Maxalt-Mlt (Rizatriptan Benzoate) - Drug Interactions, Contraindications, Overdosage, etc

DRUG INTERACTIONS

Drug Interactions

(See also PRECAUTIONS, Drug Interactions.)

Monoamine oxidase inhibitors: Rizatriptan is principally metabolized via monoamine oxidase, ‘A’ subtype (MAO-A). Plasma concentrations of rizatriptan may be increased by drugs that are selective MAO-A inhibitors (e.g., moclobemide) or nonselective MAO inhibitors [type A and B] (e.g., isocarboxazid, phenelzine, tranylcypromine, and pargyline). In a drug interaction study, when MAXALT 10 mg was administered to subjects (n=12) receiving concomitant therapy with the selective, reversible MAO-A inhibitor, moclobemide 150 mg t.i.d., there were mean increases in rizatriptan AUC and C_max of 119% and 41% respectively; and the AUC of the active N-monodesmethyl metabolite of rizatriptan was increased more than 400%. The interaction would be expected to be greater with irreversible MAO inhibitors. No pharmacokinetic interaction is anticipated in patients receiving selective MAO-B inhibitors. (See CONTRAINDICATIONS; PRECAUTIONS, Drug Interactions.)

Propranolol: In a study of concurrent administration of propranolol 240 mg/day and a single dose of rizatriptan 10 mg in healthy subjects (n=11), mean plasma AUC for rizatriptan was increased by 70% during propranolol administration, and a fourfold increase was observed in one subject. The AUC of the active N-monodesmethyl metabolite of rizatriptan was not affected by propranolol. (See PRECAUTIONS; DOSAGE AND ADMINISTRATION.)

Nadolol/Metoprolol: In a drug interactions study, effects of multiple doses of nadolol 80 mg or metoprolol 100 mg every 12 hours on the pharmacokinetics of a single dose of 10 mg rizatriptan were evaluated in healthy subjects (n=12). No pharmacokinetic interactions were observed.

Paroxetine: In a study of the interaction between the selective serotonin reuptake inhibitor (SSRI) paroxetine 20 mg/day for two weeks and a single dose of MAXALT 10 mg in healthy subjects (n=12), neither the plasma concentrations of rizatriptan nor its safety profile were affected by paroxetine (see WARNINGS and PRECAUTIONS, Information for Patients).

Oral contraceptives: In a study of concurrent administration of an oral contraceptive during 6 days of administration of MAXALT (10-30 mg/day) in healthy female volunteers (n=18), rizatriptan did not affect plasma concentrations of ethinyl estradiol or norethindrone.

OVERDOSAGE

No overdoses of MAXALT were reported during clinical trials.

Rizatriptan 40 mg (administered as either a single dose or as two doses with a 2-hour interdose interval) was generally well tolerated in over 300 patients; dizziness and somnolence were the most common drug-related adverse effects.

In a clinical pharmacology study in which 12 subjects received rizatriptan, at total cumulative doses of 80 mg (given within four hours), two subjects experienced syncope and/or bradycardia. One subject, a female aged 29 years, developed vomiting, bradycardia, and dizziness beginning three hours after receiving a total of 80 mg rizatriptan (administered over two hours); a third degree AV block, responsive to atropine, was observed an hour after the onset of the other symptoms. The second subject, a 25 year old male, experienced transient dizziness, syncope, incontinence, and a 5-second systolic pause (on ECG monitor) immediately after a painful venipuncture. The venipuncture occurred two hours after the subject had received a total of 80 mg rizatriptan (administered over four hours).

In addition, based on the pharmacology of rizatriptan, hypertension or other more serious cardiovascular symptoms could occur after overdosage. Gastrointestinal decontamination, (i.e., gastric lavage followed by activated charcoal) should be considered in patients suspected of an overdose with MAXALT. Clinical and electrocardiographic monitoring should be continued for at least 12 hours, even if clinical symptoms are not observed.

The effects of hemo- or peritoneal dialysis on serum concentrations of rizatriptan are unknown.

CONTRAINDICATIONS

MAXALT should not be given to patients with ischemic heart disease (e.g., angina pectoris, history of myocardial infarction, or documented silent ischemia) or to patients who have symptoms or findings consistent with ischemic heart disease, coronary artery vasospasm, including Prinzmetal’s variant angina, or other significant underlying cardiovascular disease (see WARNINGS ).

Because MAXALT may increase blood pressure, it should not be given to patients with uncontrolled hypertension (see WARNINGS ).

MAXALT should not be used within 24 hours of treatment with another 5-HT₁ agonist, or an ergotamine-containing or ergot-type medication like dihydroergotamine or methysergide.

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

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

MAXALT is contraindicated in patients who are hypersensitive to rizatriptan or any of its inactive ingredients.

DRUG ABUSE AND DEPENDENCE

Although the abuse potential of MAXALT has not been specifically assessed, no abuse of, tolerance to, withdrawal from, or drug-seeking behavior was observed in patients who received MAXALT in clinical trials or their extensions. The 5-HT_1B/1D agonists, as a class, have not been associated with drug abuse.