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Eletriptan hydrobromide tablets contain eletriptan hydrobromide, which is a selective 5-hydroxytryptamine 1B/1D (5-HT1B/1D) receptor agonist.

Eletriptan hydrobromide is chemically designated as (R)-3-[(1-Methyl-2-pyrrolidinyl)methyl]-5-[2-(phenylsulfonyl)ethyl]-1H-indole monohydrobromide, and it has the following chemical structure: [Chemical Structure] The molecular formula is C22H26N2O2S.

HBr, representing a molecular weight of 463.43.

Eletriptan hydrobromide is an off-white to brown color powder that is freely soluble in methanol and very slightly soluble in water.

Each eletriptan hydrobromide tablet for oral administration contains 24.23 or 48.46 mg of eletriptan hydrobromide equivalent to 20 mg or 40 mg of eletriptan, respectively.

Each tablet also contains the inactive ingredients croscarmellose sodium, FD&C yellow 6 aluminum lake, hypromellose, lactose monohydrate, magnesium stearate, microcrystalline cellulose, titanium dioxide and triacetin.

Acute migraine therapy, with or without an aura.

The health category during pregnancy: "C": There are currently insufficient studies to confirm the safe use of treatment on the foetus.

A doctor or pharmacist must be consulted before treatment is taken in case of pregnancy, and it is also recommended to avoid pregnancy during the period of treatment.

It is not known whether the medication is being released in the breast milk of the infant.

The effectiveness or safety of the treatment use in children has not been demonstrated <18.

If the patient suffers from liver, heart or arteries, the doctor who is treated must be informed before the treatment is admitted, some cases may require modified doses.

Eletriptan binds with high affinity to 5-HT1B, 5-HT1D and 5-HT1F receptors, has modest affinity for 5-HT1A, 5-HT1E, 5-HT2B and 5-HT7 receptors.

Migraines are likely due to local cranial vasodilatation and/or to the release of sensory neuropeptides (vasoactive intestinal peptide, substance P and calcitonin gene-related peptide) through nerve endings in the trigeminal system.

The therapeutic activity of eletriptan hydrobromide for the treatment of migraine headache is thought to be due to the agonist effects at the 5-HT1B/1D receptors on intracranial blood vessels (including the arterio-venous anastomoses) and sensory nerves of the trigeminal system which result in cranial vessel constriction and inhibition of pro-inflammatory neuropeptide release. 12.3 Pharmacokinetics Absorption: Eletriptan is well absorbed after oral administration with peak plasma levels occurring approximately 1.5 hours after dosing to healthy subjects.

In patients with moderate to severe migraine the median Tmax is 2.0 hours.

The mean absolute bioavailability of eletriptan is approximately 50%.

The oral pharmacokinetics are slightly more than dose-proportional over the clinical dose range.

The AUC and

Cmax of eletriptan are increased by approximately to 30% following oral administration with a high fat meal.

Eletriptan hydrobromide can be taken with or without food.

The volume of distribution of eletriptan following IV administration is 138L.

Plasma protein binding is moderate and approximately 85%.

The N-demethylated metabolite of eletriptan is the only known active metabolite.

This metabolite causes vasoconstriction similar to eletriptan in animal models.

Though the half-life of the metabolite is estimated to be about 13 hours, the plasma concentration of the N-demethylated metabolite is to 20% of parent drug and is unlikely to contribute significantly to the overall effect of the parent compound.

In vitro studies indicate that eletriptan is primarily metabolized by cytochrome P-450 enzyme CYP3A4.

The terminal elimination half-life of eletriptan is approximately 4 hours.

Mean renal clearance (CLR) following oral administration is approximately 3.9 L/h.

Non-renal clearance accounts for about 90% of the total clearance.

The pharmacokinetics of eletriptan are generally unaffected by age.

Blood pressure was increased to a greater extent in elderly subjects than in young subjects.

The pharmacokinetic disposition of eletriptan in the elderly is similar to that seen in younger adults.

There is a statistically significant increased half-life (from about 4.4 hours to 5.7 hours) between elderly (65 to 93 years of age) and younger adult subjects (18 to 45 years of age) .

The pharmacokinetics of eletriptan are unaffected by gender.

A comparison of pharmacokinetic studies run in western countries with those run in Japan has indicated an approximate 35% reduction in the exposure of eletriptan in Japanese male volunteers compared to western males.

Population pharmacokinetic analysis of two clinical studies indicates no evidence of pharmacokinetic differences between Caucasians and non-Caucasian patients.

In a study of 16 healthy females, the pharmacokinetics of eletriptan remained consistent throughout the phases of the menstrual cycle.

There was no significant change in clearance observed in subjects with mild, moderate or severe renal impairment, though blood pressure elevations were observed in this population.

Subjects with mild or moderate hepatic impairment demonstrated an increase in both AUC (34%) and half-life.

Cmax was increased by 18%.

No dose adjustment is necessary in subjects with mild or moderate hepatic impairment.

The effects of severe hepatic impairment on eletriptan metabolism have not been evaluated.

CYP3A4 inhibitors: In vitro studies have shown that eletriptan is metabolized by the CYP3A4 enzyme.

A clinical study demonstrated about a 3-fold increase in Cmax and about a 6-fold increase in the AUC of eletriptan when combined with ketoconazole.

The half-life increased from 5 hours to 8 hours and the Tmax increased from 2.8 hours to 5.4 hours.

Another clinical study demonstrated about a 2-fold increase in Cmax and about a 4-fold increase in AUC when erythromycin was co-administered with eletriptan.

It has also been shown that co-administration of verapamil and eletriptan yields about a 2-fold increase in Cmax and about a 3-fold increase in AUC of eletriptan, and that co-administration of fluconazole and eletriptan yields about a 1.4-fold increase in Cmax and about a 2-fold increase in AUC of eletriptan.

Eletriptan hydrobromide is contraindicated within at least 72 hours of treatment with the following potent CYP3A4 inhibitors: ketoconazole, itraconazole, nefazodone, troleandomycin, clarithromycin, ritonavir and nelfinavir.

Eletriptan hydrobromide should not be used within 72 hours with drugs that have demonstrated potent CYP3A4 inhibition.

The Cmax and AUC of eletriptan were increased by and 33%, respectively, in the presence of propranolol.

No interactive increases in blood pressure were observed.

No dosage adjustment appears to be needed for patients taking propranolol.

The effect of eletriptan on other drugs: The effect of eletriptan on enzymes other than cytochrome P450 has not been investigated.

In vitro human liver microsome studies suggest that eletriptan has little potential to inhibit CYP1A2, 2C9, 2E1 and 3A4 at concentrations up to 100 µM. While eletriptan has an effect on CYP2D6 at high concentration, this effect should not interfere with metabolism of other drugs when eletriptan is used at recommended doses.

There is no in vitro or in vivo evidence that clinical doses of eletriptan will induce drug metabolizing enzymes.

Therefore, eletriptan is unlikely to cause clinically important drug interactions mediated by these enzymes.

The soil is a headache therapy that narrows the blood vessels throughout the brain, reduces the concentration of certain substances in the body that are believed to be responsible for stimulating the headaches of the sister, nausea, severe sensitivity to light, sound, and other sister's symptoms.

The therapy is used to treat the headaches of the sister, and it cannot prevent seizures from being made, and many patients notice that the symptoms of the sister are completely removed after treatment while the symptoms may not be completely removed, but they are significantly reduced to be able to do their daily work.

The following adverse reactions are described elsewhere in other sections of the prescribing information: Myocardial ischemia and myocardial infarction, and Prinzmetal’s angina Arrhythmias Chest, throat, neck, and/or jaw pain/tightness/pressure Cerebrovascular events Other vasospasm reactions Medication overuse headache Serotonin syndrome Increase in blood pressure Hypersensitivity reactions 6.1 Clinical Trials Experience Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in practice.

Among 4,597 patients who treated the first migraine headache with eletriptan hydrobromide in short-term placebo-controlled trials, the most common adverse reactions reported with treatment with eletriptan hydrobromide were asthenia, nausea, dizziness, and somnolence.

These reactions appear to be dose-related.

In long-term open-label studies where patients were allowed to treat multiple migraine attacks for up to 1 year, 128 (8.3%) out of 1,544 patients discontinued treatment due to adverse reactions.

Table 1 lists adverse reactions that occurred in the subset of 5,125 migraineurs who received eletriptan doses of 20 mg, 40 mg and 80 mg or placebo in worldwide placebo-controlled clinical trials.

Only adverse reactions that were more frequent in a eletriptan hydrobromide treatment group compared to the placebo group with an incidence greater than or equal to 2% are included in Table 1.

Table 1: Adverse Reactions Incidence in Placebo-Controlled Migraine Clinical Trials: Reactions Reported by ≥ 2% Patients Treated with Eletriptan Hydrobromide and More Than Placebo Adverse Reaction Type Placebo (n=988) Eletriptan Hydrobromide 20 mg (n=431) Eletriptan Hydrobromide 40 mg (n=1774) Eletriptan Hydrobromide 80 mg (n=1932) ATYPICAL SENSATIONS Paresthesia 2% 3% 3% 4% Flushing/feeling of warmth 2% 2% 2% 2% PAIN AND PRESSURE SENSATIONS Chest – tightness/pain/pressure 1% 1% 2% 4% Abdominal – pain/discomfort/stomach pain/ cramps/pressure 1% 1% 2% 2% DIGESTIVE Dry mouth 2% 2% 3% 4% Dyspepsia 1% 1% 2% 2% Dysphagia-throat tightness/difficulty swallowing 0.2% 1% 2% 2% Nausea 5% 4% 5% 8% NEUROLOGICAL Dizziness 3% 3% 6% 7% Somnolence 4% 3% 6% 7% Headache 3% 4% 3% 4% OTHER Asthenia 3% 4% 5% 10% The frequency of adverse reactions in clinical trials did not increase when up to 2 doses of eletriptan hydrobromide were taken within 24 hours.

The incidence of adverse reactions in controlled clinical trials was not affected by gender, age, or race of the patients.

Adverse reaction frequencies were also unchanged by concomitant use of drugs commonly taken for migraine prophylaxis (e.g., SSRIs, beta blockers, calcium channel blockers, tricyclic antidepressants), estrogen replacement therapy or oral contraceptives. 6.2 Postmarketing Experience The following adverse reaction(s) have been identified during post approval use of eletriptan hydrobromide.

Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Neurological: seizure Digestive: vomiting.

The elimination half-life of eletriptan is about 4 hours, therefore monitoring of patients after overdose with eletriptan should continue for at least 20 hours or longer while symptoms or signs persist.

There is no specific antidote to eletriptan.

It is unknown what effect hemodialysis or peritoneal dialysis has on the serum concentration of eletriptan.

Eletriptan hydrobromide tablets are contraindicated in patients with: Ischemic coronary artery disease (CAD) (angina pectoris, history of myocardial infarction, or documented silent ischemia) or coronary artery vasospasm, including Prinzmetal’s angina.

Wolff-Parkinson-White syndrome or arrhythmias associated with other cardiac accessory conduction pathway disorders.

History of stroke, transient ischemic attack (TIA), or history or current evidence of hemiplegic or basilar migraine because these patients are at a higher risk of stroke.

Peripheral vascular disease.

Ischemic bowel disease.

Uncontrolled hypertension.

Recent use (i.e., within 24 hours) of another 5-hydroxytryptamine1 (5-HT1) agonist, ergotamine-containing medication, or ergot-type medication such as dihydroergotamine (DHE) or methysergide.

Hypersensitivity to eletriptan hydrobromide tablets (angioedema and anaphylaxis seen) .

Recent use (i.e., within at least 72 hours) of the following potent CYP3A4 inhibitors: ketoconazole, itraconazole, nefazodone, troleandomycin, clarithromycin, ritonavir, or nelfinavir.

The maximum recommended single dose is 40 mg. In controlled clinical trials, single doses of 20 mg and 40 mg were effective for the acute treatment of migraine in adults.

A greater proportion of patients had a response following a 40 mg dose than following a 20 mg dose.

If the migraine has not resolved by 2 hours after taking eletriptan hydrobromide tablets, or returns after transient improvement, a second dose may be administered at least 2 hours after the first dose.

The maximum daily dose should not exceed 80 mg. The safety of treating an average of more than 3 migraine attacks in a 30-day period has not been established.

Eletriptan hydrobromide tablets containing 20 mg or 40 mg eletriptan (base) as the hydrobromide salt.

Tablets 20 mg are orange colored, round, biconvex, film-coated tablets debossed with ‘EL’ on one side and ‘20’ on the other side.

They are supplied as follows

Carton of 6 (1 X 6) Unit-dose Tablets NDC 59651-104-69 Eletriptan Hydrobromide Tablets 40 mg are orange colored, round, biconvex, film-coated tablets debossed with ‘EL’ on one side and ‘40’ on the other side.

Carton of 6 (1 X 6) Unit-dose Tablets NDC 72189-517-06 Carton of 12 (2 X 6) Unit-dose Tablets NDC 59651-105-93.

Store at 20° to 25°C (68° to 77°F) .