Trimigren^® (Suppositories) Instructions for Use

Marketing Authorization Holder

Nizhpharm JSC (Russia)

ATC Code

N02CC01 (Sumatriptan)

Active Substance

Sumatriptan (Rec.INN registered by WHO)

Dosage Forms

	Trimigren®	Rectal suppositories 25 mg: 1, 2, 3, 5 or 10 pcs.
		Rectal suppositories 50 mg: 1, 2, 3, 5 or 10 pcs.

Dosage Form, Packaging, and Composition

Rectal suppositories white or almost white in color, torpedo-shaped.

Excipients: Witepsol.

1 pc. – contour cell packaging (1) – cardboard packs.
2 pcs. – contour cell packaging (1) – cardboard packs.
3 pcs. – contour cell packaging (1) – cardboard packs.
5 pcs. – contour cell packaging (1) – cardboard packs.
5 pcs. – contour cell packaging (2) – cardboard packs.

Rectal suppositories white or almost white in color, torpedo-shaped.

Excipients: Witepsol.

1 pc. – contour cell packaging (1) – cardboard packs.
2 pcs. – contour cell packaging (1) – cardboard packs.
3 pcs. – contour cell packaging (1) – cardboard packs.
5 pcs. – contour cell packaging (1) – cardboard packs.
5 pcs. – contour cell packaging (2) – cardboard packs.

Clinical-Pharmacological Group

Serotonin 5-HT₁ receptor agonist. Agent with antimigraine activity

Pharmacotherapeutic Group

Antimigraine agent

Pharmacological Action

Sumatriptan is a specific selective agonist of vascular 5-hydroxytryptamine-1 receptors (5HT_1D), and does not affect other subtypes of 5HT-serotonin receptors (5HT₂ – 5HT₇).

5HT_1D receptors are located mainly in the blood vessels of the brain, and their stimulation leads to the narrowing of these vessels.

It reduces the sensitivity of the trigeminal nerve. Both of these effects may underlie the antimigraine action of sumatriptan.

Pharmacokinetics

Plasma protein binding is 14-21%, total V_d is 170 L (2.4 L/kg). Time to reach C_max is 0.5 h. Mean C_max value is 23.2 ng/mL.

The drug is metabolized by oxidation involving monoamine oxidases (primarily isoenzyme A) to form metabolites, the main ones being the indoleacetic acid analogue of sumatriptan, which has no pharmacological activity against 5-HT1 and 5-HT2 serotonin receptors, and its glucuronide.

The half-life is 1.5 h. Plasma clearance is 1160 mL/min, renal clearance is 260 mL/min; extrarenal clearance is 40% after oral administration.

It is excreted by the kidneys, mainly in the form of metabolites – free acid or glucuronide conjugate.

Indications

• Relief of migraine attacks (especially those accompanied by vomiting) with or without aura.

ICD codes

Dosage Regimen

Rectally, 1 suppository at the onset of a migraine attack.

If migraine symptoms do not disappear or decrease after the first dose, then a second dose should not be taken to relieve the same attack. However, the drug can be used to relieve subsequent migraine attacks.

If the patient feels improvement after the first dose and then the symptoms return, a second dose can be taken within the next 24 hours. The maximum dose of sumatriptan should not exceed 300 mg within a 24-hour period.

Adverse Reactions

General

Pain, sensation of heat or tingling, feeling of pressure or heaviness. These symptoms are usually transient but can be intense and occur in any part of the body, including the chest and throat.

Flushing, dizziness, weakness, fatigue, drowsiness are usually mild or moderate and transient.

Cardiovascular system

Decreased blood pressure, bradycardia, tachycardia, transient increase in blood pressure (observed shortly after taking sumatriptan). Rarely – cardiac arrhythmias, transient ischemic-type ECG changes, myocardial infarction, coronary artery spasm. Raynaud’s syndrome sometimes develops.

Gastrointestinal tract

Nausea, vomiting, ischemic colitis (but the connection of these side effects with sumatriptan has not been established), dysphagia, abdominal discomfort.

Central nervous system and sensory organs

Dizziness, rarely seizures. Sometimes after taking sumatriptan, diplopia, flickering before the eyes, nystagmus, scotoma, and decreased visual acuity are noted. Extremely rarely, partial transient loss of vision develops. However, it should be borne in mind that visual disturbances may be associated with the migraine attack itself.

Hypersensitivity reactions

Range from skin manifestations (rash, urticaria, itching, erythema) to rare cases of anaphylaxis.

Laboratory parameters

Minor changes in the activity of “hepatic” transaminases.

Contraindications

• Hypersensitivity to any component of the drug;
• Hemiplegic, basilar and ophthalmoplegic forms of migraine;
• Ischemic heart disease (IHD) (including myocardial infarction, post-infarction cardiosclerosis, Prinzmetal’s angina), as well as the presence of symptoms suggesting IHD;
• Occlusive peripheral vascular diseases;
• Stroke or transient ischemic attack (including history);
• Uncontrolled arterial hypertension;
• Concomitant use with ergotamine or its derivatives (including methysergide);
• Use while taking MAO inhibitors or earlier than 2 weeks after discontinuation of these drugs;
• Severe impairment of liver and/or kidney function;
• Age under 18 years and over 65 years (safety and efficacy not established);
• Pregnancy and lactation period.

With caution controlled arterial hypertension; diseases in which the absorption, metabolism, or excretion of this drug may be altered (e.g., impaired renal or hepatic function); epilepsy and any conditions with a lowered seizure threshold; in patients with hypersensitivity to sulfonamides (administration of sumatriptan may cause allergic reactions, the severity of which varies from skin manifestations to anaphylaxis. Data on cross-sensitivity are limited, but caution should be exercised when prescribing sumatriptan to such patients).

Use in Pregnancy and Lactation

It is prohibited to take this drug during pregnancy and lactation.

Use in Hepatic Impairment

It is prohibited to take this drug in cases of severe liver dysfunction.

With caution: diseases in which the absorption, metabolism, or excretion of this drug may be altered (e.g., impaired liver function).

Use in Renal Impairment

It is prohibited to take this drug in cases of severe kidney dysfunction.

With caution: diseases in which the absorption, metabolism, or excretion of this drug may be altered (e.g., impaired kidney function).

Pediatric Use

Contraindicated under 18 years of age (safety and efficacy not established).

Geriatric Use

Contraindicated over 65 years of age (safety and efficacy not established).

Special Precautions

Sumatriptan should be prescribed only if the diagnosis of migraine is certain, and it should be used as early as possible after the onset of a migraine attack, although it is equally effective at any stage of the attack. It should not be used for prophylactic purposes.

As with the use of other antimigraine agents, when prescribing sumatriptan to patients with previously undiagnosed migraine or patients with atypical migraine, other potentially serious neurological conditions must be excluded. It should be noted that patients with migraine have an increased risk of developing certain cerebrovascular complications (stroke or transient ischemic attack).

Sumatriptan should not be prescribed to patients with suspected heart disease without prior examination to rule out cardiovascular pathology. Such patients include postmenopausal women, men over 40 years of age, and patients with risk factors for coronary artery disease. Although the examination does not always reveal heart disease in some patients, in very rare cases they develop cardiovascular side effects. After taking sumatriptan, transient intense pain and tightness in the chest, spreading to the neck area, may occur. If there is reason to believe that these symptoms are a manifestation of coronary artery disease, appropriate diagnostic examination should be performed.

Patients with migraine may experience drowsiness, associated both with the disease itself and with taking sumatriptan, so they should be especially careful when driving and operating machinery.

Overdose

Symptoms increased severity of side effects.

Treatment is symptomatic.

There are no data on the effect of hemodialysis or peritoneal dialysis on the plasma concentration of sumatriptan.

Drug Interactions

No interaction of sumatriptan with propranolol, flunarizine, pizotifen, and ethyl alcohol has been noted.

With simultaneous use with ergotamine, prolonged vasospasm was observed. Sumatriptan can be prescribed no earlier than 24 hours after taking drugs containing ergotamine; and conversely, drugs containing ergotamine can be prescribed no earlier than 6 hours after taking sumatriptan.

Interaction between sumatriptan and MAO inhibitors, as well as between sumatriptan and drugs from the group of selective serotonin reuptake inhibitors (SSRIs) is possible. There are isolated reports of the development of weakness, hyperreflexia, and impaired coordination in patients after taking sumatriptan and drugs from the SSRI group. If sumatriptan and SSRIs are prescribed simultaneously, the patient’s condition should be carefully monitored.

Storage Conditions

List B.

The drug should be stored in a dry place out of the reach of children at a temperature not exceeding 20°C (68°F).

Shelf Life

The shelf life is 2 years. Do not use the drug after the expiration date.

Dispensing Status

The drug is dispensed by prescription.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.