Sumafix

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT SУMAFIX (SUMAFIX)

Composition:

Active substance: sumatriptan;

One tablet contains 50 mg or 100 mg of sumatriptan in the form of sumatriptan succinate;

Excipients: sodium croscarmellose, polysorbate 80, anhydrous calcium hydrogen phosphate (A-Tab), anhydrous calcium hydrogen phosphate (Fujicalin SG), microcrystalline cellulose, sodium hydrogencarbonate, magnesium stearate.

Pharmaceutical form. Tablets.

Main physicochemical properties:

50 mg tablets: uncoated tablets, capsule-shaped, biconvex, white to almost white, with engraving "C" on one side and "33" on the other;

100 mg tablets: uncoated tablets, capsule-shaped, biconvex, white to almost white, with engraving "C" on one side and "34" on the other.

Pharmacotherapeutic group. Medicinal products used in migraine. Selective 5-HT1 serotonin receptor agonists. Sumatriptan. ATC code N02C C01.

Pharmacological properties.

Pharmacodynamics.

Sumatriptan has been shown to be a specific and selective agonist of

5-hydroxytryptamine (5HT1D) receptors, without affecting other subtypes of 5HT receptors

(5-HT2−5-HT7). Vascular 5HT1D receptors are primarily located in cranial blood vessels and mediate vasoconstriction. The carotid arterial system supplies blood to extra- and intracranial tissues, such as the meninges. It is believed that dilation and/or swelling in these vessels are the primary mechanisms underlying migraine development in humans.

Both of these mechanisms (constrictive action on cranial vessels and inhibition of trigeminal nerve activity) may contribute to the antimigraine effect of sumatriptan in humans.

The clinical effect occurs approximately 30 minutes after an oral dose of 100 mg.

Pharmacokinetics.

After oral administration, sumatriptan is rapidly absorbed, reaching 70% of maximum concentration within 45 minutes. Following a 100 mg dose, the maximum plasma concentration is 54 ng/mL. The mean absolute bioavailability after oral administration is 14%, partly due to presystemic metabolism and partly due to incomplete absorption. The elimination half-life is approximately 2 hours, although data suggest a longer terminal phase. Plasma protein binding is low (14–21%), and the mean volume of distribution is 170 liters.

Mean total plasma clearance is approximately 1160 mL/min, and mean renal clearance is approximately 260 mL/min. Non-renal clearance accounts for approximately 80% of total clearance. Sumatriptan is primarily eliminated via oxidative metabolism mediated by monoamine oxidase A.

The main metabolite, an indole acetic acid analogue of sumatriptan, is excreted mainly in urine, where it is present as free acid and glucuronide conjugate. This metabolite lacks 5HT1- or 5HT2-activity. The pharmacokinetics of orally administered sumatriptan are not significantly altered during a migraine attack.

Clinical characteristics.

Indications.

Sumafix tablets are indicated for the rapid relief of symptoms during migraine attacks, with or without aura. Sumafix should be used only when migraine has been clearly diagnosed.

Contraindications.

Hypersensitivity to any component of the drug.

Sumatriptan should not be administered to patients with myocardial infarction or ischemic heart disease, coronary artery spasm (Prinzmetal's angina), peripheral vascular disease, or to patients with symptoms or signs indicating ischemic heart disease.

Sumatriptan is contraindicated in patients with a history of cerebrovascular disorders (CVD) or transient ischemic attack (TIA).

Sumatriptan is contraindicated in patients with severe hepatic impairment. Its use is also contraindicated in patients with moderate to severe hypertension or mild uncontrolled hypertension.

Concomitant use of ergotamine or ergotamine derivatives (including methysergide) is contraindicated. Concurrent administration of any triptan/5-hydroxytryptamine receptor agonist (5-HT1) is also contraindicated (see section "Interaction with other medicinal products and other types of interactions").

Concomitant use of monoamine oxidase inhibitors (MAOIs) and sumatriptan is contraindicated. Sumatriptan should not be administered within two weeks following discontinuation of MAOIs.

Interaction with other medicinal products and other types of interactions.

There are no data on interactions between this medicinal product and propranolol, flunarizine, pizotifen, or alcohol.

Data on interactions with medicinal products containing ergotamine or other triptan/5-HT1-receptor agonists are limited. A theoretically increased risk of coronary artery spasm exists; therefore, concomitant use is contraindicated.

The required time interval between administration of sumatriptan and medicinal products containing ergotamine or other triptan/5-HT1-receptor agonists is unknown. This will also depend on the doses and types of medicinal products used. Effects may be additive. At least a 24-hour interval should be maintained between administration of products containing ergotamine or other triptan/5-HT1-receptor agonists and administration of sumatriptan.

Conversely, products containing ergotamine should not be administered earlier than 6 hours after sumatriptan administration, and at least 24 hours should elapse before administering another triptan/5-HT1-receptor agonist.

An interaction between sumatriptan and MAOIs may occur; therefore, their concomitant use is contraindicated.

There have been isolated post-marketing reports of serotonin syndrome (including altered mental status, autonomic instability, and neuromuscular abnormalities) in patients receiving selective serotonin reuptake inhibitors (SSRIs) together with sumatriptan. Serotonin syndrome has also been reported following concomitant administration of triptans and serotonin-norepinephrine reuptake inhibitors (SNRIs).

Special precautions for use.

Sumatriptan should be used only in patients with a clearly established diagnosis of migraine.

Sumatriptan is not indicated for the treatment of hemiplegic, basilar, or ophthalmoplegic migraine.

In patients with atypical symptoms or when an appropriate diagnosis for sumatriptan use has not been established prior to initiating treatment with sumatriptan, potentially serious neurological disorders (e.g., stroke, transient ischemic attack [TIA]) should be excluded.

Following administration, sumatriptan may be associated with transient symptoms, including chest pain and pressure sensations, which may be intense and radiate to the throat. If such symptoms suggest ischemic heart disease, further use of sumatriptan should be discontinued and appropriate evaluation initiated.

Sumatriptan should not be administered to patients with risk factors for ischemic heart disease without prior cardiovascular evaluation. Particular caution should be exercised in postmenopausal women and men aged 40 years or older who have such risk factors. However, such evaluation may not always detect every patient with underlying heart disease; therefore, in rare cases, severe cardiovascular complications have occurred in patients without prior cardiovascular disease.

Sumatriptan should be used with caution in patients with mild, well-controlled hypertension, as transient increases in blood pressure and peripheral vascular resistance have been observed in a small number of patients.

Post-marketing reports have described isolated cases of serotonin syndrome (including altered mental status, autonomic instability, and neuromuscular abnormalities) occurring in patients after concomitant use of SSRIs and sumatriptan. Cases of serotonin syndrome have also been reported following concomitant use of triptans and SNRIs.

If concomitant use of sumatriptan and SSRIs/SNRIs is clinically justified, appropriate patient monitoring is recommended.

Sumatriptan should be used with caution in patients with conditions that substantially impair absorption, metabolism, or elimination of drugs, such as hepatic (Child-Pugh class A or B) or renal impairment. A dose of 50 mg is recommended for patients with hepatic impairment.

Sumatriptan should be used with caution in patients with a history of seizures or other risk factors that lower the seizure threshold, as seizures have been reported in association with sumatriptan.

Allergic reactions may occur in patients with known hypersensitivity to sulfonamides following administration of sumatriptan. Reactions may range from skin hypersensitivity reactions to anaphylaxis. Data on cross-sensitivity are limited; however, caution should be exercised when prescribing sumatriptan to such patients.

Adverse effects may occur more frequently during concomitant use of triptans and herbal products containing St. John’s wort (Hypericum perforatum).

Prolonged use of any type of analgesic for headache may lead to worsening of headache. If such a situation occurs or is suspected, medical advice should be sought and treatment discontinued. Patients who experience frequent or daily headaches despite (or because of) regular use of headache medications may be diagnosed with medication-overuse headache.

This medicinal product contains less than 1 mmol of sodium (23 mg) per tablet, i.e., essentially "sodium-free".

Use during pregnancy or breastfeeding.

Pregnancy

Post-marketing data on sumatriptan use during the first trimester are available from over 1000 pregnant women. Although these data are insufficient to draw definitive conclusions, they do not indicate an increased risk of congenital malformations. Experience with sumatriptan use during the second and third trimesters is limited.

Evaluation of experimental animal studies does not indicate direct teratogenic effects or harmful effects on peri- and postnatal development. However, in rabbits, embryonic viability may be impaired.

Sumatriptan should be used during pregnancy only if the expected benefit to the mother outweighs any potential risk to the fetus.

Breastfeeding

Sumatriptan is excreted in breast milk, with an average relative infant dose of <4% following a single dose of sumatriptan. Infant exposure can be minimized by avoiding breastfeeding for 12 hours after treatment, during which any expressed breast milk should be discarded.

Breast pain and/or nipple pain have been reported in breastfeeding women after administration of sumatriptan (see section "Adverse reactions"). Such pain is usually transient and resolves within 3–12 hours.

Effect on ability to drive or operate machinery.

Somnolence may result either from migraine itself or from its treatment with Sumafix; therefore, driving or operating machinery should be avoided.

Method of Administration and Dosage

Adults

Sumatriptan tablets are indicated for the acute treatment of migraine attacks. The drug should not be used for prophylactic purposes. The recommended dose of sumatriptan should not be exceeded.

Sumatriptan should be administered as early as possible after the onset of a migraine attack, although it remains effective regardless of the stage at which it is administered.

The recommended oral dose of sumatriptan is one 50 mg tablet. Some patients may require a dose of 100 mg.

If the patient responds to the first dose but symptoms recur, a second dose may be administered within the following 24 hours, provided that the interval between two doses is at least 2 hours, and the total dose within any 24-hour period does not exceed 300 mg.

If the prescribed dose of sumatriptan proves ineffective, another dose should not be administered during the same attack. Sumatriptan may be used during subsequent attacks.

Sumatriptan is recommended as monotherapy for the treatment of migraine attacks; it should not be used concomitantly with other medications for acute migraine treatment.

Tablets should be swallowed whole with water. For patients with swallowing difficulties, the tablet may be dissolved in a small amount of water before administration.

Sumatriptan dissolved in water has a bitter taste.

Elderly Patients (over 65 years of age)

The use of sumatriptan in patients over 65 years of age is not recommended.

Children

The use of Sumafiks tablets in children and adolescents is not recommended.

Overdose

In case of overdose, the patient should be observed for at least 10 hours, and standard supportive measures should be applied as needed.

The effect of hemodialysis or peritoneal dialysis on plasma concentrations of sumatriptan has not been established.

Adverse Reactions

Adverse effects are classified by frequency of occurrence into the following categories: very common (>1/10), common (>1/100, <1/10), uncommon (>1/1000, <1/100), rare (>1/10,000, <1/1000), very rare (<1/10,000), and frequency not known (cannot be estimated from available data).

Central Nervous System

Common: dizziness, somnolence, sensory disturbances including paraesthesia and hypaesthesia.

Frequency not known: seizures, although some of these cases occurred in patients with a history of seizures or concomitant disorders predisposing to seizures; there have also been reports of seizures developing in patients without any apparent predisposing factors. Tremor, dystonia, nystagmus, scotoma.

Cardiovascular System

Common: transient increase in blood pressure occurring soon after administration, flushing.

Frequency not known: bradycardia, tachycardia, palpitations, arrhythmias, transient ischemic changes on ECG, coronary artery spasm, angina pectoris, myocardial infarction, arterial hypotension, Raynaud's phenomenon.

Respiratory, Thoracic and Mediastinal Disorders

Common: dyspnoea.

Gastrointestinal System

Common: nausea and vomiting occurred in some patients, but it is unknown whether these symptoms are related to sumatriptan or to the underlying condition.

Frequency not known: ischemic colitis, diarrhoea, dysphagia.

Musculoskeletal and Connective Tissue Disorders

Common: sensations of heaviness (these reactions are usually transient, may be intense, and may affect any part of the body, including the chest and throat); myalgia.

Frequency not known: neck stiffness, arthralgia.

General Disorders

Common: pain, sensations of warmth or cold, tightness or pressure (these reactions are usually transient, may be intense, and may affect any part of the body, including the chest and throat); feeling of weakness, increased fatigue (both reactions are mainly mild or moderate in intensity and transient).

Frequency not known: increased pain following trauma, increased pain during inflammation.

Hepatobiliary System

Very rare: slight changes in liver function tests have occasionally been observed.

Immune System

Frequency not known: hypersensitivity reactions ranging from skin hypersensitivity to anaphylaxis.

Eye Disorders

Frequency not known: flickering, diplopia, decreased visual acuity, vision loss, including reports of long-term disturbances; however, visual disturbances may also occur during a migraine attack itself.

Psychiatric Disorders

Frequency not known: anxiety.

Skin and Subcutaneous Tissue

Frequency not known: hyperhidrosis.

Reproductive System and Breast

Rare: breast pain.

Reporting of Suspected Adverse Reactions

Reporting suspected adverse reactions after marketing authorization is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals and patients, as well as their legal representatives, are encouraged to report any suspected adverse reactions and lack of efficacy via the automated pharmacovigilance information system at the following link: https://aisf.dec.gov.ua.

Shelf Life

4 years.

Storage Conditions

Store at temperatures not exceeding 30 °C in the original packaging. Keep out of the reach and sight of children.

Packaging

4 tablets in a blister pack; 5 blisters in a cardboard box with the package leaflet.

Prescription Status

Prescription only.

Manufacturer

Aurobindo Pharma Limited - Unit III / Aurobindo Pharma Limited - Unit III.

Manufacturer's Address and Place of Business

Survey No. 313, 314 - Block I, II, III, IV, Bachupally, Bachupally Mandal, Medchal-Malkajgiri District, Telangana State, 500090, India / Survey no.: 313, 314 - Block I, II, III, IV, Bachupally, Bachupally Mandal, Medchal-Malkajgiri District, Telangana State, 500090, India.