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Rapimig
Rapimig is a remedy for migraine. It is included in the category of selective agonists of serotonin 5HT1 receptors. The active ingredient is zolmitriptan.
Pharmacodynamics
Zolmitriptan is a selective agonist of recombinant serotonin 5-HT 1B / 1D vascular receptors. It has a moderate affinity for the serotonin receptors of the type 5HT 1A, but there is no noticeable affinity or drug activity with respect to serotonin conductors of the types 5HT2 and 5HT3, as well as 5HT4. In addition, it shows no activity with respect to α1-, α2-, and also β1-adrenoreceptors, histamine H1-H2 receptors, m-choline conductors and D1-D2 dopamine receptors.
The drug has vasoconstrictive properties, mainly in relation to the cranial vessels, and also prevents the release of neuropeptides (among them the vasoactive intestinal polypeptide, which is the main effector transporter of the reflex excitation reaction) and stimulates the vasodilation that underlies the mechanism of migraine appearance. It inhibits the development of a migraine attack without giving a direct analgesic effect.
In addition to stopping the attack, the drug weakens vomiting along with nausea (especially in the case of developing left-sided attacks), acoustophobia and photophobia. Visibly affects the centers of the cerebrospinal stem, which are interrelated with the development of migraine - this explains the sustainability of repeated exposure in the event of elimination of series consisting of several sequentially developing migraine attacks in one person.
Rapimig is very effective in the case of combined therapy with migraine status (a series consisting of several, recurring after each other, severe migraine attacks that last for 2-5 days). Eliminates migraines associated with menstruation.
The drug effect begins 15-20 minutes later, reaching its peak 1 hour after the use of the tablet. The greatest effect is achieved in the case of admission during a developing attack.
Pharmacokinetics
After ingestion, the medicine is well absorbed inside the digestive organs. The degree of absorption from eating does not depend. The average level of absolute bioavailability is approximately 40%. Synthesis of a substance with a plasma protein is 25%. To reach the peak level, it takes 1 hour after taking the drug. This indicator is held for a further 4-6 hours. The medicine does not accumulate in the body with repeated use.
An intense process of biotransformation takes place inside the liver, as a result of which N-desmethyl metabolite is formed, which has a 2-6-fold greater drug activity than the properties of the starting material. Approximately 1 hour, this element reaches 85% of the maximum concentration level.
Excretion of zolmitriptan is mainly caused by intrahepatic biotransformation processes, as a result of which urinary excretion of decay products is carried out.
There are 3 main decay products: heteroauxin (the main product of disintegration inside urine and plasma), N-oxide, as well as N-desmethyl analogues. Only N-desmethylated degradation product has activity. The values of this substance inside the plasma are approximately 2 times lower than the values of the initial component of the drug. This element is able to enhance the medicinal properties of zolmitriptan.
After a one-time internal intake, more than 60% of the substance is excreted in the urine (mainly under the guise of a decay product - heteroauxin), and about 30% is excreted along with the feces as a starting element. After applying the drug, the total clearance is approximately 10 ml / minute / kg (a third of this figure is the indicator of the clearance in the kidneys). The clearance in the kidneys is faster than the glomerular filtration rate, from which it can be concluded that the secretion is inside the renal tubules.
The distribution volume after IV injection is 2.4 l / kg. Synthesis with plasma protein of zolmitriptan substance, as well as its N-desmethylated decay product is rather low (about 25%). The average value of the half-life of the active component is 2.5-3 hours. The half-life of the metabolites of the substance is approximately the same, from which it can be concluded that their excretion is limited by the rate of formation.
The coefficient of purification of zolmitriptan with all its decay products inside the kidneys in people with severe or moderate forms of kidney failure is 7-8 times lower in comparison with healthy people. The AUC level of the starting material with the active decay product increased slightly (by 16 and 35%, respectively), and the half-life was extended by 1 hour, reaching 3-3.5 hours. These values are observed within the limits that were revealed during testing on volunteers.
Use of the rapimiga during pregnancy
Pregnant can use Rapimig only in situations where the probable benefit for a woman is higher than the possibility of the appearance of negative reactions in the fetus.
There is no information regarding the ingestion of zolmitriptan into breast milk, as a result of which it is necessary to take the medicine with caution during lactation. It is required to minimize the negative impact on the child - to breastfeed at least 24 hours after the use of drugs.
Contraindications
Among the contraindications of the medicine:
- intolerance of composite elements of drugs;
- moderate or severe degree of increase in blood pressure, and in addition a slight uncontrolled increase in its indices;
- presence of ischemic heart disease (this includes a history of myocardial infarction in the patient);
- variant angina pectoris;
- presence of an anamnesis of TIA and cerebrovascular disorders;
- scores less than 15 ml / min;
- Combination with ergotamine and its derivatives, and in addition with sumatriptan and naratriptan or other agonists of 5HT 1B / 1D conductors;
- pathology in the peripheral vascular region;
- persons aged less than 18, as well as over 65 years of age.
Side effects of the rapimiga
Possible side effects due to the use of drugs often develop in mild form and occur during the 4 hours after the use of the pill. Their frequency does not increase with repeated admission, and the manifestations disappear spontaneously without the need for additional therapy. Among the symptoms:
- reactions of the cardiovascular system: often there is a palpitation; less often develops tachycardia or slightly increases the level of blood pressure. Occasionally angina occurs, myocardial infarction or coronary spasm;
- manifestations from the PNS and CNS: often a sensitivity disorder is observed, and with it headaches with paresthesias or hyperesthesias, dizziness, a feeling of heat and a feeling of drowsiness;
- digestive system: mainly there is vomiting or nausea, and also dryness of the oral mucosa and abdominal pain. Occasionally, a heart attack or ischemia (of the intestinal type, or a spleen infarction), which manifests itself in the form of diarrhea with blood or pain in the peritoneum, develops;
- urogenital system: occasionally there is a polyuria or the urination process becomes more frequent. In some cases there is urgency;
- structure of muscles and bones: often develops myalgia or muscle weakness;
- systemic reactions and disorders: mainly observed asthenia, and in addition a feeling of pressure, pain or heaviness in the neck with the throat, as well as the sternum and limbs;
- immune reactions: Occasionally, there may be manifestations of hypersensitivity, including symptoms of anaphylaxis with angioneurotic edema, and hives.
Individual manifestations can be caused by migraine itself.
Dosing and administration
The medicine can not be used to prevent seizures. It is required to drink a tablet as quickly as possible after the onset of a migraine attack, although in general the effectiveness of the drug does not depend on the time of taking the pill after the onset of an attack.
It is allowed not to drink the pill with water - it can be put on the tongue so that it dissolves, and then swallowed with saliva. This form of drugs is suitable for cases when there is no water near or need to avoid vomiting with nausea, which can occur in case of liquid swallowing.
Tablets quickly dissolve inside the oral cavity, although sometimes a delay in absorption of the active component may occur, which also slows the onset of drug exposure.
Blister is required to be opened by cleaning the tablet from the foil, and not by punching it with the package.
To stop a migraine attack, you should take 1-well Rapimig pill (2.5 mg). In the absence of the effect or the repeated development of symptoms during the 24 hours it is recommended to take a second dose.
If there is a need for a repeat dose, it is required to do this at least 2 hours after the first dose. If the dosage of 2.5 mg does not give a result, it is allowed to increase a single dose to 5 mg (this dosage is considered the maximum allowable for a single dose).
A day is allowed to use no more than 10 mg of the drug. For 24 hours you can not take more than 2 doses of the drug.
With liver failure - if a person has a moderate or mild form of functional hepatic disorder, adjust the dose is not required. In the case of severe disorders, the maximum daily dose is 5 mg.
Overdose
Manifestations of an overdose: those taking a single dose of LS (in the amount of 50 mg) of volunteers developed a sedative effect. The patient should be monitored for overdose for at least 15 hours or until any signs of impairment disappear.
To eliminate the disorders, gastric lavage and the use of activated charcoal are necessary, along with symptomatic treatment (this includes ensuring air permeability inside the respiratory system, and in addition controlling the CCC and maintaining its functions). The medicine does not have a specific antidote.
There is no information on the effect of peritoneal dialysis or hemodialysis on the indices of zolmitriptan inside the serum.
Interactions with other drugs
It is permitted to use the drug together with paracetamol and rifampicin, or with substances of pizotifen or fluoxetine, with medications propranolol and metoclopramide, as well as with caffeine.
According to the information obtained after the tests with volunteers, there is no pharmacokinetic interaction of the drug with ergotamine. But thus, as in theory the probability of occurrence of coronarospasm may increase, it is recommended to use Rapimig at least 24 hours after the use of ergotamine. In addition, ergotamines are recommended to be consumed at least 6 hours after taking Rapimig.
Using moclobemide (the substance is a specific inhibitor of the MAO-A element), an insignificant increase in the AUC (by 26%) level of zolmitriptan and its active degradation product (by a factor of 3) occurred. Because of this, people who use MAO-A inhibitors are advised to use zolmitriptan in daily dosages of not more than 5 mg. Medications can not be combined if moclobemide is taken in amounts greater than 150 mg 2 times per day.
Due to the use of cimetidine (the general inhibitor of element P 450), the half-life of zolmitriptan increased by 44%, and the level of AUC by 48%. At the same time, cimetidine doubled the half-life and AUC of the N-dimethylated active decomposition product (183C91). Persons who use cimetidine should not take more than 5 mg of zolmitriptan per day. The existing general profile of drug interaction does not allow excluding the probability of interaction of the active component with inhibitors of the CYP 1A2 element. Because of this, in case of combination with substances such as quinolones (eg, ciprofloxacin), as well as fluvoxamine, it is also required to reduce dosage.
There is no pharmacokinetic interaction of zolmitriptan with fluoxetine (SSRIs), as well as selegiline (an inhibitor of the MAO-B element). But in case of a combination with reverse inhibitors of serotonin reuptake (either noradrenaline and serotonin), as well as tryptans, the development of serotonin intoxication is possible (this includes changes in the state of the psyche, anomalies of the neuromuscular function, and vegetative lability). These manifestations can have a severe form. If there is a medicinal expediency of using zolmitriptan with drugs SSRIs or SIZZSiN, it is required to perform an appropriate examination of the patient (in particular this concerns the initial period of treatment), increasing the dose or using a different serotonergic drug.
Like other 5HT 1B / 1D conductor agonists, zolmitriptan can inhibit the absorption of other drugs
Medical expert editor
Portnov Alexey Alexandrovich
Education: Kiev National Medical University. A.A. Bogomolets, Specialty - "General Medicine"
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Attention!
To simplify the perception of information, this instruction for use of the drug "Rapimig" translated and presented in a special form on the basis of the official instructions for medical use of the drug. Before use read the annotation that came directly to medicines.
Description provided for informational purposes and is not a guide to self-healing. The need for this drug, the purpose of the treatment regimen, methods and dose of the drug is determined solely by the attending physician. Self-medication is dangerous for your health.