MEGZUMA 100 MG TABLETS

Indications

• Acute migraine attacks
• Cluster headaches

Dosage

Children: For children aged 5–17 years, the initial dose is 500 micrograms once daily, taken at night, with potential increases up to 1.5 mg daily in divided doses. The maximum single dose (at night) is 1 mg.

Adults: Initially 50–100 mg, taken as soon as possible after the onset of a migraine attack. A second dose of 50–100 mg may be taken after at least 2 hours if required, but not exceeding a maximum of 300 mg per day.

Mechanism of action

Sumatriptan acts as an agonist at the 5-HT1B and 5-HT1D serotonin receptors. This activation leads to vasoconstriction of cranial blood vessels and inhibits the release of pro-inflammatory neuropeptides. It decreases carotid arterial blood flow while increasing blood flow velocity in the internal carotid artery and middle cerebral artery, effectively reducing migraine symptoms. Sumatriptan does not cross the blood-brain barrier.

Pharmacodynamics

Sumatriptan effectively constricts cranial blood vessels and prevents the release of vasoactive neuropeptides. Its pharmacodynamics are characterized by a rapid onset of action, particularly via subcutaneous injection, and a potential for medication-overuse headaches in patients using it frequently. The drug's effects are dose-dependent and vary based on the route of administration.

Pharmacokinetics

Sumatriptan is rapidly absorbed following subcutaneous injection, with peak plasma concentrations occurring within 12-15 minutes. Oral bioavailability is approximately 14%, with a half-life of about 2.5 hours. It undergoes extensive first-pass metabolism in the liver, primarily by monoamine oxidase A, leading to its metabolites which have minimal activity. The drug is primarily excreted in the urine.

Contra-indications

• Severe hypertension
• Uncontrolled hypertension
• Acute porphyrias
• History of ischemic heart disease
• Peripheral vascular disease
• Severe hepatic impairment

Adverse effects

• Dizziness
• Drowsiness
• Nausea
• Vomiting
• Dry mouth
• Diarrhea
• Fatigue
• Musculoskeletal stiffness
• Abnormal sensations (paresthesia)
• Palpitations
• Chest discomfort
• Vision changes (blurred vision)
• Serotonin syndrome
• Myocardial ischemia
• Hypersensitivity reactions

Interactions

• MAO inhibitors (e.g., moclobemide) may increase exposure to sumatriptan
• Concomitant use with other triptans or ergotamine derivatives is contraindicated due to increased risk of vasospastic reactions
• Propranolol may increase sumatriptan plasma levels

Precautions

• Monitor for signs of serotonin syndrome
• Use with caution in patients with a history of seizures
• Consider cardiovascular evaluation in patients with risk factors for coronary artery disease
• Not recommended for use in the elderly due to lack of safety data

Pregnancy

Sumatriptan should only be used in pregnancy if the benefit outweighs the risk, as safety in pregnancy has not been established.

Breast-feeding

Sumatriptan is excreted in breast milk. Caution is advised when administering to breastfeeding mothers, and it is recommended to wait at least 12 hours after administration before breastfeeding.

Storage

Store at room temperature, away from moisture and heat. Keep out of reach of children.

Formulations

• Sumatriptan 50 mg tablets
• Sumatriptan 100 mg tablets
• Sumatriptan 3 mg/0.5 ml injection
• Sumatriptan nasal spray 20 mg
• Sumatriptan orodispersible tablets 10 mg

Mechanism of action

Sumatriptan is an agonist of 5-HT_1B and 5-HT_1D. This agonism leads to constriction of cranial blood vessels and inhibits the release of pro-inflammatory neuropeptides. Sumatriptan decreases carotid arterial blood flow, but increases blood flow velocity in the internal carotid artery and middle cerebral artery.[A179734 Agonism of the 5-HT_1B and 5-HT_1D receptors also inhibits sensory neurons, preventing the release of vasoactive peptides.[A179734 Sumatriptan does not cross the blood brain barrier. Sumatriptan and other currently available drugs that are effective for acute migraine, including dihydroergotamine and ergotamine, have binding affinity for serotonin type 1 (5-HT1) receptors, particularly the 5-HT1D (also called 5-HT1Dalpha) and 5-HT1B (also called 5-HT1Dbeta) subtypes located on trigeminal sensory neurons innervating dural blood vessels. The 5-HT1B and 5-HT1D receptors function as autoreceptors, activation of which leads to inhibition of firing of serotonin neurons and a reduction in the synthesis and release of serotonin. Upon binding to these 5-HT1 receptor subtypes, sumatriptan inhibits adenylate cyclase activity via regulatory G proteins, increases intracellular calcium, and affects other intracellular events that lead to vasoconstriction and inhibition of sensory nociceptive (trigeminal) nerve firing and vasoactive neuropeptide release. Sumatriptan has the highest affinity for the 5-HT1D receptor, the most common serotonin receptor subtype in the brain, and a 2- to 17-fold lower affinity for 5-HT1A receptors; agonist activity at 5-HT1A and other serotonin receptors may be responsible for some of the adverse effects noted with administration of serotonin or serotonergic antimigraine drugs (eg, ergotamine, dihydroergotamine). Sumatriptan has essentially no affinity for (based on standard radioligand binding assays) nor pharmacologic activity at other serotonin receptors (eg, 5-HT2, 5-HT3) or at receptors of the dopamine1, dopamine2, muscarinic, histamine, benzodiazepine, or alpha1-, alpha2-, or beta-adrenergic type. Sumatriptan is a selective agonist of vascular serotonin (5-hydroxytryptamine; 5-HT) type 1-like receptors, probably the 5-HT1D and 5-HT1B subtypes. The mechanisms involved in the pathogenesis of migraine and cluster headache are not clearly understood; consequently, the precise mechanism of action of sumatriptan in the management of these disorders has not been established. However, current data suggest that sumatriptan may ameliorate migraine and cluster headache through selective constriction of certain large cranial blood vessels and/or inhibition of neurogenic inflammatory processes in the CNS. While some features of migraine clearly reflect effects on cerebral blood vessels, neurogenic mechanisms involving activation of the trigeminovascular system also have been implicated; current evidence suggests that both mechanisms may be involved. The vascular 5-HT1 receptor subtype that sumatriptan activates is present on cranial arteries in both dog and primate, on the human basilar artery, and in the vasculature of human dura mater and mediates vasoconstriction. This action in humans correlates with the relief of migraine headache. In addition to causing vasoconstriction, experimental data from animal studies show that sumatriptan also activates 5-HT1 receptors on peripheral terminals of the trigeminal nerve innervating cranial blood vessels. Such an action may also contribute to the antimigrainous effect of sumatriptan in humans. Sumatriptan selectively reduces carotid arterial blood flow and/or constricts carotid arteriovenous anastomoses in anesthetized animals without appreciable effects on arterial blood pressure or total peripheral resistance. The drug produces contraction of vascular smooth muscle in vitro in saphenous veins in dogs and humans, but such contractions are weaker than those produced by serotonin or ergot alkaloids (eg, methysergide). For m

Pharmacodynamics

Sumatriptan constricts cranial blood vessels and prevents the release of vasoactive peptides. The dose of sumatriptan varies widely by route of administration and in most cases, no more than 2 doses should be given daily. Medication overuse headaches may occur in patients who use sumatriptan frequently.