Rapimig

Rapimig is a migraine medication. It belongs to the category of selective serotonin 5HT1 receptor agonists. The active ingredient is zolmitriptan.

Indications Rapimiga

Indicated for relief of migraine attacks (may be accompanied by an aura or develop without it).

Release form

Released in tablets; 1 blister of 2 or 6 pieces. Inside a separate pack - 1 blister plate.

Pharmacodynamics

Zolmitriptan is a selective agonist of recombinant serotonin 5-HT 1B/1D vascular receptors. It has moderate affinity for serotonin receptors of the 5HT 1A type, but no significant affinity or medicinal activity for serotonin conductors of the 5HT2 and 5HT3 types, or 5HT4. In addition, it does not show activity for α1-, α2-, or β1-adrenergic receptors, histamine H1-H2 receptors, m-choline conductors, or D1-D2 dopamine receptors.

The drug has vasoconstrictive properties, mainly in relation to cranial vessels, and also prevents the release of neuropeptides (including vasoactive intestinal polypeptide, which is the main effector carrier of the reflex excitation reaction) and stimulates vasodilation, which is the basis of the mechanism of migraine. It inhibits the development of a migraine attack without having a direct analgesic effect.

In addition to stopping the attack, the drug reduces vomiting along with nausea (especially in the case of left-sided attacks), acousticophobia and photophobia. It significantly affects the centers of the brain stem, which are associated with the development of migraine - this explains the stability of repeated exposure in the case of eliminating series consisting of several successively developing migraine attacks in one person.

Rapimig is very effective in combination therapy for migraine status (a series of multiple, recurring, severe migraine attacks that last for 2-5 days). It relieves migraines associated with menstruation.

The medicinal effect begins after 15-20 minutes, reaching its peak after 1 hour after taking the tablet. The greatest effect is achieved when taken during a developing attack.

Pharmacokinetics

After oral administration, the drug is well absorbed in the digestive organs. The degree of absorption does not depend on food intake. The average level of absolute bioavailability is approximately 40%. Synthesis of the substance with plasma protein is 25%. It takes 1 hour after taking the drug to reach the peak level. This indicator is maintained for the next 4-6 hours. The drug does not accumulate in the body with repeated use.

An intensive process of biotransformation takes place inside the liver, as a result of which N-desmethyl metabolite is formed, which has 2-6 times greater medicinal activity than the properties of the original substance. In about 1 hour, this element reaches 85% of the maximum concentration level.

The excretion of zolmitriptan is largely due to intrahepatic biotransformation processes, which result in excretion of decay products in the urine.

There are 3 main decay products: heteroauxin (the main decay product in urine and plasma), N-oxide and N-desmethyl analogues. Only the N-desmethylated decay product is active. The values of this substance in plasma are approximately 2 times lower than the values of the original component of the drug. This element is capable of enhancing the medicinal properties of zolmitriptan.

After a single oral dose, more than 60% of the substance is excreted in the urine (mainly as a breakdown product, heteroauxin), and another 30% is excreted in the feces as the original element. After administration of the drug, the total clearance rate is approximately 10 ml/minute/kg (one third of this figure is the clearance rate inside the kidneys). Clearance in the kidneys is faster than the glomerular filtration rate, which suggests secretion inside the renal tubules.

The distribution volume after intravenous injection is 2.4 l/kg. Synthesis of zolmitriptan and its N-desmethylated breakdown product with plasma protein is quite low (about 25%). The average half-life of the active ingredient is 2.5-3 hours. The half-life of the substance's metabolites is approximately the same, from which it can be concluded that their excretion is limited by the rate of formation.

The clearance rate of zolmitriptan with all its decay products inside the kidneys in people with severe or moderate renal failure is reduced by 7-8 times compared to healthy people. The AUC level of the parent substance with the active decay product slightly increased (by 16 and 35%, respectively), and the half-life increased by 1 hour, reaching 3-3.5 hours. These values are observed within the limits that were identified during testing on volunteers.

Dosing and administration

The medicine cannot be used to prevent attacks. It is necessary to take the pill as soon as possible after the onset of a migraine attack, although in general the effectiveness of the medicine does not depend on the time of taking the pill after the attack.

It is allowed not to wash down the tablet with water - it can be placed on the tongue so that it dissolves, and then swallowed with saliva. This form of medicine is suitable for cases when there is no water nearby or it is necessary to avoid vomiting with nausea, which may occur in the case of washing down with liquid.

The tablets dissolve quickly in the oral cavity, although sometimes there may still be a delay in the absorption of the active component, which slows down the onset of the drug's effect.

The blister must be opened by peeling the tablet from the foil, and not by pushing it through the packaging.

To stop a migraine attack, take 1 tablet of Rapimig (2.5 mg). If there is no effect or symptoms recur within 24 hours, it is recommended to take a second dose.

If there is a need to take a second dose, it is necessary to do this at least 2 hours after the first dose. If the dosage of 2.5 mg does not give the result, it is allowed to increase the single dose to 5 mg (this dosage is considered the maximum permissible for a single dose).

No more than 10 mg of the drug is allowed per day. No more than 2 doses of the drug should be taken within 24 hours.

In case of liver failure – if a person has a moderate or mild form of functional liver disorder, no dosage adjustment is required. In case of severe disorder, the maximum daily dose is considered to be 5 mg.

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Use Rapimiga during pregnancy

Pregnant women can use Rapimig only in situations where the potential benefit to the woman outweighs the possibility of adverse reactions in the fetus.

There is no information regarding zolmitriptan getting into breast milk, therefore the drug should be taken with caution during lactation. It is necessary to minimize the negative impact on the child - breastfeed at least 24 hours after taking the drug.

Contraindications

Among the contraindications of the drug:

• intolerance to the components of the drug;
• moderate or severe increase in blood pressure, as well as a slight uncontrolled increase in its indicators;
• the presence of coronary heart disease (this includes a history of myocardial infarction in the patient’s medical history);
• variant angina;
• history of TIA and cerebrovascular disorders;
• CC values less than 15 ml/minute;
• administration in combination with ergotamine and its derivatives, as well as with sumatriptan and naratriptan or other 5HT 1B/1D agonists;
• pathologies in the peripheral vascular area;
• persons under 18 years of age and over 65 years of age.

Side effects Rapimiga

Possible side effects due to the use of drugs often develop in a mild form and occur within 4 hours after taking the pill. Their frequency does not increase with repeated use, and the manifestations themselves disappear spontaneously without the need for additional therapy. Among the symptoms:

• cardiovascular reactions: palpitations often occur; less frequently, tachycardia develops or blood pressure increases slightly. Rarely, angina pectoris, myocardial infarction, or coronary spasm occur;
• manifestations from the PNS and CNS: often there is a disturbance of sensitivity, and along with this headaches with paresthesia or hyperesthesia, dizziness, a feeling of heat and a feeling of drowsiness;
• digestive system: vomiting or nausea usually occurs, as well as dry mouth and abdominal pain. Rarely, infarction or ischemia (intestinal type; or splenic infarction) develops, which manifests itself as bloody diarrhea or abdominal pain;
• urogenital system: polyuria occasionally occurs or the urination process becomes more frequent. In some cases, urgency appears;
• muscle and bone structure: myalgia or muscle weakness often develops;
• systemic reactions and disorders: mainly asthenia is observed, and in addition a feeling of pressure, pain or heaviness in the neck and throat, as well as the sternum and limbs;
• Immune reactions: Rarely, hypersensitivity reactions may occur, including symptoms of anaphylaxis with angioedema, as well as urticaria.

Some symptoms may be caused by migraine itself.

Overdose

Overdose manifestations: volunteers who took a single dose of the drug (50 mg) developed a sedative effect. In case of overdose, the patient's condition must be monitored for at least 15 hours or until all signs of the disorder disappear.

To eliminate the disorders, gastric lavage and the use of activated carbon are necessary, as well as symptomatic treatment (this includes ensuring the patency of air within the respiratory system, as well as monitoring the work of the cardiovascular system and maintaining its functions). The drug does not have a specific antidote.

There is no information on the effect of peritoneal dialysis or hemodialysis on serum zolmitriptan levels.

Interactions with other drugs

It is allowed to use the medicine together with paracetamol and rifampicin, or with the substances pizotifen or fluoxetine, with the drugs propranolol and metoclopramide, as well as with caffeine.

According to the information obtained after tests with volunteers, there is no pharmacokinetic interaction of the drug with ergotamine. However, since in theory the probability of coronary spasm may increase, it is recommended to use Rapimig at least 24 hours after using ergotamine. In addition, ergotamines are recommended to be used at least 6 hours after taking Rapimig.

When using moclobemide (a substance that is a specific inhibitor of the MAO-A element), there was an insignificant increase in the AUC level (by 26%) of zolmitriptan, as well as its active decay product (by 3 times). As a result, people using MAO-A inhibitors are recommended to use zolmitriptan in daily doses of no more than 5 mg. The drugs cannot be combined if moclobemide is taken in amounts greater than 150 mg 2 times a day.

Cimetidine (a general inhibitor of the P 450 element) increased the half-life of zolmitriptan by 44% and the AUC by 48%. Cimetidine also increased the half-life and AUC of the N-dimethylated active decay product (183C91) by 2 times. People using cimetidine should not take more than 5 mg of zolmitriptan per day. The existing general profile of drug interactions does not allow us to exclude the possibility of interaction of the active component with inhibitors of the CYP 1A2 element. Therefore, in case of combination with substances such as quinolones (e.g. ciprofloxacin) and fluvoxamine, the dosage should also be reduced.

There is no pharmacokinetic interaction of zolmitriptan with fluoxetine (SSRI), as well as selegiline (MAO-B inhibitor). However, in case of combination with selective serotonin reuptake inhibitors (or norepinephrine and serotonin), as well as triptans, serotonin intoxication may develop (this includes changes in mental state, abnormalities of neuromuscular function, as well as vegetative lability). These manifestations can be severe. If there is a medicinal expediency of using zolmitriptan with SSRI or SSRI drugs, it is necessary to perform an appropriate examination of the patient (especially this concerns the initial period of treatment), increasing the dose or using another serotonergic drug.

Like other 5HT 1B/1D agonists, zolmitriptan can inhibit the absorption of other drugs.

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Storage conditions

Rapimig should be kept out of the reach of small children. The temperature should not exceed 30°C.

Shelf life

Rapimig is permitted to be used for a period of 3 years from the date of manufacture of the drug.