A1,
A2,
B,
C1,
C2,
D,
E,
F,
G-H,
I-K,
L,
M,
N,
O,
P1,
P2,
Q-R,
S,
T,
U-V,
W-Z
Marplan Side Effects, and Drug Interactions - Isocarboxazid
Marplan Side Effects, and Drug Interactions - Isocarboxazid
SIDE EFFECTS
Adverse Findings Observed in Short-Term, Placebo-Controlled
Trials
Systematically collected data are available from only 86 patients
exposed to Marplan, of whom only 52 received doses of ³50
mg/ day, including only 11 who were dosed at ³60
mg/ day. Because of the limited experience with systematically monitored
patients receiving Marplan 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 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 and for which the incidence
in patients treated with Marplan 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 the 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 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 below).
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 per day, and
1 of 52 (2%) who received ³50 mg
of Marplan 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 Doses of 40 to 80 mg/ day 1
|
Body System/ Adverse Event
|
PLACEBO
|
MARPLAN <50 mg
|
MARPLAN ³
50 mg
|
|
(N= 85)
|
(N= 86)
|
(N= 52) 2
|
| MISCELLANEOUS |
| Drowsy |
0%
|
4%
|
0%
|
| Anxiety |
1%
|
2%
|
0%
|
| Chills |
0%
|
2%
|
0%
|
| Forgetful |
1%
|
2%
|
2%
|
| Hyperactive |
0%
|
2%
|
0%
|
| Lethargy |
0%
|
2%
|
2%
|
| Sedation |
1%
|
2%
|
0%
|
| Syncope |
0%
|
2%
|
0%
|
| INTEGUMENTARY |
| Sweating |
0%
|
2%
|
2%
|
| MUSCULOSKELETAL |
| Heavy feeling |
0%
|
2%
|
0%
|
| CARDIOVASCULAR |
| Orthostatic hypotension |
1%
|
4%
|
4%
|
| Palpitations |
1%
|
2%
|
0%
|
| GASTROINTESTINAL |
| Dry mouth |
4%
|
9%
|
6%
|
| Constipation |
6%
|
7%
|
4%
|
| Nausea |
2%
|
6%
|
4%
|
| Diarrhea |
1%
|
2%
|
0%
|
| UROGENITAL |
| Impotence |
0%
|
2%
|
0%
|
| Urinary frequency |
1%
|
2%
|
0%
|
| Urinary hesitancy |
0%
|
1%
|
4%
|
| CENTRAL NERVOUS |
| Headache |
13%
|
15%
|
6%
|
| Insomnia |
4%
|
4%
|
6%
|
| Sleep disturbance |
0%
|
5%
|
2%
|
| Tremor |
0%
|
4%
|
4%
|
| Myoclonic jerks |
0%
|
2%
|
0%
|
| Paresthesia |
1%
|
2%
|
0%
|
| SPECIAL SENSES |
| Dizziness |
14%
|
29%
|
15%
|
1 Events reported by at least 1% of patients
treated with Marplan are presented, except for those which had an
incidence on placebo
greater than or equal to that on Marplan.
2 All patients also received Marplan at doses
# 50 mg.
Other Events Observed During the Postmarketing Evaluation of
Marplan
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 is not a controlled substance.
Physical and Psychological Dependence Marplan 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 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 patients for history
of drug abuse and follow such
patients closely, observing them for signs of misuse or abuse
(e. g., development
of tolerance, incrementations
of dose, drug seeking behavior).
DRUG INTERACTIONS
See WARNINGS, CONTRAINDICATIONS
and PRECAUTIONS sections
for information on drug
interactions.
Marplan should be administered with caution to patients receiving
Antabuse® (disulfiram, Wyeth-Ayerst Laboratories). In
a single study, rats given high intraperitoneal
doses of an MAO inhibitor
plus disulfiram experienced
severe toxicity, including
convulsions and death.
Concomitant use of Marplan and other psychotropic agents is generally
not recommended because of possible potentiating effects. This is
especially true in patients who may subject
themselves to an overdosage of drugs. If combination therapy
is needed, careful consideration should be given to the pharmacology
of all agents to be used. The monoamine
oxidase inhibitory effects
of Marplan may persist for a substantial period
after discontinuation of the drug,
and this should be borne in mind
when another drug is prescribed
following Marplan. To avoid potentiation, the physician
wishing to terminate treatment with Marplan and begin therapy
with another agent should
allow for an interval
of 10 days.
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