Zolmigren

Zolmigren is a medication used to treat migraines. It is a selective agonist of specific serotonin 5HT1-endings and contains the component zolmitriptan.

Indications Zolmigrain

It is used to relieve a migraine attack (with or without an aura).

Release form

The substance is released in tablets, packed in blister strips of 2 or 10 pieces. There is 1 packaging strip in a box.

Pharmacodynamics

Zolmitriptan is a selective agonist of specific serotonin 5-HT1B/1D-terminals of recombinant type inside human vessels. The drug shows moderate affinity for the above-mentioned terminals, without significant affinity or therapeutic activity regarding 5HT2-, and also 5HT3- and 5HT4-terminals of serotonin, α1-, α2-, β1-adrenergic terminals, and also H1- and H2-terminals of histamine, M-choline terminals and D1- and D2-terminals of dopamine.

The drug has a vasoconstrictor effect on cranial vessels, and at the same time blocks the processes of neuropeptide release (including vasoactive intestinal peptide, which is the main effector modulator of reflex excitation; it causes the process of vasodilation, which is the main one in migraine pathogenesis). It also stops the process of migraine attack occurrence, without having a direct analgesic effect.

In combination with the relief of emerging migraine attacks, the drug reduces the severity of nausea with vomiting (especially when left-sided attacks develop), as well as phono- and photophobia. In addition to the peripheral effect, it affects the brain stem centers associated with migraine attacks, which explains the repeated result during the treatment of a series consisting of several separate attacks in a row in one patient.

Zolmigren demonstrates high efficiency in combination with other drugs for the treatment of migraine status (a series of several severe, successive migraine attacks lasting for 2-5 days). It also relieves migraines that occur during menstruation. Large doses of the drug have a sedative effect and lead to the development of a feeling of drowsiness.

The medicinal effect develops after 15-20 minutes, reaching its maximum after 60 minutes of use. The maximum therapeutic effect is observed when using the drug during the development of a migraine attack.

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Pharmacokinetics

When taken orally, the drug is well absorbed, penetrating the gastrointestinal tract. The degree of its absorption is not tied to food intake. The average absolute bioavailability is approximately 40%. Synthesis with blood proteins inside the plasma is 25%. It takes 60 minutes to reach the Cmax level of the drug; therapeutic indicators of the drug inside the plasma are maintained for the next 4-6 hours. After repeated use, the therapeutic component does not accumulate.

The drug undergoes intensive hepatic biotransformation, during which an N-desmethyl derivative is formed, which has a stronger (2-6 times) therapeutic effect than the original element and some inactive metabolic products.

Excretion of the majority of the drug occurs through the kidneys - in the form of metabolic products, and approximately another 30% is excreted unchanged through the intestines.

Three major metabolic products of zolmitriptan have been identified: heteroauxin (considered the main constituent in urine and plasma), N-desmethyl and N-oxide analogues. The N-desmethylated substance is active, and the other two breakdown products are inactive.

The average half-life of zolmitriptan is 2.5-3 hours.

In females, Cmax and bioavailability values are higher than in males (while clearance values are lower).

In patients with moderate and severe renal impairment, the renal clearance rates of the active element and its metabolic products are 7-8 times lower than in volunteers. The half-life increases by 60 minutes (maximum 3-3.5 hours), while the bioavailability of zolmitriptan with its active metabolic product increases by only 16%, as well as 35%.

In individuals with liver dysfunction, the metabolism of the active component of the drug decreases in accordance with the severity of the disease.

Dosing and administration

The drug is prohibited for prophylactic use against migraine attacks. It should be taken as soon as possible after the onset of a pain attack.

You need to take 1 tablet of LS (contains 2.5 mg of the substance). If there is no effect from the use, or a relapse occurs, it is allowed to take another 1 tablet. Repeated doses should be taken at least 2 hours after taking the 1st portion.

If the 2.5 mg dosage has had a weak effect, it is allowed to increase it to 5 mg (the maximum permissible single dose). A maximum of 10 mg of the drug is allowed per day.

People with severe stages of liver dysfunction can take a maximum of 5 mg of the drug per day.

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Use Zolmigrain during pregnancy

The safety of the drug during pregnancy has not been determined. Animal tests have not determined a direct teratogenic effect of the drug, but individual data from embryotoxicity tests show that embryonic viability is reduced. Pregnant women can take Zolmigren only in situations where the likelihood of helping the woman is higher than the risk of complications in the fetus.

Tests also show that the drug is excreted in milk in nursing animals. There is no information regarding the passage of the substance into human breast milk. Because of this, nursing women should use the drug very carefully. The effect of the drug on the baby should be minimized, so feeding should be carried out at least 24 hours after using Zolmigren.

Contraindications

Main contraindications:

• the presence of strong sensitivity to medicinal elements;
• elevated blood pressure of moderate or severe severity, as well as a low-intensity, uncontrolled increase in blood pressure;
• IHD or similar manifestations, which include a history of myocardial infarction;
• spontaneous angina;
• history of cerebrovascular disorders or TIA;
• the level of CC reaching values below the 15 ml mark per minute;
• combined administration with ergotamine or substances that are its derivatives (including methysergides), and also with naratriptan or sumatriptan, and also other agonists of 5HT1B/1D endings;
• diseases affecting the function of peripheral vessels;
• use in elderly people (over 65 years of age).

Side effects Zolmigrain

Adverse symptoms when taking Zolmigren are often mild and usually temporary. They occur during the first 4 hours after taking the drug, but do not increase with repeated use; they disappear on their own, without the use of additional therapeutic measures. Among other side effects:

• immune system damage: symptoms of intolerance, including Quincke's edema, urticaria and anaphylactic reactions;
• Cardiac disorders: tachycardia, palpitations, angina pectoris or myocardial infarction, as well as coronary spasm;
• problems with the functioning of blood vessels: a slight increase in blood pressure values, as well as a transient increase in blood pressure levels;
• dysfunction of the nervous system: dizziness, paresthesia, strong feeling of heat, noticeable disturbance of sensitivity or significant feeling of drowsiness, hyperesthesia and headaches;
• manifestations affecting the gastrointestinal tract: nausea, dysphagia, abdominal pain, dry mouth, vomiting, and also ischemia or infarction (for example, intestinal form or infarction of the spleen), manifested in the form of bloody diarrhea or pain in the peritoneum;
• disorders of urinary or renal function: increased frequency of urination, polyuria, as well as imperative urges to urinate;
• lesions of the musculoskeletal structure and connective tissues: pain or a feeling of weakness in the muscles;
• systemic disorders: a feeling of constriction, severe heaviness or pressure, or pain in the neck or throat, and also inside the sternum or limbs, or asthenia.

Some symptoms may be a consequence of the migraine itself.

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Overdose

Volunteers who took a single dose of zolmitriptan (0.05 g) experienced a sedative effect.

The half-life of the element is 2.5-3 hours, which is why in case of overdose the victim's condition should be monitored for at least the next 15 hours or until the symptoms disappear. The drug has no antidote.

In severe poisoning, intensive care measures must be taken, including ensuring free passage of air through the respiratory tract, adequate ventilation with oxygenation, and, in combination with this, monitoring and support of the cardiovascular system.

There are no data on how peritoneal dialysis and hemodialysis affect serum component values.

Interactions with other drugs

It is permissible to combine the medicinal component with paracetamol or rifampicin, caffeine, and also with metoclopramide, propranolol, fluoxetine and pizotifen.

Due to the fact that in theory the probability of coronary spasm in the patient may increase, the drug should be used at least 24 hours after taking drugs containing ergotamine. Also, on the contrary, drugs containing ergotamine are used at least 6 hours after taking Zolmigren.

After using moclobemide (a specific MAO-A IM drug), a small increase in AUC (by 26%) was observed for zolmitriptan, as well as a 3-fold increase in the same indicator for the active metabolic product. In this regard, individuals using MAO-A IM drugs should take a maximum of 5 mg of zolmitriptan per day. The drugs are prohibited to be used simultaneously with the introduction of moclobemide in a portion of more than 0.15 g 2 times per day.

When cimetidine (a systemic P450 inhibitor) is used, the half-life of zolmitriptan increases by 44% and the AUC by 48%. In addition, cimetidine doubles the half-life and AUC of the active metabolic product, the N-dimethylated component (183C91). People using cimetidine should take a maximum of 5 mg of Zolmigren per day.

Taking into account the general parameters of interaction, it is quite possible that there may be a connection with specific medications that slow down the activity of the CYP 1A2 component. Because of this, when combining such compounds (fluvoxamine and quinolones (this group includes ciprofloxacin)), the dosages also need to be reduced.

When triptans are used in combination with SSRIs or SNRIs, serotonin intoxication has been reported (symptoms include autonomic instability, changes in mental status, and neuromuscular abnormalities).

Like other 5HT1B/1D agonists, the drug can slow the rate of absorption of other therapeutic drugs.

It is necessary to refrain from combined use of the drug with other agonists of the 5-HT1B/1D element for a period of at least 24 hours after taking them, and vice versa.

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Storage conditions

Zolmigren should be kept in a place closed to children. Temperature indicators are a maximum of 25°C.

Shelf life

Zolmigren can be used within 3 years from the date of manufacture of the drug.

Application for children

The drug is not prescribed in pediatrics.

Analogues

Analogues of the drug are Rapimig, Antimigren, Relpax with Migrepam and Imigran, and in addition to this, Amigrenin, Rizamigren, Stopmigren with Sumamigren and Frovamigran with Migranol. The list also includes Rizatriptan-Farmaten, Rapimed, Amigren, Sumatriptan and Antimigren-Zdorovye.

Reviews

Zolmigren gets a lot of good reviews. Most patients who took the drug to eliminate migraine attacks note its high effectiveness. For many, this remedy turned out to be the only one that brings results.