Chlorpromazine Side Effects

Not all side effects for chlorpromazine may be reported. You should always consult a doctor or healthcare professional for medical advice. Side effects can be reported to the FDA here.

For the Consumer

Applies to chlorpromazine: oral tablets, parenteral injection

Side effects include:

Extrapyramidal reactions (e.g., Parkinson-like symptoms, dystonia, akathisia, tardive dyskinesia), drowsiness, dizziness, skin reactions or rash, dry mouth, orthostatic hypotension, amenorrhea, galactorrhea, weight gain.

For Healthcare Professionals

Applies to chlorpromazine: compounding powder, injectable solution, oral capsule extended release, oral concentrate, oral syrup, oral tablet, rectal suppository

General

General side effects have included cases of muscle necrosis after repeated injections of chlorpromazine. The low pH of parenteral chlorpromazine solutions may be responsible for the necrosis. Subcutaneous injections should be avoided.[Ref]

Nervous system

Nervous system side effects are common and include sedation, drowsiness and rarely seizures. Tardive dyskinesia, dystonia, pseudoparkinsonism, increased neuromuscular excitability, and the neuroleptic malignant syndrome have also been reported.[Ref]

The drowsiness associated with chlorpromazine therapy may resolve after several doses.

Tardive dyskinesia involves involuntary, dyskinetic, repetitive movements and may be more common in elderly women receiving chlorpromazine. Tardive dyskinesia may be irreversible and is related to both the duration of therapy and the total amount of drug consumed. Frequent discontinuation and resumption of therapy may predispose patients to the development of tardive dyskinesia.

Dystonias frequently involve tongue protrusions, muscle rigidity, torticollis, and opisthotonos. Dystonias usually resolve after neuroleptic discontinuation, but may require antihistamine and antiparkinsonian therapy if symptoms are severe or if respiration is compromised. Treatment of dystonic reactions and extrapyramidal effects, in addition to general supportive measures, may include judicious use of one or more of the following: benztropine, trihexyphenidyl, biperiden or diphenhydramine.

Pseudoparkinsonism involves flat facies, pill- rolling tremor, shuffling gait, and cogwheel rigidity. Pseudoparkinsonism symptoms may respond to judicious use of one or more of the following: benztropine, trihexyphenidyl, biperiden or diphenhydramine.

Fever, altered consciousness, autonomic dysfunction and muscle rigidity are the hallmarks of the neuroleptic malignant syndrome. The neuroleptic malignant syndrome is associated with a case fatality rate of about 20%. Immediate discontinuation of neuroleptic therapy and intensive monitoring and supportive care are indicated.

Seizures associated with chlorpromazine have been reported, but many of the reports involve patients with a history of seizures or underlying organic brain disease.[Ref]

Psychiatric

Psychiatric side effects including psychotic symptoms, excitability, and reversible catatonic states have been reported. There may also be rare paradoxical psychiatric effects with chlorpromazine therapy.[Ref]

Hematologic

Hematologic side effects have included reversible agranulocytosis (which occurs in about one out of 10,000 patients). Hemolytic anemia, thrombocytopenia, and eosinophilia have also been reported.[Ref]

A 40% decrease in platelet counts was observed in 21% of patients on chlorpromazine in one study. The thrombocytopenia persisted for up to 6 months after discontinuation of chlorpromazine.

Some clinicians have suggested that any sign or symptom of infection in patients on chlorpromazine therapy should be evaluated with a complete blood count and differential.[Ref]

Cardiovascular

Cases of cardiopulmonary arrest in otherwise healthy young patients have been reported rarely. Edema in association with chlorpromazine therapy has also been reported rarely.

Hypotension is more likely in patients with intravenous administration.[Ref]

Cardiovascular side effects have included profound orthostatic hypotension and reflex tachycardia. These effects may subside after several doses. Chlorpromazine has mild negative inotropic properties, which may be important in some patients with a history of congestive heart failure. ECG changes include prolongation of the PR interval, prolongation of QTc segments, diffuse T-wave flattening, and ST segment depression.[Ref]

Hypersensitivity

Hypersensitivity side effects to chlorpromazine are usually mild and presents as an urticarial rash. Pustular eruptions, severe anaphylaxis and angioedema have been reported rarely.[Ref]

Rare cases of anaphylaxis, toxic epidermal necrolysis, and angioedema have been reported. A case of contact dermatitis associated with crushed chlorpromazine tablets has been reported.[Ref]

Hepatic

Chlorpromazine- induced cholestatic jaundice usually resolves without sequelae 2 to 8 weeks after discontinuation of the drug. However, severe and prolonged jaundice, resembling primary biliary cirrhosis, has been reported in a minority of cases. The prognosis of this condition is generally favorable. However, progression to biliary cirrhosis has been reported.

A case of chronic active hepatitis associated with chlorpromazine has been reported. A Danish study has reported 5 cases of fatal hepatitis associated with chlorpromazine. A recent study of 10,502 users of chlorpromazine has reported 14 illnesses which were considered to be compatible with drug induced liver disease. The frequency of drug induced liver disease in that group was 1.3 per 1,000 users of chlorpromazine.

Monitoring of liver function tests during chlorpromazine therapy may be helpful in patients with liver disease.[Ref]

Hepatic side effects including mild reversible elevations of liver function tests have been reported. Cholestatic jaundice has been reported in as many as 1% of patients taking chlorpromazine, however many clinicians believe that the reported frequency of cholestatic jaundice may be referable to impurities in early formulations of the drug. Severe hepatitis has also been reported.[Ref]

Immunologic

In one study 35% of patients on chlorpromazine tested positive for the lupus anticoagulant. In another study of 64 patients on chlorpromazine, 45% tested positive for the lupus anticoagulant, 39% for positive ANA titers, 34% for the anticardiolipin antibody, 50% for rheumatoid factor, and 27% for an elevation in IgM.

A case of Henoch-Schonlein purpura has been associated with chlorpromazine.

Chlorpromazine- induced antiphospholipid antibody syndrome developed in a patient after taking chlorpromazine 100 mg daily for a year. Symptoms included encephalopathy, seizures (i.e., generalized tonic-clonic, status epilepticus), confusion, and drowsiness. All symptoms resolved following discontinuation of chlorpromazine.[Ref]

Immunologic side effects have included a variety of adverse immunologic effects including antiphospholipid antibody syndrome which appear to be related to the total dose consumed.[Ref]

Gastrointestinal

The gastrointestinal side effects may result from the anticholinergic properties of chlorpromazine.[Ref]

Gastrointestinal side effects including dry mouth, constipation, and less commonly, diarrhea have been reported.[Ref]

Endocrine

Endocrine side effects including hyperglycemia, hyperprolactinemia, galactorrhea, amenorrhea, and the syndrome of inappropriate secretion of antidiuretic hormone have been reported.[Ref]

Dermatologic

Dermatologic side effects including skin hyperpigmentation has been reported in patients after long-term chlorpromazine therapy (doses of 500 to 1,500 mg over 2 to 3 years). The hyperpigmentation commonly presents as a gray- blue discoloration in exposed areas, including the eyelids.[Ref]

The hyperpigmentation associated with chlorpromazine therapy appears to be reversible in some patients after discontinuation of chlorpromazine and initiation of alternative neuroleptic therapy. Contact dermatitis has been reported in a person who crushed chlorpromazine tablets for a patient. Leukocytoclastic vasculitis associated with Henoch-Schonlein purpura has been reported during chlorpromazine use.[Ref]

Genitourinary

Genitourinary side effects including urinary retention, impotence and priapism have been associated with chlorpromazine therapy.[Ref]

Ocular

Chlorpromazine may induce lens and corneal pigmentary changes which have produced visual impairment such as halos around lights, hazy vision, photophobia, and watering eyes. One case of orbital cellulitis has been reported following the retrobulbar injection of chlorpromazine for intractable pain in a patient with irreversible blindness.

Ocular changes seem to be related to dosage levels and/or duration of therapy. Therefore, long term chlorpromazine patients on moderate to high dosage levels should have periodic ocular examinations.[Ref]

Ocular side effects have been reported primarily in patients receiving chlorpromazine for two or more years in dosages of 300 mg daily or more. Ocular changes are characterized by deposition of fine particulate matter in the lens and cornea. In more advanced cases, star- shaped opacities have also been reported in the anterior portion of the lens. The nature of the deposits has not been reported. Anterior capsular cataracts have also been reported. Some visual impairment has been reported in a small number of patients with more severe ocular changes. Epithelial keratopathy and pigmentary retinopathy have also been reported. Reports suggest that the eye lesions may regress after withdrawal of the drug.[Ref]

References

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