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
Thioridazine Warnings, Precautions, Pregnancy, Nursing, Abuse - Thioridazine
Thioridazine Warnings, Precautions, Pregnancy, Nursing, Abuse - Thioridazine
WARNINGS
Tardive Dyskinesia
Tardive dyskinesia,
a syndrome consisting
of potentially irreversible, involuntary, dyskinetic
movements may develop in patients treated with neuroleptic (antipsychotic)
drugs. Although the prevalence
of the syndrome appears to be highest among the elderly, especially
elderly women, it is impossible to rely upon prevalence
estimates to predict, at the inception of neuroleptic
treatment, which patients
are likely to develop the syndrome. Whether neuroleptic
drug products differ in
their potential to
cause tardive dyskinesia
is unknown.
Both the risk of developing
the syndrome and the
likelihood that it will become irreversible
are believed to increase as the duration
of treatment and the total cumulative
dose of neuroleptic
drugs administered to the patients increase. However, the syndrome
can develop, although much less commonly, after relatively brief
treatment periods
at low doses.
There is no known treatment
for established cases of tardive
dyskinesia, although the syndrome
may remit, partially or completely, if neuroleptic treatment is
withdrawn. Neuroleptic treatment,
itself, however, may suppress (or partially suppress) the signs
and symptoms of the syndrome
and thereby may possibly mask
the underlying disease
process. The effect that
symptomatic suppression has upon the long- term
course of the syndrome
is unknown.
Given these considerations, neuroleptics should be prescribed in
a manner that is most likely to minimize the occurrence of tardive
dyskinesia. Chronic neuroleptic treatment
should generally be reserved for patients who suffer from a chronic
illness that, 1) is
known to respond to neuroleptic
drugs, and, 2) for whom alternative, equally effective, but potentially
less harmful treatments are not available or appropriate. In
patients who do require chronic treatment,
the smallest dose and the
shortest duration of
treatment producing a satisfactory clinical
response should be
sought. The need for continued
treatment should be
re- assessed periodically.
If signs and symptoms of tardive
dyskinesia appear
in a patient on neuroleptics,
drug discontinuation should be considered. However, some patients
may require treatment despite the presence of the syndrome.
(For further information about the description of tardive
dyskinesia and its clinical
detection, please refer to the sections on PATIENT
INFORMATION and ADVERSE
REACTIONS).
Neuroleptic Malignant Syndrome (NMS)
A potentially fatal symptom
complex sometimes referred
to as Neuroleptic Malignant Syndrome (NMS) has been reported in
association with
antipsychotic drugs. Clinical manifestations of NMS are hyperpyrexia,
muscle rigidity, altered
mental status
and evidence of autonomic
instability (irregular
pulse or blood pressure,
tachycardia, diaphoresis,
and cardiac dysrhythmias).
The diagnostic evaluation
of patients with this syndrome
is complicated. In arriving at a diagnosis,
it is important to identify cases where the clinical presentation
includes both serious medical
illness (e.g., pneumonia,
systemic infection,
etc.) and untreated or inadequately treated extrapyramidal signs
and symptoms (EPS). Other important considerations in the differential
diagnosis include central
anticholinergic
toxicity, heat
stroke, drug fever and
primary central
nervous system
(CNS) pathology.
The management of NMS should include 1) immediate
discontinuation of antipsychotic drugs and other drugs not essential
to concurrent therapy, 2) intensive
symptomatic treatment
and medical monitoring,
and 3) treatment of any concomitant
serious medical problems
for which specific
treatments are available. There is no
general agreement about specific
pharmacological treatment regimens for uncomplicated NMS.
If the patient requires
antipsychotic drug treatment
after recovery from NMS, the potential
reintroduction of drug
therapy should be carefully
considered. The patient
should be carefully monitored, since recurrences of NMS have been
reported.
General
It has been suggested in regard to phenothiazines
in general, that people who have demonstrated a hypersensitivity
reaction (e.g., blood
dyscrasias, jaundice) to one may be more prone
to demonstrate a reaction
to others. Attention should be paid to the fact that phenothiazines
are capable of potentiating central
nervous system
depressants (e.g., anesthetics, opiates, alcohol, etc.) as well
as atropine and phosphorus
insecticides. Physicians should carefully consider benefit
versus risk when treating
less severe disorders.
Reproductive studies in animals and clinical
experience to date
have failed to show a teratogenic
effect with thioridazine.
However, in view of the desirability of keeping the administration
of all drugs to a minimum during pregnancy,
thioridazine should be given only when the benefits derived from
treatment exceed the
possible risks to mother
and fetus.
PRECAUTIONS
Leukopenia and/or agranulocytosis
and convulsive seizures
have been reported but are infrequent. Thioridazine has been shown
to be helpful in the treatment
of behavioral disorders in epileptic
patients, but anticonvulsant medication should also be maintained.
Pigmentary retinopathy,
which has been observed primarily in patients taking larger than
recommended doses, is characterized by diminution of visual
acuity, brownish coloring
of vision, and impairment
of night vision; examination
of the fundus discloses
deposits of pigment. The possibility of this complication
may be reduced by remaining within the recommended limits of dosage.
Where patients are participating in activities requiring complete
mental alertness (e.g., driving) it is advisable to administer the
phenothiazines cautiously and to increase the dosage
gradually. Female patients appear to have a greater tendency to
orthostatic hypotension
than male patients. The
administration
of epinephrine should
be avoided in the treatment
of drug- induced hypotension
in view of the fact that phenothiazines
may induce a reversed epinephrine
effect on occasion. Should
a vasoconstrictor
be required, the most suitable are norepinephrine
and phenylephrine.
Neuroleptic drugs elevate prolactin
levels; the elevation
persists during chronic administration. Tissue culture
experiments indicate that approximately one- third of human
breast cancers are prolactin
dependent in vitro, a factor
of potential importance
if the prescription
of these drugs is contemplated in a patient
with a previously detected breast
cancer. Although disturbances such
as galactorrhea,
amenorrhea, gynecomastia,
and impotence have been reported, the clinical
significance of elevated serum
prolactin levels is unknown for most patients. An
increase in mammary
neoplasms has been found in rodents after chronic
administration
of neuroleptic drugs.
Neither clinical studies
nor epidemiologic studies conducted to date, however, have shown
an association between
chronic administration
of these drugs and mammary
tumorigenesis; the available evidence
is considered too limited to be conclusive at this time.
Concurrent administration
of propranolol (100 mg and
800 mg daily) has been reported
to produce increases in plasma
levels of thioridazine (approximately 50 to 400 percent) and its
metabolites (approximately 80 to 300 percent).
It is recommended that a daily dose
in excess of 300 mg be reserved
for use only in severe neuropsychiatric conditions.
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