Sumatriptan: Side Effects, Mechanism of Action, Interactions, Indications, Uses and Contraindications

It is a synthetic drug that belongs to the triptan class of drugs. It is used to treat cluster headaches and migraines.

It works by narrowing the blood vessels in the brain, relieving headaches.

Do not take this medicine if you are allergic to its formula, if you have a history of heart problems , blood vessel disease, high blood pressure, or liver problems.

Tell your doctor if you have a history of kidney problems, seizures, breathing problems, high cholesterol, diabetes, obesity, if you are pregnant or breastfeeding, and if you are taking any other medications.

Side effects

Besides its desired effect, Sumatriptan can cause some unwanted effects as well. In such cases, you should seek medical attention immediately.

This is not an exhaustive list of side effects . Inform your doctor if you experience any adverse drug reaction.

  • Neck Pain.
  • Dizziness.
  • Feeling of heaviness
  • Drowsiness.
  • Soft spot.
  • Nausea.
  • Dry mouth.
  • Jaw pain
  • Aesthesia (tingling or pricking sensation).
  • Throat pain.
  • Warm feeling.

Sumatriptan is available in tablet form and is most effective when taken early after the onset of a headache. Although, the injected Sumatriptan is more effective than other formulations.

Tablets content

The tablets contain Sumatriptan (as succinate), an agonist of the selective 5-hydroxytryptamine receptor subtype 1. Sumatriptan succinate is chemically designated as 3- [2- (dimethylamino) ethyl] -N-methyl-indole-5-methanesulfonamide succinate.

Mechanism of action

Sumatriptan is an agonist for a vascular 5-hydroxytryptamine receptor subtype 1 (probably a member of the 5-HT 1D family) that has only weak affinity for 5-HT 1A, 5-HT 5A, and 5-HT receptors. 7 and affinity is not significant (as measured using standard radioligand binding assays).

The vascular 5-HT 1 receptor subtype that activates Sumatriptan is present in the cranial arteries in both the dog and primate, in the human basilar artery and in the vasculature of the human dura mater and mediates vasoconstriction.

This action in humans is correlated with migraine relief.

In addition to causing vasoconstriction, experimental data from animal studies show that Sumatriptan also activates 5-HT 1 receptors on the peripheral terminals of the trigeminal nerve that innervate the cranial vessels.

Such action may also contribute to the antimigraine effect of Sumatriptan in humans.

Interactions with other medications

Special populations

Renal insufficiency

The effect of renal impairment on the pharmacokinetics of Sumatriptan has not been examined, but little clinical effect is expected as Sumatriptan is largely metabolized to an inactive substance.

Hepatic impairment

The liver plays an important role in the presystemic clearance of orally administered Sumatriptan. Consequently, the bioavailability of sumatriptan after oral administration may be markedly increased in patients with liver disease.

In a small study of patients with hepatic impairment (N = 8) matched for sex, age, and weight with healthy subjects, patients with hepatic impairment had an approximately 70% increase in AUC and C max and by a maximum of 40 minutes earlier. compared to healthy ones.

Years

The pharmacokinetics of oral Sumatriptan in the elderly (mean age 72 years, 2 men and 4 women) and in patients with migraine (mean age 38 years, 25 men and 155 women) was similar to that of healthy men (mean age ), 30 years).

Gender

In a study comparing women to men, no pharmacokinetic differences were observed between the sexes for AUC, C max, t max, and half-life.

Carrera

Systemic clearance and Cmax of Sumatriptan were similar in healthy black (N = 34) and Caucasian (N = 38) male subjects.

Drug interactions

Monoamine oxidase (MAO) inhibitors

Treatment with MAO-A inhibitors generally leads to increased plasma levels of Sumatriptan.

Due to first-pass effects on hepatic and intestinal metabolism, the increase in systemic exposure after concomitant administration of an MAO-A inhibitor with oral Sumatriptan is greater than after concomitant administration of monoamine oxidase inhibitors. (MAOI) with subcutaneous Sumatriptan.

In a study of 14 healthy women, pretreatment with an MAO-A inhibitor decreased the clearance of subcutaneous Sumatriptan.

Under the conditions of this experiment, the result was a 2-fold increase in the area under the curve of Sumatriptan plasma concentration x time (AUC), corresponding to a 40% increase in elimination half-life.

This interaction was not evident with an MAO-B inhibitor.

A small study evaluating the effect of pretreatment with an MAO-A inhibitor on the bioavailability of a 25 mg oral Sumatriptan tablet resulted in an approximately 7-fold increase in systemic exposure.

Alcohol

Alcohol consumed 30 minutes prior to ingestion of Sumatriptan had no effect on the pharmacokinetics of Sumatriptan.

Indications and use

Sumatriptan succinate tablets are indicated for the treatment of migraine attacks with or without aura in adults.

Sumatriptan succinate tablets are not intended for prophylactic migraine therapy or for use in the treatment of basilar or hemiplegic migraine.

The safety and efficacy of Sumatriptan succinate tablets have not been established for cluster headache, which is present in an older, predominantly male population.

Contraindications

Sumatriptan succinate tablets should not be administered to patients with a history, symptoms, or signs of cardiac, cerebrovascular, or peripheral vascular syndromes.

In addition, patients with other significant underlying cardiovascular diseases should not receive Sumatriptan succinate tablets.

Ischemic cardiac syndromes include, but are not limited to, angina pectoris of any type (for example, stable exertional angina pectoris and vasospastic forms of angina pectoris, such as Prinzmetal variant), all forms of infarction of myocardium, and silent myocardial ischemia.

Stroke syndromes include, but are not limited to, strokes of any kind, as well as transient ischemic attacks. Peripheral vascular disease includes, but is not limited to, ischemic bowel disease.

Because Sumatriptan Suction Tablets can increase blood pressure, they should not be given to patients with uncontrolled hypertension.

Interactions with other medications and precautions

Sumatriptan tablets should not be administered to patients with hemiplegic or basilar migraine.

Sumatriptan tablets and any medications that contain ergotamine or ergotamine (such as dihydroergotamine or methysergide) should not be used within 24 hours of each other, nor should sumatriptan or another 5-HT 1 agonist be present.

Sumatriptan tablets are contraindicated in patients with hypersensitivity to Sumatriptan or any of its components.

Sumatriptan tablets are contraindicated in patients with severe hepatic impairment.

Warnings

Sumatriptan succinate tablets should only be used when a clear diagnosis of migraine headache has been established.

Risk of ischemia and / or myocardial infarction and other adverse cardiac events

Sumatriptan should not be administered to patients with documented ischemic or vasospastic coronary artery disease (CAD).

It is strongly recommended that Sumatriptan not be administered to patients in whom an undiagnosed CAD is not predicted by the presence of risk factors (eg, hypertension, hypercholesterolemia, smoking, obesity, diabetes, family history of CAD).

Also to women with surgical or physiological menopause.

Equally or administered to men over 40 years of age unless cardiovascular evaluation provides satisfactory clinical evidence that the patient is reasonably free of coronary artery disease and ischemic myocardial disease or other significant underlying cardiovascular disease.

The sensitivity of cardiac diagnostic procedures to detect cardiovascular disease or predisposition to coronary artery vasospasm is modest at best.

For patients with predictive risk factors for CAD, who are determined to have a satisfactory cardiovascular evaluation, it is strongly recommended that the first dose of Sumatriptan tablets be administered in a physician’s office or similar and equipped medical facility. .

This recommendation should be followed unless the patient has previously received Sumatriptan.

Because cardiac ischemia can occur in the absence of clinical symptoms, an electrocardiogram (ECG) should be considered on the first occasion of use during the interval immediately after Sumatriptan tablets, in these patients with risk factors.

It is recommended that patients who are long-term intermittent users of Sumatriptan and who have or develop risk factors predictive of CAD, as described above, undergo periodic interval cardiovascular evaluation as they continue to use Sumatriptan.

The systematic approach described above is intended to reduce the likelihood that patients with unrecognized cardiovascular disease will be inadvertently exposed to Sumatriptan.

Cardiac events and drug-related deaths

Serious adverse cardiac events, including acute myocardial infarction, life-threatening heart rhythm disorders, and death have been reported within hours after administration of Sumatriptan Succinate injection or Sumatriptan Succinate tablets.

Considering the degree of use of Sumatriptan in patients with migraine, the incidence of these events is extremely low.

The fact that Sumatriptan can cause coronary vasospasm, that some of these events occurred in patients with no prior history of heart disease and with a documented absence of CAD, and the close proximity of events with the use of Sumatriptan support the conclusion that some of these cases caused by the drug.

However, in many cases, where underlying coronary disease is known, the relationship is uncertain.

Premarket experience with Sumatriptan

Of the 6,348 patients with migraine who participated in pre-marketing controlled and uncontrolled clinical trials of oral Sumatriptan, 2 experienced adverse clinical events shortly after receiving oral Sumatriptan that may have reflected coronary vasospasm.

None of these adverse events were associated with a serious clinical outcome.

Among the more than 1,900 migraine patients who participated in premarketing controlled clinical trials of subcutaneous Sumatriptan, there were 8 patients who experienced clinical events during or shortly after receiving Sumatriptan that may have reflected coronary artery vasospasm.

Six of these 8 patients had ECG changes consistent with transient ischemia, but without accompanying clinical signs or symptoms. Of these 8 patients, 4 had findings suggesting CAD or predictive risk factors for CAD prior to inclusion in the study.

Among approximately 4,000 patients with migraine who participated in controlled and uncontrolled clinical trials of Sumatriptan nasal spray, 1 patient experienced an asymptomatic subendocardial infarction possibly following a coronary vasospastic event.

Post-marketing experience with Sumatriptan

Serious cardiovascular events, some of which have resulted in death, have been reported in association with the use of Sumatriptan succinate injection or Sumatriptan succinate tablets.

The uncontrolled nature of post-marketing surveillance, however, makes it impossible to definitively determine the proportion of reported cases that were actually caused by Sumatriptan or to reliably assess causality in individual cases.

From a clinical point of view, the longer the latency between the administration of Sumatriptan and the onset of the clinical event, the less likely that the association is causal.

Consequently, interest has focused on events that begin within 1 hour of the administration of Sumatriptan.

Cardiac events that have been observed to appear in the first hour after Sumatriptan administration include: coronary artery vasospasm, transient ischemia, myocardial infarction, ventricular tachycardia, ventricular fibrillation, cardiac arrest, and death.

Some of these events occurred in patients who had no CAD findings and appear to represent the consequences of coronary artery vasospasm.

However, among the national reports of serious cardiac events within 1 hour of Sumatriptan administration, almost all patients had predictive risk factors for CAD and the presence of significant underlying factors.

Drug-associated cerebrovascular events and deaths

Cerebral hemorrhage, subarachnoid hemorrhage, cerebrovascular accident, and other cerebrovascular events have been reported in patients treated with oral or subcutaneous sumatriptan, and some have resulted in deaths.

The Sumatriptan’s relationship to these events is uncertain. In several cases, it seems possible that the cerebrovascular events were primary, Sumatriptan was administered with the incorrect belief that the symptoms experienced were a consequence of the migraine when they were not.

As with other acute migraine therapies, before treating headaches in patients who have not previously been diagnosed as migraineurs with atypical symptoms, care must be taken to exclude other potentially serious neurological conditions.

Other events related to vasospasm

Sumatriptan can cause vasospastic reactions other than coronary artery vasospasm. Peripheral vascular ischemia and colonic ischemia with abdominal pain and bloody diarrhea have been reported.

Very rare cases of transient and permanent blindness and significant partial vision loss have been reported with the use of Sumatriptan. Visual disturbances can also be part of a migraine attack.

Serotonin syndrome

The development of a life-threatening serotonin syndrome can occur with triptans, including treatment with Sumatriptan, particularly during combined use with selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs). .

If concomitant treatment with Sumatriptan and an SSRI (eg, fluoxetine, paroxetine, sertraline, fluvoxamine, citalopram, escitalopram) or SNRI (eg, venlafaxine, duloxetine) is clinically warranted, careful patient observation is recommended , particularly during the start it increases.

Symptoms of serotonin syndrome can include:

  • Changes in mental status (eg, agitation, hallucinations, coma).
  • Autonomic instability (eg, tachycardia, labile blood pressure, hyperthermia).
  • Neuromuscular aberrations (eg, hyperreflexia, incoordination).
Increased blood pressure

A significant elevation in blood pressure, including hypertensive crisis, has been reported rarely in patients with and without a history of hypertension.

Sumatriptan is contraindicated in patients with uncontrolled hypertension.

Sumatriptan should be administered with caution in patients with controlled hypertension as transient increases in blood pressure and peripheral vascular resistance have been observed in a small proportion of patients.

Concomitant drug use

In patients taking MAO-A inhibitors, the plasma levels of Sumatriptan achieved after treatment with the recommended doses are 7 times higher after oral administration than those obtained under other conditions.

Consequently, concomitant administration of sumatriptan succinate tablets and an MAO-A inhibitor is contraindicated.

Hypersensitivity

On rare occasions, hypersensitivity reactions (anaphylaxis / anaphylactoid) have occurred in patients receiving Sumatriptan.

Such reactions can be life threatening or fatal. In general, hypersensitivity reactions to medications are more likely to occur in individuals with a history of sensitivity to multiple allergens.

Precautions

General

Chest discomfort and stiff jaw or neck have been reported after the use of Sumatriptan succinate tablets and have also been reported infrequently after administration of Sumatriptan nasal spray.

Tightness in the chest, jaw, or neck is relatively common after administration of Sumatriptan injection.

Only rarely have these symptoms been associated with ischemic changes on the ECG.

However, because sumatriptan can cause coronary artery vasospasm, patients with signs or symptoms suggestive of angina after Sumatriptan should be evaluated for the presence of CAD.

Evaluation will also establish a predisposition to Prinzmetal variant angina before receiving additional doses of Sumatriptan, and they should be monitored electrocardiographically if similar symptoms are resumed and recur.

Sumatriptan should also be administered with caution to patients with conditions that may impair the absorption, metabolism, or excretion of drugs, such as impaired liver or kidney function.

There have been rare reports of seizures after administration of Sumatriptan.

Sumatriptan should be used with caution in patients with a history of epilepsy or conditions associated with a lowered seizure threshold.

Care must be taken to exclude other potentially serious neurological conditions before treating headaches in patients who have not previously been diagnosed with migraine or who experience a headache that is atypical for them.

There have been rare reports in which patients received Sumatriptan for severe headaches that were later shown to be secondary to an evolving neurological injury.

For a given attack, if a patient does not respond to the first dose of Sumatriptan, the diagnosis of migraine should be reconsidered before the administration of a second dose.

Overuse of acute migraine treatments has been associated with exacerbation of headache (medication abuse headache) in susceptible patients. Withdrawal of treatment may be necessary.

Binding to tissues containing melanin

In rats treated with a single subcutaneous dose (0.5 mg / kg) or oral dose (2 mg / kg) of radiolabeled Sumatriptan, the elimination half-life of radioactivity from the eye was 15 and 23 days, respectively, suggesting that Sumatriptan and / or its metabolites bind to melanin in the eye.

Because there could be a build-up in melanin-rich tissues over time, this raises the possibility that Sumatriptan may cause toxicity in these tissues after prolonged use.

However, no retinal effects related to Sumatriptan treatment were observed in any of the oral or subcutaneous toxicity studies.

Although no systematic monitoring of ophthalmological function was performed in clinical trials, and no specific recommendations for ophthalmological monitoring are offered.

Corneal opacities

Sumatriptan causes corneal opacities and defects in the corneal epithelium in dogs; This raises the possibility that these changes could occur in humans.

Although patients were not systematically evaluated for these changes in clinical trials, and specific recommendations for monitoring are not offered, prescribers should be aware of the possibility of these changes.