Adverse Findings Observed in Short-Term, Placebo-Controlled Trials
Systematically collected data are available from only 86 patients exposed to Marplan (isocarboxazid) , of whom only 52 received doses of ≥ 50 mg/day, including only 11 who were dosed at ≥ 60 mg/day. Because of the limited experience with systematically monitored patients receiving Marplan (isocarboxazid) at the higher end of the currently recommended dose range of up to 60 mg/day, caution is indicated in patients for whom a dose of 40 mg/day is exceeded (see WARNINGS).
The table that follows enumerates the incidence, rounded to the nearest percent, of treatment emergent adverse events that occurred among 86 depressed patients who received Marplan (isocarboxazid) at doses ranging from 20 to 80 mg/day in placebo-controlled trials of 6 weeks in duration. Events included are those occurring in 1% or more of patients treated with Marplan (isocarboxazid) and for which the incidence in patients treated with Marplan (isocarboxazid) was greater than the incidence in placebo-treated patients.
The prescriber should be aware that these figures cannot be used to predict the incidence of adverse events in the course of usual medical practice where patient characteristics and other factors differ from those which prevailed in clinical trials. Similarly, the cited frequencies cannot be compared with figures obtained from other clinical investigations involving different treatments, uses, and investigators. The cited figures, however, do provide the prescribing physician with some basis for estimating the relative contribution of drug and non-drug factors to the adverse event incidence rate in the population studied.
The commonly observed adverse event that occurred in Marplan (isocarboxazid) patients with an incidence of 5% or greater and at least twice the incidence in placebo patients were nausea, dry mouth, and dizziness (see Table). In three clinical trials for which the data were pooled, 4 of 85 (5%) patients who received placebo, 10 of 86 (12%) who received < 50 mg of Marplan (isocarboxazid) per day, and 1 of 52 (2%) who received ≥ 50 mg of Marplan (isocarboxazid) per day prematurely discontinued treatment. The most common reasons for discontinuation were dizziness, orthostatic hypotension, syncope, and dry mouth.
Treatment-Emergent Adverse Events Incidence in Placebo-Controlled Clinical Trials with Marplan (isocarboxazid) Doses of 40 to 80 mg/day1
|MARPLAN < 50 mg
|MARPLAN (isocarboxazid) ≥ 50 mg
|CENTRAL NERVOUS SYSTEM|
| 1Events reported by at least 1% of patients treated with Marplan (isocarboxazid) are presented, except for those that had an incidence on placebo greater than or equal to that on Marplan (isocarboxazid) .
2All patients also received Marplan (isocarboxazid) at doses < 50 mg.
Other Events Observed During the Postmarketing Evaluation of Marplan (isocarboxazid)
Isolated cases of akathisia, ataxia, black tongue, coma, dysuria, euphoria, hematologic changes, incontinence, neuritis, photosensitivity, sexual disturbances, spider telangiectases, and urinary retention have been reported. These side effects sometimes necessitate discontinuation of therapy. In rare instances, hallucinations have been reported with high dosages, but they have disappeared upon reduction of dosage or discontinuation of therapy. Toxic amblyopia was reported in one psychiatric patient who had received isocarboxazid for about a year; no causal relationship to isocarboxazid was established. Impaired water excretion compatible with the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) has been reported.
DRUG ABUSE AND DEPENDENCE
Controlled Substance Class
Marplan (isocarboxazid) is not a controlled substance.
Physical and Psychological Dependence
Marplan (isocarboxazid) has not been systematically studied in animals or humans for its potential for abuse, tolerance, or physical dependence. There have been reports of drug dependency in patients using doses of Marplan (isocarboxazid) significantly in excess of the therapeutic range. Some of these patients had a history of previous substance abuse. The following withdrawal symptoms have been reported: restlessness, anxiety, depression, confusion, hallucinations, headache, weakness, and diarrhea. Consequently, physicians should carefully evaluate Marplan (isocarboxazid) patients for history of drug abuse and follow such patients closely, observing them for signs of misuse or abuse (eg, development of tolerance, incrementations of dose, drug-seeking behavior).