Rapimed (Tablets) Instructions for Use

Marketing Authorization Holder

Actavis Group PTC ehf. (Iceland)

Manufactured By

Actavis hf. (Iceland)

ATC Code

N02CC01 (Sumatriptan)

Active Substance

Sumatriptan (Rec.INN registered by WHO)

Dosage Forms

	Rapimed	Film-coated tablets, 50 mg: 2, 3, 6, 12, 18 or 24 pcs.
		Film-coated tablets, 100 mg: 2, 3, 6, 12, 18 or 24 pcs.

Dosage Form, Packaging, and Composition

Film-coated tablets white, oval, biconvex, with a score on both sides and on the side, with the engraving “SN” on one side and “50” on the other.

Excipients : lactose monohydrate – 70 mg, croscarmellose sodium – 6 mg, anhydrous lactose (Pharmatose DCL 21) – 105.7 mg, microcrystalline cellulose (Avicel PH 102) – 45.3 mg, magnesium stearate – 3 mg.

Film coating composition lactose monohydrate – 4.32 mg, mannitol – 2.76 mg, titanium dioxide – 2.4 mg, talc – 1.8 mg, triacetin – 0.72 mg.

2 pcs. – blisters (1) – cardboard packs.
3 pcs. – blisters (1) – cardboard packs.
3 pcs. – blisters (2) – cardboard packs.
3 pcs. – blisters (4) – cardboard packs.
3 pcs. – blisters (6) – cardboard packs.
3 pcs. – blisters (8) – cardboard packs.

Film-coated tablets white, oval, biconvex, with the engraving “SN” on one side and “100” on the other.

Excipients : lactose monohydrate – 140 mg, croscarmellose sodium – 12 mg, anhydrous lactose (Pharmatose DCL 21) – 211.4 mg, microcrystalline cellulose (Avicel PH 102) – 90.6 mg, magnesium stearate – 6 mg.

Coating composition lactose monohydrate – 8.64 mg, mannitol – 5.52 mg, titanium dioxide – 4.8 mg, talc – 3.6 mg, triacetin – 1.44 mg.

2 pcs. – blisters (1) – cardboard packs.
3 pcs. – blisters (1) – cardboard packs.
3 pcs. – blisters (2) – cardboard packs.
3 pcs. – blisters (4) – cardboard packs.
3 pcs. – blisters (6) – cardboard packs.
3 pcs. – blisters (8) – cardboard packs.

Clinical-Pharmacological Group

Serotonin 5-HT₁ receptor agonist. Agent with antimigraine activity

Pharmacotherapeutic Group

Antimigraine agent

Pharmacological Action

Antimigraine drug. A specific selective agonist of serotonin 5-HT_1D (5-hydroxytryptamine subtype 1D) receptors, localized mainly in the blood vessels of the brain, does not act on other subtypes of serotonin 5-HT receptors (5-HT₂-5-HT₇). Causes vasoconstriction of the carotid arterial bed, which supplies blood to the extracranial and intracranial tissues (vasodilation of the meningeal vessels and/or their edema is the main mechanism of migraine development in humans), without having a significant effect on cerebral blood flow.

Suppresses the activity of receptors of the endings of afferent fibers of the trigeminal nerve in the dura mater (as a result, the release of sensory neuropeptides decreases). Both of these effects may underlie the antimigraine action of sumatriptan.

Eliminates nausea and photophobia associated with a migraine attack.

In 50-70% of cases, it quickly relieves an attack when taken orally at a dose of 25-100 mg. Within 24 hours, a relapse may develop in 1/3 of cases, requiring re-administration.

The clinical effect is usually noted 30 minutes after oral administration.

Pharmacokinetics

Absorption

After oral administration, it is rapidly absorbed from the gastrointestinal tract. After 45 minutes, the concentration of sumatriptan in plasma reaches 70% of C_max. Bioavailability is 14% (due to presystemic metabolism and incomplete absorption). After oral administration of sumatriptan at a dose of 100 mg, C_max in blood plasma is 54 ng/ml.

Distribution

Plasma protein binding is 14-21%. Total V_d– 170 l (2.4 l/kg).

Metabolism

It is metabolized by oxidation with the participation of MAO (mainly isoenzyme A) with the formation of the main metabolite – the indoleacetic analogue of sumatriptan, which does not have pharmacological activity against serotonin 5-HT₁ and 5-HT₂ receptors.

Excretion

T_1/2 of sumatriptan – about 2 hours. Plasma clearance – 1160 ml/min, renal clearance – 260 ml/min; extrarenal clearance – 80% of total clearance.

It is excreted by the kidneys, mainly in the form of metabolites (97% after oral administration) – free acid or glucuronide conjugate.

Indications

• Migraine (relief of attacks, with or without aura).

ICD codes

Dosage Regimen

The drug is taken orally. The tablet should be swallowed whole with water.

Treatment should be started as early as possible after the onset of a migraine attack (although the drug is effective at any stage of the attack).

For relief of acute migraine attacks the recommended dose for adults is 50 mg once a day. Some patients may require a higher dose of 100 mg. If symptoms do not disappear or decrease after taking the first dose, then the drug should not be taken again 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 recur, a second dose can be taken within the next 24 hours with an interval of at least 2 hours after taking the first dose. The maximum dose of sumatriptan is 300 mg within 24 hours.

Adverse Reactions

General reactions: pain, feeling 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, feeling of weakness, feeling of tiredness, drowsiness are usually mild or moderate and transient.

From the cardiovascular system: decreased blood pressure, transient increased blood pressure (observed shortly after taking sumatriptan), bradycardia, tachycardia (including ventricular), arrhythmias, angina pectoris; heart rhythm disturbances, transient ischemic-type ECG changes, myocardial infarction, coronary artery spasm; in isolated cases – Raynaud’s syndrome.

From the digestive system: nausea, vomiting, ischemic colitis (the connection of these side effects with sumatriptan has not been established), dysphagia, abdominal discomfort.

Motor disorders: feeling of stiffness (these symptoms are usually transient but can be intense and occur in any part of the body, including the chest and throat); tremor, neck muscle rigidity.

From the nervous system: sensory disturbances, including paresthesia; seizures (in some cases they were observed in patients with a history of seizures or in conditions predisposing to seizures; in some patients no predisposing factors were identified), dystonia.

From the senses: diplopia, flickering of “flies” before the eyes, nystagmus, scotoma, decreased visual acuity. Extremely rarely, partial transient loss of vision develops. However, it should be borne in mind that visual disturbances may be associated with migraine attacks.

Allergic reactions: skin rash (including urticaria and erythematous rashes), skin itching, anaphylactic reactions.

From laboratory parameters: minor changes in the activity of liver transaminases.

From the respiratory system: shortness of breath, nosebleed.

Contraindications

• Hemiplegic, basilar or ophthalmoplegic forms of migraine;
• Coronary artery disease (including suspected);
• Angina pectoris (including Prinzmetal’s angina);
• Myocardial infarction (including history);
• Post-infarction cardiosclerosis;
• Uncontrolled arterial hypertension;
• Occlusive peripheral vascular diseases;
• Stroke or transient ischemic cerebrovascular accident (including history);
• 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;
• Childhood and adolescence under 18 years;
• Elderly age (over 65 years);
• Pregnancy;
• Lactation period (within 24 hours after taking the drug);
• Hypersensitivity to the components of the drug.

With caution

• Epilepsy (including any conditions with a reduced seizure threshold);
• Controlled arterial hypertension;
• Impaired liver and kidney function;
• In patients with hypersensitivity to sulfonamides (allergic reactions are possible, ranging from skin manifestations to anaphylaxis).

Use in Pregnancy and Lactation

The use of the drug is contraindicated during pregnancy and lactation (breastfeeding).

Use in Hepatic Impairment

Contraindicated in severe liver dysfunction.

Use in Renal Impairment

Contraindicated in severe renal impairment.

Pediatric Use

Contraindicated in children and adolescents under 18 years of age.

Geriatric Use

Contraindicated in elderly patients (over 65 years of age).

Special Precautions

Sumatriptan should be prescribed only if the diagnosis of migraine is not in doubt, and it should be used as early as possible after the onset of a migraine attack, although it is equally effective when used at any stage of the attack.

The drug is not intended for the prevention of migraine (administration during a migraine aura before the onset of other symptoms may not prevent the development of headache).

As with the use of other antimigraine drugs, 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 cerebrovascular complications (stroke or transient cerebrovascular accident).

In patients at risk from the cardiovascular system, therapy should not be started without a preliminary examination (women in the postmenopausal period, men over 40 years of age, persons with risk factors for the development of coronary artery disease). The examination performed does not always reveal heart disease in some patients. In very rare cases, serious cardiovascular adverse reactions may occur in patients with no history of cardiovascular pathology. After taking the drug, 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, an appropriate diagnostic examination should be performed.

It should be prescribed with caution to patients with controlled arterial hypertension, since in some cases transient increases in blood pressure and systemic vascular resistance have been observed; patients suffering from diseases in which the absorption, metabolism or excretion of sumatriptan may be significantly altered (for example, impaired renal or liver function).

There are very rare reports of the development of serotonin syndrome (including mental disorders, autonomic lability and neuromuscular disorders) after taking selective serotonin reuptake inhibitors (SSRIs) and sumatriptan. Serotonin syndrome has also been reported with the concomitant use of triptans and serotonin and norepinephrine reuptake inhibitors (SNRIs). In case of concomitant use of SSRIs/SNRIs and sumatriptan, careful monitoring of this group of patients should be carried out.

Sumatriptan should be used with caution in patients with a history of epilepsy or organic brain lesions with a reduced 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.

Abuse of drugs intended to relieve migraine attacks is associated with increased headaches in sensitive patients (medication-overuse headache). In this case, the possibility of drug withdrawal should be considered.

If there is no effect after the first dose, the diagnosis should be clarified.

Experience with the use of sumatriptan in patients over 65 years of age is limited (no significant difference in pharmacokinetics compared to younger patients is observed).

The recommended dose of sumatriptan should not be exceeded.

Effect on ability to drive vehicles and operate machinery

During the treatment period, patients must be careful when driving vehicles and engaging in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Overdose

Symptoms: when taken orally at a dose of up to 400 mg, no other adverse reactions are observed, except for those previously listed.

Treatment: symptomatic therapy, monitoring the patient’s condition for at least 10 hours. 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 ethanol has been noted.

With simultaneous administration with ergotamine and ergotamine-containing drugs, prolonged vasospasm is possible. Sumatriptan can be prescribed no earlier than 24 hours after taking drugs containing ergotamine; and vice versa, drugs containing ergotamine can be prescribed no earlier than 6 hours after taking sumatriptan.

Interaction between sumatriptan and MAO inhibitors is possible (reduction in the intensity of sumatriptan metabolism, increase in its concentration).

Serotonin syndrome may develop with the combined use of sumatriptan and drugs from the SSRI and SNRI groups.

The likelihood of side effects increases with the combined use of sumatriptan with St. John’s wort preparations.

Storage Conditions

The drug should be stored out of the reach of children, in a dry, light-protected place at a temperature not exceeding 30°C (86°F).

Shelf Life

Shelf life – 3 years.

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.