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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: January 25, 2017.



Clorazepate is a benzodiazepine used as an anticonvulsant as adjunctive therapy in management of epilepsy and as an anxiolytic for therapy of anxiety and alcohol withdrawal. Therapy with clorazepate is not associated with serum aminotransferase elevations, and cases of clinically apparent liver injury from clorazepate have been reported but are very rare.


Clorazepate (klor az' e pate) is a benzodiazepine with particular activity against spread of seizure activity in several animal models. The antiseizure activity of the benzodiazepines is mediated by their ability to enhance gamma-aminobutryic acid (GABA) mediated inhibition of synaptic transmission through binding to the GABA A receptor. Clorazepate is used both as an anticonvulsant and anxiolytic agent. Clorazepate was approved in the United States in 1972 and currently more than 3 million prescriptions are filled yearly. Current indications are as adjunctive therapy in management of partial seizures and for treatment of anxiety disorders and acute alcohol withdrawal. Clorazepate is available in generic forms and under the brand name Tranxene in tablets and capsules in concentrations of 3.75, 7.5, 11.25, 15 and 22.5 mg. Delayed release formulations are also available. The recommended initial dose for adults with seizures is 7.5 mg three times daily, with gradual dose increases generally to an average dose of 30 to 60 mg daily and not in excess of 90 mg daily. Common side effects of clorazepate include drowsiness, lethargy, ataxia, dysarthria and dizziness. Tolerance develops to these side effects, but tolerance can also develop to the therapeutic effects.


Clorazepate, as with other benzodiazepines, is rarely associated with serum ALT elevations, and clinically apparent liver injury from clorazepate is extremely rare. A few only partially convincing case reports of acute hepatocellular injury from clorazepate have been reported. Rare instances of drug induced liver injury have been reported with other benzodiazepines, such as chlordiazepoxide, diazepam, flurazepam, triazolam and alprazolam. In benzodiazepine related cases of acute liver injury, the latency has ranged from a few weeks to 6 months; the typical pattern of liver enzyme elevations has been cholestatic or mixed, but instances of hepatocellular patterns have also been reported. The injury is usually mild to moderate in severity and self-limited. Fever and rash have not been described nor has autoantibody formation.

Likelihood score: D (possible but rare cause of clinically apparent liver injury).

Mechanism of Injury

The liver injury from benzodiazepines is probably due to a rarely produced intermediate metabolite.

Outcome and Management

The few case reports of hepatic injury due to clorazepate were followed by complete recovery. No cases of acute liver failure or vanishing bile duct injury due to clorazepate have been described. There is no information about cross reactivity with other benzodiazepines (clonazepam, lorazepam or diazepam), but some degree of cross sensitivity should be assumed.

Drug Class: Anticonvulsants, Benzodiazepines


Case 1. Acute hepatitis-like injury due to clorazepate.

[Modified from: Parker JLW. Potassium clorazepate (Tranxene)-induced jaundice. Postgrad Med J 1979; 55: 908-910. PubMed Citation]

A 27 year old man developed jaundice and fever, 2 months after starting clorazepate (15 mg increasing 30 mg once daily) for depression. He had poor appetite and had lost 9.5 kilograms since starting the drug. Clorazepate was continued for another two months, at which time he was found to have jaundice and hepatomegaly. Blood tests showed total bilirubin of 8.6 mg/dL, ALT 880 U/L, AST 620 U/L, GGT 104 U/L (normal <45) and alkaline phosphatase 29 KA units (normal <13). He had no rash, fever or eosinophilia and autoantibodies were negative. Clorazepate was stopped. He underwent three liver biopsies over the next five months showing an acute cholestatic hepatitis with gradual resolution, but residual minimal portal lymphocytic infiltrates and thin portal-to-portal fibrosis.

Key Points

Pattern: Hepatocellular (R=16)
Severity: 3+ (jaundice and hospitalization)
Latency: 2 months
Recovery: Complete recovery over 5 months
Other: None mentioned


Acute hepatitis with cholestatic feature arose between 2 and 4 months after starting clorazepate. The pattern of liver enzyme elevations suggested hepatocellular injury. Liver biopsies showed mild fibrosis that was still present five months later. Tests to exclude hepatitis A and B were not done and tests for hepatitis C were not available when this case was reported.



Clorazepate – Tranxene®




Product labeling at DailyMed, National Library of Medicine, NIH


57109-90-7 C16-H10-Cl-N4-O3.K.H-K-O
Clorazepate chemical structure


References updated: 25 January 2017

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