguish the effects or underlying disease processes from drug-induced effects), dizziness or vertigo, tingling, nasal discomfort, atypical sensation and sensations of pain, heaviness, pressure or tightness.
Serious adverse events that have been reported rarely including coronary artery vasospasm, transient myocardial ischemia, myocardial infarction, ventricular tachycardia, ventricular fibrillation, stroke, subarachnoid hemorrhage. (See table.)

Click on icon to see table/diagram/image

Because of presystemic clearance of Sumatriptan via MAO-A so that the use of MAO-A inhibitors with Sumatriptan may decrease Sumatriptan clearance and increase half-life and blood concentrations of Sumatriptan. Moreover patients receiving Sumatriptan should be cautioned about risk of serotonin syndrome when concomitant use of MAO-A inhibitors (e.g. moclobemide). Concurrent use of Sumatriptan and MAO-A inhibitors or use of Sumatriptan within 2 weeks of discontinuance of MAO-A inhibitor therapy is contraindicated.
Because ergot alkaloids have been reported to cause prolonged vasospastic reactions and the vasoconstrictor effects of these drugs may be additive to those of Sumatriptan. The use of Sumatriptan within 24 hours of treatment with an ergot-containing medication is contraindicated.
Concurrent use Sumatriptan with selective serotonin-reuptake inhibitors (SSRI: e.g. fluoxetine, fluvoxamine, paroxetine, sertraline) or norepinephrine-reuptake inhibitors (SNRIs: e.g. duloxetine) can cause serotonin syndrome. If use concurrently 5-HT₁ receptor agonists with SSRIs or SNRIs.
The risk of vasospastic reactions may be increased. Coadministration of two 5-HT₁ agonist within 24 hours of each other is contraindicated.

Store 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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