Migraine and headache:
Indications for: MAXALT
Acute treatment of migraine with or without aura.
Limitations of Use:
Use only where a clear diagnosis of migraine has been established. Not for use in the management of hemiplegic or basilar migraine. Not for prevention of migraine attacks. Safety and effectiveness has not been established for cluster headache.
Adults: Maxalt Tablets
The efficacy of Maxalt Tablets was established in four multicenter, randomized, placebo-controlled trials. Patients enrolled in these studies were primarily female (84%) and Caucasian (88%), with a mean age of 40 years (range of 18 to 71). Patients were instructed to treat a moderate to severe headache. Headache response, defined as a reduction of moderate or severe headache pain to no or mild headache pain, was assessed for up to 2 hours (Study 1) or up to 4 hours after dosing (Studies 2, 3 and 4). Associated symptoms of nausea, photophobia, and phonophobia and maintenance of response up to 24 hours post-dose were evaluated. A second dose of Maxalt Tablets was allowed 2 to 24 hours after dosing for treatment of recurrent headache in Studies 1 and 2. Additional analgesics and/or antiemetics were allowed 2 hours after initial treatment for rescue in all four studies.
In all studies, the percentage of patients achieving headache response 2 hours after treatment was significantly greater in patients who received either Maxalt 5 or 10 mg compared to those who received placebo. In a separate study, doses of 2.5 mg were not different from placebo. Doses greater than 10 mg were associated with an increased incidence of adverse effects. The following percentages of patients achieved headache response 2 hours after treatment of initial headache in Studies 1 through 4:
Maxalt 5 mg: 62% (n=458; P <.05 in comparison with placebo); Maxalt 10 mg: 71% (n=456; P <.05 in comparison with 5 mg) vs placebo: 35% (n=304)
Maxalt 5 mg: Not applicable (NA); Maxalt 10 mg: 77% (n=320; P <.05 in comparison with placebo) vs placebo: 37% (n=82)
Maxalt 5 mg: 63% (n=352; P <.05 in comparison with placebo); Maxalt 10 mg: NA vs placebo: 23% (n=80)
Maxalt 5 mg: 60% (n=164; P <.05 in comparison with placebo); Maxalt 10 mg: 67% (n=385; P <.05 in comparison with placebo) vs placebo: 40% (n=159)
For patients with migraine-associated photophobia, phonophobia, and nausea at baseline, there was a decreased incidence of these symptoms following administration of Maxalt compared to placebo.
Efficacy was unaffected by the presence of aura; by the gender, or age of the patient; or by concomitant use of common migraine prophylactic drugs (e.g., beta-blockers, calcium channel blockers, tricyclic antidepressants) or oral contraceptives. In two additional similar studies, efficacy was unaffected by relationship to menses. There were insufficient data to assess the impact of race on efficacy.
≥18yrs: Initially 5 or 10mg; may repeat after 2hrs; max 30mg/24hrs. Concomitant propranolol: 5mg; max 15mg/24hrs. The safety of treating, on average, more than 4 headaches in a 30-day period has not been established.
<6yrs: not established. 6–17yrs (<40kg): 5mg; (≥40kg): 10mg. Concomitant propranolol (≥40kg only): max 5mg/24hrs. The efficacy and safety of treating with ≥1 dose/24hrs have not been established.
Ischemic coronary artery disease (eg, angina pectoris, history of MI, documented silent ischemia). Other significant cardiovascular disease. Coronary artery vasospasm (eg, Prinzmetal's angina). History of stroke or TIA. Peripheral vascular disease. Ischemic bowel disease. Uncontrolled hypertension. Basilar or hemiplegic migraine. Within 24 hours of other 5-HT1 agonists or ergot-type drugs. During or within 2 weeks after discontinuing MAOIs.
Confirm diagnosis. Exclude underlying cardiovascular disease; supervise 1st dose and monitor ECG in patients with multiple risk factors (eg, increased age, diabetes, hypertension, smoking, obesity, strong family history of coronary artery disease). Monitor cardiovascular function in long-term intermittent use. Discontinue if life-threatening cardiac rhythm disturbances (including ventricular tachycardia/fibrillation), cerebrovascular events occur. Rule out non-coronary vasospastic reactions if suspected. ODT tabs: Phenylketonuria. Elderly. Pregnancy. Nursing mothers.
Selective 5-HT1B/1D receptor agonist.
See Contraindications. Potentiated by propranolol (see Adults, Children). Serotonin syndrome with concomitant SSRIs, SNRIs, TCAs, MAOIs; discontinue if suspected.
Asthenia, fatigue, somnolence, chest/throat/neck/jaw pressure/pain, dizziness; arrhythmias, cerebrovascular events, other vasospasms, hypertension, medication overuse headache.
The total radioactivity of the administered dose recovered over 120 hours in urine and feces was 82% and 12%, respectively, following a single 10-mg oral administration of 14C-rizatriptan. Following oral administration of 14C-rizatriptan, rizatriptan accounted for about 17% of circulating plasma radioactivity. Approximately 14% of an oral dose is excreted in urine as unchanged rizatriptan while 51% is excreted as indole acetic acid metabolite, indicating substantial first pass metabolism. The plasma half-life of rizatriptan in males and females averages 2-3 hours.
Gender: The mean AUC0-∞ and Cmax of rizatriptan (10 mg orally) were about 30% and 11% higher in females as compared to males, respectively, while Tmax occurred at approximately the same time.
Hepatic impairment: Following oral administration in patients with hepatic impairment caused by mild to moderate alcoholic cirrhosis of the liver, plasma concentrations of rizatriptan were similar in patients with mild hepatic insufficiency compared to a control group of subjects with normal hepatic function; plasma concentrations of rizatriptan were approximately 30% greater in patients with moderate hepatic insufficiency.
Renal impairment: In patients with renal impairment (creatinine clearance 10-60 mL/min/1.73 m2), the AUC0-∞ of rizatriptan was not significantly different from that in subjects with normal renal function. In hemodialysis patients, (creatinine clearance <2 mL/min/1.73 m2), however, the AUC for rizatriptan was approximately 44% greater than that in patients with normal renal function.
Generic Drug Availability: