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DRUG INTERACTIONS
Monoamine Oxidase Inhibitors
(See CONTRAINDICATIONS, WARNINGS, and DOSAGE AND ADMINISTRATION.)
Serotonergic Drugs
(See CONTRAINDICATIONS and WARNINGS.)
Drugs Affecting Hepatic Metabolism
The metabolism and pharmacokinetics of REMERON (mirtazapine) Tablets may be affected by the induction or inhibition of drug-metabolizing enzymes.
Drugs that are Metabolized by and/or Inhibit Cytochrome P450 Enzymes
CYP Enzyme Inducers
(these studies used both drugs at steady state)
Phenytoin
In healthy male patients (n=18), phenytoin (200 mg daily) increased mirtazapine (30 mg daily) clearance about 2-fold, resulting in a decrease in average plasma mirtazapine concentrations of 45%. Mirtazapine did not significantly affect the pharmacokinetics of phenytoin.
Carbamazepine
In healthy male patients (n=24), carbamazepine (400 mg b.i.d.) increased mirtazapine (15 mg b.i.d.) clearance about 2-fold, resulting in a decrease in average plasma mirtazapine concentrations of 60%.
When phenytoin, carbamazepine, or another inducer of hepatic metabolism (such as rifampicin) is added to mirtazapine therapy, the mirtazapine dose may have to be increased. If treatment with such a medicinal product is discontinued, it may be necessary to reduce the mirtazapine dose.
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OVERDOSAGE
Human Experience
There is very limited experience with REMERON (mirtazapine) Tablets overdose. In premarketing clinical studies, there were 8 reports of REMERON overdose alone or in combination with other pharmacological agents. The only drug overdose death reported while taking REMERON was in combination with amitriptyline and chlorprothixene in a non-US clinical study. Based on plasma levels, the REMERON dose taken was 30 to 45 mg, while plasma levels of amitriptyline and chlorprothixene were found to be at toxic levels. All other premarketing overdose cases resulted in full recovery. Signs and symptoms reported in association with overdose included disorientation, drowsiness, impaired memory, and tachycardia. There were no reports of ECG abnormalities, coma, or convulsions following overdose with REMERON alone.
Overdose Management
Treatment should consist of those general measures employed in the management of overdose with any drug effective in the treatment of major depressive disorder. Ensure an adequate airway, oxygenation, and ventilation. Monitor cardiac rhythm and vital signs. General supportive and symptomatic measures are also recommended. Induction of emesis is not recommended. Gastric lavage with a large-bore orogastric tube with appropriate airway protection, if needed, may be indicated if performed soon after ingestion, or in symptomatic patients. Activated charcoal should be administered. There is no experience with the use of forced diuresis, dialysis, hemoperfusion, or exchange transfusion in the treatment of mirtazapine overdosage. No specific antidotes for mirtazapine are known.
In managing overdosage, consider the possibility of multiple-drug involvement. The physician should consider contacting a poison control center for additional information on the treatment of any overdose. Telephone numbers for certified poison control centers are listed in the Physicians' Desk Reference (PDR).
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CONTRAINDICATIONS
Hypersensitivity
REMERON (mirtazapine) Tablets are contraindicated in patients with a known hypersensitivity to mirtazapine or to any of the excipients.
Monoamine Oxidase Inhibitors
The use of monoamine oxidase inhibitors (MAOIs) intended to treat psychiatric disorders with REMERON Tablets or within 14 days of stopping treatment with REMERON is contraindicated because of an increased risk of serotonin syndrome. The use of REMERON within 14 days of stopping an MAOI intended to treat psychiatric disorders is also contraindicated (see WARNINGS and DOSAGE AND ADMINISTRATION).
Starting REMERON in a patient who is being treated with MAOIs such as linezolid or intravenous methylene blue is also contraindicated because of an increased risk of serotonin syndrome (see WARNINGS and DOSAGE AND ADMINISTRATION).
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DRUG ABUSE AND DEPENDENCE
Controlled Substance Class
REMERON (mirtazapine) Tablets are not a controlled substance.
Physical and Psychologic Dependence
REMERON (mirtazapine) Tablets have not been systematically studied in animals or humans for its potential for abuse, tolerance, or physical dependence. While the clinical trials did not reveal any tendency for any drug-seeking behavior, these observations were not systematic and it is not possible to predict on the basis of this limited experience the extent to which a CNS-active drug will be misused, diverted and/or abused once marketed. Consequently, patients should be evaluated carefully for history of drug abuse, and such patients should be observed closely for signs of REMERON misuse or abuse (e.g., development of tolerance, incrementations of dose, drug-seeking behavior).
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