Relpax
Relpax - General Information
Relpax is a second generation triptan drug developed by Pfizer Inc for the treatment of migraine headaches. [Wikipedia]
Pharmacology of Relpax
Relpax is a selective 5-hydroxytryptamine 1B/1D receptor agonist. 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. Relpax has also been shown to inhibit trigeminal nerve activity in the rat.
Relpax for patients
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.
What is RELPAX?
RELPAX is a prescription medicine used to treat migraine headaches in adults. RELPAX is not for other types of headaches.
What is a Migraine Headache?
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.
How Does RELPAX Work?
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.
Who should not take RELPAX? Do not take RELPAX if you:
· have uncontrolled high blood pressure.
· have heart disease or a history of heart disease.
· have hemiplegic or basilar migraine (if you are not sure about this, ask your doctor).
· have or had a stroke or problems with your blood circulation.
· have serious liver problems.
· have taken any of the following medicines in the last 24 hours: other "triptans" like almotriptan (Axert®), frovatriptan (FrovaTM), naratriptan (AmergeÒ), rizatriptan (MaxaltÒ), sumatriptan (ImitrexÒ), zolmitriptan (ZomigÒ); ergotamines like Bellegral-SÒ, CafergotÒ, ErgomarÒ, WigraineÒ; dihydroergotamine like D.H.E. 45Ò or MigranalÒ; or methysergide (SansertÒ). These medicines have side effects similar to RELPAX.*
· have taken the following medicines within at least 72 hours: ketoconazole (NizoralÒ), itraconazole (SporonoxÒ), nefazodone (SerzoneÒ), troleandomycin (TAOÒ), clarithromycin (BiaxinÒ), ritonavir (NorvirÒ), and nelfinavir (ViraceptÒ). These medicines may cause an increase in the amount of RELPAX in the blood.*
· are allergic to RELPAX or any of its ingredients. The active ingredient is eletriptan. The inactive ingredients are listed at the end of this leaflet. Tell your doctor about all the medicines you take or plan to take, including prescription and nonprescription medicines, supplements, and herbal remedies. Your doctor will decide if you can take RELPAX with your other medicines. 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.
How should I take RELPAX?
RELPAX comes in 20 mg and 40 mg tablets. When you have a migraine headache, take your medicine as directed by your doctor.
· Take one RELPAX tablet as soon as you feel a migraine coming on.
· If your headache improves and then comes back after 2 hours, you can take a second tablet.
· If the first tablet did not help your headache at all, do not take a second tablet without talking with your doctor.
· Do not take more than two RELPAX tablets in any 24-hour period.
What are the possible side effects of RELPAX?
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:
· nausea
· weakness
· tiredness
· pain or pressure sensation (e.g., in the chest or throat)
In very rare cases, patients taking triptans may experience serious side effects, including heart attacks.
Call your doctor right away if you have:
· severe chest pains
· shortness of breath
This is not a complete list of side effects. Talk to your doctor if you develop any symptoms that concern you.
What to do in case of an overdose?
Call your doctor or poison control center or go to the ER.
General advice about RELPAX
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 www.RELPAX.com.
What are the ingredients in RELPAX?
Active ingredient: eletriptan hydrobromide
Inactive ingredients: microcrystalline cellulose, lactose, croscarmellose sodium, magnesium stearate, titanium dioxide, hypromellose, triacetin, and FD&C Yellow No. 6 aluminum lake.
Store RELPAX Tablets at room temperature 15-30°C (59-86°F).
*The brands listed are the trademarks of their respective owners and are not trademarks of Pfizer Inc.
Rx only © 2002 PFIZER INC
Distributed by: Roerig Division of Pfizer Inc, NY, NY 10017 , 70-5586-00-0
Issued December 2002
Relpax Interactions
Ergot-containing drugs: Ergot-containing drugs have been reported to cause prolonged vasospastic reactions. Because these effects may be additive, use of ergotamine-containing or ergot-type medications (like dihydroergotamine [DHE] or methysergide) and eletriptan within 24 hours of each other is not recommended.
CYP3A4 Inhibitors: Eletriptan is metabolized primarily by CYP3A4.
Monoamine Oxidase Inhibitors: Eletriptan is not a substrate for monoamine oxidase (MAO) enzymes, therefore there is no expectation of an interaction between eletriptan and MAO inhibitors.
Propranolol:The Cmax and AUC of eletriptan were increased by 10 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.
Selective serotonin reuptake inhibitors (SSRIs): SSRIs (e.g., fluoxetine, fluvoxamine, paroxetine, sertraline) have been reported, rarely, to cause weakness, hyperreflexia, and incoordination when coadministered with 5-HT1 agonists. If concomitant treatment with eletriptan and an SSRI is clinically warranted, appropriate observation of the patient is advised.
Other 5-HT1 agonists: Concomitant use of other 5-HT1 agonists within 24 hours of RELPAX treatment is not recommended.
Drug/Laboratory Test Interactions: RELPAX Tablets are not known to interfere with commonly employed clinical laboratory tests.
Carcinogenesis: Lifetime carcinogenicity studies, 104 weeks in duration, were carried out in mice and rats by administering eletriptan in the diet. In rats, the incidence of testicular interstitial cell adenomas was increased at the high dose of 75 mg/kg/day. The estimated exposure (AUC) to parent drug at that dose was approximately 6 times that achieved in humans receiving the maximum recommended daily dose (MRDD) of 80 mg, and at the no-effect dose of 15 mg/kg/day it was approximately 2 times the human exposure at the MRDD. In mice, the incidence of hepatocellular adenomas was increased at the high dose of 400 mg/kg/day. The exposure to parent drug (AUC) at that dose was approximately 18 times that achieved in humans receiving the MRDD, and the AUC at the no-effect dose of 90 mg/kg/day was approximately 7 times the human exposure at the MRDD.
Mutagenesis: Eletriptan was not mutagenic in bacterial or mammalian cell assays in vitro, testing negative in the Ames reverse mutation test and the hypoxanthine-guanine phosphoribosyl transferase (HGPRT) mutation test in Chinese hamster ovary cells. It was not clastogenic in two in vivo mouse micronucleus assays. Results were equivocal in in vitro human lymphocyte clastogenicity tests, in which the incidence of polyploidy was increased in the absence of metabolic activation (-S9 conditions), but not in the presence of metabolic activation.
Impairment of Fertility: In a rat fertility and early embryonic development study, doses tested were 50, 100 and 200 mg/kg/day, resulting in systemic exposures to parent drug in rats, based on AUC, that were 4, 8 and 16 times MRDD, respectively, in males and 7, 14 and 28 times MRDD, respectively, in females. There was a prolongation of the estrous cycle at the 200 mg/kg/day dose due to an increase in duration of estrus, based on vaginal smears. There were also dose-related, statistically significant decreases in mean numbers of corpora lutea per dam at all 3 doses, resulting in decreases in mean numbers of implants and viable fetuses per dam. This suggests a partial inhibition of ovulation by eletriptan. There was no effect on fertility of males and no other effect on fertility of females.
Pregnancy: Pregnancy Category C: In reproductive toxicity studies in rats and rabbits, oral administration of eletriptan was associated with developmental toxicity (decreased fetal and pup weights and an increased incidence of fetal structural abnormalities). Effects on fetal and pup weights were observed at doses that were, on a mg/m2 basis, 6 to 12 times greater than the clinical maximum recommended daily dose (MRDD) of 80 mg. The increase in structural alterations occurred in the rat and rabbit at doses that, on a mg/m2 basis, were 12 times greater than (rat) and approximately equal to (rabbit) the MRDD. When pregnant rats were administered eletriptan during the period of organogenesis at doses of 10, 30 or 100 mg/kg/day, fetal weights were decreased and the incidences of vertebral and sternebral variations were increased at 100 mg/kg/day (approximately 12 times the MRDD on a mg/m2 basis). The 100 mg/kg dose was also maternally toxic, as evidenced by decreased maternal body weight gain during gestation. The no-effect dose for developmental toxicity in rats exposed during organogenesis was 30 mg/kg, which is approximately 4 times the MRDD on a mg/m2 basis.
When doses of 5, 10 or 50 mg/kg/day were given to New Zealand White rabbits throughout organogenesis, fetal weights were decreased at 50 mg/kg, which is approximately 12 times the MRDD on a mg/m2 basis. The incidences of fused sternebrae and vena cava deviations were increased in all treated groups. Maternal toxicity was not produced at any dose. A no-effect dose for developmental toxicity in rabbits exposed during organogenesis was not established, and the 5 mg/kg dose is approximately equal to the MRDD on a mg/m2 basis. There are no adequate and well-controlled studies in pregnant women; therefore, eletriptan should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Nursing Mothers: Eletriptan is excreted in human breast milk. In one study of 8 women given a single dose of 80 mg, the mean total amount of eletriptan in breast milk over 24 hours in this group was approximately 0.02% of the administered dose. The ratio of eletriptan mean concentration in breast milk to plasma was 1:4, but there was great variability. The resulting eletriptan concentration-time profile was similar to that seen in the plasma over 24 hours, with very low concentrations of drug (mean 1.7 ng/mL) still present in the milk 18-24 hours post dose. The N-desmethyl active metabolite was not measured in the breast milk. Caution should be exercised when RELPAX is administered to nursing women.
Pediatric Use: 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. 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.
Geriatric Use: 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 CLINICAL PHARMACOLOGY). 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).
Relpax Contraindications
RELPAX Tablets should not be given to patients with ischemic heart disease (e.g., angina pectoris, history of myocardial infarction, or documented silent ischemia) or to patients who have symptoms, or findings consistent with ischemic heart disease, coronary artery vasospasm, including Prinzmetal's variant angina, or other significant underlying cardiovascular disease. RELPAX Tablets should not be given to patients with cerebrovascular syndromes including (but not limited to) strokes of any type as well as transient ischemic attacks. RELPAX Tablets should not be given to patients with peripheral vascular disease including (but not limited to) ischemic bowel disease. Because RELPAX Tablets may increase blood pressure, it should not be given to patients with uncontrolled hypertension. RELPAX Tablets should not be administered to patients with hemiplegic or basilar migraine. RELPAX Tablets should not be used within 24 hours of treatment with another 5-HT1 agonist, an ergotamine-containing or ergot-type medication such as dihydroergotamine (DHE) or methysergide. RELPAX Tablets should not be used in patients with known hypersensitivity to eletriptan or any of its inactive ingredients. RELPAX Tablets should not be given to patients with severe hepatic impairment.
Additional information about Relpax
Relpax Indication: For the acute treatment of migraine with or without aura in adults.
Mechanism Of Action: Relpax 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, and little or no affinity for 5-HT2A, 5-HT2C, 5-HT3, 5-HT4, 5-HT5A and 5-HT6 receptors. Relpax has no significant affinity or pharmacological activity at adrenergic alpha1, alpha2, or beta; dopaminergic D1 or D2; 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-HT1 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-HT1 receptors on sensory nerve endings in the trigeminal system results in the inhibition of pro-inflammatory neuropeptide release.
Drug Interactions: Citalopram Increased risk of CNS adverse effects
Clarithromycin This macrolide increases the effect and toxicity of eletriptan
Dihydroergotamine Possible severe and prolonged vasoconstriction
Dihydroergotoxine Possible severe and prolonged vasoconstriction
Ergotamine Possible severe and prolonged vasoconstriction
Erythromycin This macrolide increases the effect and toxicity of eletriptan
Escitalopram Increased risk of CNS adverse effects
Fluoxetine Increased risk of CNS adverse effects
Fluvoxamine Increased risk of CNS adverse effects
Itraconazole This potent CYP3A4 inhibitor increases the effect and toxicity of the triptan
Ketoconazole This potent CYP3A4 inhibitor increases the effect and toxicity of the triptan
Methylergonovine Possible severe and prolonged vasoconstriction
Methysergide Possible severe and prolonged vasoconstriction
Nefazodone Increased risk of CNS adverse effects
Nelfinavir The protease inhibitor increases the effect and toxicity of eletriptan
Paroxetine Increased risk of CNS adverse effects
Ritonavir The protease inhibitor increases the effect and toxicity of eletriptan
Sertraline Increased risk of CNS adverse effects
Venlafaxine Increased risk of CNS adverse effects
Troleandomycin The macrolide increases the effect and toxicity of eletriptan
Ergonovine Possible severe and prolonged vasoconstriction
Food Interactions: Exposure to the product (area below curve) and maximum concentrations are increased when product is taken with a high-fat meal.
Generic Name: Eletriptan
Synonyms: Not Available
Drug Category: Anti-migraine Agents; Vasoconstrictor Agents; Anti-inflammatory Agents; Selective Serotonin Agonists
Drug Type: Small Molecule; Approved
Other Brand Names containing Eletriptan: Relpax;
Absorption: Well absorbed after oral administration with a mean absolute bioavailability of approximately 50%.
Toxicity (Overdose): Based on the pharmacology of the 5-HT1B/1D agonists, hypertension or other more serious cardiovascular symptoms could occur on overdose.
Protein Binding: Plasma protein binding is moderate and approximately 85%.
Biotransformation: In vitro studies indicate that eletriptan is primarily metabolized by cytochrome P-450 enzyme CYP3A4. The N-demethylated metabolite of eletriptan is the only known active metabolite.
Half Life: The terminal elimination half-life of eletriptan is approximately 4 hours.
Dosage Forms of Relpax: Tablet Oral
Chemical IUPAC Name: 3-[[(2R)-1-methylpyrrolidin-2-yl]methyl]-5-(2-phenylsulfonylethyl)-1H-indole
Chemical Formula: C22H26N2O2S
Eletriptan on Wikipedia: https://en.wikipedia.org/wiki/Eletriptan
Organisms Affected: Humans and other mammals
