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LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012-.

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LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet].

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Last Update: July 1, 2020.



Prochlorperazine is a phenothiazine used primarily as an antiemetic agent. In rare instances, prochlorperazine can cause clinically apparent acute and chronic cholestatic liver injury.


Prochlorperazine (proe" klor per' a zeen) is a tricyclic aliphatic phenothiazine which acts by postsynaptic inhibition of dopamine receptors. Prochlorperazine has other peripheral and central nervous system effects, producing both alpha adrenergic stimulation and blocking histamine- and serotonin-mediated effects. Prochlorperazine is indicated primarily for the therapy of nausea and vomiting. Prochlorperazine also has antianxiety and antipsychotic effects, but is used less commonly for these indications compared to the major phenothiazines such as chlorpromazine, fluphenazine, perphenazine, thioridazine and trifluoperazine. Prochlorperazine was approved for use in the United States in 1956 and is still widely used in therapy of nausea and vomiting. Prochlorperazine is available in generic forms as tablets of 5, 10 and 25 mg, in long acting capsules of 15 mg, as an oral solution of 5 mg/ 5 mL, as suppositories of 2.5, 5 and 25 mg, and in parenteral forms. Prochlorperazine is also available under the brand names of Compazine and Compro. Typical doses for nausea are 5 to 10 mg three to four times daily. Common side effects are similar to other phenothiazines and include drowsiness, dizziness, headache, blurred vision, dry mouth, constipation, tremor, restlessness, muscle spasms and weight gain. Rare but potentially severe adverse events (which apply to most antipsychotic agents) include an increased risk for death in the elderly with dementia-related psychosis, neuroleptic malignant syndrome, tardive dyskinesia and orthostatic hypotension.


Liver test abnormalities are uncommon during prochlorperazine therapy, perhaps because it is rarely given long term or in high doses chronically. Aminotransferase elevations can occur during therapy, but they are usually mild, asymptomatic and transient and reversible even with continuation of medication. Rare instances of clinically apparent acute liver injury have been reported due to prochlorperazine which resemble the cholestatic liver injury associated with chlorpromazine. The onset of jaundice is usually within 1 to 4 weeks, and the pattern of serum enzyme elevations is typically cholestatic or mixed. Immunoallergic features (fever and eosinophilia) occur in some cases, but they are usually mild and self-limited; autoantibodies are rare. Liver biopsy typically shows a cholestatic hepatitis. Importantly, prochlorperazine jaundice can be prolonged and has been associated with rare cases of vanishing bile duct syndrome (Case 1) that can be fatal or ultimately require liver transplantation.

Likelihood score: B (uncommon but likely cause of clinically apparent liver injury).

Mechanism of Injury

The mechanism by which prochlorperazine causes serum aminotransferase elevations is not known but is likely shared with other phenothiazines. Several features of the clinical presentation of prochlorperazine hepatotoxicity (short latency period, fever, eosinophilia) suggest a hypersensitivity reaction, and rechallenge typically causes a rapid recurrence of injury. Prochlorperazine is extensively metabolized by the liver via sulfoxidation and oxidation, and some instances of serum aminotransferase elevations as well as more clinically apparent liver injury may be caused by production of a toxic intermediate of its metabolism.

Outcome and Management

The serum aminotransferase elevations that occur on prochlorperazine therapy are usually transient and do not require dose modification or discontinuation of therapy. The acute cholestatic hepatitis caused by prochlorperazine is typically self-limited and benign but should prompt immediate discontinuation. A small proportion of cases are followed by prolonged jaundice and cholestasis and features of vanishing bile duct syndrome. Many patients with chronic cholestasis eventually improve, but they may have persistent enzyme elevations and biliary cirrhosis. Fatalities from prochlorperazine jaundice have been reported. Rechallenge with phenothiazines usually causes a prompt recurrence of the liver injury and should be avoided.

Drug Class: Gastrointestinal Agents; Antipsychotic Agents

Other Drugs in the Subclass, Phenothiazines: Chlorpromazine, Fluphenazine, Perphenazine, Thioridazine, Trifluoperazine


Case 1. Prolonged cholestatic liver injury due to prochlorperazine.(1)

A 68 year old man was treated with trimethoprim/sulfamethoxazole (800/400 mg three times daily) for one week and prochlorperazine (10 mg daily) for 4 weeks for suspected otitis media. A few weeks after stopping prochlorperazine, he developed jaundice and pruritus. When first seen, one month after stopping medications, serum bilirubin was 18.4 mg/dL, alkaline phosphatase was 1.5 times normal and ALT was minimally elevated (Table). Tests for viral hepatitis and abdominal ultrasound were normal. After persistence of jaundice for 3 months, a liver biopsy was done which showed centrilobular cholestasis with minimal hepatocyte necrosis or portal inflammation. The intralobular bile ducts were normal. He continued to have jaundice and severe pruritus and developed skin hyperpigmentation. Tests for hepatitis B and mitochondrial antibody were negative. Endoscopic retrograde cholangiopancreatography was normal. Serum bilirubin levels peaked 4 months after presentation and then began to decline, not becoming normal until one year later. Pruritus and hyperpigmentation also resolved, but serum alkaline phosphatase and GGT levels remained elevated. A repeat liver biopsy, done two years after onset and 9 months after resolution of jaundice and symptoms, showed minimal cholestasis but bridging hepatic fibrosis and paucity of intralobular bile ducts. Two-and-a-half years after onset, serum alkaline phosphatase levels were still abnormal but he had no symptoms.

Key Points

Medication:Prochlorperazine (10 mg daily for 4 weeks)
Severity:4+ (prolonged jaundice and hepatic fibrosis)
Latency:3 weeks
Recovery:Incomplete after 2 years
Other medications:Trimethoprim/sulfamethoxazole

Laboratory Values

Time After
Time After
Alk P*
Chlorpromazine (50 mg daily) given for nausea for 4 weeks
1 month04911618.4
3 months8021026.2Biopsy #1
4 months8821919.3ERCP normal
6 months8536511.2
10 months654302.6
1 year12 months604101.5
2 years22 months854451.0Biopsy #2
Normal Values <42 <90 <1.2

Some values estimated from Figure 1 and bilirubin converted from μmol/L to mg/dL.


A typical example of the evolution of an acute cholestatic hepatitis to prolonged cholestasis and vanishing bile duct syndrome. The patient eventually improved and was asymptomatic, but alkaline phosphatase levels were persistently elevated and liver biopsy showed paucity of intralobular bile ducts and bridging hepatic fibrosis. Not all cases of vanishing bile duct syndrome progress to hepatic failure and eventual clinical improvement is common. Long term follow up on such cases usually demonstrates well compensated and nonprogressive cirrhosis and persistence of mild elevations in serum alkaline phosphatase.



Prochlorperazine – Generic, Compazine®, Compro®


Gastrointestinal Agents; Antipsychotic Agents


Product labeling at DailyMed, National Library of Medicine, NIH


Prochlorperazine 58-38-8 C20-H24-Cl-N3-S image 134971659 in the ncbi pubchem database


Lok AS, Ng IO. Prochlorperazine-induced chronic cholestasis. J Hepatol. 1988;6:369–73. [PubMed: 3392386]


References updated: 01 July 2020

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    (26 year old man with alcoholism and tuberculosis developed fever and jaundice 24 days after starting a third course of prochlorperazine; serum enzyme and bilirubin levels were not provided).
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    (68 year old man developed jaundice 4 weeks after starting prochlorperazine [peak bilirubin 26 mg/dL, ALT 50-90 U/L, Alk P 120-500 U/L], jaundice and pruritus persisting for more than a year, but then gradual clinical improvement but with persistent enzyme elevations, and biopsy 22 months after onset showed fibrosis and paucity of bile ducts: Case 1).
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