Note: Some adverse effects of Thorazine (chlorpromazine) may be more likely to occur, or occur
with greater intensity, in patients with special medical problems, e.g., patients
with mitral insufficiency or pheochromocytoma have experienced severe hypotension
following recommended doses.
Drowsiness, usually mild to moderate, may occur, particularly during
the first or second week, after which it generally disappears. If troublesome,
dosage may be lowered.
B Overall incidence has been low, regardless of indication or dosage. Most
investigators conclude it is a sensitivity reaction. Most cases occur between
the second and fourth weeks of therapy. The clinical picture resembles infectious
hepatitis, with laboratory features of obstructive jaundice, rather than those
of parenchymal damage. It is usually promptly reversible on withdrawal of the
medication; however, chronic jaundice has been reported.
There is no conclusive evidence that preexisting liver disease makes patients
more susceptible to jaundice. Alcoholics with cirrhosis have been successfully
treated with Thorazine (chlorpromazine) without complications. Nevertheless,
the medication should be used cautiously in patients with liver disease. Patients
who have experienced jaundice with a phenothiazine should not, if possible,
be reexposed to Thorazine (chlorpromazine) or other phenothiazines.
If fever with grippe-like symptoms occurs, appropriate liver studies should
be conducted. If tests indicate an abnormality, stop treatment.
Liver function tests in jaundice induced by the drug may mimic extrahepatic
obstruction; withhold exploratory laparotomy until extrahepatic obstruction
Hematological Disorders, including agranulocytosis, eosinophilia, leukopenia,
hemolytic anemia, aplastic anemia, thrombocytopenic purpura and pancytopenia
have been reported.
Agranulocytosis — Warn patients to report the sudden appearance
of sore throat or other signs of infection. If white blood cell and differential
counts indicate cellular depression, stop treatment and start antibiotic and
other suitable therapy.
Most cases have occurred between the fourth and tenth weeks of therapy; patients
should be watched closely during that period.
Moderate suppression of white blood cells is not an indication for stopping
treatment unless accompanied by the symptoms described above.
Hypotensive Effects — Postural hypotension, simple tachycardia,
momentary fainting and dizziness may occur after the first injection; occasionally
after subsequent injections; rarely, after the first oral dose. Usually recovery
is spontaneous and symptoms disappear within 1 / 2 to 2 hours. Occasionally,
these effects may be more severe and prolonged, producing a shock-like condition.
To minimize hypotension after injection, keep patient lying down and observe
for at least 1 / 2 hour. To control hypotension, place patient in head-low position
with legs raised. If a vasoconstrictor is required, Levophed® *** and Neo-Synephrine®
§ are the most suitable. Other pressor agents, including epinephrine, should
not be used as they may cause a paradoxical further lowering of blood pressure.
EKG Changes — particularly nonspecific, usually reversible Q and
T wave distortions— have been observed in some patients receiving phenothiazine
tranquilizers, including Thorazine (chlorpromazine).
Note: Sudden death, apparently due to cardiac arrest, has been reported.
Neuromuscular (Extrapyramidal) Reactions — Neuromuscular reactions
include dystonias, motor restlessness, pseudo-parkinsonism and tardive dyskinesia,
and appear to be dose-related. They are discussed in the following paragraphs:
Dystonias: Symptoms may include spasm of the neck muscles, sometimes
progressing to acute, reversible torticollis; extensor rigidity of back muscles,
sometimes progressing to opisthotonos; carpopedal spasm, trismus, swallowing
difficulty, oculogyric crisis and protrusion of the tongue.
These usually subside within a few hours, and almost always within 24 to 48
hours after the drug has been discontinued.
In mild cases, reassurance or a barbiturate is often sufficient. In moderate
cases, barbiturates will usually bring rapid relief. In more severe adult cases,
the administration of an anti-parkinsonism agent, except levodopa, usually produces
rapid reversal of symptoms. In children (1 to 12 years of age), reassurance
and barbiturates will usually control symptoms. (Or, parenteral Benadryl®
ll may be useful. See Benadryl prescribing information for appropriate children's
dosage.) If appropriate treatment with anti-parkinsonism agents or Benadryl
fails to reverse the signs and symptoms, the diagnosis should be reevaluated.
Suitable supportive measures such as maintaining a clear airway and adequate
hydration should be employed when needed. If therapy is reinstituted, it should
be at a lower dosage. Should these symptoms occur in children or pregnant patients,
the drug should not be reinstituted.
Motor Restlessness: Symptoms may include agitation or jitteriness and
sometimes insomnia. These symptoms often disappear spontaneously. At times these
symptoms may be similar to the original neurotic or psychotic symptoms. Dosage
should not be increased until these side effects have subsided.
If these symptoms become too troublesome, they can usually be controlled by
a reduction of dosage or change of drug. Treatment with anti-parkinsonian agents,
benzodiazepines or propranolol may be helpful.
Pseudo-parkinsonism: Symptoms may include: mask-like facies, drooling,
tremors, pillrolling motion, cogwheel rigidity and shuffling gait. In most cases
these symptoms are readily controlled when an anti-parkinsonism agent is administered
concomitantly. Anti-parkinsonism agents should be used only when required. Generally,
therapy of a few weeks to 2 or 3 months will suffice. After this time patients
should be evaluated to determine their need for continued treatment. (Note:
Levodopa has not been found effective in antipsychotic-induced pseudo-parkinsonism.)
Occasionally it is necessary to lower the dosage of Thorazine (chlorpromazine)
or to discontinue the drug.
Tardive Dyskinesia: As with all antipsychotic agents, tardive dyskinesia
may appear in some patients on long-term therapy or may appear after drug therapy
has been discontinued. The syndrome can also develop, although much less frequently,
after relatively brief treatment periods at low doses. This syndrome appears
in all age groups. Although its prevalence appears to be highest among elderly
patients, especially elderly women, it is impossible to rely upon prevalence
estimates to predict at the inception of antipsychotic treatment which patients
are likely to develop the syndrome. The symptoms are persistent and in some
patients appear to be irreversible. The syndrome is characterized by rhythmical
involuntary movements of the tongue, face, mouth or jaw (e.g., protrusion of
tongue, puffing of cheeks, puckering of mouth, chewing movements). Sometimes
these may be accompanied by involuntary movements of extremities. In rare instances,
these involuntary movements of the extremities are the only manifestations of
tardive dyskinesia. A variant of tardive dyskinesia, tardive dystonia, has also
There is no known effective treatment for tardive dyskinesia; anti-parkinsonism
agents do not alleviate the symptoms of this syndrome. If clinically feasible,
it is suggested that all antipsychotic agents be discontinued if these symptoms
appear. Should it be necessary to reinstitute treatment, or increase the dosage
of the agent, or switch to a different antipsychotic agent, the syndrome may
It has been reported that fine vermicular movements of the tongue may be an
early sign of the syndrome and if the medication is stopped at that time the
syndrome may not develop.
Adverse Behavioral Effects — Psychotic symptoms and catatonic-like
states have been reported rarely.
Other CNS Effects— Neuroleptic Malignant Syndrome (NMS) has been
reported in association with antipsychotic drugs. (See WARNINGS.) Cerebral
edema has been reported.
Convulsive seizures (petit mal and grand mal) have been reported, particularly
in patients with EEG abnormalities or history of such disorders.
Abnormality of the cerebrospinal fluid proteins has also been reported.
Allergic Reactions of a mild urticarial type or photosensitivity are seen.
Avoid undue exposure to sun. More severe reactions, including exfoliative dermatitis,
have been reported occasionally.
Contact dermatitis has been reported in nursing personnel; accordingly, the
use of rubber gloves when administering Thorazine (chlorpromazine) liquid or injectable is recommended.
In addition, asthma, laryngeal edema, angioneurotic edema and anaphylactoid
reactions have been reported.
Endocrine Disorders: Lactation and moderate breast engorgement may occur
in females on large doses. If persistent, lower dosage or withdraw drug. False-positive
pregnancy tests have been reported, but are less likely to occur when a serum
test is used. Amenorrhea and gynecomastia have also been reported. Hyperglycemia,
hypoglycemia and glycosuria have been reported.
Autonomic Reactions: Occasional dry mouth; nasal congestion; nausea;
obstipation; constipation; adynamic ileus; urinary retention; priapism; miosis
and mydriasis, atonic colon, ejaculatory disorders/impotence.
Special Considerations in Long-Term Therapy: Skin pigmentation and ocular
changes have occurred in some patients taking substantial doses of Thorazine
(chlorpromazine) for prolonged periods.
Skin Pigmentation — Rare instances of skin pigmentation have been
observed in hospitalized mental patients, primarily females who have received
the drug usually for 3 years or more in dosages ranging from 500 mg to 1500
mg daily. The pigmentary changes, restricted to exposed areas of the body, range
from an almost imperceptible darkening of the skin to a slate gray color, sometimes
with a violet hue. Histological examination reveals a pigment, chiefly in the
dermis, which is probably a melanin-like complex. The pigmentation may fade
following discontinuance of the drug.
Ocular Changes — Ocular changes have occurred more frequently
than skin pigmentation and have been observed both in pigmented and nonpigmented
patients receiving Thorazine (chlorpromazine) usually for 2 years or more in
dosages of 300 mg daily and higher. Eye changes are characterized by deposition
of fine particulate matter in the lens and cornea. In more advanced cases, star-shaped
opacities have also been observed in the anterior portion of the lens. The nature
of the eye deposits has not yet been determined. A small number of patients
with more severe ocular changes have had some visual impairment. In addition
to these corneal and lenticular changes, epithelial keratopathy and pigmentary
retinopathy have been reported. Reports suggest that the eye lesions may regress
after withdrawal of the drug.
Since the occurrence of eye changes seems to be related to dosage levels and/or
duration of therapy, it is suggested that long-term patients on moderate to
high dosage levels have periodic ocular examinations.
Etiology — The etiology of both of these reactions is not clear,
but exposure to light, along with dosage/duration of therapy, appears to be
the most significant factor. If either of these reactions is observed, the physician
should weigh the benefits of continued therapy against the possible risks and,
on the merits of the individual case, determine whether or not to continue present
therapy, lower the dosage, or withdraw the drug.
Other Adverse Reactions: Mild fever may occur after large I.M. doses.
Hyperpyrexia has been reported. Increases in appetite and weight sometimes occur.
Peripheral edema and a systemic lupus erythematosus-like syndrome have been
Note: There have been occasional reports of sudden death in patients receiving
phenothiazines. In some cases, the cause appeared to be cardiac arrest or asphyxia
due to failure of the cough reflex.
No information provided.