Drug Interactions between Bromhist-PDX and furazolidone

CONTRAINDICATED: By inhibiting serotonin metabolism, monoamine oxidase inhibitors (MAOIs) may potentiate the pharmacologic activity of serotonergic agents such as serotonin reuptake inhibitors, 5-HT1 receptor agonists, ergot alkaloids, buspirone, dextromethorphan, and most antidepressants. The result may be an increased risk of serotonin syndrome, which is a rare but serious and potentially fatal condition thought to result from hyperstimulation of brainstem 5-HT1A and 2A receptors. Symptoms of the serotonin syndrome may include mental status changes such as irritability, altered consciousness, confusion, hallucinations, and coma; autonomic dysfunction such as tachycardia, hyperthermia, diaphoresis, shivering, blood pressure lability, and mydriasis; neuromuscular abnormalities such as hyperreflexia, myoclonus, tremor, rigidity, and ataxia; and gastrointestinal symptoms such as abdominal cramping, nausea, vomiting, and diarrhea.

MANAGEMENT: In general, serotonergic agents should not be used concurrently with MAOIs or other agents that possess MAOI activity (e.g., furazolidone, methylene blue, procarbazine). At least 14 days should elapse between discontinuation of MAOI therapy and initiation of treatment with serotonergic agents. A washout period of 5 to 14 days is usually recommended when switching from another antidepressant to an MAOI; however, the individual product labeling should be consulted.

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CONTRAINDICATED: Indirect- or mixed-acting sympathomimetic amines may precipitate severe hypertensive reactions and hyperpyrexia in patients treated with monoamine oxidase inhibitors (MAOIs). Death has occurred in some reported cases. The mechanism involves a synergistic sympathomimetic effect due to enhanced norepinephrine storage in adrenergic neurons (MAOI activity) and increased liberation of catecholamines (indirect sympathomimetic activity). Although the interaction has primarily involved nonselective MAOIs, hypertensive crisis has been reported in a patient taking ephedrine with the recommended dosage of a selective MAO-B inhibitor.

MANAGEMENT: In general, indirect- and mixed-acting sympathomimetic agents should not be used concurrently with MAOIs or other agents that possess MAOI activity (e.g., furazolidone, methylene blue, procarbazine). At least 14 days should elapse between discontinuation of MAOI therapy and initiation of treatment with sympathomimetic agents.

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MONITOR: Central nervous system- and/or respiratory-depressant effects may be additively or synergistically increased in patients taking multiple drugs that cause these effects, especially in elderly or debilitated patients. Sedation and impairment of attention, judgment, thinking, and psychomotor skills may increase.

MANAGEMENT: During concomitant use of these drugs, patients should be monitored for potentially excessive or prolonged CNS and respiratory depression. Cautious dosage titration may be required, particularly at treatment initiation. Ambulatory patients should be counseled to avoid hazardous activities requiring mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.

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GENERALLY AVOID: Coadministration of monoamine oxidase inhibitors (MAOIs) and antihistamines may result in additive central nervous system depressant effects. In addition, limited data suggest that MAOIs may potentiate and prolong the anticholinergic effects of antihistamines due to inhibition of catecholamine degradation, which may lead to overstimulation of the sympathetic nervous system. In one published report, a woman who had been on phenelzine 30 mg/day for six months developed irritability and visual hallucinations two months following the addition of cyproheptadine 2 mg at bedtime to treat phenelzine-induced anorgasmia. The hallucinations cleared over 48 hours following the discontinuation of her medications. In another published report, a patient developed delirium with symptoms of aggression, paranoia, and vivid auditory as well as visual hallucinations after two days of receiving diphenhydramine 300 mg/day and linezolid 600 mg every 12 hours. The patient also had tachycardia, very warm skin, and possibly blurred vision (as evidenced by constant squinting). Central anticholinergic intoxication and dopaminergic hyperactivity were suspected. Symptoms subsided over four days following the discontinuation of diphenhydramine, while linezolid was continued with no subsequent sequelae. In a third report, a patient developed visual hallucinations associated with confusion and disorientation after nine days of linezolid and antihistamine therapy, including dexchlorpheniramine and cetirizine for the first four days and hydroxyzine for the next five. Physical examination did not reveal any focal neurological signs, myoclonus or ataxia, and cerebral CT scan and EEG were within normal limits. Symptoms resolved two days after linezolid was discontinued.

MANAGEMENT: Prescribing antihistamines in combination with MAOIs or other agents that possess MAOI activity (e.g., furazolidone, linezolid, procarbazine) should generally be avoided. If concomitant treatment is unavoidable, patients should be counseled to avoid hazardous activities requiring mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities. It may be appropriate to monitor some patients for increased anticholinergic effects (e.g., constipation, urinary retention, fever, heat intolerance, blurred vision, confusion, hallucinations, dizziness, palpitations, arrhythmias, syncope), since certain populations such as the elderly and those with underlying organic brain disease tend to be more sensitive to these effects and may be susceptible to anticholinergic intoxication. It should be noted that the manufacturers of many of the sedating antihistamines (e.g., chlorpheniramine, dexchlorpheniramine, diphenhydramine, pheniramine, promethazine) consider their use within 14 days of MAOIs to be contraindicated.

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