Relpax, 40mg pills, 2pcs

Composition

Orange-colored film-coated tablets, round, biconvex, engraved with “REP 40” on one side and “Pfizer” on the other.

1 tab. of eletriptan hydrobromide 48.485 mg, which corresponds to the content of eletriptan 40 mg

Auxiliary substances:

microcrystalline cellulose – 93.015 mg,

lactose monohydrate-46 mg,

croscarmellose sodium-10 mg,

magnesium stearate-2.5 mg.

Composition of the film shell:

opadray orange OY-LS-23016 (hypromellose, lactose monohydrate, titanium dioxide (E 171), triacetin, dye sunny sunset yellow with aluminum varnish (E 110)) – 6 mg, opadray transparent YS-2-19114-A (hypromellose, triacetin) – 1 mg

Pharmacological action

Pharmacodynamics

A drug used for migraines.

Eletriptan is a representative of the group of selective serotonin 5-HT 1B – and 5-HT 1D – receptor agonists, which are located mainly in the blood vessels of the brain. When these receptors are stimulated, vasoconstriction occurs, in particular, in the carotid arteries, which leads to a decrease in headache.

Eletriptan also has a high affinity for serotonin 5-HT 1F receptors, has a moderate effect on serotonin 5-HT 1A -,5-HT 2B -,5 – HT 1E-and 5-HT 7-receptors, compared to sumatriptan, eletriptan shows significantly greater selectivity for serotonin receptors located in the carotid arteries than in the coronary and femoral arteries. The ability of eletriptan to constrict intracranial blood vessels, as well as its inhibitory effect on neurogenic inflammation, may determine its antimigrenous activity.

Pharmacokinetics

Suction

After oral use, eletriptan is rapidly and fairly fully absorbed from the gastrointestinal tract (absorption is about 81%). In both men and women, the absolute oral bioavailability is about 50%. The time to reach cmax in blood plasma was on average 1.5 hours after oral use. In the therapeutic dose range (20-80 mg), the pharmacokinetics of eletriptan are characterized by a linear relationship.

Cmax of eletriptan in blood plasma and AUC increased by approximately 20-30% when taking the drug after eating fatty foods. When taken orally during a migraine attack, AUC decreased by approximately 30%, and the time to reach cmax in blood plasma increased to 2.8 hours.

Distribution

With regular use (20 mg 3 times / day) for 5-7 days, the pharmacokinetics of eletriptan remained linear with predictable accumulation. When administered in higher doses (40 mg 3 times/day and 80 mg 2 times/day) for 7 days, the accumulation of eletriptan exceeded the expected (by approximately 40%).

The vd of eletriptan when administered intravenously is 138 liters, which indicates a good distribution in the tissue. Eletriptan is moderately protein bound (approximately 85%).

Metabolism

In vitro studies indicate that the primary metabolism of eletriptan occurs under the action of the CYP3A4 isoenzyme in the liver. This fact is confirmed by an increase in plasma concentrations of eletriptan with simultaneous use of erythromycin, which is a powerful selective inhibitor of CYP3A4. In vitro studies also show a small involvement of CYP2D6 in the metabolism of eletriptan, although clinical studies have not revealed any signs of polymorphism of this enzyme.

Two major circulating metabolites were identified, which account for a significant portion of the total plasma radioactivity after use of 14C-labeled eletriptan. The metabolite formed as a result of N-oxidation was not active in animal experiments in vitro. A metabolite formed as a result of N-demethylation. Its activity was comparable to that of eletriptan in animal studies in vitro. The third component of the radioactive plasma has not been identified; it is believed that it is a mixture of hydroxylated metabolites, which are also excreted in the urine and feces.

The concentration of the active N-demethylated metabolite in blood plasma is only 10-20% of the concentration of eletriptan and, accordingly, does not significantly contribute to its therapeutic effect.

Deduction

The total plasma clearance of eletriptan after intravenous use is on average 36 l / h, and T 1/2 is approximately 4 h. The average renal clearance after oral use is approximately 3.9 l/h. The proportion of extrarenal clearance is approximately 90% of the total clearance; this indicates that eletriptan is mainly excreted as metabolites in the urine and faeces.

Pharmacokinetics in special clinical cases

The results of a meta-analysis of clinical and pharmacological studies and population pharmacokinetic analysis indicate that gender does not have a clinically significant effect on the concentration of eletriptan in blood plasma.

Elderly and senile people (65-93 years) showed a small and statistically insignificant decrease (by 16%) in the clearance of eletriptan and a statistically significant increase in T 1/2 (from approximately 4.4 to 5.7 hours) compared to those in young adults. Age did not affect the frequency of side effects.

The pharmacokinetics of eletriptan (40 mg and 80 mg) in adolescents aged 12-17 years with migraine who took the drug during the inter-seizure period were similar to those in healthy adults.

In children aged 7-11 years, the clearance of eletriptan does not differ from that in adolescents, while they have a lower Vd. Plasma concentrations of the drug exceed the expected levels after taking eletriptan at the same dose in adults.

Patients with hepatic impairment (Child-Pugh class A and B) showed a statistically significant increase in AUC (34%) and T 1/2, as well as a slight increase in Cmax (18%), but these small changes are not considered clinically insignificant.

In patients with mild (creatinine clearance 61-89 ml / min), moderate (creatinine clearance 31-60 ml / min) and severe (creatinine clearance

Indications

For rapid relief (relief) of migraine attacks with or without aura.

Use during pregnancy and lactation

There is no clinical experience of using Relpax during pregnancy. The use of the drug is possible only in cases where the intended benefit of therapy for the mother exceeds the potential risk to the fetus.

Eletriptan is excreted in breast milk in women. With a single dose of Relpax 80 mg, excretion in breast milk within 24 hours averaged 0.02% of the dose taken. The risk of exposure to eletriptan in a newborn can be minimized if you do not breastfeed it within 24 hours after taking Relpax.

In experimental studies on animals, Relpax did not have a teratogenic effect.

Use in children

Contraindication: children and adolescents under 18 years of age (data on the effectiveness and safety of the drug in this age group are limited).

Use in children

Contraindication: children and adolescents under 18 years of age (data on the effectiveness and safety of the drug in this age group are limited).

Contraindications

• Severe violations of liver function;
• uncontrolled hypertension;
• ischemic heart disease: angina; Prinzmetal’s angina; myocardial infarction; confirmed asymptomatic myocardial ischemia; suspected coronary artery disease;
• occlusive peripheral vascular disease;
• cerebrovascular accident or transient ischemic attack in history;
• within 24 hours before or after taking Relpax cannot be applied ergotamine or derivatives of ergotamine (including metisergid);
• simultaneous reception of Relaxa with other agonists of serotonin 5-HT 1 receptor;
• childhood and adolescence to 18 years (since the effectiveness and safety of the drug in this age group have not determined);
• Hypersensitivity to eletriptan and other components of the drug.

Use in patients with liver function disorders

Contraindication: severe liver function disorders

In patients with impaired liver function (Child-Pugh class A and B), there was a statistically significant increase in AUC (34%) and T1 / 2, as well as a slight increase in Cmax (18%), but these small changes are not considered clinically insignificant.

No dose adjustment is required in patients with mild to moderate hepatic impairment. In patients with severe hepatic impairment, the efficacy and safety of Relpax have not been studied, so the drug is contraindicated in such cases.

Use in patients with impaired renal function

In patients with mild (creatinine clearance 61-89 ml / min), moderate (creatinine clearance 31-60 ml / min) and severe (creatinine clearance

In patients with impaired renal function, the hypertensive effect of Relpax increases, so you should be careful to prescribe the drug in doses exceeding 40 mg. When using Relpax at doses of 60 mg or more (in the therapeutic dose range), a small and transient increase in blood pressure was recorded, which increased to a greater extent in patients with impaired renal function and in elderly patients (such changes were not accompanied by clinical consequences).

Side effects

In general, Relpax is well tolerated. Usually, side effects are transient, mild or moderate, and go away on their own without additional treatment.The frequency of adverse reactions in patients taking the drug 2 times within 24 hours in the same dose to stop the attack is similar to those in patients taking the drug once. The main side effects reported during Relpax treatment are typical for the entire class of serotonin 5-HT1 receptor agonists.

Serious cardiovascular side effects, in some cases fatal, have been reported with serotonin 5-HT1 receptor agonists, including Relpax. These reactions were extremely rare and were observed mainly in patients with concomitant risk factors.

• The following adverse reactions were observed in patients taking Relpax at therapeutic doses (with a frequency of ≥1%, compared with placebo). Determination of the frequency of adverse reactions:
• often (≥1/100 to <1/10),
• infrequently (≥1/1000 to 1/100),
• rarely (≥1/10,000 to 1/1000).

From the respiratory system: often-pharyngitis, rhinitis, a feeling of “tightness” in the throat; sometimes-dyspnea, yawning; rarely-respiratory tract infections, bronchial asthma, changes in the timbre of the voice.

From the lymphatic system: rarely-lymphadenopathy.

From the side of metabolism: infrequently – anorexia.

Mental disorders: infrequently-impaired thinking, agitation, confusion, depersonalization, euphoria, depression, insomnia; rarely-emotional lability.

From the nervous system: often-drowsiness, headache, dizziness, tingling sensation or other sensory disorders, muscle hypertonus, hypesthesia, myasthenia gravis; infrequently-tremor, hyperesthesia, ataxia, hypokinesia, speech disorders, stupor, impaired taste sensations.

From the sensory organs: often-vertigo; infrequently-visual impairment, eye pain, photophobia and lacrimation disorders, pain in the ears, ringing in the ears; rarely-conjunctivitis.

From the cardiovascular system: often-palpitation, tachycardia; rarely-angina, increased blood pressure, bradycardia, shock.

From the digestive system: often-abdominal pain, nausea, dry mouth, dyspepsia; infrequently-diarrhea, glossitis; rarely-constipation, esophagitis, tongue edema, belching, hyperbilirubinemia, increased ACT activity.

From the skin and subcutaneous tissue: often-increased sweating; infrequently-rash, pruritus; rarely-skin diseases, urticaria.

From the musculoskeletal system: often-back pain, muscle pain; infrequently-joint pain, osteoarthritis and bone pain; rarely-arthritis, myopathy, myalgia, convulsions.

From the urinary system: infrequently-frequent urination, polyuria.

From the side of the reproductive system: rarely-pain in the mammary glands, menorrhagia.

General disorders: often-a feeling of warmth or “hot flashes” to the face, chills, asthenia, chest symptoms (pain, feeling of compression, pressure); infrequently – general weakness, swelling of the face, thirst, peripheral edema.

Side effects reported in post-marketing studies

From the nervous system: rarely-fainting states.

From the cardiovascular system: arterial hypertension.

From the digestive system: rarely-ischemic colitis, vomiting.

Allergic reactions: angioedema.

Interaction

Effect of other drugs on eletriptan

Concomitant use of erythromycin (1 g) and ketoconazole (400 mg), which are potent specific inhibitors of CYP3A4, revealed a significant increase in the cmax (2 and 2.7 times, respectively) and AUC (3.6 and 5.9 times, respectively) of eletriptan. These effects were accompanied by an increase in T 1/2 of eletriptan from 4.6 to 7.1 hours with erythromycin and from 4.8 to 8.3 hours with ketoconazole. Therefore, Relpax should not be used in combination with potent CYP3A4 inhibitors, in particular ketoconazole, itraconazole, erythromycin, clarithromycin, josamycin and protease inhibitors (ritonavir, indinavir and nelfinavir).

The interaction of Relpax with beta-blockers, tricyclic antidepressants, selective serotonin reuptake inhibitors and flunarizine has not been revealed, but the results of special clinical studies on interaction with these drugs are currently absent (with the exception of propranolol).

Population pharmacokinetic analysis of clinical studies showed that the effect of the following drugs on the pharmacokinetics of Relpax is unlikely: beta-blockers, tricyclic antidepressants, selective serotonin reuptake inhibitors, estrogen-containing HRT drugs and estrogen-containing oral contraceptives, calcium channel blockers.

Eletriptan is not an MAO substrate. In this regard, the interaction of Relpax and MAO inhibitors is not expected, and no special studies of their interaction have been conducted.

When propranolol (160 mg), verapamil (480 mg), or fluconazole (100 mg) is co – administered, eletriptan’s cmax increases by 1.1,2.2, and 1.4 times, respectively, and its AUC increases by 1.3,2.7, and 2 times. These changes are considered clinically insignificant, since they were not accompanied by an increase in blood pressure or an increase in the frequency of adverse events compared to those with the use of eletriptan alone.

Oral use of caffeine / ergotamine 1 and 2 hours after Relpax leads to a small but additive increase in blood pressure, which could be predicted based on the pharmacological properties of these drugs. In this regard, drugs containing ergotamine, or derivatives of ergotamine (including dihydroergotamine ) do not prescribe within 24 hours after taking Relpax.

Conversely, Relpax can be prescribed no earlier than 24 hours after taking ergotamine-containing drugs.

Effect of eletriptan on other drugs

There are no in vitro or in vivo data indicating that Relpax in clinical doses inhibits or induces cytochrome P 450 isoenzymes. A clinically significant interaction of Relpax due to the effect on these enzymes seems unlikely.

Interaction with serotonergic drugs

Concomitant use of 5-HT serotonin receptor agonists, including eletriptan, with drugs with serotonergic activity, such as selective serotonin reuptake inhibitors and selective serotonin and norepinephrine reuptake inhibitors, may increase the risk of serotonin syndrome.

Caution should be exercised when concomitant use of eletriptan and serotonergic drugs is clinically necessary. Such patients should be carefully monitored, especially at the beginning of treatment and when increasing the dose of each drug.

How to take, course of use and dosage

The drug is prescribed inside. Tablets should be swallowed whole, washed down with water.

If a migraine headache occurs, Relpax should be taken as early as possible after the onset of a migraine headache, but the drug is also effective at a later stage of a migraine attack.

For adult patients (aged 18-65 years), the recommended starting dose is 40 mg. If the migraine headache stops, but then resumes within 24 hours, then Relpax can be prescribed again in the same dose.

If a second dose is needed, it should be taken no earlier than 2 hours after the first dose.

If the first dose of Relpax does not reduce the headache within 2 hours, then the second dose should not be taken to stop the same attack, since in clinical studies the effectiveness of such treatment has not been proven. At the same time, patients who failed 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 achieve an adequate effect, then a dose of 80 mg may be effective for subsequent migraine attacks.

The daily dose should not exceed 160 mg.

Overdose

Symptoms: it is possible to develop arterial hypertension or other disorders of the cardiovascular system.

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

Special instructions

It is not recommended to use Relpax in combination with potent inhibitors of the CYP3A4 isoenzyme, in particular, with ketoconazole, itraconazole, erythromycin, clarithromycin, josamycin and protease inhibitors such as ritonavir, indinavir and nelfinavir. In addition, Relpax should not be taken within 72 hours after the end of taking inhibitors of the CYP3A4 isoenzyme.

Like other serotonin 5-HT1 receptor agonists, Relpax should only be used when the diagnosis of migraine is clear.

Relpax, like other serotonin 5-HT1 receptor agonists, should not be prescribed for the treatment of “atypical” headaches that may be associated with serious diseases (stroke, aneurysm rupture), when vasoconstriction of the brain can be harmful.

Cases of cerebral hemorrhage, subarachnoid hemorrhage, stroke, or other cerebrovascular disorders, in some cases fatal, have been reported with the use of serotonin 5-HT1 receptor agonists. In several cases, a cerebrovascular disorder was the main disease and serotonin 5-HT1 receptor agonists were used incorrectly, treating the symptoms as signs of migraine.Keep in mind that patients with migraines may have an increased risk of cerebrovascular complications (such as stroke, hemorrhage, and transient ischemic attack).

Concomitant use of eletriptan and SSRIs (e. g. fluoxetine, paroxetine, sertraline, fluvoxamine, citalopram, escitalopram) and SSRIs (e. g. venlafaxine, duloxetine) may lead to the development of potentially life-threatening serotonin syndrome. This syndrome may present with the following symptoms: disturbed mental status (e. g. agitation, hallucinations, coma), instability of the autonomic nervous system (e. g. tachycardia, blood pressure fluctuations, hyperthermia), impaired neuromuscular function (e. g. hyperreflexia, impaired coordination), and/or symptoms of impaired digestive function (e. g. nausea, vomiting, diarrhea).

It is not recommended to use Relpax in patients with risk factors for CHD (for example, arterial hypertension, hypercholesterolemia, smoking, obesity, diabetes mellitus, a burdened family history, women in a state of surgical or physiological menopause, or men over 40 years of age). until a thorough examination of the circulatory system is performed and cardiovascular disease is excluded.

The sensitivity of methods for assessing the state of the cardiovascular system is rather low. In this regard, if the patient’s medical history, ECG or other diagnostic procedures show signs that are characteristic of arterial vasospasm or myocardial ischemia, it is not recommended to use eletriptan.

In patients with risk factors for cardiovascular disease, but who have assessment of the cardiovascular system showed a satisfactory result, it is recommended that the first dose of eletriptan to take under the supervision of a physician, except for patients who had previously received eletriptan. Because myocardial ischemia can occur in the absence of clinical symptoms, should consider an EKG immediately after ingestion, Relpax.

Patients with risk factors for cardiovascular diseases, as described above, who receive eletriptan for a long time, but with interruptions, should periodically undergo a cardiovascular examination, as they continue therapy with eletriptan.

Systematic adherence to the recommendations outlined above leads to a decrease in the number of cases when patients with unknown cardiovascular diseases receive eletriptan therapy.

Cases of severe cardiac dysfunction, including myocardial infarction, life-threatening cardiac arrhythmias, and deaths that developed in the first few hours after taking the drug, have been reported with serotonin 5-HT1 receptor agonists. Given the widespread use of serotonin 5-HT1 receptors in patients with migraines, the frequency of these reactions is extremely low.

The following reports were received during clinical trials. Among patients who underwent diagnostic coronary angiography, one patient receiving intravenous eletriptan (Cmax 127 ng / ml, equivalent to 60 mg of eletriptan for oral use) with a history of angina pectoris, hypertension, and hypercholesterolemia experienced a feeling of tightness in the chest, and coronary angiospasm (confirmed by angiography)was detected no ECG changes characteristic of ischemia. In addition, one case of atrial fibrillation has been reported in a patient with a history of atrial fibrillation.

In the post-marketing period, cases of severe cardiovascular complications, some of which were fatal, were reported. In very rare cases, these complications occurred in the absence of any signs of cardiovascular disease. However, given the difficulty of monitoring reports received in the post-marketing period, it is not possible to definitively determine the relationship of these cases with the use of eletriptan.

Relpax should not be prescribed without a preliminary examination to patients who are likely to have cardiovascular diseases or are at increased risk of developing them. Systemic studies of eletriptan in patients with heart failure have not been conducted. The use of eletriptan, as well as other serotonin 5-HT1 receptor agonists, is not recommended in these patients.

Relpax is effective in treating migraines with and without aura and migraines associated with the menstrual cycle. Relpax, taken during the appearance of the aura, does not prevent the development of headaches, so it should only be taken during the headache phase.

Clinical studies have shown that Relpax is also effective for relieving the symptoms that accompany migraines, such as nausea, vomiting, photophobia, phonophobia, and for treating the return of headaches during an attack.

Relpax should not be taken prophylactically.

When using Relpax in therapeutic doses of 60 mg or more, a small and transient increase in blood pressure was recorded.

Blood pressure increased to a greater extent in patients with impaired renal function and the elderly.

It should be borne in mind that the unlimited use of anti-migraine medications can lead to chronic daily headaches. Cases of excessive use of any triptans are most often observed in patients with daily headaches.

Influence on the ability to drive vehicles and work with mechanisms

In some cases, migraines themselves or taking serotonin 5-HT1 receptor agonists, including Relpax, may be accompanied by drowsiness or dizziness. Patients who perform work that requires increased attention, such as driving vehicles and working with complex mechanisms, should exercise caution during migraine attacks and after taking Relpax.

Form of production

Coated tablets.

Storage conditions

Store at a temperature not exceeding 30°C, out of the reach of children.

Shelf

life is 3 years.

Active ingredient

Eletriptan

Conditions of release from pharmacies

By prescription

Dosage form

Tablets

Purpose

For adults under 65 years of age as prescribed by a doctor, For adults as prescribed by a doctor

Indications

Migraine