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 Warnings, Precautions, Pregnancy, Nursing, Abuse - Isocarboxazid
Marplan Warnings, Precautions, Pregnancy, Nursing, Abuse - Isocarboxazid
WARNINGS
Second Line Status
Marplan can cause serious
side effects. It is not
recommended as initial
therapy but should be
reserved for patients who have not responded satisfactorily to other
antidepressants.
Hypertensive Crises
The most important reaction
associated with MAO inhibitors
is the occurrence of hypertensive
crises, which have sometimes been fatal,
resulting from the co-administration of MAOIs and certain drugs
and foods (see Contraindications).
These crises are characterized by some or all of the following
symptoms: occipital headache
which may radiate frontally,
palpitation, neck
stiffness or soreness, nausea
or vomiting, sweating
(sometimes with fever
and sometimes with cold, clammy skin), and photophobia. Either tachycardia
or bradycardia may be present, and associated constricting chest
pain and dilated pupils
may occur. Intracranial bleeding,
sometimes fatal, has been
reported in association with the increase in blood
pressure.
Blood pressure should
be followed closely in patients taking Marplan to detect any pressor
response. Therapy should be discontinued immediately if palpitations
or frequent headaches occur during Marplan therapy
as these symptoms may be prodromal
of a hypertensive
crisis.
If a hypertensive
crisis occurs, Marplan
should be discontinued, and therapy to lower blood
pressure should be
instituted immediately. Although there has been no
systematic study
of treatment of hypertensive
crises, phentolamine (available as Regitine®, Novartis) has
been used and is recommended at a dosage
of 5 mg I. V. Care should
be taken to administer the drug
slowly in order to avoid
producing an excessive hypotensive
effect. Fever should be managed by means of external
cooling. Other symptomatic and supportive measures may be desirable
in particular cases. Parenteral reserpine should not be used.
Warnings to the Patient
Patients should be instructed to report
promptly the occurrence of headache or other unusual symptoms, i.
e., palpitation
and or tachycardia,
a sense of constriction
in the throat or chest,
sweating, dizziness,
neck stiffness, nausea,
or vomiting. Patients should be warned against eating the foods
listed under CONTRAINDICATIONS
while on Marplan therapy
and should also be told not to drink alcoholic beverages. The patient
should also be warned about the possibility of hypotension and faintness,
as well as drowsiness
sufficient to impair performance
of potentially hazardous tasks, such
as driving a car or operating machinery.
Patients should also be cautioned not to take
concomitant medications,
whether prescription
or over-the- counter
drugs such as cold, hay
fever, or weight-reducing preparations, without the advice of a
physician. They should be advised not to consume excessive amounts
of caffeine in any
form. Likewise, they should inform their physicians and their dentist
about the use of Marplan.
Limited Experience with Marplan at Higher Doses
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 ADVERSE REACTIONS).
PRECAUTIONS
General
Hypotension
Hypotension has been observed during Marplan therapy. Symptoms
of postural hypotension
are seen most commonly, but not exclusively, in patients with preexistent
hypertension; blood pressure
usually returns rapidly to pretreatment
levels upon discontinuation of the drug. Dosage increases should
be made more gradually in patients showing a tendency toward hypotension
at the beginning of therapy. Postural hypotension
may be relieved by having the patient
lie down until blood
pressure returns to
normal. When Marplan is combined with phenothiazine
derivatives or other compounds known to cause
hypotension, the
possibility of additive
hypotensive effects should be considered.
Lowered Seizure Threshold
Because Marplan lowers the convulsive threshold in some animal
experiments, suitable precautions should be taken if epileptic
patients are treated. Marplan appears to have varying effects in
epileptic patients;
while some have a decrease in frequency
of seizures, others have more seizures.
Drugs that lower the seizure
threshold, including MAO
inhibitors, should not be used with Amipaque® (metrizamide,
Sanofi Winthrop Pharmaceuticals). As with other MAO
inhibitors, Marplan should be discontinued at least 48 hours before
myelography and
should not be resumed for at least 24 hours postprocedure.
Hepatotoxicity
There is a low incidence
of altered liver function
or jaundice in patients
treated with Marplan. In
the past, it was difficult to differentiate most cases of drug-induced
hepatocellular
jaundice from viral
hepatitis although
this is no longer true. Periodic
liver chemistry tests
should be performed during Marplan therapy; use of the drug
should be discontinued at the first sign
of hepatic dysfunction
or jaundice.
Suicide
In depressed
patients, the possibility of suicide
should always be considered and adequate precautions taken. Exclusive
reliance on drug therapy
to prevent suicidal attempts is unwarranted, as there may be a delay
in the onset of therapeutic
effect or an increase
in anxiety or agitation. Also, some patients fail to respond to
drug therapy
or may respond only temporarily. The strictest supervision, and
preferably hospitalization, are required.
Use in Patients with Concomitant Illness MAO
inhibitors can suppress anginal pain
that would otherwise serve as a warning of myocardial
ischemia.
In patients with impaired renal
function, Marplan should be used cautiously to prevent accumulation.
Some MAO inhibitors have
contributed to hypoglycemic episodes in diabetic
patients receiving insulin
or glycemic agents. Marplan should therefore be used with caution
in diabetics using these drugs.
Marplan may aggravate coexisting symptoms in depression,
such as anxiety and agitation.
Use Marplan with caution in hyperthyroid patients because of their
increased sensitivity
to pressor amines.
Marplan should be used cautiously in hyperactive or agitated patients,
as well as in schizophrenic patients, because it may cause
excessive stimulation. Activation of mania/ hypomania
has been reported in a small proportion of patients with major affective
disorder who were treated
with marketed antidepressants.
Drug Interactions
See DRUG INTERACTIONS section.
Carcinogenesis, Mutagenesis, Impairment of Fertility
Long term studies to evaluate
carcinogenic potential
have not been conducted with this drug,
and there is no information
concerning mutagenesis
or impairment of fertility.
Pregnancy Category C
The potential reproductive
toxicity of isocarboxazid
has not been adequately evaluated in animals. It is also not known
whether isocarboxazid can cause embryo/ fetal
harm when administered to a pregnant
woman or can affect reproductive
capacity. Marplan should be given to a pregnant
woman only if clearly
needed.
Nursing Mothers
Levels of excretion
of isocarboxazid and or
its metabolites in human milk have not been determined, and effects
on the nursing infant
are unknown. Marplan should be used in women who are nursing
only if clearly needed.
Pediatric Use
Marplan is not recommended for use in patients under 16 years of
age, as safety and effectiveness
in pediatric populations
have not been demonstrated.
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