Migraine and headache:

Indications for: RELPAX

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.

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. 

Adult Dosage:

≥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 Dosage:

<18yrs: not established.

RELPAX 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 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.

RELPAX Classification:

Selective 5-HT1B/1D receptor agonist.

RELPAX Interactions:

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

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.

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.

Drug 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.

Generic Drug Availability:

YES

How Supplied:

Tabs 20mg—6; 40mg—6, 12