ZOMIG
Active material: Zolmytryptan
When ATH: N02CC03
CCF: Serotoninovыh agonist 5-HT1-receptors. Protivomigrenoznoy drug with activity
ICD-10 codes (testimony): G43
When CSF: 02.16.05.01
Manufacturer: ASTRAZENECA UK Ltd. (Great Britain)
Pharmaceutical form, composition and packaging
Pills, coated yellow color, round, lenticular, labeled “FROM” on one side.
| 1 tab. | |
| zolmitriptan | 2.5 mg |
Excipients: lactose bezvodnaya, microcrystalline cellulose, sodium starch glycolate, magnesium stearate, Purified water, polyethylene glycol, dye.
3 PC. – blisters (1) – packs cardboard.
Pharmacological action
Selective agonist 5NT1-receptors, protivomigrenoznyj drug.
Has high affinity towards 5NT1(B)/1 d-receptors and moderate affinity to 5HT1A-Receptor. Zolmitriptan shows no significant pharmacological activity towards 5HT2-, 5HT3-, 5HT4-Receptor, a1-, a2-, b1-adrenoceptor, histamine H1-, H2-Receptor, muskarinovym receptors, dopaminovym type receptors 1 and 2. Blood vessels and vessels of the dura mater by afferent fibers are innervated by the trigeminal nerve. In experiments on animals introduction zolmitriptana calls, Thanks to its agonist properties 5NT1(B)/1 d-receptors receptacles, vasoconstriction, associated with suppressed release of peptide, calcitonin gene-related, vazoaguogo intestinalnogo peptide and substance p. Vasoconstriction and inhibition of the release of neuropeptides, expected, are the cause of improving the State in a fit of migraine, in particular, reduce the intensity of pain not later than 1 h after administration of the drug and reduce nausea, vomiting, fotofobia and fonofobii, associated with migraine.
In addition to the perifericheskomu effects of zolmitriptan has effects on brain stem nuclei, involved in the development of migraine attacks, that explains the sustained effect of repeated use in the treatment of several of migraine attacks in one patient. With the onset of a migraine is marked vasodilatation due to the activation of reflex excitation, supported by the ortodromnymi fibres of the trigeminal nerve and cerebral innervaciej parasympathetic through release vazoaguogo intestinalnogo peptide, as the main jeffektornogo neurotransmitter. Zolmitriptan is blocking this reflex arousal and release vazoaguogo intestinalnogo peptide.
Pharmacokinetics
Absorption
After intake of rapidly absorbed and zolmitriptan (at least 64%).
75% Cmax It reached within 1 no; measured concentration in the plasma was retained for the next 4-6 no. Zolmitriptana absorption does not depend on the meals.
When administered a single dose of zolmitriptan and its active metabolite are proportional to dose-dependent AUC and Cmax in the range of doses from 2.5 to 50 mg.
Mean absolute bioavailability – about 40%.
After repeated admission to cumulation of the drug was not observed.
Distribution
Plasma protein binding is low (about 25%).
Metabolism
It is metabolized in the liver to form 3 major metabolites: indole-acetic acid (the main metabolite in plasma and urine), N-oxide and N-desmetil analogues. N-desmetilirovannyj metabolite (183Q91) It is active, but two other metabolita inactive. N-desmetil-metabolite (183Q91) has in 2-6 times greater agonist activity 5HT1D-receptors, than zolmitriptan (According to animal experiments). The concentration of N-desmetil-metabolita (183Q91) plasma is approximately half of the concentration zolmitriptana, and, Consequently, We can assume, that this metabolite contributes to the therapeutic effect of Zomiga.
Deduction
More 60% product, imposed as a single oral dose, excreted in the urine (mostly in the form of indole-acetic metabolite), and about 30% provided with faeces, mainly unchanged.
Average T1/2 zolmitriptana 4.7 no. T1/2 its metabolites is approximately the same, that involves deducing as their education.
Pharmacokinetics in special clinical situations
In patients with moderate and severe renal insufficiency, the severity of kidney klirens zolmitriptana and its metabolites in the 7-8 times lower compared to healthy volunteers, Although the AUC zolmitriptana and active metabolita increases slightly (on 16% and 35% respectively), a T1/2 increases by 1 no (to 3-3.5 no).
When evaluating the pharmacokinetics of zolmitriptana in liver diseases of different severity has been shown to increase AUC by 94% and Cmax on 50% under moderate human liver, and accordingly on the 226% and 47% in case of severe violations of the liver, compared with healthy volunteers. The formation of metabolites (incl. active) decreases in liver diseases. For metabolite 183 with 91 AUC and cmax decreases in the 33% and 44% in the Group of patients with moderate liver and 82% and 90% in patients with severe violations of the liver.
T1/2 zolmitriptana in the Group of patients with moderate liver amounted 7.3 no, in patients with severe violations of the liver – 12 no. T1/2 metabolites, respectively amounted to 5.7 no, 7.5 and h 7.8 no.
There was no pharmacokinetic interaction with ergotaminom.
Pharmacokinetics zolmitriptana in healthy older people is similar to farmakokinetika in healthy young people.
The simultaneous introduction of zolmitriptana with ergotaminom/caffeine was good and did not increase the frequency of adverse reactions or changes in HELL than with the introduction of only zolmitriptana.
Selegiline («MAO inhibitor type in) and Fluoxetine (selective serotonin reuptake inhibitor) have no influence on the pharmacokinetic parameters of zolmitriptana.
Testimony
-mild asthma migraine with aura or no aura.
Dosage regimen
The recommended dose for edema attack of migraine – 2.5 mg.
If symptoms persist or arise during 24 no, You may want to retry reception dose Zomiga. While repeated dose should not be taken during 2 hours after the first dose. If after applying the Zomiga dose 2.5 mg therapeutic effect is not achieved, for short follow-up of migraine attacks, you can use the drug in a dose 5 mg.
Clinically meaningful effect manifests itself within 1 h after administration Zomiga.
The drug does not depend on, After some time after the attack was adopted by pill, However, it is recommended to take Zomig as early as possible since the beginning of migrenoznoj headache.
If you experience repeated migraine attacks a total dose of Zomig, adopted during 24 no, should not exceed 10 mg.
Patients with mild to moderate hepatic impairment dose adjustment is required, at severe hepatic dysfunction recommended maximum dose, adopted during 24 no, is 5 mg.
Patients with impaired renal function It does not require correction mode Zomig.
Side effect
In describing the side effects, the following criteria frequency of occurrence: often – ≥1%, but <10%; rarely – ≥0.01%, but <0.1%; rarely – <0.01%.
From the central and peripheral nervous system: often – sensory disturbances, asthenia, dizziness, a feeling of heaviness and stiffness in the limbs, narrowing glotke, neck, and in the thoracic region (not accompanied by ischemic ECG changes), paresthesia, drowsiness, feeling the heat; rarely – headache.
From the digestive system: often – nausea, dry mouth; rarely – abdominal pain, hemorrhagic diarrhea, ishemicheskiy colitis, infarction of spleen, ischemia or infarction of the bowel.
On the part of the musculoskeletal system: often – myalgia, muscular weakness.
Cardio-vascular system: rarely – tachycardia, heartbeat; rarely – angina, coronary vasospasm, myocardial infarction, Transient hypertension (very rarely accompanied by clinically significant symptoms).
From the urinary system: rarely – polyuria, frequent urination.
Allergic reactions: rarely – anaphylactic reactions, angioedema, hives.
Zomig, usually, well tolerated. Adverse reactions expressed easy or moderately, are transient in nature and resolved spontaneously without treatment.
Possible adverse reactions tend to occur during 4 h after administration of the drug and not increased with taking repeated doses.
Contraindications
- Uncontrolled hypertension;
- CHD;
- Angiospastic angina (Prinzmetal angina);
is a cerebrovascular accident or transient ischemic attack in history;
-combined use with ergotaminom or its derivatives or other agonists 5NT1(B)/1 d-serotonin receptors;
WPW syndrome or arrhythmias, associated with other additional ways of spending pulse;
- Hypersensitivity to the drug.
FROM caution prescribers elderly patients (safety and efficacy of Zomiga in persons older than 65 years have not been studied).
Pregnancy and lactation
Clinical trials of drugs in pregnancy did not take place. Use Zomiga when pregnancy is possible only in cases, When the intended benefits to the mother outweighs the potential risk to the fetus.
IN experimental studies on laboratory animals teratogenic action of zolmitriptana not detected.
The caution should decide on the possibility of appointing Zomiga during lactation (breast-feeding).
IN experimental studies found, What is the lactating milk zolmitriptan animals. Zolmitriptana allocation data with breast milk people have no.
Cautions
Zomig is not intended for the prevention of migraines.
Zomig has a pronounced effect in migraine with aura and migraine without aura and, if, associated with menstruation. The efficacy is not affected by age and gender of the patient, duration of attack, the presence of nausea before taking the medication and the use of conventional drugs for prophylaxis of migraine attacks.
The drug should be used only when the diagnosis. Before using the drug should exclude other possible serious neurological condition.
There are currently no data on the use of Zomiga in gemiplegicheskoj or Basilar migraine.
In patients with migraine may be increased risk of cerebral circulation. Patients, host agonists 5NT1(B)/1 d-serotonin receptors, There were hemorrhagic stroke, subarahnoidalnyj stroke, ischemic stroke and other cerebrovascular accident.
Very rarely while using this class of drugs (agonists 5NT1(B)/1 d-serotonin receptors) There have been spasms of the coronary vessels, Angina Pectoris or myocardial infarction. Patients with high risk of disease before applying the product, it is recommended to conduct a survey on the State of the cardiovascular system. In very rare cases of serious cardiovascular complications may develop in patients, no indication of cardiovascular diseases in history.
When applying Zomiga (as with other serotonin agonists 5NT1(B)/1 d-receptors) reported an abnormal feeling in the heart. If you experience chest pains or symptoms of ISCHEMIC HEART DISEASE should stop taking zolmitriptana to a proper medical examination.
Zomig might cause slight tranzithornoe AD (as with other serotonin agonists 5NT1(B)/1 d-receptors) regardless of the presence of hypertension in history; very rarely this ad was clinically pronounced.
When applying Zomiga (as with other serotonin agonists 5NT1(B)/1 d-receptors) There were rarely anaphylacticskie anaphylactoidnye reaction/.
Excessive use of protivomigrenoznyh drugs can lead to an increase in the frequency of headaches, that potentially require treatment.
Use in Pediatrics
Safety and efficacy of Zomiga u children and adolescents under the age of 18 years not installed.
Effects on ability to drive vehicles and management mechanisms
There was no significant deterioration in the performance of psychomotor tests when taken in the dose to Zomiga 20 mg. Unlikely, that use of the drug will lead to deterioration of the patient's ability to engage in potentially hazardous activities, but the patient should be warned about the possibility of the development of sleepiness.
Overdose
Symptoms: the one-time admission Zomiga dose 50 mg inside usually celebrated sedation.
Treatment: patient monitoring must continue for at least 15 no (T1/2 zolmitriptana – 2.5-3 no), or until the preserved overdose symptoms. No specific antidote. When expressed intoxication recommended intensive therapy activities, including IVL, as well as monitoring and maintenance functions of the cardiovascular system. Unknown, What effect on the concentration of zolmitriptana in serum have hemodialysis and peritoneal dialysis.
Drug Interactions
No data, confirmatory, that the accompanying preparations for prophylaxis of migraine (beta-blockers, digidroergotamin, pizotifen) has had any effect on the effectiveness or adverse effects Zomiga.
Pharmacokinetic parameters and tolerability of Zomiga did not change the combined application with paracetamol, metoklopramidom and ergotaminom.
Studies in healthy volunteers shown the absence of clinically significant interactions between Zomigom and ergotaminom, However, increasing the risk of coronary vazospazma is theoretically possible. In this connection, we recommend that you follow the interval (minimum 24 no) between the abolition of jergotaminosoderzhashhih drugs and appointment Zomiga. After the cancellation of Zomiga should appoint jergotaminosoderzhashhie drugs not previously, than 6 no.
Concomitant intake of other agonists 5NT1(B)/1 d-serotonin receptors during 12 h after administration Zomiga should be deleted.
After the introduction of moclobemide (inhibitor of Mao type a) noted a slight increase in (on 26%) AUC zolmitriptana and AUC threefold increase its active metabolite. Therefore, the maximum recommended dose of Zomiga, adopted during 24 no, for patients, at the same time receiving MAO inhibitors of type a, should not exceed 5 mg.
After taking cimetidine (inhibitor of the enzyme cytochrome p 450) There was an increase in T1/2 zolmitriptana on 44% and increase AUC by 48%. T1/2 and AUC of the active demetilirovannogo metabolita N grew twice, for patients, receiving cimetidine, the recommended maximum dose of Zomig, adopted during 24 no, is 5 mg.
Based on the public profile of interaction zolmitriptana, You cannot exclude the possibility of its interaction with izofermenta inhibitors of CYP1A2. Hence, in a joint application of drugs of this type (fluvoxamine and antibiotics hinolonovogo series) It is recommended that you reduce the overall dose Zomiga, adopted during the 24 no, to 5 mg.
After the introduction of rifampicin were reported clinically significant changes in pharmacokinetics zolmitriptana or its active metabolites.
When there is the opportunity to interact with St. John's wort preparations (Hypericum perforatum), that can increase the risk of adverse effects (how and when applied to other agonists 5NT1(B)/1 d-serotonin receptors).
Conditions of supply of pharmacies
The drug is released under the prescription.
Conditions and terms
List B. The drug should be stored out of reach of children at or below 30 ° C. Do not use beyond the expiration date, stated on the packaging or blister. Shelf life – 2 year.
