Relpax® (Relpax®)

Composition Pharmacodynamics Indications Carefully Contraindications Dosing and Administration Side effects Form release / dosage
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Active substanceEletriptanEletriptan
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  • Relpax®
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    Pfizer Inc.     USA
    • Dosage form: & nbspfilm coated tablets
    Composition:

    Each film-coated tablet contains:

    Active substance:

    eletriptan hydrobromide 24,242 mg / 48.485 mg (equivalent to 20 mg or 40 mg eletriptan);

    Excipients: cellulose microcrystalline 46.508 mg / 93.015 mg, lactose monohydrate 23 mg / 46 mg, croscarmellose sodium 5 mg / 10 mg, magnesium stearate 1.25 mg / 2.5 mg; film sheath: opadrai orange OY-LS-23016 3 mg / 6 mg (hypromellose, lactose monohydrate, titanium dioxide (E171), triacetin, dye sunset yellow with varnish aluminum (E110); opadray transparent YS-2-19114-A 0.5 mg / 1 mg (hypromellose, triacetin).

    Description:

    Tablets with a dosage of 20 mg:

    orange round biconvex tablets, film-coated, engraved "REP 20 "on one side and "Pfizer" - on the other side of the Tablets dosage 40 mg:

    orange round biconvex tablets, film-coated, engraved "REP 40 "on one side and "Pfizer" - on the other side

    Pharmacotherapeutic group:antimigraine agent
    ATX: & nbsp

    N.02.C.C.06   Eletriptan

    Pharmacodynamics:

    Eletriptan is a representative of the group of selective agonists of serotonin vascular 5-HT1B and neuronal 5-HT1D receptors. Eletriptan also has a high affinity for 5-HT1F serotonin receptors and has a moderate effect on 5-HT1A, 5-HT2B, 5-HT1E and 5-HT7 serotonin receptors.

    In comparison with sumatriptan, eletriptan exhibits much greater selectivity for serotonin receptors located in the carotid arteries than for serotonin receptors located in the coronary and femoral arteries. The ability of eletriptan to narrow the intracranial blood vessels, as well as its inhibitory effect against neurogenic inflammation, can determine its antimigraine activity.

    Pharmacokinetics:
    Suction
    After oral administration eletriptan quickly and quite fully absorbed in the gastrointestinal tract (GIT): (absorption is about 81%). Absolute bioavailability for ingestion in men and women is about 50%. The time to reach the maximum concentration in the blood plasma (TCmax) averaged 1.5 hours after ingestion. In the range of therapeutic doses from 20 mg to 80 mg, the pharmacokinetics of eletriptan are characterized by a linear relationship.
    The maximum concentration (Сmах) of eletriptan and the area under the concentration-time curve (AUC) increased by approximately 20-30% when taking the drug after eating fatty foods.When ingestion during a migraine attack, the AUC decreased by about 30%, and the Tmax in the blood plasma increased to 2.8 hours.
    With regular use (20 mg three times daily) for 5-7 days, the pharmacokinetics of eletriptan remained linear with predictable cumulation. When administered at higher doses (40 mg three times a day and 80 mg twice daily) for more than 7 days, the cumulation of eletriptan exceeded the expected (by about 40%).
    Distribution
    The volume of distribution of eletriptan for intravenous administration is 138 liters, which indicates a good distribution in tissues. Eletriptan moderately binds to blood plasma proteins (approximately 85%).
    Metabolism
    In vitro studies indicate that the primary metabolism of eletriptan occurs under the action of the cytochrome P450 isoenzyme CYP3A4 in the liver. This fact is confirmed by an increase in the concentration of eletriptan in the blood plasma with the simultaneous administration of erythromycin, which is a potent selective inhibitor of the CYP3A4 isoenzyme. In vitro studies also show that the CYP2D6 isoenzyme contributes to the metabolism of eletriptan, although in clinical studies the effect of polymorphism of this enzyme on the pharmacokinetics of eletriptan has not been revealed.
    Two main circulating metabolites have been identified, the proportion of which constitutes a significant part of the total radioactivity of blood plasma after the administration of eletriptan labeled with C14 isotope.
    In the in vitro experiments, the metabolite formed as a result of N-oxidation did not have activity, while the metabolite formed as a result of N-demethylation was comparable in activity to eletriptan. The third component of radioactive plasma is not identified. It is believed that it is a mixture of hydroxylated metabolites, which are also excreted by the kidneys and through the intestine.
    The concentration of active N-demethylated metabolite in blood plasma is only 10-20% of the eletriptan concentration and, accordingly, does not make a significant contribution to its therapeutic effect.
    Excretion
    The total clearance of eletriptan from blood plasma after intravenous administration averages 36 l / h, and the half-life (T1 / 2) is about 4 hours. The average renal clearance after oral administration is about 3.9 l / h. The proportion of non-primary clearance is about 90% of the total clearance; this indicates that eletriptan is excreted mainly in the form of metabolites by the kidneys and through the intestine.
    Pharmacokinetics in specific patient groups
    Floor
    The results of the meta-analysis of clinical pharmacological studies and population pharmacokinetic analysis indicate that the sex does not have a clinically significant effect on the concentration of eletriptan in the blood plasma.
    Elderly people (over 65)
    In elderly people (65-93 years) a small and statistically unreliable
    The decrease in eletriptan clearance by 16% and a statistically significant increase in T1 / 2 (from about 4.4 to 5.7 hours) compared to those in young people. The effect of eletriptan on blood pressure in the elderly can be more pronounced compared with patients of a younger age.
    Impaired liver function
    A statistically significant increase in AUC (by 34%) and T1 / 2, as well as a slight increase in Cmax (by 18%), was found in patients with impaired hepatic function (stages A and B according to the Child-Pugh classification), however, these changes are not clinically significant .
    Impaired renal function
    In patients with a lung (creatinine clearance 61-89 ml / min), moderate (creatinine clearance 31-60 ml / min) or pronounced(creatinine clearance <30 ml / min), renal dysfunction did not reveal statistically significant changes in the pharmacokinetics of eletriptan or the degree of its binding to plasma proteins.
    Indications:Curbing migraine attacks with or without aura
    Contraindications:

    Hypersensitivity to eletriptan or to any other component of the drug.

    Severe liver dysfunction.

    Age under 18 years (data on the efficacy and safety of the drug in this age group are limited).

    Simultaneous reception with inhibitors CYP3A4 (ketoconazole, itraconazole, erythromycin, clarithromycin, josamycin) and protease inhibitors (ritonavir, indinavir and nelfinavir).

    As with other 5-hydroxytryptamine type I receptor agonists (5-HT1) Contraindications to the use of eletriptan are justified by its pharmacodynamic properties:

    uncontrolled arterial hypertension;

    - spasm of the coronary arteries, ischemic heart disease (angina pectoris, Prinzmetal angina, suffered myocardial infarction, confirmed asymptomatic myocardial ischemia) or suspicion of its presence;

    - arrhythmia;

    - heart failure;

    - occlusive diseases of peripheral vessels;

    - impaired cerebral circulation or transient ischemic attack in the anamnesis;

    - joint application with other agonists 5-HT1 receptors;

    - during the 24 hours before or after taking eletriptan, ergotamine or ergotamine derivatives, including the ergotamine, should not be used. metisergide (see section "Interaction with other drugs").

    Relpax ® is not indicated for relief of hemiplegic, ophthalmoplegic or basilar migraine.

    Patients with rare hereditary diseases such as lactose intolerance, lactase deficiency or glucose-lactose malabsorption should not take the drug.

    Carefully:

    Serotonin syndrome: with simultaneous use of eletriptan with other drugs that have serotonergic activity, such as SSRIs (selective serotonin reuptake inhibitors) and SSRIs (selective serotonin and norepinephrine reuptake inhibitors), caution should be exercised. in some cases, there were reports of the development of serotonin syndrome with the simultaneous administration of eletriptan and other serotonergic drugs.

    The use of the drug in a dose above 40 mg in patients with impaired renal function (because in such patients the effect of eletriptan on blood pressure is increased).

    Pregnancy and lactation:

    There are no clinical trials of Relpax® in pregnant women. In animal studies, the drug did not have a teratogenic effect. Relpaks® should be given only when the expected benefit to the mother is significantly greater than the possible risk to the fetus.

    Relpaks® is excreted in breast milk in women. With a single administration of Relpax® at a dose of 80 mg excretion in breast milk for 24 hours was an average of 0.02% of the dose. The risk of exposure to a newborn can be minimized if you do not breast-feed it within 24 hours after taking eletriptan.

    Dosing and Administration:

    Inside.

    Tablets should be swallowed whole, washed down with water.

    When migraine headache occurs Relpax® should be taken as soon as possible, however, the drug is also effective at a later stage of a migraine attack.

    Adults (18-65 years)

    The recommended initial dose is 40 mg.

    If the headache resumes within 24 hours: If migraine headache is stopped, but then resumes within 24 hours, Relpax® can be re-administered at the same dose. If a second dose is needed, it should be taken no earlier than 2 hours after the first dose.

    In the absence of effect: if the first dose of Relpax® does not lead to a reduction in headache within 2 hours, then the second dose should not be taken to stop the attack, as in clinical trials the effectiveness of such treatment has not been proven. In this case, patients who did not manage to stop the attack, can give an effective clinical response at the next attack.

    If taking the drug at a dose of 40 mg does not allow for an adequate effect, then in subsequent migraine attacks, an effective dose of 80 mg can be effective.

    The daily dose should not exceed 160 mg.

    In patients with mild or moderate dysfunction of the liver, a dose change is not required.

    Side effects:

    In general, Relpax® well tolerated

    Usually side effects are transient, weak or moderately expressed and pass independently without additional treatment. The incidence of adverse reactions in patients taking the drug in the same dose twice within 24 h for arresting an attack are similar in patients who take it once.

    The main side effects recorded at treatment with Relpax® are typical for the whole class of agonists 5-HT1 -serotonin receptors.

    When using agonists 5-HT1 - serotonin receptors, including of Relpax®, there have been reports of serious cardiovascular side effects, in some cases fatal. These reactions were extremely rare and were observed mainly in patients with concomitant risk factors.

    In patients taking Relpax® in therapeutic doses were observed the following adverse reactions (with a frequency of ≥ 1% and higher compared with placebo). These phenomena were distributed according to the following frequency categories: Frequent (≥ 1/100 to <1/10), unadvanced (≥ 1/1000 to <1/100) or rare (≥ 1/10000 to <1/1000) .

    Infections:

    Frequent: pharyngitis and rhinitis.

    Rare: respiratory tract infections.

    Infringements from lymphatic system:

    Rare: lymphadenopathy.

    Disturbances in nutrition and metabolism substances:

    Infrequent: anorexia.

    Mental disorders:

    Infrequent: disturbance of thinking, agitation, confusion,

    depersonalization, euphoria, depression, insomnia.

    Rare: emotional lability.

    Violations from the nervous system:

    Frequent: drowsiness, headache, dizziness, a feeling of "pricking" or other sensory disorders, hypertonic muscle, hypoesthesia, myasthenia gravis.

    Infrequent: tremor, hyperesthesia, ataxia, hypokinesia, speech impairment, stuporosis, a violation of taste.

    Disorders from the side of the organ of vision:

    Infrequent: impaired vision, pain in the eyes, photophobia and lacrimation.

    Rare: conjunctivitis.

    Violations from the organs of hearing and equilibrium:

    Frequent: Vertigo.

    Infrequent: pain in the ears, ringing in the ears.

    Violations from the side of the cardio- cardiovascular system:

    Frequent: feeling of palpitations and tachycardia.

    Rare: angina pectoris arterial pressure, aetiology, shock.

    Respiratory, Thoracic and mediastinal disorders:

    Frequent: feeling of "restraint" in the throat.

    Infrequent: shortness of breath, yawning.

    Rare: bronchospasm and tone change vote.

    Infringements from digestive system:

    Frequent: abdominal pain, nausea, dryness mucous membrane of the oral cavity and dyspepsia.

    Infrequent: diarrhea, glossitis.

    Rare: constipation, esophagitis, edema of the tongue, eructation.

    Infringements from hepatobiliary system:

    Rare: hyperbilirubinemia, increased activity ACT (aspartate aminotransferase).

    Disturbances from the skin and subcutaneous tissue:

    Frequent: increased sweating.

    Infrequent: rash, itchy skin.

    Rare: skin diseases, hives.

    Disturbances from the musculoskeletal system, connective and

    bone tissue:

    Frequent: pain in the back, pain in the muscles.

    Infrequent: pain in the joints, arthrosis and pain in the bones.

    Rare: arthritis, myopathy, myalgia, convulsions.

    Infringements from urinary system:

    Infrequent: disorders of the urethra (rapid urination, polyuria).

    Infringements from reproductive system and dairy glands:

    Rare: pain in the mammary glands, Menorrhagia.

    Common violations:

    Frequent: sensation of warmth or "hot flashes" heat to face, chills, asthenia, symptoms with side of the chest (pain, feeling compression, pressure).

    Infrequent: general weakness, swelling face, thirst, peripheral edema.

    In post-marketing research the following undesirable effects:

    Disorders from the immune system system:

    allergic reactions, angioedema.

    Violations from the nervous system:

    rare cases of syncope states.

    Disorders from the vascular system:

    increase of arterial pressure.

    Heart Disease:

    ischemia or myocardial infarction, spasm coronary arteries.

    Infringements from digestive system:

    as with the use of some other agonists 5-HT 1B / 1D -serotonin receptors, rare reports were received of ischemic colitis, vomiting.

    Overdose:

    In case of overdose, it is possible to expect the development of arterial hypertension and other disorders, from the side of the cardiovascular system.

    Treatment: gastric lavage, symptomatic therapy. Since T1/2 eletriptan is about 4 hours in the case of an overdose of the drug, patients should be observed for at least 20 hours or until the clinical symptoms of an overdose disappear. The effect of hemodialysis and peritoneal dialysis on the concentration of eletriptan inblood plasma is unknown.

    Interaction:

    The effect of other drugs on the pharmacokinetics of eletriptan With the simultaneous administration of erythromycin (1000 mg) and ketoconazole (400 mg), which are potent specific inhibitors of the isoenzyme CYP3A4, FROMmOh eletriptan increased by 2 and 2.7 times, respectively, a AUC eletriptan - in 3,6 and 5,9 times, respectively. Here T1/2 eletriptan increased from 4.6 hours to 7.1 hours with the use of erythromycin and from 4.8 hours to 8.3 hours - with the use of ketoconazole (see section "Pharmacokinetics"). Therefore, Relaks® should not be used in combination with powerful inhibitors of isoenzyme CYP3A4, in particular ketoconazole, itraconazole, erythromycin, clarithromycin, josamycin and protease inhibitors (ritonavir, indinavir and nelfinavir).

    The interactions of Relpax® with beta-blockers, tricyclic antidepressants, selective serotonin reuptake inhibitors and flunarizine have not been identified, however, the results of special clinical studies of inter-drug interactions are not yet available (with the exception of propranolol, see below).

    Population pharmacokinetic analysis of clinical studies has shown that the following drugs hardly affect the pharmacokinetics of eletriptan: beta adrenoblockers, tricyclic antidepressants, selective serotonin reuptake inhibitors, estrogen-containing hormone replacement drugs, estrogen-containing oral contraceptives and calcium channel blockers.

    Because the eletriptan is not a substratum of MAO, the pharmacokinetic interaction of Relpax® and MAO inhibitors is unlikely, and no special studies of their interaction have been conducted.

    With the simultaneous use of propranolol in a dose of 160 mg, verapamil at a dose of 480 mg or fluconazole at a dose of 100 mg CmOh eletriptan increased in 1,1, 2,2 and 1,4 times, and AUC - in 1,3, 2,7 and 2,0 times, respectively. These changes are not clinically significant, as they were not accompanied by an increase in blood pressure or an increase in the incidence of adverse events compared with the use of a single eletriptan.

    Taking caffeine / ergotamine inside 1 hour and 2 hours after taking Relpax® leads to a slight but additive increase in blood pressure, which could be predicted based on the pharmacological properties of these drugs.In this connection, preparations containing ergotamine or ergotaminopodobnye means, in particular dihydroergotamine, should not be administered within 24 hours after receiving Relpaksa®. In contrast, Relpaks® be administered no sooner than 24 hours after receiving ergotaminosoderzhaschih preparations.

    Effect of eletriptan on other drugs

    At therapeutic doses revealed no influence (inhibition or induction) on drug cytochrome P450 system.

    Interaction with serotonergic drugs

    Simultaneous use of 5-HT receptor agonists, incl. eletriptan, with drugs having serotonergic activity such as SSRIs (selective serotonin reuptake inhibitors) and SNRI (selective serotonin reuptake inhibitor and a norepinephrine) may increase the risk for serotonin syndrome. In the case of clinical necessity of simultaneous use of eletriptan and serotonergic drugs caution. Such patients should be carefully observed, especially at the beginning of treatment and with increasing doses of each drug.

    Special instructions:

    The use of Relpax® in combination with potent inhibitors of isoenzyme is not recommended CYP3A4, in particular ketoconazole, itraconazole, erythromycin, clarithromycin, josamycin and HIV protease inhibitors, such as ritonavir, indinavir and nelfinavir (see section "Interaction with other drugs. ") In addition, Relpax® should not be taken within 72 hours after the end of taking isoenzyme inhibitors CYP3A4.

    Like other agonists 5-HT1- serotonin receptors, Relpax® should be used only in those cases, when the diagnosis of migraine is not in doubt. Relpaks®, like other agonists 5-HT1 serotonin receptors should not be prescribed for the treatment of "atypical" headaches, which can be associated with serious diseases (stroke, aneurysm rupture), when the narrowing of the cerebral vessels can be harmful.

    Against the background of the use of agonists 5-HTV serotonin receptors cases of development of cerebral hemorrhage, subarachnoid hemorrhage, stroke or other cerebrovascular disorders, in some cases with a fatal outcome.In several cases, cerebrovascular disease was a major disease and agonists of 5- HT1-serotonin receptors were applied incorrectly, treating the symptoms as signs of migraine. It should be noted that patients with migraine may be at increased risk of cerebrovascular complications (for example, stroke, hemorrhage and transient ischemic attack).

    With simultaneous use of eletriptan and SSRIs (for example, fluoxetine, paroxetine, sertraline, fluvoxamine, citalopram, escitalopram) and SSRIs (for example, venlafaxine, duloxetine) may develop a potentially life-threatening serotonin syndrome (see "With caution" and "Interaction with other medicines.") This syndrome can be manifested by the following symptoms: a mental disorder (eg, agitation, hallucinations, coma), instability of the autonomic nervous system , tachycardia, fluctuating blood pressure, hyperthermia), a violation of the function of the neuromuscular system (eg, hyperreflexia, violation coordination) and / or symptoms of impaired digestive system function (eg, nausea, vomiting, diarrhea).

    It is not recommended to use Rellax® in patients with risk factors for coronary heart disease (eg, hypertension, hypercholesterolemia, smoking, obesity, diabetes, family history, women in the state of surgical or physiological menopause or men over the age of 40) until a thorough examination of the circulatory system is carried out and cardiovascular disease is eliminated.

    The sensitivity of methods for assessing the state of the cardiovascular system is rather small. In this regard, if in the patient's history, on the ECG or during other diagnostic procedures, signs characteristic of arterial vasospasm or myocardial ischemia were found, eletriptan not recommended (see section "Contraindications").

    In patients with risk factors cardiovascular diseases, but in which the assessment of the state of the cardiovascular system showed a satisfactory result, it is recommended that the first dose of eletriptan be taken under the supervision of a physician, except for patients who previously received eletriptan. Since myocardial ischemia can occur in the absence of clinical symptoms, consideration should be given to conducting an electrocardiographic study immediately after taking Relpax®.

    Patients with risk factors for cardiovascular disease, as described above, receiving eletriptan long, but with interruptions, should periodically undergo examination of the cardiovascular system, as they continue therapy with eletriptan. Systematic adherence to the above recommendations leads to a reduction in cases where patients with undiagnosed cardiovascular diseases receive eletriptan therapy.

    With the use of 5HT agonists1- Serotonin receptors reported cases of severe cardiac function disorders, including myocardial infarction, life-threatening heart rhythm abnormalities and deaths that developed in the first few hours after taking the drug. Given the breadth of the use of 5HT agonists1- serotonin receptors in patients with migraine, the frequency of occurrence of these reactions is extremely low.

    During the clinical trials, the following reports were received.Among patients who underwent diagnostic coronary angiography, one patient receiving eletriptan intravenously (Cmax 127 ng / ml, equivalent to 60 mg of eletriptan for ingestion) angina history, hypertension and hypercholesterolemia, a feeling of tightness in the chest, and was also detected episode of coronary vasospasm (confirmed by angiography) without ECG changes typical for ischaemia . In addition, one case of atrial fibrillation was reported in a patient with a similar history of rhythm disorder.

    In the postmarketing period, cases of severe cardiovascular complications, some of which were fatal, were reported. In very rare cases, these complications arose in the absence of any signs of cardiovascular disease, cardiovascular disease. Nevertheless, given the difficulty of monitoring the messages received in postmarketing period, it is impossible to definitively determine the relationship of these cases with the reception of eletriptan. Relpaks® should not be prescribed without a preliminary examination patients who are likely to have cardiovascular diseases or have an increased risk of their development (see.section "Contraindications"). System studies of eletriptan in patients with heart failure have not been conducted. The use of eletriptan, as well as other agonists 5HT1- serotonin receptors, in these patients is not recommended.

    Relpax® is effective in treating migraine with aura and without aura and migraine accompanying the menstrual cycle. Relpaks®, taken during the appearance of the aura, does not prevent the development of a headache, so it should be taken only during the phase of the headache.

    Clinical studies have established that Relpax® is also effective in relieving the symptoms accompanying migraines, such as nausea, vomiting, photophobia, phonophobia, and in treating the return of a headache during an attack.

    Relpaks® should not be taken prophylactically.

    When using the drug Relpaks® in therapeutic doses of 60 mg or more recorded a slight transient increase in blood pressure. Arterial pressure increased more often in patients with impaired renal function (maximal systolic pressure increased by 14-17 mm Hg, and diastolic by 14-21 mm Hg. from baseline and 3-4 mm Hg. higher than in healthy volunteers) and old people.

    It should be taken into account that the unrestricted use of antimigraine medicines can lead to chronic daily headaches. Cases of excessive use of any tryptans are most often observed in patients with daily headaches.

    Effect on the ability to drive transp. cf. and fur:

    In some patients, migraine or admission of agonists 5NT1- serotonin receptors, including eletriptanmay be accompanied by drowsiness or dizziness. When performing tasks that require increased attention, such as driving car and work with complex equipment, caution should be exercised during migraine attacks and after taking Relpax®.

    Form release / dosage:

    Tablets, film-coated 20 mg or 40 mg.

    Packaging:

    2, 3, 4, 6 or 10 tablets in a blister of PVC / aluminum foil.

    1, 2, 3, 4, 5, 6 or 10 blisters into the cardboard Pack together with instructions on how to application.

    On the front side of the cardboard bundle for the purpose of controlling the first opening is applied a perforated line reminiscent of the shape of the semirings. The side surfaces of the pack tightly adhere to the packaging of the preparation

    Storage conditions:

    Store at a temperature not exceeding 30 ° C.

    Keep out of the reach of children.

    Shelf life:

    3 years

    Do not use after the expiration date printed on the package.

    Terms of leave from pharmacies:On prescription
    Registration number:П N014827 / 01
    Date of registration:24.04.2009
    The owner of the registration certificate: Pfizer Inc. Pfizer Inc. USA
    Manufacturer: & nbsp
    Representation: & nbspPfizer H. Si. Pi. CorporationPfizer H. Si. Pi. Corporation
    Information update date: & nbsp28.11.2015
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