Relpax

— THERAPEUTIC CATEGORIES —
  • Migraine and headache
PAGE CONTENTS
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  • Generic Name & Formulations
  • Indications
  • Dosage and Administration
  • Contraindications
  • Boxed Warnings
  • Warnings/Precautions
  • Pharmacokinetics
  • Interactions
  • Adverse Reactions
  • Clinical Trials
  • Note
  • Patient Counseling

    • Relpax Generic Name & Formulations

    Legal Class

    Rx

    General Description

    Eletriptan (as HBr) 20mg, 40mg; tabs.

    Pharmacological Class

    Selective 5-HT1B/1D receptor agonist.

    How Supplied

    Tabs 20mg—6; 40mg—6, 12

    How Supplied

    Relpax Tablets containing 20 mg or 40 mg eletriptan (base) as the hydrobromide salt. Relpax Tablets are orange, round, convex shaped, film-coated tablets with appropriate debossing.

    Relpax Tablets are supplied in the following strengths and package configurations: 

    • Tablet Strength: 40mg; Debossing: REP40 and PFIZER; Package Configuration: Carton of 12 tablets (two blisters of 6 tablets in each carton) or blister of 6 tablets. 

    • Tablet Strength: 20mg; Debossing: REP20 and PFIZER; Package Configuration Blister of 6 tablets.

    Storage

    Store at 20ºC to 25ºC (68ºF to 77ºF); excursions permitted between 15ºC to 30ºC (59ºF to 86ºF) [see USP Controlled Room Temperature].

    Manufacturer

    Pfizer Inc.

    Generic Availability

    YES

    Mechanism of Action

    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. The therapeutic activity of Relpax 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.

    Relpax Indications

    Indications

    Acute treatment of migraine with or without aura. Limitations of use: Use only after a clear diagnosis of migraine has been established. Not indicated for the prophylactic therapy of migraine. Not indicated for the treatment of cluster headache.

    Relpax Dosage and Administration

    Adult

    ≥18yrs: 20mg or 40mg once; max single dose: 40mg. Reevaluate if no response. May repeat once after 2 hours; max 80mg/day. The safety of treating an average of more than 3 headaches in a 30-day period has not been established.

    Children

    <18yrs: not established.

    Relpax Contraindications

    Contraindications

    Ischemic coronary artery disease (angina pectoris, history of MI, or documented silent ischemia) or coronary artery vasospasm, including Prinzmetal's angina. Wolff-Parkinson-White syndrome. Arrhythmias associated with other cardiac accessory conduction pathway disorders. History of stroke, TIA, or hemiplegic or basilar migraine. Peripheral vascular disease. Ischemic bowel disease. Uncontrolled hypertension. Within 24hrs of other 5-HT1 agonists, ergotamines, or ergot-type drugs (eg, methysergide, dihydroergotamine). Within 72hrs of potent CYP3A4 inhibitors (eg, ketoconazole, itraconazole, nefazodone, troleandomycin, clarithromycin, ritonavir, nelfinavir).

    Relpax Boxed Warnings

    Not Applicable

    Relpax Warnings/Precautions

    Warnings/Precautions

    Confirm diagnosis. Exclude underlying cardiovascular disease, supervise 1st dose, and consider monitoring ECG in patients with likelihood of unrecognized coronary disease (eg, increased age, hypertension, obesity, diabetes, smokers, strong family history). Monitor cardiovascular function in long-term intermittent use. Discontinue if arrhythmias or serotonin syndrome occurs. Possible cerebrovascular events, peripheral or GI vascular ischemia and infarction, Raynaud's syndrome following use of 5-HT1 agonists. Monitor BP during treatment. Severe hepatic impairment: not recommended. Elderly. Pregnancy. Nursing mothers: avoid breastfeeding for 24hrs after treatment.

    Warnings/Precautions

    Myocardial Ischemia, Myocardial Infarction, and Prinzmetal’s Angina

    • Relpax is contraindicated in patients with ischemic or vasospastic CAD. Rare reports of serious cardiac adverse reactions, including acute myocardial infarction, occurring within a few hours following administration of Relpax. 

    • Prior to treatment, perform a cardiovascular evaluation in triptan-naïve patients who have multiple cardiovascular risk factors (eg, increased age, diabetes, hypertension, smoking, obesity, strong family history of CAD). Do not administer if there is evidence of CAD or coronary artery vasospasm (see Contraindications). For patients with multiple cardiovascular risk factors who have a negative cardiovascular evaluation, consider administering the first Relpax dose in a medically-supervised setting and performing an electrocardiogram (ECG) immediately following administration and consider periodic cardiovascular evaluation in intermittent long-term users of Relpax. 

    Arrhythmias

    • Life-threatening disturbances of cardiac rhythm including ventricular tachycardia and ventricular fibrillation leading to death have been reported within a few hours following the administration of 5-HT1 agonists. Discontinue Relpax if these disturbances occur. 

    • Relpax is contraindicated in patients with Wolff-Parkinson-White syndrome or arrhythmias associated with other cardiac accessory conduction pathway disorders.

    Chest, Throat, Neck and/or Jaw Pain/Tightness/Pressure 

    • Perform a cardiac evaluation if patients who are at high cardiac risk experience sensations of tightness, pain, and pressure in the chest, throat, neck, and jaw after treatment with Relpax.

    • Relpax is contraindicated in patients with CAD or Prinzmetal’s variant angina.

    Cerebrovascular Events 

    • Cerebral hemorrhage, subarachnoid hemorrhage, and stroke have occurred in patients treated with 5-HT1 agonists, and some have resulted in fatalities. 

    • Exclude other potentially serious neurological conditions before treating headaches in patients not previously diagnosed as migraineurs, and in migraineurs who present with symptoms atypical for migraine. Relpax is contraindicated in patients with a history of stroke or transient ischemic attack.

    Other Vasospasm Reactions 

    • May cause non-coronary vasospastic reactions, such as peripheral vascular ischemia, gastrointestinal vascular ischemia and infarction (presenting with abdominal pain and bloody diarrhea), and Raynaud’s syndrome. 

    • Rule out a vasospastic reaction before receiving additional Relpax doses in patients who experience symptoms or signs suggestive of a non-coronary vasospastic reaction following the use of any 5-HT1 agonist.

    Medication Overuse Headache

    • Overuse of acute migraine drugs (e.g. ergotamine, triptans, opioids, or combination of these drugs for 10 or more days per month) may lead to exacerbation of headache (medication overuse headache). 

    • Medication overuse headache may present as migraine-like daily headaches or as a marked increase in frequency of migraine attacks. 

    • May be necessary to detoxify patients, including withdrawal of the overused drugs, and treatment of withdrawal symptoms (which often includes a transient worsening of headache). 

    Serotonin Syndrome

    • The onset of symptoms usually occurs within minutes to hours of receiving a new or a greater dose of a serotonergic medication. 

    • Discontinue if serotonin syndrome is suspected. 

    Increase in Blood Pressure  

    • Significant elevation in blood pressure, including hypertensive crisis with acute impairment of organ systems, has been reported on rare occasions in patients treated with 5-HT1 agonists, including patients without a history of hypertension. 

    • Monitor blood pressure. Relpax is contraindicated in patients with uncontrolled hypertension.

    Anaphylactic/Anaphylactoid Reactions 

    • There have been reports of anaphylaxis, anaphylactoid, and hypersensitivity reactions including angioedema in patients receiving Relpax. Such reactions can be life threatening or fatal. 

    • Relpax is contraindicated in patients with a history of hypersensitivity reaction to Relpax.

    Pregnancy Considerations

    Risk Summary 

    • Available human data on the use of Relpax in pregnant women are not sufficient to draw conclusions about drug-associated risk for major birth defects and miscarriage.

    Clinical Considerations 

    • Disease-Associated Maternal and/or Embryo/Fetal Risk: Women with migraine may be at increased risk of preeclampsia and gestational hypertension during pregnancy.

    Nursing Mother Considerations

    Risk Summary  

    • There are no data on the effects of eletriptan on the breastfed infant or the effects of eletriptan on milk production.  

    • The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Relpax and any potential adverse effects on the breastfed child from Relpax or from the underlying maternal condition. 

    • Infant exposure can be minimized by avoiding breastfeeding for 24 hours after treatment. 

    Pediatric Considerations

    Safety and effectiveness in pediatric patients have not been established. 

    Geriatric Considerations

    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. In clinical trials, there were no apparent differences in efficacy or the incidence of adverse reactions between patients under 65 years of age and those 65 and above.

    Hepatic Impairment Considerations

    The effect of severe hepatic impairment on Relpax metabolism has not been evaluated. Relpax is not recommended for use in patients with severe hepatic impairment.

    Other Considerations for Specific Populations

    Age: 

    • 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)

    Relpax 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 20 to 30% following oral administration with a high fat meal. Relpax can be taken with or without food.  

    Distribution

    The volume of distribution of eletriptan following IV administration is 138L. Plasma protein binding is moderate and approximately 85%. 

    Metabolism

    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 10-20% 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.

    Elimination

    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.

    Relpax Interactions

    Interactions

    Methysergide, other ergotamines, other 5-HT1 agonists, or potent CYP3A4 inhibitors: see Contraindications. Serotonin syndrome with SSRIs, SNRIs, TCAs, or MAOIs.

    Relpax Adverse Reactions

    Adverse Reactions

    Asthenia, nausea, dizziness, somnolence, dry mouth, paresthesia, chest/throat/neck/jaw symptoms (pain, pressure, tightness), drug overuse headache (detox may be needed), dyspepsia, abdominal pain; rare: serious cardiovascular events, anaphylactoid reactions.

    Relpax Clinical Trials

    Clinical Trials

    The efficacy of Relpax in the acute treatment of migraines was evaluated in 8 randomized, double-blind placebo-controlled studies. All 8 studies used 40 mg, and 7 studies evaluated an 80 mg dose and 2 studies included a 20 mg dose.  

    In all 8 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. Maintenance of response was assessed for up to 24 hours post dose. 

    In the adult studies, patients were allowed to take a second dose of Relpax or other medication 2 to 24 hours after the initial treatment for both persistent and recurrent headaches. The studies also assessed associated symptoms such as nausea, vomiting, photophobia and phonophobia.

    In the seven adult studies, results showed a significantly greater percentage of patients treated with Relpax at all doses achieved headache response 2 hours after treatment compared with those who received placebo. The following percentages of patients achieved headache response 2 hours after treatment in Studies 1 through 7: 

    • Study 1:

      • Relpax 20 mg: 54.3% (n=129; P <.05); Relpax 40 mg: 65% (n=117; P <.05); Relpax 80 mg: 77.1% (n=118; P <.05) vs placebo: 23.8% (n=126)

    • Study 2:

      • Relpax 20 mg: Not applicable (NA); Relpax 40 mg: 61.6% (n=430; P <.05); Relpax 80 mg: 64.6% (n=446; P <.05) vs placebo: 19% (n=232)

    • Study 3:

      • Relpax 20 mg: 47.3% (n=273; P <.05); Relpax 40 mg: 61.9% (n=281; P <.05); Relpax 80 mg: 58.6% (n=290; P <.05) vs placebo: 21.7% (n=276)

    • Study 4:

      • Relpax 20 mg: NA; Relpax 40 mg: 62.3% (n=175; P <.05); Relpax 80 mg: 70% (n=170; P <.05) vs placebo: 39.5% (n=86)

    • Study 5:

      • Relpax 20 mg: NA; Relpax 40 mg: 53.9% (n=206; P <.05); Relpax 80 mg: 67.9% (n=209; P <.05) vs placebo: 20.6% (n=102)

    • Study 6:

      • Relpax 20 mg: NA; Relpax 40 mg: 63.9% (n=169; P <.05); Relpax 80 mg: 66.9% (n=160; P <.05) vs placebo: 31.3% (n=80)

    • Study 7:

      • Relpax 20 mg: NA; Relpax 40 mg: 57.5% (n=492; P <.05); Relpax 80 mg: NA vs placebo: 29.5% (n=122)

    For patients with migraine-associated photophobia, phonophobia, and nausea at baseline, treatment with Relpax achieved a decreased incidence of these symptoms compared with placebo. 

    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 Note

    Not Applicable

    Relpax Patient Counseling

    Patient Counseling

    Myocardial Ischemia and/or Infarction, Prinzmetal’s Angina, Other Vasospastic Reactions, and Cerebrovascular Events 

    • Inform patients that Relpax may cause serious cardiovascular adverse reactions such as myocardial infarction or stroke, which may result in hospitalization and even death. Instruct patients to be alert for the signs and symptoms of chest pain, shortness of breath, weakness, slurring of speech, and instruct them to ask for medical advice when observing any indicative sign or symptoms; serious cardiovascular reactions may occur without warning symptoms. Instruct patients to seek medical advice if they have symptoms of other vasospastic reactions.

    Anaphylactic/Anaphylactoid Reactions 

    • Inform patients that anaphylactic/anaphylactoid reactions have occurred and can be life threatening or fatal. 

    Medication Overuse Headache

    • Inform patients that use of drugs to treat acute migraines for 10 or more days per month may lead to an exacerbation of headache, and encourage patients to record headache frequency and drug use (e.g., by keeping a headache diary).

    Serotonin Syndrome

    • Inform patients about the risk of serotonin syndrome with the use of Relpax or other triptans, particularly during combined use with selective serotonin reuptake inhibitors (SSRIs) or serotonin and norepinephrine reuptake inhibitors (SNRIs).

    Pregnancy 

    • Advise patients to notify their healthcare provider if they become pregnant or intend to become pregnant during therapy.

    Lactation 

    • Inform patients to notify their healthcare provider if they are breastfeeding or plan to breastfeed.

    Cost Savings Program

    Relpax Savings Card & Resources: https://www.relpax.com/savings

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