Composition, form of production and packaging
The tablets covered with a film cover of yellow color, round, biconcave, with engraving "Z" on one side.
1 tab.
zolmitriptan 2.5 mg
Excipients: lactose anhydrous - 100 mg, microcrystalline cellulose - 15 mg, sodium carboxymethyl starch - 3 mg, magnesium stearate - 1.5 mg.
Sheath composition: macrogol 8000 - 200 mcg, dye yellow (OY-22906) 3.1 mg.
The composition of the dye: hypromellose - 1.923 mg, titanium dioxide - 963 Ојg, macrogol 400 - 192 Ојg, ferric oxide yellow oxide (E172) - 22 Ојg.
2 pcs. - blisters (1) - packs of cardboard.
3 pcs. - blisters (1) - packs of cardboard.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2010.
PHARMACHOLOGIC EFFECT
Selective 5HT 1 -receptor agonist, antimigrenous drug.
Has a high affinity for 5HT 1B / 1D- receptors and moderate affinity for 5HT 1A -receptors. Zolmitriptan does not show significant pharmacological activity with respect to 5HT 2 -, 5HT 3 -, 5HT 4 -receptors,? 1 -,? 2 -,? 1- adrenoreceptors, histamine H 1 -, H 2 -receptors, muscarinic receptors, dopamine receptors type 1 and 2. Blood vessels and vessels of the dura mater are innervated by the afferent fibers of the trigeminal nerve. In animal experiments, the administration of zolmitriptan causes, due to its properties of the 5HT1B / 1D receptor agonist, vasoconstriction associated with inhibition of the release of the peptide associated with the calcitonin gene, the vasoactive intestinal peptide and the substance P. Vessel contraction and inhibition of the release of neuropeptides, are the cause of an improvement in the state of migraine attacks, in particular, a decrease in the intensity of pain no later than 1 hour after taking the drug and reducing nausea, vomiting, f oto- phobia and phonophobia associated with migraine.
In addition to peripheral action, zolmitriptan has an effect on the brain stem nuclei involved in the development of migraine attacks, which explains the persistent re-use effect in the treatment of several migraine attacks in one patient. With a migraine attack, vasodilation is noted due to the activation of reflex excitation supported by trigeminal nerve orthodontic fibers and parasympathetic innervation of cerebral vessels through the release of the vasoactive intestinal peptide as the main effector neurotransmitter. Zolmitriptan blocks this reflex excitation and the release of the vasoactive intestinal peptide.
PHARMACOKINETICS
Suction
After ingestion zolmitriptan is quickly and well absorbed (at least 64%).
75% C max is reached within 1 hour; the determined concentration in the plasma persists for the next 4-6 hours. Absorption of zolmitriptan does not depend on the intake of food.
When taking a single dose of zolmitriptan and its active metabolite have a proportionally dose-dependent AUC and C max in the dose range of 2.5 to 50 mg.
The average absolute bioavailability is approximately 40%.
With repeated intake of cumulation of the drug was not observed.
Distribution
Binding to plasma proteins is low (about 25%).
Metabolism
Metabolised in the liver with the formation of 3 major metabolites: indole-acetic acid (the main metabolite in plasma and urine), N-oxide and N-desmethyl analogues.The N-desmethylated metabolite (183C91) is active, and the other two metabolites are inactive. N-desmethyl-metabolite (183C91) has 2-6 times more agonist activity of 5HT 1D- receptors than zolmitriptan (according to animal experiments). The concentration of N-desmethyl metabolite (183C91) in plasma is approximately half the concentration of zolmitriptan, and therefore it can be assumed that this metabolite contributes to the therapeutic effect of Zomig.
Excretion
More than 60% of the drug, administered as a single oral dose, is excreted in the urine (mainly as an indole-acetic metabolite), and about 30% is excreted with feces, mostly unchanged.
The mean T 1/2 of zolmitriptan is 4.7 p. T 1/2 of its metabolites are about the same as that which implies excretion as they are formed.
Pharmacokinetics in special clinical cases
In patients with moderate and severe renal insufficiency, the renal clearance of zolmitriptan and its metabolites is 7-8 times lower in comparison with healthy volunteers, although the ZUC of zolmitriptan and the active metabolite increases slightly (by 16% and 35%, respectively), and T 1 / 2 increases by 1 hour (up to 3-3.5 hours).
In assessing the pharmacokinetics of zolmitriptan in liver diseases of varying severity, AUC increased by 94% and C max by 50% with moderate violations of the liver function, and by 226% and 47%, respectively, with severe violations of the liver function compared to healthy volunteers. The formation of metabolites (including active metabolites) decreases with liver diseases. For the metabolite 183C91, the AUC and C max values ​​are reduced by 33% and 44% in the group of patients with moderate impairment of liver function and by 82% and 90% in patients with severe impairment of liver function.
T 1/2 of zolmitriptan in the group of patients with moderate impairment of liver function was 7.3 h, in patients with severe impairment of liver function - 12 h. T 1/2metabolites accordingly were 5.7 h, 7.5 h and 7.8 h.
There was no pharmacokinetic interaction with ergotamine.
The pharmacokinetics of zolmitriptan in healthy elderly people is similar to the pharmacokinetics in healthy young people.
Simultaneous administration of zolmitriptan with ergotamine / caffeine was tolerated well and did not lead to an increase in the frequency of adverse reactions or changes in blood pressure compared with the administration of zolmitriptan alone.
Selegiline (MAO inhibitor type B) and fluoxetine (selective serotonin reuptake inhibitor) do not affect the pharmacokinetic parameters of zolmitriptan.
INDICATIONS
- arresting migraine attacks with an aura or without an aura.
DOSING MODE
The recommended dose for arresting a migraine attack is 2.5 mg.
If symptoms persist or reappear within 24 hours, a second dose of Zomiga may be required. In this case, the repeated dose should not be taken within 2 hours after the first dose. If after the application of Zomig in a dose of 2.5 mg therapeutic effect is not achieved, to stop the subsequent attacks of migraine, you can use the drug in a dose of 5 mg.
Clinically significant effect is manifested within 1 hour after taking Zomiga.
The effectiveness of the drug does not depend on the time after the onset of the attack, a pill was taken, but it is recommended to take Zomig as soon as possible after the onset of migraine headache.
In the event of repeated attacks of migraine, the total dose of Zomiga taken within 24 hours should not exceed 10 mg.
Patients with mild and moderate impairment of liver function are not required to adjust the dose, with severe violations of liver function, the recommended maximum dose of the drug taken within 24 hours is 5 mg.
Patients with impaired renal function do not need correction of the dosage regimen Zomiga.
SIDE EFFECT
When describing side effects, the following criteria for the frequency of occurrence were used: often -? 1%, but <10%; rarely -? 0.01%, but <0.1%; very rarely - <0.01%.
From the side of the central nervous system and the peripheral nervous system: often - impaired sensitivity, asthenia, dizziness, a feeling of heaviness and stiffness in the extremities, tightness in the throat, neck, and in the thoracic region (not accompanied by ischemic changes in the ECG), paresthesia, drowsiness, sensation of heat;rarely - a headache.
On the part of the digestive system: often - nausea, dry mouth; very rarely - abdominal pain, hemorrhagic diarrhea, ischemic colitis, spleen infarction, ischemia or intestinal infarction.
From the musculoskeletal system: often - myalgia, muscle weakness.
From the cardiovascular system: rarely - tachycardia, palpitations; very rarely - angina pectoris, coronary artery spasm, myocardial infarction, transient arterial hypertension (very rarely accompanied by clinically significant symptoms).
From the urinary system: very rarely - polyuria, frequent urination.
Allergic reactions: rarely - anaphylactic reactions, angioedema, hives.
Zomig, as a rule, well tolerated. Adverse reactions are easily or moderately expressed, transient in nature and resolved spontaneously without treatment.
Possible adverse reactions often occur within 4 hours after taking the drug and do not increase with repeated doses.
CONTRAINDICATIONS
uncontrolled arterial hypertension;
- IHD;
angiospastic angina (Prinzmetal angina);
- disorders of cerebral circulation or transient ischemic attacks in the anamnesis;
- combined use with ergotamine or its derivatives or other 5HT 1B / 1D- 5-serotonin receptor agonists;
- WPW syndrome or arrhythmias associated with other additional pathways of impulse conduction;
- Hypersensitivity to the components of the drug.
With caution appoint the drug to elderly patients (safety and efficacy of Zomiga in persons older than 65 years have not been studied).
PREGNANCY AND LACTATION
Clinical studies of the drug during pregnancy have not been conducted. Application Zomiga in pregnancy is possible only in cases where the intended benefit to the mother exceeds the possible risk to the fetus.
In experimental studies on laboratory animals teratogenic effects of zolmitriptan were not revealed.
With caution should decide the possibility of appointment Zomiga during lactation (breastfeeding).
In experimental studies , it has been established that zolmitriptan is excreted with milk from lactating animals. There are no data on the isolation of zolmitriptan with human milk.
APPLICATION FOR FUNCTIONS OF THE LIVER
Patients with impaired renal function do not need correction of the dosage regimen Zomiga.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
Patients with mild and moderate impairment of liver function are not required to adjust the dose, with severe violations of liver function, the recommended maximum dose of the drug taken within 24 hours is 5 mg.
APPLICATION FOR CHILDREN
Safety and effectiveness of Zomiga in children and adolescents under the age of 18 years have not been established.
APPLICATION IN ELDERLY PATIENTS
With caution appoint the drug to elderly patients.
SPECIAL INSTRUCTIONS
Zomig is not intended to prevent migraine attacks.
Zomig has a pronounced effect on migraine with aura and without aura and migraine associated with menstruation. The effectiveness of the drug does not affect the sex and age of the patient, the duration of the attack, the presence of nausea before taking the drug and the use of conventional drugs to prevent migraine attacks.
The drug should be used only if the diagnosis is established. Before using the drug should exclude other possible serious neurological conditions.
Currently, there is no data on the use of Zomig in hemiplegic or basilar migraine.
In patients with migraine, the risk of developing cerebral circulation disorders may be increased. Hemorrhagic stroke, subarachnoid stroke, ischemic stroke and other disorders of cerebral circulation were observed in patients taking 5HT 1B / 1D -serotonin receptor agonists.
Very rarely, when this class of drugs was used (5HT 1B / 1D -serotonin receptor agonists), coronary spasms, angina pectoris, or myocardial infarction were noted.Patients with a high risk of developing ischemic heart disease before starting the use of the drug is recommended to conduct a survey of the state of the cardiovascular system. In very rare cases, serious cardiovascular complications can develop in patients who have no history of cardiovascular disease.
When using Zomig (as well as other agonists of serotonin 5HT 1B / 1D- receptors), atypical sensations in the heart region were reported. If chest pain or symptoms of IHD occur, stop taking zolmitriptan before performing an appropriate medical examination.
Zomig can cause a slight transient increase in blood pressure (as well as other agonists of serotonin 5HT 1B / 1D- receptors), regardless of the history of arterial hypertension; very rarely this increase in blood pressure was clinically pronounced.
When using Zomig (as well as other agonists of serotonin 5HT 1B / 1D- receptors), anaphylactic / anaphylactoid reactions were rarely noted.
Excessive use of antimigraine drugs may lead to an increased incidence of headache, which potentially requires withdrawal of treatment.
Use in Pediatrics
Safety and effectiveness of Zomiga in children and adolescents under the age of 18 years have not been established.
Impact on the ability to drive vehicles and manage mechanisms
There was no significant deterioration in the performance of psychomotor tests when taking Zomig in a dose of up to 20 mg. It is unlikely that the use of the drug will lead to a deterioration in the patient's ability to engage in potentially hazardous activities, but the patient should be warned about the possibility of developing drowsiness.
OVERDOSE
Symptoms: with a single dose of Zomiga in a dose of 50 mg orally, there was usually a sedative effect.
Treatment: Patients should be monitored for at least 15 hours (T 1/2 Zolmitriptan - 2.5-3 h), or while symptoms of overdose persist. There is no specific antidote. When severe intoxication, intensive care, including IVL, and monitoring and maintaining the function of the cardiovascular system are recommended. It is not known what effect hemodialysis and peritoneal dialysis have on the concentration of zolmitriptan in the serum.
DRUG INTERACTION
There is no evidence that concomitant medication for migraine prevention (beta-blockers, dihydroergotamine, pisotifen) has any effect on the efficacy or undesirable effects of Zomig.
Pharmacokinetic parameters and tolerability of Zomig did not change when combined with paracetamol, metoclopramide and ergotamine.
In the course of studies in healthy volunteers, the absence of clinically significant interaction between Zomig and ergotamine has been shown, but an increased risk of developing coronary vasospasm is theoretically possible. In this regard, it is recommended to observe the interval (minimum 24 hours) between the abolition of ergotamine-containing drugs and the appointment of Zomig. After Zomig's cancellation, ergotamine-containing drugs should be administered no earlier than 6 hours later.
Concomitant administration of other 5HT 1B / 1D -serotonin receptor agonists within 12 hours after taking Zomiga should be excluded.
After the administration of moclobemide (MAO type A inhibitor), there was a slight increase (by 26%) of Zolmitriptan AUC and a threefold increase in the AUC of its active metabolite. Therefore, the maximum recommended dose of Zomiga, taken within 24 hours, for patients receiving simultaneously MAO type A inhibitors should not exceed 5 mg.
After taking cimetidine (inhibitor of cytochrome P450 enzymes), an increase in T 1/2 of zolmitriptan by 44% and an increase in AUC by 48% were noted. T 1/2 and AUC of the active N-demethylated metabolite was doubled, and therefore the recommended maximum dose of Zomig taken within 24 hours for patients taking cimetidine is 5 mg.
Based on the general profile of zolmitriptan interaction, it is impossible to exclude the possibility of its interaction with inhibitors of the isoenzyme CYP1A2.Therefore, when combined with this type of drugs (fluvoxamine and quinolone antibiotics), it is recommended to reduce the total dose of Zomig taken within 24 hours to 5 mg.
After the administration of rifampicin, there were no clinically significant changes in the pharmacokinetics of zolmitriptan or its active metabolites.
When combined, there is the possibility of interaction with Hypericum perforatum (Hypericum perforatum) preparations, which can increase the risk of unwanted effects (as with other 5HT 1B / 1D -serotonin receptor agonists).
TERMS OF RELEASE FROM PHARMACY
The drug is released by prescription.
TERMS AND CONDITIONS OF STORAGE
List B. The drug should be stored out of the reach of children at a temperature below 30 В° C. Do not use after the expiration date indicated on the package or blister.Shelf life - 2 years.
