Zomig® Rapimlt (Zomig Rapimelt)

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Composition Pharmacodynamics Indications Carefully Contraindications Dosing and Administration Side effects Form release / dosage
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Active substanceZolmitriptanZolmitriptan
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  • 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: & nbsppills
    Composition:

    1 tablet contains:

    Active Ingredient: zolmitriptan 2.5 mg.

    Auxiliary Ingredients: orange flavoring SN027512 0.4 mg, aspartame 5.0 mg, silicon dioxide colloid 0.3 mg, crospovidone 10.0 mg, citric acid anhydrous 1.5 mg, magnesium stearate 2.0 mg, mannitol 60.8 mg, sodium Hydrocarbonate 2.5 mg, microcrystalline cellulose 15.0 mg.

    Description:

    Round flat cylindrical tablets of white color with a bevel, with a slight orange odor; on one side of the tablet is Z engraving.

    Pharmacotherapeutic group:Anti-migraine means
    ATX: & nbsp

    N.02.C.C.03   Zolmitriptan

    Pharmacodynamics:

    Zolmitriptan is a selective 5HT agonist1B/1D-receptors, the stimulation of which leads to vasoconstriction. Has a high affinity for recombinant 5HT1B/1D-receptor and moderate affinity for 5HT1Areceptors. Zolmitriptan has no affinity and does not show significant pharmacological activity with respect to 5HT2, 5HT3, 5HT4, 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 head pain, 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-desmethylmetabolite) 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 (Cmax). Cmax is achieved within 1.5 hours (75% Cmax- within 1 hour); the maximum concentration of the drug in the plasma 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 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 due to 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. Three main metabolites have been identified: indoleacetic acid (the main metabolite found in plasma and urine), N-oxide and N-desmethyl derivatives.The N-desmethylated metabolite is active, and the other two metabolites do not exhibit pharmacological activity. The concentration of N-desmethyl metabolite in plasma is about 2 times lower than that of zolmitriptan. Therefore, it can be assumed that this metabolite contributes to the therapeutic effect of Zomig® Rapimelt. More than 60 % zolmitriptan, administered as a single oral dose, is excreted in the urine (mainly as an indole acetate metabolite) and about 30% is excreted with feces, 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 the N-desmethylated metabolite is 4.7 hours and 5.7 hours in healthy volunteers, 7.3 hours and 7.5 hours in patients with moderate hepatic impairment and 12 hours and 7.8 hours in patients with pronounced 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 the AUC of zolmitriptan and the 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 AUC increase of 226 %, Cmax - by 47%, half-life - up to 12 hours. At the same time, there was a decrease in the concentration of metabolites of zolmitriptan, including the active metabolite.

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

    Indications:

    Coping migraine attacks with an aura or without an aura.

    Contraindications:
    • Hypersensitivity to any components of the drug.
    • Children under 18 years old.
    • 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.
    • Severe renal insufficiency (creatinine clearance less than 15 ml / min).
    • Joint application with other agonists of serotonin 5HT1B/1Dreceptors (eg, sumatriptan, naratriptan), ergotamine or its derivatives (including methyl ester), and within 24 hours after their cancellation.
    • Joint application with MAO-A inhibitors and within 14 days after their cancellation. Intolerance to galactose, deficiency of lactase or glucose-galactose malabsorption.
    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.

    Lactation

    Zolmitriptan penetrates the milk of lactating animals. It is not known whether the zolmitriptan in the breast milk of nursing women. Therefore, it is necessary to be cautious about the appointment of Zomig® Rapimelt to women breastfeeding. It is recommended that breastfeeding be stopped for the duration of therapy with Zomig® Rapimelt.

    Termination of breastfeeding for 24 hours to minimize the impact of zolmitriptan on an infant.

    Dosing and Administration:

    The recommended dose of Zomig® Rapimelt to relieve a migraine attack is 2.5 mg. Zomig® Rapimelt is recommended to be taken as soon as possible after the onset of headache, however, the drug is also effective when taken at a later date after the onset of an attack.

    The tablet should be put on the tongue. Within a few seconds, it dissolves on the surface of the tongue, and it can be swallowed with saliva without water. Zomig® Rapimelt can be used to avoid nausea and vomiting accompanying fluid intake during a migraine attack, as well as in situations where it is not possible to take the pill with water.

    Blister with Zomig® Rapimelt tablets should be opened according to the scheme given on the aluminum foil of the blister (do not press the tablet through the foil).

    If migraine symptoms occur again within 24 hours, you can take a second dose of Zomig® Rapimelt. Do not take a second dose earlier than 2 hours after taking the first dose of Zomig® Rapimelt. 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 dose of 2.5 mg / for the removal of subsequent migraine attacks, Zomig® Rapimelt can be used at a dose of 5 mg. Do not take more than 2 doses of Zomig® Rapimelt per day. The total dose of zolmitriptan taken within 24 hours should not exceed 10 mg.

    Zomig® Rapimelt 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. Efficacy of zolmitriptan in a placebo-controlled clinical trial in patients aged 12 to 17 yearsnot installed. The use of Zomig® Rapimelt 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 Zomig® Rapimelt 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, impaired liver function, the total dose of zolmitriptan taken within a day should not exceed 5 mg.

    Renal insufficiency

    Correction of the dose is not required if the creatinine clearance is above 15 ml / min. (see the sections "Contraindications" Pharmacokinetics ").

    Interaction with other drugs requiring dose adjustment

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

    Side effects:

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

    The frequency of adverse reactions is given in the form of the following gradation: very often (≥1 / 10); often (≥1 / 100, <1/10); infrequently (≥1 / 1000, <1/100); rarely (≥1 / 10000, <1/1000); very rarely (<1/10000).

    Frequently ≥1 / 100, <1/10

    From the central nervous system

    sensitivity disorders; dizziness; headache; hyperesthesia; paresthesia; drowsiness; feeling of "warmth" or "cold"; vertigo

    From the side of the cardiovascular system

    heart palpitations

    From the gastrointestinal tract

    abdominal pain; nausea; vomiting; dry mouth; dyspepsia; dysphagia

    From the musculoskeletal system

    muscle weakness; myalgia

    General disorders

    asthenia; inertia; a feeling of restraint, of breathing; pain or feeling restless in the throat, neck, chest or extremities; increased sweating

    Infrequently (≥1 / 1000, <1/100)

    From the cardiovascular system:

    tachycardia; a slight increase in blood pressure; transient increase in blood pressure; arrhythmia*; fainting*

    From the urinary system:

    polyuria, frequent urination

    Rarely (> 1/10000, <1/1000)

    From the immune system

    hypersensitivity reactions, including, hives, angioedema, edema and anaphylactic reactions

    From the side of the cardiovascular system

    bradycardia *, extrasystole *, postural hypotension *, prolongation of QT interval *, thrombophlebitis *

    Very rarely (<1/10000)

    From the side of the cardiovascular system

    myocardial infarction **; angina **; coronary angiospasm **

    From the gastrointestinal tract:

    ischemia or infarction (eg, ischemia, or intestinal infarction, spleen infarction), the symptoms of which may be diarrhea with blood and abdominal pain

    From the urinary system

    compulsive urge to urinate

    * the cause-and-effect relationship with taking the drug is not reliably established

    ** These adverse events and transient myocardial ischemia are also noted in the post-marketing application of the drug. Since messages are received spontaneously from a population of an unknown size, it is impossible to reliably estimate the frequency and cause-and-effect relationship with taking the drug.

    Some of these symptoms may be migraine symptoms.

    Overdose:

    Symptoms

    With a single intake of healthy volunteers zolmitriptan at a dose of 50 mg orally, there was usually a sedative effect. The half-life of zolmitriptan is 2.5 to 3 hours (see section "Pharmacokinetics"), therefore, in case of an overdose, follow-up of the patient should be continued 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 combined 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%) of Zolmitriptan AUC and a three-fold increase in the AUC of its active metabolite. After taking cimetidine, a cytochrome P450 inhibitor, there was an increase in T½ Zolmitriptan by 44% and an increase in AUC by 48%. T½ and AUC of the active N-desmethylated metabolite were 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 the interaction of Zomig® Rapimelt, one can not exclude the possibility of its interaction with inhibitors of the cytochrome P450 isoenzyme CYP1A2. Therefore, for patients taking selective inhibitors of the CYP1A2 isoenzyme (eg, fluvoxamine, ciprofloxacin Other quinolones), the total dose of zolmitriptan adopted for one day should not exceed 5 mg. The pharmacokinetic interaction of zolmitriptan with selegiline (MAO-A inhibitor) and fluoxetine (SSRIs) has not been confirmed. However, with the combined use of tryptanes and SSRIs or SIOZsin, cases of the development of serotonin syndrome have been described (see section "Special instructions").

    Like other 5HT agonists1B/1D-receptors, zolmitriptan can slow the absorption of other drugs.

    Side effects can be more frequent with the joint administration of tryptanes and herbal preparations containing St. John's Wort (Hypericum perforatum).

    Special instructions:

    Zomig® Rapimelt 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, family history of coronary artery disease with respect to coronary artery disease) are recommended to carry out a cardiovascular examination, it is necessary to monitor blood pressure and ECG (see Fig. section "Contraindications"). Particular attention should be given to postmenopausal women and men over 40 years of age if these risk factors are present. However, not all patients in the survey can identify cardiovascular diseases,and in very rare cases, serious cardiovascular complications can develop in patients who have not had an indication of a 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 about sensations of severity, pressure, or constriction in the heart (see "Side Effects" section). If chest pain occurs or symptoms of coronary heart disease, Zolmitriptan should be discontinued before appropriate medical examination.

    As in the case of other serotonin 5HT agonists1B/1D-receptors, transient - increased 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 joint administration of tryptanes and herbal preparations containing St. John's Wort (Hypericum perforatum).There was a development of serotonin syndrome with combined use of tryptanes and selective inhibitorsserotonin reuptake (SSRIs) or serotonin and noradrenaline reuptake inhibitors (SSRIs). 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 with the concomitant use of Zomig® Rapimelt and SSRIs or SIOZsin, especially during the initiation of therapy, increasing the dose, or adding another drug that interferes with the metabolism of serotonin (see "Interaction 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 activities require a high rate of psychomotor reactions (for example, driving or other mechanisms) are advised to be cautious because of the possible development of drowsiness and other migraine symptoms.

    Form release / dosage:

    Tablets 2.5 mg.

    Packaging:2 tablets per blister of aluminum foil and PVC; 1 blister in a cardboard box with instructions for use.
    Storage conditions:

    At temperatures not higher than 30 ° C, in places inaccessible to children.

    Shelf life:

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

    Terms of leave from pharmacies:On prescription
    Registration number:LP-001022
    Date of registration:18.10.2011
    Expiration Date:18.10.2016
    Date of cancellation:2016-03-14
    The owner of the registration certificate:AstraZeneca UK LtdAstraZeneca UK Ltd United Kingdom
    Manufacturer: & nbsp
    Representation: & nbspAstraZeneca Pharmaceuticals Ltd.AstraZeneca Pharmaceuticals Ltd.
    Information update date: & nbsp17.10.2017
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