RELPAKS
Active material: Eletriptan
When ATH: N02CC06
CCF: Serotoninovыh agonist 5-HT1-receptors. Protivomigrenoznoy drug with activity
ICD-10 codes (testimony): G43
When CSF: 02.16.05.01
Manufacturer: PFIZER (Germany)
Pharmaceutical form, composition and packaging
Pills, coated orange, round, lenticular, Engraved “REP 40” on one side and “Pfizer” – another.
| 1 tab. | |
| eletriptan (in the form of hydrobromide) | 40 mg |
Excipients: microcrystalline cellulose, lactose monohydrate, sodium croscarmellose, magnesium stearate, пленочная оболочка Opadry Orange OY-LS-23016 и Opadry Clear YS-2-19114-A.
2 PC. – blisters (1) – packs cardboard.
Pharmacological action
Protivomigrenozny drug. Eletriptan is a representative group of selective serotonin agonist of vascular 5-HT1B– nejronalʹnyh and 5-NT1D-receptors. Eletriptan has also high affinity to serotonin 5-HT1F-Receptor, that may be related to its mechanism of action protivomigrenoznomu, and has a moderate effect on the serotonin 5-HT1A-, 5-NT2B-, 5-NT1IS– and 5-NT7-receptors.
Compared with sumatriptan, Eletriptan exhibits a significantly greater selectivity to serotonin receptors, located in the carotid arteries, than in the coronary and femoral arteries. Ability eletriptan narrowing intracranial blood vessels, as well as its inhibitory effect against neurogenic inflammation may condition its protivomigrenoznuyu Activity.
Pharmacokinetics
Absorption
After oral eletriptan quickly and adequately absorbed from the gastrointestinal tract (absorption sostavlyaet about 81%). Men and women have the absolute oral bioavailability is about 50%. Tmax after ingestion plasma averaged 1.5 no. The range of therapeutic dosages (20-80 mg) eletriptan pharmacokinetics is characterized by a linear dependence.
Cmax eletriptan in plasma and AUC increased by about 20-30% while taking the drug after eating fatty foods. When administered during a migraine attack AUC decreased by approximately 30%, Tmax in the blood plasma was increased to 2.8 no.
With regular use (by 20 mg 3 times / day) during 5-7 days pharmacokinetics of eletriptan remained linear with a predictable cumulation. When administered in higher doses (40 mg 3 times / day and 80 mg 2 times / day) during 7 days exceeded the expected accumulation of eletriptan (about 40%).
Distribution
Vd if eletriptan / in the introduction of 138 l, indicating good distribution in the tissue. Eletriptan moderately associated with malnutrition (about 85%).
Metabolism
In vitro studies suggest that, that the primary metabolism occurs under the action of eletriptan isoenzyme CYP3A4 in the liver. This fact is confirmed by increasing concentrations of eletriptan in the blood plasma, while the use of erythromycin, which is a potent selective inhibitor of CYP3A4. In vitro studies also show a small part in the metabolism of CYP2D6 eletriptan, Although clinical studies have not revealed the clinical effect of polymorphism of the enzyme on the pharmacokinetic parameters of eletriptan.
Identified two major circulating metabolite, which account for a significant portion of the total plasma radioactivity after administration of eletriptan, labeled 14FROM. Metabolite, resulting from the oxidation of N-, He had no activity in animal in vitro. Metabolite, resulting from N-demethylation, of activity was comparable to eletriptanom in animal studies in vitro. The third component of the radioactive plasma is not identified, believe, it is a mixture of hydroxylated metabolites, which are also excreted in the urine and feces.
The concentration of the N-demethylated active metabolite in plasma is only 10-20% the concentration of eletriptan and accordingly does not contribute significantly to its therapeutic effect.
Deduction
The total clearance of eletriptan from blood plasma after / in the averages 36 l /, a T1/2 – about 4 no. The average renal clearance after oral administration is approximately 3.9 l /. The share of extrarenal clearance is approximately 90% of the total clearance; this indicates, that eletriptan output, mainly, in the form of metabolites in urine and faeces.
Pharmacokinetics in special clinical situations
Paul
The results of a meta-analysis of clinical and pharmacological studies and population pharmacokinetic analysis suggests, that the floor has no clinically significant impact on the concentration in the blood plasma of eletriptan.
Elderly patients (senior 65 years)
The elderly (65-93 year) found small and statistically non-significant decrease (on 16%) clearance of eletriptan and a statistically significant increase in T1/2 (approximately 4.4 to 5.7 no) compared to those of young adults. Effect of eletriptan on blood pressure in the elderly may be more pronounced compared to younger patients.
Adolescents 12-17 years
Pharmacokinetics эletriptana (40 mg 80 mg) in adolescents aged 12-17 years with migraine, taking the drug in the interictal period, It was similar to that in healthy adults.
Children 7-11 years
In children 7-11 s clearance of eletriptan is no different from that of adolescents, while they below Vd. Concentrations of drug in plasma levels higher than expected it after taking eletriptan at the same dose in adults.
Abnormal liver function
In patients with impaired liver function (Classes A and B in Child-Pugh) a statistically significant increase in AUC (on 34%) and T1/2, as well as a slight increase in Cmax (on 18%), However, these small changes are not considered clinically insignificant.
Impaired renal function
Patients with mild (CC 61-89 ml / min), moderate (CC 31-60 ml / min) and expressed (CC<30 ml / min) impaired renal function showed no significant changes in the pharmacokinetics of eletriptan or its binding to plasma proteins.
Testimony
- Relief of migraine with aura and without aura.
Dosage regimen
The drug is prescribed inside. The tablets should be swallowed whole, drinking water.
When a migraine headache Relpaks® It should be taken as early as possible after the start of migraine headaches, However, the drug is effective and at a later stage of a migraine attack.
To adult patients (aged 18-65 years) The recommended starting dose is 40 mg.
If migraine headache docked, but then resumed within 24 no, the Relpaks® You can be assigned repeatedly at the same dose. If you need a second dose, it should be taken no earlier than, than 2 hours after the first dose.
If the first dose Relpaksa® It does not lead to a reduction in headache during 2 no, for the relief of the same attack should not take a second dose, tk. in clinical studies, the effectiveness of this treatment has not been proven. Thus patients, who have failed to stop the attack, may provide an effective clinical response at the next attack.
If the drug at a dose of 40 mg does not allow for adequate effect, then in subsequent migraine attacks can be effective dose 80 mg.
The daily dose should not exceed 160 mg.
Side effect
Patients, taking Relpaks® at therapeutic doses, The following adverse reactions have been observed (a frequency ≥1% compared to placebo).
From the body as a whole: asthenia, backache, pain and tightness in the chest, chills.
Cardio-vascular system: sensation of heat or hot flashes to the face, palpitations, tachycardia, anginal pain, increased blood pressure.
From the central and peripheral nervous system: drowsiness, dizziness, paresthesia, headache, gipesteziya, Sweating, feeling “coma” in the throat, syncope (rarely).
From the digestive system: stomach ache, dry mouth, nausea, dyspepsia, ishemicheskiy colitis (rarely).
On the part of the musculoskeletal system: myasthenia, myalgia.
The respiratory system: pharyngitis.
On the part of the immune system: allergic reactions (some of which may be severe), incl. rash, itch, hives.
Common side effects, registered in the treatment Relpaksom®, They are typical of the entire class of agonists of serotonin 5-HT1-receptors.
Overall Relpaks® well tolerated. Usually, side effects are transient in nature, slightly or moderately expressed and tested independently without additional treatment. The frequency and severity of adverse reactions in patients, taking the drug 2 times in one and the same dose for cupping, similar to those of patients, taking the drug once.
Contraindications
- Severe liver;
- Uncontrolled hypertension;
- CHD (angina, Prinzmetal angina, myocardial infarction, confirmed asymptomatic myocardial ischemia) or suspected,;
- Occlusive peripheral vascular disease;
- Cerebrovascular accident or transient ischemic attack in history;
- During 24 hours before or after taking Relpaksa® can not be used ergotamine or derivatives of ergotamine (incl. methysergide);
- Simultaneous reception Relpaksa® with other agonists of serotonin 5-HT1-receptors;
- Childhood and adolescence up 18 years (tk. the efficacy and safety of the drug in this age group may not be established);
- Hypersensitivity to the drug.
Pregnancy and lactation
Clinical experience with Relpaksa® during pregnancy is not. Use of the drug is possible only in cases, when the anticipated benefits of therapy to the mother outweighs the potential risk to the fetus.
Eletriptan is excreted in breast milk in women. In one clinical study 8 Women received a single dose of the drug 80 mg. Withdrawal of eletriptan in breast milk over the 24 h averaged 0.02% dose. Nonetheless, during breastfeeding Relpaks® should be used with caution. The risk of exposure to the drug in the newborn can be minimized, if you do not breastfeed for 24 h after administration Relpaksa®.
Cautions
We do not recommend the use of Relpaksa® in combination with potent inhibitors of CYP3A4, in particular, ketoconazole, itraconazole, Erythromycin, clarithromycin, josamycin and protease inhibitors, such as ritonavir, indinavir and nelfinavir.
Like other agonists of serotonin 5-HT1-receptors, Relpaks® It should be applied only in cases, when the diagnosis of migraine is not in doubt. Relpaks® It is not indicated for the relief of hemiplegic, oftalmoplegicheskoy or basilar migraine.
Relpaks® effective in the treatment of migraine with aura and migraine without aura and, concomitant menstrual cycle. Relpaks®, received during an appearance aura, It does not prevent the development of headaches, it should be taken only during the headache phase.
Relpaks®, as the other agonists of serotonin 5-HT1-receptors, should not be prescribed for the treatment of “atypical” headaches, which may be associated with serious diseases (stroke, aneurysm rupture), When narrowing of cerebral vessels can be harmful.
Relpaks® should not be taken prophylactically.
Relpaks® should not be given without prior examination of the patient, which is probably the presence or increased risk of cardiovascular disease.
In patients with mild or moderate hepatic impairment dose modification is not required. In patients with severe hepatic impairment efficacy and safety Relpaksa® not investigated, Therefore, in such cases, the drug is contraindicated.
In patients with impaired renal hypertensive effect is enhanced Relpaksa®, therefore, caution should be prescribed the drug in doses, exceeding 40 mg. When using Relpaksa® doses 60 mg, and more (in the therapeutic dose range) recorded a slight and transient increase in blood pressure, which rises to a greater extent when the kidney function and elderly patients (such changes were not accompanied by clinical consequences).
Effects on ability to drive vehicles and operate machinery
In some cases, the very migraine or reception agonists of serotonin 5-HT1-receptors, including Relpaks®, They may be accompanied by drowsiness or dizziness. Patients in the performance of work, requiring greater attention, such as driving and working with complex mechanisms, caution should be exercised during migraine attacks and after administration of Relpaksa®.
Overdose
Symptoms: may develop hypertension or other more serious violations of the cardiovascular system.
Treatment: maintenance therapy. T1/2 Eletriptan is about 4 no, so in case of an overdose must be monitored for patients, at least, during 20 hours or until the disappearance of clinical symptoms. Effect of hemodialysis and peritoneal dialysis on serum concentrations of eletriptan not known.
Drug Interactions
The influence of other drugs on eletriptan
When concomitant administration of erythromycin (1 g) and ketoconazole (400 mg), It is a potent specific inhibitors of CYP3A4, revealed a significant increase in Cmax (in 2 and 2.7 fold, respectively) и AUC (in 3.6 and 5.9 fold, respectively) eletriptan. These effects were accompanied by an increase in T1/2 with eletriptan 4.6 to 7.1 h when using erythromycin and 4.8 to 8.3 h when using ketoconazole. Therefore Relpaks® should not be used in combination with potent inhibitors of CYP3A4, particularly ketoconazole, itraconazole, Erythromycin, clarithromycin, josamycin and protease inhibitors (ritonavirom, indinavir and nelfinavir).
Interaction Relpaksa® with beta-blockers, tricyclic antidepressants, selective serotonin reuptake inhibitors and flunarizine have been identified, but the results of the special clinical interaction studies with these drugs currently available (except for propranolol).
Population pharmacokinetic analysis of clinical studies have shown, that the effect of these drugs on the pharmacokinetics of Relpaksa® maloveryatno: beta-blockers, tricyclic antidepressants, selective serotonin reuptake inhibitor, estrogenosoderzhaschie HRT and oral contraceptives estrogenosoderzhaschie, Calcium channel blockers.
Eletriptan is not a substrate of MAO. In this regard, the interaction is assumed not Relpaksa® and MAO inhibitors, special studies of their interaction was conducted.
With simultaneous use of propranolol (160 mg), verapamil (480 mg) or fluconazole (100 mg) Cmax eletriptan increases respectively 1.1, 2.2 and 1.4 times, and its AUC – in 1.3, 2.7 and 2 times. These changes are considered to be clinically insignificant, tk. they were not accompanied by an increase in blood pressure or increase in frequency of adverse events, as compared with that in the application of eletriptan.
Caffeine / ergotamine in through 1 and 2 h after Relpaksa® results in a slight, but additive increase blood pressure, which can be predicted on the basis of the pharmacological properties of these drugs. In this connection, preparations, containing ergotamine, ergotamine derivatives or (incl. digidroergotamin) should not be given within 24 h after administration Relpaksa®.
And vice versa, Relpaks® It can be administered no earlier than 24 h after administration of drugs ergotaminosoderzhaschih.
Effect of eletriptan on other drugs
These in vitro or in vivo that, that Relpaks® clinical doses inhibits or induces cytochrome P450 isozymes absent. Clinically significant interaction Relpaksa®, due to the influence of these enzymes, it seems unlikely.
Conditions of supply of pharmacies
The drug is released under the prescription.
Conditions and terms
The drug should be stored out of reach of children at or above 30 ° C. Shelf life – 3 year.
