Imitrex (Sumatriptan Succinate) - Drug Interactions, Contraindications, Overdosage

DRUG INTERACTIONS

Drug/Laboratory Test Interactions

IMITREX Tablets are not known to interfere with commonly employed clinical laboratory tests.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenesis

In carcinogenicity studies, rats and mice were given sumatriptan by oral gavage (rats, 104 weeks) or drinking water (mice, 78 weeks). Average exposures achieved in mice receiving the highest dose (target dose of 160 mg/kg/day) were approximately 40 times the exposure attained in humans after the maximum recommended single oral dose of 100 mg. The highest dose administered to rats (160 mg/kg/day, reduced from 360 mg/kg/day during week 21) was approximately 15 times the maximum recommended single human oral dose of 100 mg on a mg/m² basis. There was no evidence of an increase in tumors in either species related to sumatriptan administration.

Mutagenesis

Sumatriptan was not mutagenic in the presence or absence of metabolic activation when tested in 2 gene mutation assays (the Ames test and the in vitro mammalian Chinese hamster V79/HGPRT assay). In 2 cytogenetics assays (the in vitro human lymphocyte assay and the in vivo rat micronucleus assay) sumatriptan was not associated with clastogenic activity.

Impairment of Fertility

In a study in which male and female rats were dosed daily with oral sumatriptan prior to and throughout the mating period, there was a treatment-related decrease in fertility secondary to a decrease in mating in animals treated with 50 and 500 mg/kg/day. The highest no-effect dose for this finding was 5 mg/kg/day, or approximately one half of the maximum recommended single human oral dose of 100 mg on a mg/m² basis. It is not clear whether the problem is associated with treatment of the males or females or both combined. In a similar study by the subcutaneous route there was no evidence of impaired fertility at 60 mg/kg/day, the maximum dose tested, which is equivalent to approximately 6 times the maximum recommended single human oral dose of 100 mg on a mg/m² basis.

OVERDOSAGE

Patients (N = 670) have received single oral doses of 140 to 300 mg without significant adverse effects. Volunteers (N = 174) have received single oral doses of 140 to 400 mg without serious adverse events.

Overdose in animals has been fatal and has been heralded by convulsions, tremor, paralysis, inactivity, ptosis, erythema of the extremities, abnormal respiration, cyanosis, ataxia, mydriasis, salivation, and lacrimation. The elimination half-life of sumatriptan is approximately 2.5 hours (see CLINICAL PHARMACOLOGY), and therefore monitoring of patients after overdose with IMITREX Tablets should continue for at least 12 hours or while symptoms or signs persist.

It is unknown what effect hemodialysis or peritoneal dialysis has on the serum concentrations of sumatriptan.

CONTRAINDICATIONS

IMITREX Tablets should not be given to patients with history, symptoms, or signs of ischemic cardiac, cerebrovascular, or peripheral vascular syndromes. In addition, patients with other significant underlying cardiovascular diseases should not receive IMITREX Tablets. Ischemic cardiac syndromes include, but are not limited to, angina pectoris of any type (e.g., stable angina of effort and vasospastic forms of angina such as the Prinzmetal variant), all forms of myocardial infarction, and silent myocardial ischemia. Cerebrovascular syndromes include, but are not limited to, strokes of any type as well as transient ischemic attacks. Peripheral vascular disease includes, but is not limited to, ischemic bowel disease (see WARNINGS).

Because IMITREX Tablets may increase blood pressure, they should not be given to patients with uncontrolled hypertension.

Concurrent administration of MAO-A inhibitors or use within 2 weeks of discontinuation of MAO-A inhibitor therapy is contraindicated (see CLINICAL PHARMACOLOGY: Drug Interactions and PRECAUTIONS: Drug Interactions).

IMITREX Tablets should not be administered to patients with hemiplegic or basilar migraine.

IMITREX Tablets and any ergotamine-containing or ergot-type medication (like dihydroergotamine or methysergide) should not be used within 24 hours of each other, nor should IMITREX and another 5-HT ₁ agonist.

IMITREX Tablets are contraindicated in patients with hypersensitivity to sumatriptan or any of their components.

IMITREX Tablets are contraindicated in patients with severe hepatic impairment.