Expiration date: 04/2022
Structure and Composition:
1 tablet contains Eletriptan (hydrobromide salt) 40 mg
Excipients: lactose monohydrate MCC Croscarmellose Sodium Magnesium Stearate
film coating: Opadry Orange OY-LS-23016 (hypromellose, lactose monohydrate, titanium dioxide (E171), triacetin, dye sunset yellow with lacquered aluminum (E110) Opadry clear YS-2-19114-A (hypromellose, triacetin)
Description pharmaceutical form:
Tablets 40 mg: orange round biconvex, film-coated, engraved with «REP 40 'on one side and« Pfizer »- on the other side.
Suction. After oral eletriptan quickly and adequately absorbed from the gastrointestinal tract, absorption is approximately 81%. The absolute oral bioavailability in men and women is about 50%. Tmax plasma in an average of 1.5 hours after ingestion. The therapeutic dose range from 20 mg to 80 mg of eletriptan pharmacokinetics characterized by a linear relationship.
Eletriptan Cmax and AUC were increased by about 20-30% while taking the drug after ingestion of fatty foods. When administered during the migraine attack AUC was decreased by about 30%, and Tmax in the blood plasma was increased to 2.8 hours.
With regular use (20 mg 3 times daily) for 5-7 days, the pharmacokinetics of eletriptan remained linear with a predictable cumulation. When administered at higher doses (40 mg three times daily and 80 mg 2 times a day) exceeds the expected (about 40%) for more than 7 days cumulation eletriptan.
Distribution. Vd eletriptan by intravenous administration of 138 l, which indicates good tissue distribution. Eletriptan binds moderately to plasma proteins (approximately 85%).
Metabolism. in vitro studies suggest that the primary metabolism occurs under the action of eletriptan CYP3A4 isoenzyme of cytochrome P450 in the liver. This fact is confirmed by an increase in plasma concentrations of eletriptan while taking erythromycin, which is a potent selective inhibitor of CYP3A4 isoenzyme. in vitro studies also show that CYP2D6 isozyme contributes to the metabolism of eletriptan, although clinical trials revealed no effect of the enzyme polymorphism on the pharmacokinetics of eletriptan.
It identified 2 major circulating metabolite, which account for a significant portion of the total radioactivity in blood plasma after administration of eletriptan, 14C-labeled carbon.
In experiments in vitro metabolite resulting from the N-oxidation had no activity, while the metabolite resulting from the N-demethylation, was comparable in activity eletriptanom. The third component of the radioactive plasma is not identified. It is believed that it is a mixture of hydroxylated metabolites which are also excreted by the kidneys and the bowel.
The concentration of the N-demethylated active metabolite in plasma is 10-20% of the total concentration of eletriptan and thus does not contribute significantly to its therapeutic effect.
Withdrawal. Eletriptan Total clearance from plasma after intravenous administration is an average of 36 l / h, and the half-life (T1 / 2) -. Approximately 4 hours Average renal clearance after ingestion of about 3.9 l / h. Ratio nonrenal clearance is about 90% of this total clearance indicating that eletriptan derived mainly as metabolites via the kidneys and intestines.
Pharmacokinetics in special patient groups
Floor. Meta-analysis of clinical and pharmacological studies and population pharmacokinetic analysis indicate that the floor has no clinically significant impact on the concentration in the blood plasma of eletriptan.
Older people (over 65 years). In elderly (65-93 years) showed small and statistically insignificant decrease in clearance of 16% of eletriptan and a statistically significant increase in T1 / 2 (approximately 4.4 to 5.7 hours) as compared to these parameters in young people. Effect of eletriptan on blood pressure in the elderly may be more pronounced when compared with younger patients.
Abnormal liver function. In patients with impaired hepatic function (steps A and B for the classification of Child-Pugh) revealed a statistically significant increase in AUC (34%) and T1 / 2, as well as a slight increase in the Cmax (18%), but these changes are not clinically significant .
Impaired renal function. In patients with mild (Cl creatinine 61--89 mL / min), moderate (Cl creatinine 31-60 ml / min) or severe (Cl creatinine <30 ml / min) renal dysfunction did not reveal statistically significant changes in the pharmacokinetics of eletriptan or degree its binding to plasma proteins.
Description of the pharmacological actions:
Eletriptan is a representative of the group of serotonin agonists, selective 5-HT1B- vascular and neuronal 5-HT1D-receptor. Eletriptan has also high affinity for 5-HT1F-receptors and has a moderate effect on the 5-HT1A-, 5-HT2B-, 5-HT1E- and 5-HT7-receptors.
In comparison with sumatriptan, eletriptan exhibits a significantly greater selectivity to serotonin receptors located in the carotid arteries than at serotonin receptors located in the coronary and femoral arteries. Ability eletriptan narrowing of intracranial blood vessels, as well as its inhibitory effect against neurogenic inflammation may condition its protivomigrenoznuyu activity.
Relief of migraine with aura or without aura.
- Hypersensitivity to eletriptanu or any other component of the drug
- severe liver function abnormalities
- age of 18 years (data on the efficacy and safety of the drug in this age group is limited)
- concomitant use with inhibitors of CYP3A4 (ketoconazole, itraconazole, erythromycin, clarithromycin, josamycin) and protease inhibitors (ritonavir, indinavir and nelfinavir).
Like other receptor agonist of 5-hydroxytryptamine type I (5-HT1), listed below are contraindications to the use of eletriptan justified its pharmacodynamic properties:
- uncontrolled hypertension
- Ischemic heart disease (angina pectoris, Prinzmetal angina, myocardial infarction, confirmed asymptomatic myocardial ischemia) or suspicion of its presence
- occlusive peripheral vascular disease
- cerebrovascular accident or transient ischemic attack in history
- concomitant use with other agonists of 5-HT1-receptors
- for 24 hours before or after administration of ergotamine eletriptan can not be used or ergotamine derivatives, including methysergide (see. "Interaction" section)
- relief of hemiplegic, basilar migraine or oftalmoplegicheskoy
- rare hereditary diseases (lactose intolerance, lactase deficiency or glucose-lactose malabsorption).
- serotonin syndrome: while the use of eletriptan with other drugs having serotonergic activity such as SSRIs and selective serotonin reuptake inhibitors and norepinephrine (SNRI), care must be taken because in some cases there were reports about the development of serotonin syndrome while taking eletriptan and other serotonergic drugs
- use of the drug in doses greater than 40 mg in patients with impaired renal function (as in these patients the effect of eletriptan Naadam is enhanced).
Application of pregnancy and breastfeeding:
Relpax clinical experience in pregnant women is not. In animal studies, the drug had no teratogenic effects. Relpax should be administered only in cases where the expected benefit to the mother is significantly greater than the potential risk to the fetus.
Relpax excreted in breast milk in women. In single dose Relpax 80 mg excretion in breast milk within 24 hours by an average of 0.02% of the dose. The risk of exposure to the drug in the newborn can be minimized if you do not breastfeed for 24 hours after taking eletriptan.
In general, Relpax 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 dosage a double cupping are similar to those in patients taking it once. Major side effects registered in treating Relpax are typical for the entire class of agonists of 5-HT1-receptors.
Patients taking therapeutic doses Relpax , the following adverse reactions were observed (with frequency & ge1% or higher compared with placebo). These phenomena were divided into the following categories according to the frequency: often - & ge1 / 100 to <1/10 uncommon - & ge1 / 1,000 to <1/100 rarely - & ge1 / 10,000 to <1/1000.
Infections: often - pharyngitis and rhinitis rare - respiratory infection.
Violations of the lymphatic system: rarely - lymphadenopathy.
Eating disorders and metabolism: rarely - anorexia.
Mental disorders: Infrequent - abnormal thinking, agitation, confusion, depersonalisation, euphoria, depression, insomnia rarely - emotional lability.
Disorders of the nervous system: often - drowsiness, headache, dizziness, tingling or other sensory disturbances, muscle hypertonicity, hypoesthesia, myasthenia infrequent - tremor, hyperaesthesia, ataxia, hypokinesia, speech disorder, stuporous state, dysgeusia.
Violations of the organ of vision: rarely - blurred vision, eye pain, photophobia, and lacrimation violation rarely - conjunctivitis.
Violations of the hearing and balance: often - vertigo uncommon - ear pain, ringing in the ears.
Violations by the CCC: often - heart palpitations, and tachycardia rarely - angina, increased blood pressure, bradycardia, shock.
Respiratory, thoracic and mediastinal disorders: often - a feeling of tightness in the throat, seldom - dyspnoea, yawning rarely - asthma and voice changes timbre.
Disorders of the digestive system: often - abdominal pain, nausea, dry mouth, dyspepsia and rarely - diarrhea, glossitis, rarely - constipation, oesophagitis, swelling of the tongue, belching.
Violations of the hepatobiliary system: rarely - hyperbilirubinemia, elevated AST.
Violations of the skin and subcutaneous tissue: often - increased sweating rare - rash, itching, rarely - skin diseases, urticaria.
Violations of the musculoskeletal system, connective tissue and bone: often - back pain, pain in the muscles rarely - arthralgia, arthrosis and bone pain, rarely - arthritis, myopathy, myalgia, convulsions.
Violations of the urinary system: rarely - violations of the urinary tract (frequent urination, polyuria).
Violations of the reproductive system and breast cancer: rarely - breast pain, menorrhagia.
General disorders: often - a sensation of heat or hot flashes to the face, chills, fatigue, symptoms of the chest (pain, feeling of compression pressure), rarely - weakness, swelling of the face, thirst, peripheral edema.
In post-marketing studies have reported the following adverse effects:
- Violations of the immune system: allergic reactions.
- Disorders of the nervous system: Rare cases of syncope.
- Violations of the vascular system: arterial hypertension.
- Disorders of the digestive system: how to have and some of the other 5-HT1B / 1D-agonists, rare reports have been received of ischemic colitis, vomiting.
The influence of other drugs on the pharmacokinetics of eletriptan
When concomitant administration of erythromycin (1000 mg) and ketoconazole (400 mg), which are potent inhibitors of specific isoenzyme CYP3A4, Cmax increased eletriptan in 2 and 2.7 times respectively, and the AUC of eletriptan - 3.6 and 5.9 times respectively. Thus T1 / 2 eletriptan increased from 4.6 to 7.1 hours when using erythromycin and from 4.8 to 8.3 parts - when using ketoconazole (see "Pharmacokinetics" section.). Thus Relpax not be used in combination with potent inhibitors isoenzyme CYP3A4, including ketoconazole, itraconazole, erythromycin, clarithromycin, josamycin and protease inhibitors (ritonavir, indinavir and nelfinavir).
Relpax interaction with beta-blockers, tricyclic antidepressants, SSRIs and flunarizine have been identified, but the results of specific clinical trials drug interactions is available (except for propranolol).
Population pharmacokinetic analysis of clinical studies have shown that these drugs are unlikely to affect the pharmacokinetics of eletriptan: beta-blockers, tricyclic antidepressants, SSRIs, estrogensoderzhaschie hormone replacement drugs, estrogensoderzhaschie oral contraceptive drugs and BPC.
Since eletriptan is not a MAO substrate pharmacokinetic interaction Relpax and MAO inhibitors is unlikely, and not conducted special studies of their interaction.
With simultaneous use of propranolol at a dose of 160 mg of verapamil dose of 480 mg fluconazole and 100 mg of eletriptan Cmax increased by 1.1, 2.2 and 1.4 times, and AUC - 1.3, 2.7 and 2 0 times respectively. These changes are not clinically significant, because they were not accompanied by increases in blood pressure or increase in frequency of adverse events compared to the use of eletriptan.
Caffeine / ergotamine inside after 1 and 2 hours after administration Relpax leads to a small, but increased blood pressure additive, which could have been predicted based on the pharmacological properties of these preparations. In this regard, preparations containing ergotamine or ergotaminopodobnye means, in particular, dihydroergotamine, should not be administered within 24 hours after receiving Relpax, Relpax can be administered no earlier than 24 hours after taking the drugs ergotaminosoderzhaschih.
Effect of eletriptan on other drugs
At therapeutic doses, did not reveal the effect (inhibition or induction) of the drug on the cytochrome P450 system.
Interaction with serotonergic drugs
The simultaneous use of agonists of 5-HT receptors, including eletriptan, with drugs having serotonergic activity such as SSRIs and SNRIs, may increase the risk of serotonin syndrome. In the case of clinical need simultaneous use of eletriptan and serotonergic drugs with caution. Such patients should be carefully monitored, especially in the beginning of the treatment and increase the dose of each drug.
Dosage and administration:
Inside. swallowing whole with water.
When a migraine headache Relpax should be taken as soon as possible, but the drug is effective in the later stages of a migraine attack.
Adults (18-65 years). The recommended starting dose is 40 mg.
If the headache is resumed for 24 hours, if docked migraine headache, but then resumed for 24 hours, then re Relpax can assign the same dose. If a second dose is needed, it should be taken no earlier than 2 hours after the first dose.
If no effect: if first dose Relpax does not reduce headache within 2 hours, then should not take a second dose for relief of attack, since in clinical studies, the effectiveness of this treatment has not been proven. At the same time, patients who failed to stop an attack, can provide an effective clinical response at the next attack.
If administration in a dose of 40 mg is not conducive to an adequate effect, in subsequent migraine attacks may be an effective dose of 80 mg.
The daily dose should not exceed 160 mg.
In patients with mild or moderate hepatic impairment dose modification is required.
Symptoms: the development of hypertension and other violations by the CCC.
Treatment: gastric lavage, symptomatic therapy. Since the T1 / 2 of eletriptan is about 4 hours, in the case of drug overdose, patients should be observed for at least 20 hours or until the disappearance of clinical symptoms of an overdose. Influence of hemodialysis and peritoneal dialysis, the concentration in the blood plasma of eletriptan unknown.
Relpax not recommended in combination with potent inhibitors isozymes CYP3A4, including ketoconazole, itraconazole, erythromycin, clarithromycin, josamycin and protease inhibitors such as ritonavir, indinavir and nelfinavir (cm. "Interaction").
Like other agonists of 5-HT1-receptors, Relpax should be used only in cases where the diagnosis of migraine is not in doubt. Relpax as the other agonists of 5-HT1-receptors, should not be administered for the treatment of atypical headaches that can be associated with serious diseases (stroke, aneurysm rupture), when the constriction of cerebral vessels can be harmful.
Relpax should not be used without prior examination of patients who likely to have cardiovascular disease or at increased risk of development (see. "Contraindications"). System study of eletriptan in patients with heart failure have not been performed. The use of eletriptan, as well as other agonists 5NT1 receptors in these patients is not recommended.
Relpax effective in the treatment of migraine with aura and migraine without aura and accompanying menstrual cycle. Relpax received during the appearance of the aura, it does not prevent the development of a headache, so it should only be taken during the headache phase.
In clinical studies have shown that Relpax is effective also for the relief of symptoms associated with a migraine, such as nausea, vomiting, photophobia, phonophobia, and return the treatment of headache during an attack.
Relpax should not be taken preventively.
When using Relpax in therapeutic doses of 60 mg or more recorded a slight and transient increase in blood pressure. For the most part it was increased in patients with impaired renal function and the elderly.
Effects on ability to drive and use machines. In some patients, migraine itself or reception agonist of 5-HT1-receptors, including eletriptan may be accompanied by dizziness or drowsiness. When performing tasks that require attention, such as driving and working with complex equipment, care should be taken during migraine attacks and after administration of Relpax.