WARNINGS
Amitriptyline HCl may block the antihypertensive action
of guanethidine or similarly acting compounds.
It should be used with caution in patients with a history
of seizures and, because of its atropine-like action,
in patients with a history of urinary retention, angle-closure
glaucoma or increased intraocular pressure. In patients
with angle-closure glaucoma, even average doses may precipitate
an attack.
Patients with cardiovascular disorders should be watched
closely. Tricyclic antidepressant drugs, including amitriptyline
HCl, particularly when given in high doses, have been
reported to produce arrhythmias, sinus tachycardia, and
prolongation of the conduction time. Myocardial infarction
and stroke have been reported with drugs of this class.
Close supervision is required when amitriptyline HCl
is given to hyperthyroid patients or those receiving thyroid
medication.
Amitriptyline HCl may enhance the response to alcohol
and the effects of barbiturates and other CNS depressants.
In patients who may use alcohol excessively, it should
be borne in mind that the potentiation may increase the
danger inherent in any suicide attempt or overdosage.
Delirium has been reported with concurrent administration
of amitriptyline and disulfiram.
Usage in Pregnancy: Teratogenic
effects were not observed in mice, rats, or rabbits when
amitriptyline was given orally at doses of 2 to 40 mg/kg/day
(up to 13 times the maximum recommended human amitriptyline
dose of 150 mg/day or 3 mg/kg/day for a 50 kg patient).
Studies in literature have shown amitriptyline to be teratogenic
in mice and hamsters when given by various routes of administration
at doses of 28 to 100 mg/kg/day (9 to 33 times the maximum
recommended human dose), producing multiple malformations.
Another study in the rat reported that an oral dose of
25 mg/kg/day (8 times the maximum recommended human dose)
produced delays in ossification of fetal vertebral bodies
without other signs of embryotoxicity. In rabbits, an
oral dose of 60 mg/kg/day (20 times the maximum recommended
human dose) was reported to cause incomplete ossification
of the cranial bones.
Amitriptyline has been shown to cross the placenta. Although
a causal relationship has not been established, there
have been a few reports of adverse events, including CNS
effects, limb deformities, or developmental delay, in
infants whose mothers had taken amitriptyline during pregnancy.
There are no adequate and well-controlled studies in
pregnant women. Amitriptyline HCl should be used during
pregnancy only if the potential benefit to the mother
justifies the potential risk to the fetus.
Nursing Mothers: Amitriptyline
is excreted into breast milk. In one report in which a
patient received amitriptyline 100 mg/day while nursing
her infant, levels of 83 - 141 ng/ml were detected in
the mother's serum. Levels of 135 - 151 ng/ml were found
in the breast milk, but no trace of the drug could be
detected in the infant's serum.
Because of the potential for serious adverse reactions
in nursing infants from amitriptyline, a decision should
be made whether to discontinue nursing or to discontinue
the drug, taking into account the importance of the drug
to the mother.
Use in Pediatric Patients:
In view of the lack of experience with the use of this
drug in children, it is not recommended at the present
time for patients under 12 years of age.
PRECAUTIONS
Schizophrenic patients may develop increased symptoms
of psychosis; patients with paranoid symptomatology may
have an exaggeration of such symptoms. Depressed patients,
particularly those with known manic-depressive illness,
may experience a shift to mania or hypomania. In these
circumstances the dose of amitriptyline may be reduced
or a major tranquilizer such as perphenazine may be administered
concurrently.
The possibility of suicide in depressed patients remains
until significant remission occurs. Potentially suicidal
patients should not have access to large quantities of
this drug. Prescriptions should be written for the smallest
amount feasible.
Concurrent administration of amitriptyline HCl and electroshock
therapy may increase the hazards associated with such
therapy. Such treatment should be limited to patients
for whom it is essential.
When possible, the drug should be discontinued several
days before elective surgery.
Both elevation and lowering of blood sugar levels have
been reported.
Amitriptyline HCl should be used with caution in patients
with impaired liver function.
Information for the Patient:
While on therapy with amitriptyline HCl, patients should
be advised as to the possible impairment of mental and/or
physical abilities required for performance of hazardous
tasks, such as operating machinery or driving a motor
vehicle.
Geriatric Use: Clinical experience
has not identified differences in responses between elderly
and younger patients. In general, dose election for an
elderly patient should be cautious, usually starting at
the low end of the dosing range, reflecting the greater
frequency of decreased hepatic function, concomitant disease
and other drug therapy in elderly patients.
Geriatric patients are particularly sensitive to the
anticholinergic side effects of tricyclic antidepressants
including amitriptyline HCl. Peripheral anticholinergic
effects include tachycardia, urinary retention, constipation,
dry mouth, blurred vision, and exacerbation of narrow-angle
glaucoma. Central nervous system anticholinergic effects
include cognitive impairment, psychomotor slowing, confusion,
sedation, and delirium. Elderly patients taking amitriptyline
HCl may be at increased risk for falls. Elderly patients
should be started on low doses of amitriptyline HCl and
observed closely (see DOSAGE AND ADMINISTRATION).
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