Migraine and headache:
Indications for: ZOMIG
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 prevention of migraine attacks. Safety and effectiveness of Zomig have not been established for cluster headache. Nasal Spray: also, not recommended in patients with moderate to severe hepatic impairment.
The efficacy of Zomig tablets in the acute treatment of migraine headaches was demonstrated in five randomized, double-blind, placebo-controlled studies (Studies 1, 2, 3, 4, and 5), of which two utilized the 1 mg dose, two utilized the 2.5 mg dose and four utilized the 5 mg dose. In Study 1, patients treated their headaches in a clinic setting. In the other studies, patients treated their headaches as outpatients. In Study 4, patients who had previously used sumatriptan were excluded, whereas in the other studies no such exclusion was applied.
Patients enrolled in these 5 studies were predominantly female (82%) and Caucasian (97%) with a mean age of 40 years (range 12-65). 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 at 1, 2, and, in most studies, 4 hours after dosing. Associated symptoms such as nausea, photophobia, and phonophobia were also assessed. Maintenance of response was assessed for up to 24 hours post-dose. A second dose of Zomig tablets or other medication was allowed 2 to 24 hours after the initial treatment for persistent and recurrent headache. The frequency and time to use of these additional treatments were also recorded. In all studies, the effect of Zomig was compared to placebo in the treatment of a single migraine attack.
In all five studies, a significantly greater proportion of patients who received Zomig 1 mg, 2.5 mg, and 5mg doses (except for the 1 mg dose in the smallest study) achieved headache responses 2 hours after treatment compared to those who received placebo. The following percentages of patients achieved headache response 2 hours after treatment in Studies 1 through 5:
Zomig 1 mg: 27% (n=22); Zomig 2 mg: Not applicable (NA); Zomig 5 mg: 60% (n=20; P <.05 in comparison with placebo and 1mg) vs placebo: 16% (n=19)
Zomig 1 mg: NA; Zomig 2 mg: NA; Zomig 5 mg: 66% (n=179; P <.05 in comparison with placebo) vs placebo: 19% (n=88)
Zomig 1 mg: 50% (n=140; P <.05 in comparison with placebo); Zomig 2mg: 65% (n=260; P <.05 in comparison with placebo and 1mg); Zomig 5 mg: 67% (n=245; P <.05 in comparison with placebo and 1mg) vs placebo: 34% (n=121)
Zomig 1 mg: NA; Zomig 2 mg: NA; Zomig 5 mg: 59% (n=491; P <.05 in comparison with placebo) vs placebo: 44% (n=55)
Zomig 1 mg: NA; Zomig 2 mg: 62% (n=178; P <.05 in comparison with placebo); Zomig 5 mg: NA vs placebo: 36% (n=92)
For patients with migraine associated photophobia, phonophobia, and nausea at baseline, there was a decreased incidence of these symptoms following administration of Zomig tablets as compared with placebo.
The efficacy of Zomig was unaffected by presence of aura; duration of headache prior to treatment; relationship to menses; gender, age, or weight of the patient; pre-treatment nausea or concomitant use of common migraine prophylactic drugs.
≥18yrs: Initially 1.25–2.5mg; max single dose: 5mg. If headache returns, may repeat after 2 hrs; max 10mg/day. Reevaluate if no response after 1st dose. The safety of treating an average of more than 3 headaches in a 30-day period has not been established. Moderate to severe hepatic impairment: 1.25mg; severe hepatic impairment: max 5mg/day. Concomitant cimetidine: max single dose: 2.5mg, not to exceed 5mg in 24hr period. ZMT: do not break tabs; dissolve on tongue and swallow without water (not for use in moderate to severe hepatic impairment).
<18yrs: not recommended.
Ischemic coronary artery disease disease (angina pectoris, history of MI, documented silent ischemia). Other significant underlying cardiovascular disease. Coronary artery vasospasm (eg, Prinzmetal's angina). Wolff-Parkinson-White syndrome or 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 24 hours of ergot-type drugs or other 5-HT1 agonists. During or within 2 weeks after discontinuing MAOIs (type A).
Confirm diagnosis. Exclude underlying cardiovascular disease, supervise 1st dose, and consider monitoring ECG in patients with likelihood of unrecognized coronary disease (eg, postmenopausal women, men over age 40, hypertension, hypercholesterolemia, obesity, diabetes, smokers, strong family history). Discontinue if disturbances in cardiac rhythm occur. Rule out vasospastic reaction before receiving additional doses. Monitor cardiovascular function in long-term intermittent use. Medication overuse headache: detox may be needed. Hepatic dysfunction. Monitor BP. Elderly. Pregnancy. Nursing mothers.
Selective 5-HT1B/1D receptor agonist.
MAOIs (type A), methysergide, other ergotamines, other 5-HT1 agonists: see Contraindications. Serotonin syndrome with SSRIs, SNRIs, TCAs, MAOIs; discontinue if suspected. Absorption and half-life increased by cimetidine.
Neck/throat/jaw pain/tightness/pressure, dizziness, paresthesia, asthenia, somnolence, warm/cold sensation, nausea, heaviness sensation, dry mouth; rare: serious cardiac events. Nasal spray: also taste disturbances, local reactions.
Total radioactivity recovered in urine and feces was 65% and 30% of the administered dose, respectively. Mean total plasma clearance is 31.5 mL/min/kg, of which one-sixth is renal clearance. The renal clearance is greater than the glomerular filtration rate suggesting renal tubular secretion.
Generic Drug Availability:
Tabs (YES); ZMT tabs, sprayer (NO)
Tabs, ZMT tabs 2.5mg—6; Tabs, ZMT tabs 5mg—3; Single-dose sprayer—6