Migrepam® (Mygrepam®)

Composition Pharmacodynamics Indications Carefully Contraindications Dosing and Administration Side effects Form release / dosage
Read on
Active substanceZolmitriptanZolmitriptan
Similar drugsTo uncover
  • Zomig®
    pills inwards 
    AstraZeneca UK Ltd     United Kingdom
  • Zomig® Rapimlt
    pills inwards 
    AstraZeneca UK Ltd     United Kingdom
  • Migrepam®
    pills inwards 
    OBOLENSKOE PHARMACEUTICAL ENTERPRISE, CJSC     Russia
    • Dosage form: & nbsptfilm-covered laths
    Composition:

    1 tablet contains:

    Active substance: zolmitriptan 2.5 mg;

    Excipients: lactose anhydrous 98.0 mg, microcrystalline cellulose 15.0 mg, carboxymethyl starch sodium (sodium starch glycolate) 3.0 mg, magnesium stearate 1.5 mg;

    Excipients for the shell: hypromellose (hydroxypropylmethylcellulose 2.4 mg, macrogol 6000 (polyethylene glycol 6000) 0.55 mg, titanium dioxide 0.6 mg, talc 0.39 mg, iron oxide yellow 0.06 mg.

    Description:

    Round, biconvex tablets, covered with a film coating of yellow color. On the cross section, the nucleus is white or almost white in color.

    Pharmacotherapeutic group:Anti-migraine means
    ATX: & nbsp

    N.02.C.C.03   Zolmitriptan

    Pharmacodynamics:

    Zolmitriptan is a selective agonist of serotonin 5HT1B/1D-receptors, the stimulation of which leads to vasoconstriction. Has a high affinity for recombinant serotonin 5HT1B/1D-receptor and moderate affinity for serotonin 5HT1Areceptors. Zolmitriptan has no affinity and does not show significant pharmacological activity with respect to serotonin 5HT2, 5HT3, 5NT4, adrenergic, histamine, muscarinic and dopaminergic receptors.

    The introduction of zolmitriptan to laboratory animals led to vasoconstriction in the basin of the carotid artery. In addition, the results of studies in laboratory animals indicate that zolmitriptan blocks the central and peripheral activity of the trigeminal nerve by inhibiting the release of the peptide associated with the calcitonin gene, the vasoactive intestinal peptide and the P. substance

    In clinical studies, the effect of zolmitriptan on headache and other symptoms of migraine (such as nausea, photophobia, phonophobia) was noted after 1 hour and increased in the period from 2 to 4 hours after taking the drug.

    Zolmitriptan is equally effective for migraine with aura, migraine without an aura and migraine associated with menstruation. Reception zolmitriptana during aura did not prevent migraine headache, so the drug should be taken after the onset of a pain attack.

    Pharmacokinetics:

    After oral administration zolmitriptan quickly and fully absorbed (minimum 64%). Absorption of zolmitriptan does not depend on food intake. The average absolute bioavailability is approximately 40%. The average volume of distribution is 7.0 l / kg. The association with plasma proteins is low (approximately 25%). The active metabolite of zolmitriptan (N-dezmethylmetabolite) is also a serotonin 5HT agonist1B/1D - receptors, 2-6 times more powerful than zolmitriptan. When receiving a healthy volunteer single dose in the range of 2.5 to 50 mg zolmitriptan and its active metabolite have a dose-dependent area under the concentration-time curve (AUC) and the maximum concentration in the blood plasma (CmOh). FROMmOh is achieved within 1.5 hours (75% CmOh - within 1 hour) and is maintained for the next 4-6 hours. When several doses were taken, cumulation of the drug was not observed. Within 4 hours after taking the drug inside during a migraine attack, the concentration of zolmitriptan and its metabolites in the blood plasma was lower than in the case of taking the drug during the interictal period. This is probably due to a decrease in the absorption of zolmitriptan. associated with a slowdown in the emptying of the stomach during a migraine attack.

    Zolmitriptan is eliminated mainly by hepatic biotransformation with the subsequent excretion of metabolites in the urine. There are three main metabolites: indoleacetic acid (the main metabolite found in blood plasma and urine), N- oxide and N-des methyl derivatives. Na desmethylated metabolite is active, and the other two metabolites do not exhibit pharmacological activity. Concentration N-desmethyl metabolite in plasma is about 2 times less than the concentration of zolmitriptan. Therefore, it can be assumed that this metabolite contributes to the therapeutic effect of the drug Migrepam. More than 60% of zolmitriptan administered as a single oral dose is excreted in the urine (mainly in the form of an indole acetic metabolite) and about 30% is excreted through the intestine, mostly unchanged. The average total plasma clearance of zolmitriptan is 31.5 ml / min / kg, one-sixth of which is renal clearance. Kidney clearance is higher than the value of glomerular filtration, which implies the presence of tubular secretion.

    The mean half-life of zolmitriptan and N-decomethylated metabolite is 4.7 hours and 5.7 hours in healthy volunteers, 7.3 hours and 7.5 hours in patients with moderate impairment of liver function and 12 hours and 7.8 hours in patients with severe impaired liver function, respectively .

    The renal clearance of zolmitriptan and its metabolites is 7-8 times lower in patients with moderate and severe renal failure compared to healthy individuals, although AUC zolmitriptan and active metabolite increases insignificantly (by 16% and 35%, respectively) with an increase in the half-life for 1 hour (up to 3-3.5 hours). The values ​​of these pharmacokinetic parameters did not go beyond the values ​​noted in healthy volunteers.

    In patients with impaired hepatic function, the metabolism of zolmitriptan was slowed, proportional to the severity of the liver function disorder. In patients with a marked impairment of liver function compared to healthy volunteers, an increase AUC by 226%, CmOh - by 47%, half-life - up to 12 hours. At the same time, there was a decrease in the concentration of zolmitriptan metabolites, including the active metabolite.

    Pharmacokinetic parameters in healthy elderly people are similar to those of young healthy volunteers.

    Indications:Coping migraine attacks with aura and without aura.
    Contraindications:

    Hypersensitivity to zolmitriptan and other components that make up the drug.

    Age to 18 years.

    Elderly - over 65 years of age (efficacy and safety of use not studied).

    Pregnancy period (safety of use not studied).

    Hemiplegic, basilar and ophthalmoplegic migraine.

    Uncontrolled hypertension.

    Cardiac ischemia.

    Coronary vasospasm / angina of Prinzmetal.

    Diseases of peripheral arteries.

    Violation of the cerebral circulation (including stroke or transient ischemic attack) in the anamnesis.

    Wolff-Parkinson-White syndrome or arrhythmias associated with other additional ways of impulse conduction.

    Renal failure of severe severity (creatinine clearance less than 15 ml / min).

    Simultaneous use with other agonists of serotonin 5HT1B/1D receptors (for example, sumatriptan, naratriptanom), ergotamine or its derivatives (including methezegidom), and also within 24 hours after their cancellation.

    Simultaneous use with MAO-A inhibitors and within 14 days after their cancellation.

    Lactose intolerance, lactase deficiency, glucose-galactose malabsorption (lactose is included in the formulation).

    Carefully:Severe liver dysfunction.
    Pregnancy and lactation:

    Pregnancy

    The safety of zolmitriptan during pregnancy has not been studied. The results of animal studies did not reveal direct teratogenic effects. However, some data from embryotoxicity studies suggest a possible decrease in the viability of embryos. The use of the drug is contraindicated during pregnancy.

    Breastfeeding period

    Zolmitriptan penetrates the milk of lactating animals. It is not known whether the zolmitriptan in the breast milk of women during breastfeeding. Therefore, it is necessary to be cautious about the appointment of the drug to women during breastfeeding. Termination of breastfeeding for 24 hours to minimize the impact of zolmitriptan on an infant.

    Dosing and Administration:

    Tablets are taken internally with water.

    The recommended dose of the drug to relieve a migraine attack is 2.5 mg (1 tablet).It is recommended to take the drug as soon as possible after the onset of the headache, but the drug is also effective when taken at a later date after the onset of the attack. If migraine symptoms occur again within 24 hours, you can take a second dose of Migrepam®. Do not take a second dose earlier than 2 hours after taking the first dose. If there is no clinical effect after taking the first dose, the benefits of re-taking the drug during the same attack are unlikely.

    If the patient has not achieved a therapeutic effect after taking a 2.5 mg dose, Migrepam® 5 mg (2 tablets) can be used to relieve subsequent migraine attacks.

    Do not take more than 2 doses of Migrepam® per day. The total dose of zolmitriptan taken within 24 hours should not exceed 10 mg (4 tablets).

    Migrepam® is not indicated for the prevention of migraine.

    Use in special patient groups

    Children and adolescence

    The efficacy and safety of zolmitriptan in children under 12 years of age has not been studied. The effectiveness of zolmitriptan in a placebo-controlled clinical trial in patients aged 12 to 17 years is not established. The use of Migrepam® in children and adolescents is not recommended.

    Elderly age

    The efficacy and safety of zolmitriptan in patients older than 65 years is not established. Therefore, the use of Migrepam® in elderly patients is not recommended.

    Impaired liver function

    Correction of the dose for mild and moderate liver dysfunction is not required. For patients with severe impairment of liver function, the total dose of zolmitriptan taken within 24 hours should not exceed 5 mg.

    Renal insufficiency

    Correction of the dose is not required if the creatinine clearance is above 15 ml / min. The drug is contraindicated in renal failure of severe severity (creatinine clearance less than 15 ml / min).

    Interaction with other drugs requiring dose adjustment

    For patients receiving cimetidine or selective inhibitors of the isoenzyme CYP1A2 (e.g., fluvoxamine, ciprofloxacin and other quinolones), the total dose of zolmitriptan taken within 24 hours should not exceed 5 mg.

    Side effects:

    Unwanted reactions with zolmitriptan usually occur within 4 hours after taking the drug, are transient in nature and resolved spontaneously without treatment.The frequency of unwanted reactions does not increase with the use of repeated doses.

    The incidence of unwanted reactions is presented according to the WHO classification: very often (≥1 / 10 cases), often (≥1 / 100 and <1/10 cases) infrequently (≥1 / 1000 and <1/100 cases), rarely (≥ 1/10000 and <1/1000 cases) and very rarely (<1/10000 cases).

    From the central nervous system: often - a violation of sensitivity, dizziness, hyperesthesia, paresthesia, drowsiness, a feeling of "heat" or "cold", vertigo.

    From the side of the cardiovascular system: often - a feeling of palpitations; infrequently - tachycardia, a slight increase in blood pressure, transient increase in blood pressure; very rarely - myocardial infarction, angina pectoris, coronary angiospasm.

    From the gastrointestinal tract: often - abdominal pain, nausea, vomiting, dry mouth, dyspepsia, dysphagia; very rarely - ischemia or infarction (for example, ischemia or infarction of the gut, spleen infarction), the symptoms of which can be diarrhea with an admixture of blood and abdominal pain.

    From the musculoskeletal system: often - muscle weakness, myalgia.

    From the urinary system: infrequently - polyuria, frequent urination; very rarely - mandatory urge to urinate.

    From the immune system: rarely - hypersensitivity reactions, including, hives, angioedema and anaphylactic reactions.

    General disorders: often - asthenia, inertia, a feeling of restraint of breathing, pain or a feeling of restraint in the pharynx, neck, chest or extremities, increased sweating.

    Some of these symptoms may be migraine symptoms.

    If any of the unwanted reactions listed in the manual is aggravated, or if you notice other undesirable reactions not listed in the instructions, tell your doctor.

    Overdose:

    Symptoms

    With a single administration of zolmitriptan in a dose of 50 mg by healthy volunteers, a sedative effect was usually noted. The half-life of zolmitriptan is 2.5-3 hours, therefore, in case of an overdose, the patient should be monitored for at least 15 hours or until there are symptoms of an overdose.

    Treatment

    There is no specific antidote for zolmitriptan. In case of severe intoxication, intensive care measures are recommended, including restoring and maintaining airway patency, ensuring adequate oxygenation and ventilation of the lungs, as well as monitoring and supporting the function of the cardiovascular system.

    The effect of hemodialysis and peritoneal dialysis on the concentration of zolmitriptan in serum is not established.

    Interaction:

    In studies on the interaction of zolmitriptan with caffeine, ergotamine, dihydroergotamine, paracetamol, metoclopramide, pisotifen, fluoxetine, rifampicin, and propranolol, no clinically significant changes in the pharmacokinetic parameters of zolmitriptan and its active metabolite have been identified.

    The results of studies involving healthy volunteers indicate that there is no pharmacokinetic and clinically significant interaction between zolmitriptan and ergotamine. However, due to the theoretical risk of coronary angiospasm, the simultaneous use of these drugs is contraindicated. It is recommended that zolmitriptan not earlier than 24 hours after taking medications ergotamine or its derivatives.

    After using moclobemide (MAO-A inhibitor), there was a slight increase (by 26%) AUC zolmitriptan and a threefold increase AUC its active metabolite.

    After taking cimetidine, a cytochrome P inhibitor450, there was an increase in the half-life of zolmitriptan by 44% and an increase AUC on 48%. Half-life and AUC active N-decomethylated metabolite doubled. Therefore, for patients receiving cimetidine, the total dose of zolmitriptan taken within 24 hours should not exceed 5 mg. Based on the general profile of zolmitriptan interaction, one can not exclude the possibility of its interaction with isoenzyme inhibitors CYP1A2 cytochrome P450. Therefore, for patients taking selective inhibitors of isoenzyme CYP1A2 (e.g., fluvoxamine, ciprofloxacin Other quinolones), the total dose of zolmitriptan adopted for one day should not exceed 5 mg.

    Pharmacokinetic zolmitriptan interaction with selegiline (MAO-B inhibitor) and fluoxetine (selective serotonin reuptake inhibitor (SSRI) was not confirmed. However, while the use of triptans and SSRIs or SIOZSiN (selective serotonin reuptake inhibitors and noradrenaline) cases of serotonin syndrome have been described (see section "Special instructions.") Like other serotonin 5 agonists HT1B/1D receptors, zolmitriptan can slow the absorption of other drugs.

    Side effects may be more frequent with the simultaneous administration of tryptanes and herbal preparations containing St. John's wort (Hypericum perforatum).
    Special instructions:

    The drug Migrepam ® can be used only in cases of clearly diagnosed migraine. Prior to the appointment of zolmitriptan, as well as other means for arresting migraine, it is necessary to exclude other possible serious neurological diseases in patients with a previously unidentified migraine, as well as in patients with a diagnosed migraine in the presence of atypical symptoms.

    Zolmitriptan is not indicated for the treatment of hemiplegic, basilar and ophthalmoplegic migraine.

    In patients taking serotonin 5HT agonists1B/1D -receptors, there were violations of cerebral circulation, including strokes. Patients with migraine may be at risk of developing certain disorders of the cerebral circulation.

    Do not use zolmitriptan in patients with Wolff-Parkinson-White syndrome or arrhythmias associated with other additional pathways of impulse conduction.

    Very rarely when this class of drugs is used (serotonin 5HT agonists1B/1D -receptors), coronary angiospasm, angina pectoris, and myocardial infarction.

    Before prescribing zolmitriptan, patients with risk factors for developing coronary heart disease (eg, smoking, hypertension, hyperlipidemia, diabetes mellitus, a family history of coronary artery disease associated with coronary artery disease) are recommended to conduct a cardiovascular examination, it is necessary to control blood pressure and an electrocardiogram. Particular attention should be given to postmenopausal women and men over 40 years of age if these risk factors are present. Nevertheless, not all patients can detect cardiovascular diseases during the examination, and in very rare cases serious cardiovascular complications can develop in patients who had no history of cardiovascular disease.

    As in the case of the use of other agonists of serotonin 5HT1B/1D -receptors, when zolmitriptan was used, it was reported on the sensations of gravity, pressure, or constriction in the region of the heart. If there is pain in the chest area or symptoms of coronary heart disease, stop taking zolmitriptan untilconducting an appropriate medical examination.

    As in the case of other serotonin 5HT agonists1B/1D -receptors, transient increase in blood pressure was noted in patients regardless of the history of arterial hypertension (very rarely this increase in blood pressure was clinically pronounced). Do not exceed the recommended dose of zolmitriptan.

    Side effects can be more frequent with the simultaneous administration of tryptanes and herbal preparations containing St. John's Wort (perforated)Hypericum perforatum). There was a development of serotonin syndrome with the simultaneous use of triptans and SSRIs or SIOZsin. Serotonin syndrome may include the following signs and symptoms: changes in mental state, vegetative and neuromuscular symptoms. It is recommended that patients be carefully monitored while prescribing Migrepam® and SSRIs or SIOZsin, especially during the initiation of therapy, increasing the dose, or adding another drug that affects serotonin metabolism (see "Interactions with Other Drugs").

    Excessive use of antimigraine drugs can lead to an increased incidence of headache, which potentially requires withdrawal of treatment. If a patient has frequent or daily headaches, despite regular use of drugs to treat this condition, one should remember the possibility of developing a headache with excessive use of drugs for headache therapy.

    Effect on the ability to drive transp. cf. and fur:

    There was no significant deterioration in the performance of psychomotor tests when taking zolmitriptan in a dose of up to 20 mg. Patients whose activity requires a high rate of psychomotor reactions (for example, driving a vehicle or mechanisms) are advised to exercise caution because of the possible development of drowsiness and other migraine symptoms.

    Form release / dosage:

    Tablets, film-coated, 2.5 mg.

    Packaging:

    By 2. 3, 5, 10 tablets in a contour mesh box made of polyvinylchloride film and aluminum foil printed lacquered.

    For 1, 2 contour squares, together with instructions for use, are placed in a pack of cardboard.

    Storage conditions:

    At a temperature of no higher than 25 ° C.

    Keep out of the reach of children.

    Shelf life:

    3 years.

    Do not use after the expiry date printed on the package.

    Terms of leave from pharmacies:On prescription
    Registration number:LP-003701
    Date of registration:23.06.2016
    Expiration Date:23.06.2021
    The owner of the registration certificate:OBOLENSKOE PHARMACEUTICAL ENTERPRISE, CJSC OBOLENSKOE PHARMACEUTICAL ENTERPRISE, CJSC Russia
    Manufacturer: & nbsp
    Representation: & nbspOBOLENSKOE PHARMACEUTICAL ENTERPRISE, CJSCOBOLENSKOE PHARMACEUTICAL ENTERPRISE, CJSCRussia
    Information update date: & nbsp24.04.2018
    Illustrated instructions
      Instructions
      Up