Instructions for Zolmigren film-coated tablets 2.5 mg No. 2
Composition
active ingredient: zolmitriptan;
1 tablet contains zolmitriptan in terms of 100% substance 2.5 mg;
excipients: lactose monohydrate, microcrystalline cellulose 102, sodium starch glycolate (type A), magnesium stearate;
shell composition: Sepifilm 752 Blanc (hydroxypropylmethylcellulose, microcrystalline cellulose, polyethylene glycol (macrogol 40), titanium dioxide (E 171)), iron oxide yellow (E 172).
Dosage form
Film-coated tablets.
Main physicochemical properties: round tablets with a biconvex surface, film-coated, pale brown-yellow in color.
Pharmacotherapeutic group
Drugs used in migraine. Selective serotonin 5HT1 receptor agonists. Zolmitriptan. ATC code N02C C03.
Pharmacological properties
Pharmacodynamics.
Zolmitriptan is a selective agonist of recombinant 5-HT1B/1D serotonin receptors of human vessels. It has moderate affinity for serotonin 5-HT1A receptors, has no significant affinity or pharmacological activity for 5HT2-, 5HT3-, 5HT4-serotonin receptors, a1-, a2-, b1-adrenergic receptors, H1-, H2-histamine receptors, M-choline receptors, D1-, D2-dopaminergic receptors. The drug causes vasoconstriction mainly of cranial vessels, blocks the release of neuropeptides, in particular vasoactive intestinal peptide, which is the main effector transmitter of reflex excitation, causing vasodilation, which is the basis of the pathogenesis of migraine. Stops the development of a migraine attack without direct analgesic action. Along with the relief of migraine attacks, it reduces nausea, vomiting (especially in left-sided attacks), photo- and phonophobia. In addition to the peripheral action, it affects the brainstem centers associated with migraine, which explains the persistent repeated effect in the treatment of a series of several migraine attacks in one patient. Highly effective in the complex treatment of status migrainosus (a series of several severe, consecutive migraine attacks lasting 2-5 days). Eliminates migraine associated with menstruation. High doses have a sedative effect and cause drowsiness.
The drug begins to act within 15-20 minutes and reaches a maximum 1 hour after administration. The maximum effect is observed when administered during the development of an attack.
Pharmacokinetics.
After oral administration, it is well absorbed in the digestive tract. The absorption of the drug does not depend on food intake. The average absolute bioavailability is approximately 40%. Binding to plasma proteins is 25%. The time to reach the maximum concentration is 1 hour, the therapeutic concentration in plasma is maintained for the next 4-6 hours. With repeated administration, cumulation of the drug is not observed. It is subject to intensive biotransformation in the liver with the formation of an N-desmethyl derivative, which has 2-6 times greater pharmacological activity than the original compound, and a number of inactive metabolites. It is excreted from the body mainly by the kidneys in the form of metabolites, about 30% - by the intestines in unchanged form. Three main metabolites of zolmitriptan are known: indoleacetic acid (the main metabolite in plasma and urine), N-oxide and N-desmethyl analogues. The N-desmethylated metabolite is active, and the other two metabolites are inactive. The average half-life (T1/2) of zolmitriptan is 2.5-3 hours. In women, the maximum concentration and bioavailability of the drug are higher, and the total clearance is lower than in men. In patients with moderate and severe renal failure, the renal clearance of zolmitriptan and its metabolites is 7-8 times lower than in healthy volunteers, the half-life increases by an hour (up to 3-3.5 hours), while the bioavailability of zolmitriptan and its active metabolite increases by only 16% and 35%. In hepatic failure, the metabolism of zolmitriptan decreases in proportion to its degree.
Indication
Relief of migraine attacks with and without aura.
Contraindication
Increased individual sensitivity to the components of the drug.
Moderate or severe arterial hypertension, as well as mild uncontrolled hypertension. Ischemic heart disease or similar symptoms, including a history of myocardial infarction. Angiospastic angina (Prinzmetal's angina). Cerebrovascular disorders and transient ischemic attack (TIA) in history. Creatinine clearance below 15 ml/min. Simultaneous use of ergotamine, ergotamine derivatives (including methysergide), sumatriptan, naratriptan or other 5HT1B/1D receptor agonists. Peripheral vascular disease. Do not use in elderly patients (over 65 years of age).
Interaction with other medicinal products and other types of interactions
Based on data obtained with the participation of healthy volunteers, no pharmacokinetic interaction or any interaction of clinical significance has been observed between zolmitriptan and ergotamine. Since the risk of coronary spasm may theoretically increase, it is recommended that Zolmigren® be taken no earlier than 24 hours after taking ergotamine-containing drugs. Conversely, it is recommended that an ergotamine-containing drug be taken no earlier than 6 hours after taking Zolmigren®.
After administration of moclobemide, a specific MAO-A inhibitor, a small increase (26%) in the AUC (area under the curve) of zolmitriptan and a three-fold increase in the AUC of the active metabolite were observed. Therefore, patients taking MAO-A inhibitors are advised to take zolmitriptan at a dose not exceeding 5 mg per day. The drugs should not be used concomitantly while taking moclobemide at doses exceeding 150 mg twice daily.
After administration of cimetidine, a general P450 inhibitor, the half-life of zolmitriptan increased by 44% and the AUC by 48%. In addition, cimetidine doubled the half-life and AUC of the active N-dimethylated metabolite (183C91). It is recommended that patients taking cimetidine should not exceed 5 mg of zolmitriptan per day.
Based on the general interaction profile, the possibility of interactions with specific CYP 1A2 inhibitors cannot be excluded. Therefore, when using similar compounds such as fluvoxamine and quinolones (e.g. ciprofloxacin), a dose reduction is also recommended.
From a pharmacokinetic perspective, selegiline (MAO-B inhibitor) and fluoxetine (SSRI) do not interact with zolmitriptan.
Serotonin syndrome (including altered mental status, autonomic lability, neuromuscular abnormalities) has been reported following concomitant use of triptans and selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs).
Like other 5HT1B/1D receptor agonists, zolmitriptan may slow the absorption of other drugs.
Concomitant use of zolmitriptan with other 5-HT1B/1D agonists within 24 hours and vice versa should be avoided.
Application features
The drug should only be used in cases where the diagnosis of migraine is clearly established. Before starting treatment for headache, other neurological conditions should be excluded in patients who have not previously been diagnosed with migraine and in those who have atypical symptoms with an established diagnosis of migraine.
The drug should not be taken for hemiplegic, basilar, and ophthalmoplegic migraine.
Stroke and other cerebrovascular events may occur in patients taking 5HT1B/1D agonists. It should be noted that patients with migraine are at increased risk of cerebrovascular events.
Zolmigren® should not be prescribed to patients with symptoms of Wolff-Parkinson-White syndrome or arrhythmias associated with other accessory cardiac conduction pathways.
In isolated cases, as with other 5HT1B/1D agonists, coronary spasm, angina pectoris and myocardial infarction may occur. Zolmigren® should not be used in patients with risk factors for coronary heart disease (e.g. smoking, high blood pressure, hyperlipidemia, diabetes mellitus, heredity) without prior examination for cardiovascular disease. Particular attention should be paid to postmenopausal women and men over 40 years of age with such risk factors. However, examination does not allow to identify every patient with cardiac disease, therefore, isolated cases of serious cardiac events have occurred in patients without a history of cardiovascular disorders.
As with other 5HT1B/1D agonists, a feeling of heaviness, pressure or squeezing in the heart area may occur after taking zolmitriptan. If chest pain or symptoms characteristic of ischemic heart disease occur, Zolmigren® should be discontinued and the patient should be examined.
As with other 5HT1B/1D agonists, transient increases in blood pressure may occur in patients with a history of hypertension as well as in patients with normal blood pressure. Very rarely, such increases in blood pressure have been associated with serious clinical manifestations. The recommended dose of Zolmigren® should not be exceeded.
With the simultaneous use of triptans and herbal preparations containing St. John's wort, the frequency of adverse reactions may increase.
Prolonged use of any painkiller for headaches may worsen the pain. In such a situation, treatment should be discontinued and a doctor should be consulted. The diagnosis of overmedication headache should be suspected in patients with frequent or daily headaches that are not relieved by regular medication use.
The drug contains lactose, therefore patients with rare hereditary forms of galactose intolerance, lactase deficiency or glucose-galactose malabsorption syndrome should not use the drug.
Use during pregnancy or breastfeeding
Pregnancy
The safety of zolmitriptan during pregnancy has not been established. Animal studies have not shown a direct teratogenic effect. However, some data from embryotoxicity studies indicate a decrease in embryo viability. Zolmigren® should be used during pregnancy only if the potential therapeutic effect for the mother outweighs the potential risk to the fetus/child.
Breast-feeding
Studies have shown that zolmitriptan passes into the milk of lactating animals. There is no data on the passage of zolmitriptan into human breast milk. Therefore, women should use the drug with caution during breastfeeding. The effect on the infant should be minimized, for which reason the infant should not be breastfed for less than 24 hours after taking the drug.
Ability to influence reaction speed when driving vehicles or other mechanisms
When the drug was administered to a small group of healthy volunteers at a dosage of up to 20 mg, no significant effect on the results of psychomotor tests was noted.
But drivers of vehicles and people whose work requires increased concentration of attention should be warned that in the event of a migraine attack, drowsiness and other symptoms may develop.
Method of administration and doses
The drug is not intended for use in the prevention of migraine attacks. Zolmigren® is recommended to be used as soon as possible after the onset of a migraine attack.
Adults are prescribed 1 tablet (2.5 mg of zolmitriptan). In the absence of effect or in case of recurrence of pain, 1 tablet can be taken again. If necessary, a second dose can be taken no earlier than 2 hours after the first dose.
If the 2.5 mg dose is not effective, the single dose may be increased to 5 mg (maximum single dose). The maximum daily dose is 10 mg.
For patients with mild and moderate hepatic impairment, no dose adjustment is required. For patients with severe hepatic impairment, the daily dose of the drug should not exceed 5 mg.
With creatinine clearance above 15 ml/min, dose adjustment is not required.
Do not use in elderly patients (over 65 years of age).
Children
The drug should not be used to treat children.
Overdose
Sedation was observed in volunteers who took a single dose of zolmitriptan 50 mg.
The elimination half-life of zolmitriptan is 2.5 to 3 hours, therefore the patient should be observed for at least 15 hours after overdose or until symptoms resolve. There is no specific antidote.
In case of severe intoxication, intensive care procedures are recommended, including ensuring a patent airway, adequate oxygenation and ventilation, and monitoring and maintaining cardiovascular function.
It is not known how hemodialysis and peritoneal dialysis affect the serum concentration of zolmitriptan.
Adverse reactions
Side effects are usually mild, usually transient, appear within 4 hours after taking the drug, do not increase in frequency after repeated use, and disappear spontaneously without any additional treatment.
Immune system disorders: Hypersensitivity reactions including urticaria, angioedema and anaphylactic reactions.
Cardiac: palpitations, tachycardia, myocardial infarction, angina pectoris, coronary spasm.
Vascular: slight increase in blood pressure, temporary increase in blood pressure.
From the nervous system: sensory disturbances, dizziness, headache, hyperesthesia, paresthesia, drowsiness, feeling of heat.
Gastrointestinal: abdominal pain, nausea, vomiting, dry mouth, dysphagia, ischemia or infarction (e.g. intestinal ischemia, intestinal infarction, splenic infarction), which may manifest as bloody diarrhea or abdominal pain.
Renal and urinary disorders: polyuria, increased urinary frequency, urgency to urinate.
Musculoskeletal and connective tissue disorders: muscle weakness, muscle pain.
General disorders: asthenia, feeling of heaviness, tightness, pain or pressure in the throat, neck, chest and extremities.
Certain symptoms may be due to the migraine itself.
Expiration date
3 years.
Do not use the drug after the expiration date indicated on the package.
Storage conditions
Store in the original packaging at a temperature not exceeding 25 °C.
Keep out of reach of children.
Packaging
2 or 10 tablets in a blister.
1 blister per pack.
Vacation category
According to the recipe.
Producer
PJSC "Farmak".
Location of the manufacturer and its business address
Ukraine, 04080, Kyiv, Frunze St., 74.
