Relpax Information
Relpax () Description
Relpax () (eletriptan) Tablets contain eletriptan hydrobromide, which is a selective 5-hydroxytryptamine 1B/1D (5-HT1B/1D) receptor agonist. Eletriptan 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:
The empirical formula is CHNOS . HBr, representing a molecular weight of 463.40. Eletriptan hydrobromide is a white to light pale colored powder that is readily soluble in water.
Each Relpax () Tablet for oral administration contains 24.2 or 48.5 mg of eletriptan hydrobromide equivalent to 20 mg or 40 mg of eletriptan, respectively. Each tablet also contains the inactive ingredients microcrystalline cellulose NF, lactose NF, croscarmellose sodium NF, magnesium stearate NF, titanium dioxide USP, hypromellose, triacetin USP and FD&C Yellow No. 6 aluminum lake.
Relpax () Clinical Pharmacology
Eletriptan binds with high affinity to 5-HT, 5-HT and 5-HT receptors, has modest affinity for 5-HT, 5-HT, 5-HT and 5-HT receptors, and little or no affinity for 5-HT, 5-HT, 5-HT, 5-HT, 5-HT and 5-HT receptors. Eletriptan has no significant affinity or pharmacological activity at adrenergic alpha, alpha, or beta; dopaminergic D or D; muscarinic; or opioid receptors.
Two theories have been proposed to explain the efficacy of 5-HT receptor agonists in migraine. One theory suggests that activation of 5-HT receptors located on intracranial blood vessels, including those on the arteriovenous anastomoses, leads to vasoconstriction, which is correlated with the relief of migraine headache. The other hypothesis suggests that activation of 5-HT receptors on sensory nerve endings in the trigeminal system results in the inhibition of pro-inflammatory neuropeptide release.
In the anesthetized dog, eletriptan has been shown to reduce carotid arterial blood flow, with only a small increase in arterial blood pressure at high doses. While the effect on blood flow was selective for the carotid arterial bed, decreases in coronary artery diameter were observed. Eletriptan has also been shown to inhibit trigeminal nerve activity in the rat.
Relpax () Clinical Studies
The efficacy of Relpax () in the acute treatment of migraines was evaluated in eight randomized, double-blind placebo-controlled studies. All eight studies used 40 mg. Seven studies evaluated an 80 mg dose and two studies included a 20 mg dose.
In all eight studies, randomized patients treated their headaches as outpatients. Seven studies enrolled adults and one study enrolled adolescents (age 11 to 17). Patients treated in the seven adult studies were predominantly female (85%) and Caucasian (94%) with a mean age of 40 years (range 18 to 78). In all studies, patients were instructed to treat a moderate to severe headache. Headache response, defined as a reduction in headache severity from moderate or severe pain to mild or no pain, was assessed up to 2 hours after dosing. Associated symptoms such as nausea, vomiting, photophobia and phonophobia were also assessed.
Maintenance of response was assessed for up to 24 hours post dose. In the adult studies, a second dose of Relpax () Tablets or other medication was allowed 2 to 24 hours after the initial treatment for both persistent and recurrent headaches. The incidence and time to use of these additional treatments were also recorded.
In the seven adult studies, the percentage of patients achieving headache response 2 hours after treatment was significantly greater among patients receiving Relpax () Tablets at all doses compared to those who received placebo. The two-hour response rates from these controlled clinical studies are summarized in Table 1.
The estimated probability of achieving an initial headache response within 2 hours following treatment is depicted in Figure 1.
For patients with migraine-associated photophobia, phonophobia, and nausea at baseline, there was a decreased incidence of these symptoms following administration of Relpax () as compared to placebo.
Two to 24 hours following the initial dose of study treatment, patients were allowed to use additional treatment for pain relief in the form of a second dose of study treatment or other medication. The estimated probability of taking a second dose or other medications for migraine over the 24 hours following the initial dose of study treatment is summarized in Figure 2.
The efficacy of Relpax () was unaffected by the duration of attack; gender or age of the patient; relationship to menses; or concomitant use of estrogen replacement therapy/oral contraceptives or frequently used migraine prophylactic drugs.
In a single study in adolescents (n=274), there were no statistically significant differences between treatment groups. The headache response rate at 2 hours was 57% for both Relpax () 40 mg Tablets and placebo.
Relpax () Indications And Usage
Relpax () is indicated for the acute treatment of migraine with or without aura in adults.
Relpax () is not intended for the prophylactic therapy of migraine or for use in the management of hemiplegic or basilar migraine (see ). Safety and effectiveness of Relpax () Tablets have not been established for cluster headache, which is present in an older, predominantly male population.
Relpax () Warnings
Relpax () Tablets should only be used where a clear diagnosis of migraine has been established.
Eletriptan should not be used within at least 72 hours of treatment with the following potent CYP3A4 inhibitors: ketoconazole, itraconazole, nefazodone, troleandomycin, clarithromycin, ritonavir, and nelfinavir. Eletriptan should not be used within 72 hours with drugs that have demonstrated potent CYP3A4 inhibition and have this potent effect described in the , or sections of their labeling (see and ).
In a coronary angiographic study of rapidly infused intravenous eletriptan to concentrations exceeding those achieved with 80 mg oral eletriptan in the presence of potent CYP3A4 inhibitors, a small dose-related decrease in coronary artery diameter similar to that seen with a 6 mg subcutaneous dose of sumatriptan was observed.
Because of the potential of 5-HT agonists to cause coronary vasospasm, eletriptan should not be given to patients with documented ischemic or vasospastic coronary artery disease (CAD) (see ). It is strongly recommended that eletriptan not be given to patients in whom unrecognized CAD is predicted by the presence of risk factors (e.g., hypertension, hypercholesterolemia, smoker, obesity, diabetes, strong family history of CAD, female with surgical or physiological menopause, or male over 40 years of age) unless a cardiovascular evaluation provides satisfactory clinical evidence that the patient is reasonably free of coronary artery and ischemic myocardial disease or other significant underlying cardiovascular disease. The sensitivity of cardiac diagnostic procedures to detect cardiovascular disease or predisposition to coronary artery vasospasm is modest, at best. If, during the cardiovascular evaluation, the patient's medical history, electrocardiographic, or other investigations reveal findings indicative of, or consistent with coronary artery vasospasm or myocardial ischemia, eletriptan should not be administered (see ).
For patients with risk factors predictive of CAD, who are determined to have a satisfactory cardiovascular evaluation, it is strongly recommended that administration of the first dose of eletriptan take place in the setting of a physician's office or similar medically staffed and equipped facility unless the patient has previously received eletriptan. Because cardiac ischemia can occur in the absence of clinical symptoms, consideration should be given to obtaining on the first occasion of use an electrocardiogram (ECG) during the interval immediately following administration of Relpax () Tablets, in these patients with risk factors.
It is recommended that patients who are intermittent long-term users of 5-HT agonists including Relpax () Tablets, and who have or acquire risk factors predictive of CAD, as described above, undergo periodic cardiovascular evaluation as they continue to use Relpax () Tablets.
The systematic approach described above is intended to reduce the likelihood that patients with unrecognized cardiovascular disease will be inadvertently exposed to eletriptan.
Serious adverse cardiac events, including acute myocardial infarction, life-threatening disturbances of cardiac rhythm, and death have been reported within a few hours following the administration of 5-HT agonists including Relpax () . Considering the extent of use of 5-HT agonists in patients with migraine, the incidence of these events is extremely low.
Premarketing experience with eletriptan among the 7,143 unique individuals who received eletriptan during premarketing clinical trials: In a clinical pharmacology study, in subjects undergoing diagnostic coronary angiography, a subject with a history of angina, hypertension and hypercholesterolemia, receiving intravenous eletriptan (Cmax of 127 ng/mL equivalent to 60 mg oral eletriptan), reported chest tightness and experienced angiographically documented coronary vasospasm with no ECG changes of ischemia.
There was also one report of atrial fibrillation in a patient with a past history of atrial fibrillation.
Postmarketing experience with eletriptan: Serious cardiovascular events, some resulting in death, have been reported in association with the use of Relpax () . In very rare cases, these events have occurred in the absence of known cardiovascular diseases. The uncontrolled nature of postmarketing surveillance, however, makes it impossible to determine definitively if the cases were actually caused by eletriptan or to reliably assess causation in individual cases.
Significant elevation in blood pressure, including hypertensive crisis, has been reported on rare occasions in patients receiving 5-HT agonists with and without a history of hypertension. In clinical pharmacology studies, oral eletriptan (at doses of 60 mg or more) was shown to cause small, transient dose-related increases in blood pressure, predominantly diastolic, consistent with its mechanism of action and with other 5-HT agonists. The effect was more pronounced in renally impaired and elderly subjects. A single patient with hepatic cirrhosis received eletriptan 80 mg and experienced a blood pressure of 220/96 mm Hg five hours after dosing. The treatment-related event persisted for seven hours.
Eletriptan is contraindicated in patients with uncontrolled hypertension (see ).
An 18% increase in mean pulmonary artery pressure was seen following dosing with another 5-HT agonist in a study evaluating subjects undergoing cardiac catheterization.
Relpax () Precautions
See at the end of this labeling for the text of the separate leaflet provided for patients.
Patients should be cautioned about the risk of serotonin syndrome with the use of Relpax () or other triptans, especially during combined use with selective serotonin reuptake inhibitors (SSRIs) or serotonin norepinephrine reuptake inhibitors (SNRIs).
Safety and effectiveness of Relpax () Tablets in pediatric patients have not been established; therefore, Relpax () is not recommended for use in patients under 18 years of age.
The efficacy of Relpax () Tablets (40 mg) in patients 11–17 was not established in a randomized, placebo-controlled trial of 274 adolescent migraineurs (see ). Adverse events observed were similar in nature to those reported in clinical trials in adults. Postmarketing experience with other triptans includes a limited number of reports that describe pediatric patients who have experienced clinically serious adverse events that are similar in nature to those reported rarely in adults. Long-term safety of eletriptan was studied in 76 adolescent patients who received treatment for up to one year. A similar profile of adverse events to that of adults was observed. The long-term safety of eletriptan in pediatric patients has not been established.
Eletriptan has been given to only 50 patients over the age of 65. 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 (see ). In clinical trials, there were no apparent differences in efficacy or the incidence of adverse events between patients under 65 years of age and those 65 and above (n=50).
There is a statistically significantly 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) (see ).
Relpax () Adverse Reactions
Serious cardiac events, including some that have been fatal, have occurred following the use of 5-HT agonists including Relpax () . These events are extremely rare and most have been reported in patients with risk factors predictive of CAD. Events reported have included coronary artery vasospasm, transient myocardial ischemia, myocardial infarction, ventricular tachycardia, and ventricular fibrillation (see , and ).
Among 4,597 patients who treated the first migraine headache with Relpax () in short-term placebo-controlled trials, the most common adverse events reported with treatment with Relpax () were asthenia, nausea, dizziness, and somnolence. These events 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 events.
Table 2 lists adverse events 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. The events cited reflect experience gained under closely monitored conditions of clinical trials in a highly selected patient population. In actual clinical practice or in other clinical trials, those frequency estimates may not apply, as the conditions of use, reporting behavior, and the kinds of patients treated may differ.
Only adverse events that were more frequent in a Relpax () treatment group compared to the placebo group with an incidence greater than or equal to 2% are included in Table 2.
Relpax () is generally well tolerated. Across all doses, most adverse reactions were mild and transient. The frequency of adverse events in clinical trials did not increase when up to 2 doses of Relpax () were taken within 24 hours. The incidence of adverse events in controlled clinical trials was not affected by gender, age, or race of the patients. Adverse event 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 and oral contraceptives.
In the paragraphs that follow, the frequencies of less commonly reported adverse clinical events are presented. Because the reports include events observed in open studies, the role of Relpax () Tablets in their causation cannot be reliably determined. Furthermore, variability associated with adverse event reporting, the terminology used to describe adverse events, etc., limit the value of the quantitative frequency estimates provided. Event frequencies are calculated as the number of patients reporting an event divided by the total number of patients (N=4,719) exposed to Relpax () . All reported events are included except those already listed in Table 2, those too general to be informative, and those not reasonably associated with the use of the drug. Events are further classified within body system categories and enumerated in order of decreasing frequency using the following definitions: frequent adverse events are those occurring in at least 1/100 patients, infrequent adverse events are those occurring in 1/100 to 1/1000 patients and rare adverse events are those occurring in fewer than 1/1000 patients.
The following adverse reaction(s) have been identified during postapproval use of Relpax () . 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
Relpax () Drug Abuse And Dependence
Although the abuse potential of Relpax () has not been assessed, no abuse of, tolerance to, withdrawal from, or drug-seeking behavior was observed in patients who received Relpax () in clinical trials or their extensions. The 5-HT agonists, as a class, have not been associated with drug abuse.
Relpax () Overdosage
No significant overdoses in premarketing clinical trials have been reported. Volunteers (N=21) have received single doses of 120 mg without significant adverse effects. Daily doses of 160 mg were commonly employed in Phase III trials. Based on the pharmacology of the 5-HT agonists, hypertension or other more serious cardiovascular symptoms could occur on overdose.
The elimination half-life of eletriptan is about 4 hours (see ) and therefore monitoring of patients after overdose with eletriptan should continue for at least 20 hours, or longer should symptoms or signs persist.
There is no specific antidote to eletriptan. In cases of severe intoxication, intensive care procedures are recommended, including establishing and maintaining a patent airway, ensuring adequate oxygenation and ventilation, and monitoring and support of the cardiovascular system.
It is unknown what effect hemodialysis or peritoneal dialysis has on the serum concentration of eletriptan.
Relpax () Dosage And Administration
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 (see ). Individuals may vary in response to doses of Relpax () Tablets. The choice of dose should therefore be made on an individual basis. An 80 mg dose, although also effective, was associated with an increased incidence of adverse events. Therefore, the maximum recommended single dose is 40 mg.
If after the initial dose, headache improves but then returns, a repeat dose may be beneficial. If a second dose is required, it should be taken at least 2 hours after the initial dose. If the initial dose is ineffective, controlled clinical trials have not shown a benefit of a second dose to treat the same attack. The maximum daily dose should not exceed 80 mg.
The safety of treating an average of more than 3 headaches in a 30-day period has not been established.
Relpax () How Supplied
Relpax () Tablets of 40 mg eletriptan (base) as the hydrobromide. NDC 21695-871-40. Relpax () Tablets are orange, round, convex shaped, film-coated tablets with appropriate debossing.
They are supplied in the following strength and package configuration:
Relpax ()
Relpax () Patient Summary Of Informationrelpax (eletriptan Hydrobromide)
Please read this information before you start taking Relpax () and each time you renew your prescription. Remember, this summary does not take the place of discussions with your doctor. You and your doctor should discuss Relpax () when you start taking your medication and at regular checkups.
Relpax () is a prescription medicine used to treat migraine headaches in adults. Relpax () is not for other types of headaches.
Migraine is an intense, throbbing headache. You may have pain on one or both sides of your head. You may have nausea and vomiting, and be sensitive to light and noise. The pain and symptoms of a migraine headache can be worse than a common headache. Some women get migraines around the time of their menstrual period. Some people have visual symptoms before the headache, such as flashing lights or wavy lines, called an aura.
Treatment with Relpax () reduces swelling of blood vessels surrounding the brain. This swelling is associated with the headache pain of a migraine attack. Relpax () blocks the release of substances from nerve endings that cause more pain and other symptoms like nausea, and sensitivity to light and sound.
It is thought that these actions contribute to relief of your symptoms by Relpax () .
Tell your doctor about all the medicines you take or plan to take, including prescription and non-prescription medicines, supplements, and herbal remedies. Your doctor will decide if you can take Relpax () with your other medicines.
Some medicines used in treating depression such as the selective serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs) may cause a condition called serotonin syndrome especially during combined use with certain migraine medications. Your doctor needs to know if you are taking any of these medicines, when taking Relpax () .
Tell your doctor if you know that you have any of the following: risk factors for heart disease like high cholesterol, diabetes, smoking, obesity, menopause, or a family history of heart disease or stroke.
Relpax () comes in 20 mg and 40 mg tablets. When you have a migraine headache, take your medicine as directed by your doctor.
Relpax () is generally well tolerated. As with any medicine, people taking Relpax () may have side effects. The side effects are usually mild and do not last long.
The most common side effects of Relpax () are:
In very rare cases, patients taking triptans, such as Relpax () , may experience serious side effects, including heart attacks. if you have:
Some patients taking triptans may have a reaction called serotonin syndrome particularly during combined use with certain types of antidepressants, SSRIs or SNRIs. Symptoms may include confusion, hallucinations, fast heart beat, feeling faint, fever, sweating, muscle spasm, difficulty walking and/or diarrhea. Call your doctor right away if you have any of these symptoms after taking Relpax () .
This is not a complete list of side effects. Talk to your doctor if you develop any symptoms that concern you.
Call your doctor or poison control center or go to the ER.
Medicines are sometimes prescribed for conditions that are not mentioned in patient information leaflets. Do not use Relpax () for a condition for which it was not prescribed. Do not give Relpax () to other people, even if they have the same symptoms you have.
This leaflet summarizes the most important information about Relpax () . If you would like more information about Relpax () , talk with your doctor. You can ask your doctor or pharmacist for information on Relpax () that is written for health professionals. You can also call 1-866-4Relpax () (1-866-473-5729) or visit our web site at
Active ingredient: eletriptan hydrobromide
Inactive ingredients: microcrystalline cellulose, lactose, croscarmellose sodium, magnesium stearate, titanium oxide, hypromellose, triacetin, and FD&C Yellow No. 6 aluminum lake.
Store Relpax () Tablets at room temperature 15–30°C (59–86°F).
LAB 0077-7.0May 2008
Repackaged by:
Rebel Distributors Corp
Thousand Oaks, CA 91320
Relpax () Principal Display Panel
