Lansoprazole is a proton pump inhibitor (PPI) and a potent inhibitor of gastric acidity which is widely used in the therapy of gastroesophageal reflux and peptic ulcer disease. Dexlansoprazole is an isomer of lansoprazole that has a similar spectrum of activity and toxicities. Lansoprazole therapy is associated with a low rate of transient and asymptomatic serum aminotransferase elevations and is a reported, but very rare cause of clinically apparent liver injury.


Lansoprazole (lan soe' pra zole), like other PPIs, binds to and inactivates the hydrogen/ potassium (H+/K+) ATPase of gastric parietal cells, causing inhibition of the proton pump that transports H+ into the gastric lumen, the final common step in gastric acid production. Lansoprazole is a prodrug and is converted to the active form in the acidic secretory canaliculi of parietal cells. Because the inhibition is irreversible, acid secretion is suppressed for 24 to 48 hours, until new proton pump molecules have been synthesized and transported to the cell membrane. Lansoprazole was the second PPI approved for use in the United States (1995) and dexlansoprazole, a stereoisomer, was approved for use in 2009. Lansoprazole is available in 15 and 30 mg delayed release capsules and tablets, as well as granules for oral suspension and in vials for parenteral use under the brand name of Prevacid. Over-the-counter formulations have also become available. The typical dose in adults with peptic ulcer disease is 15 mg daily for 4 to 8 weeks and similar dose chronically for maintenance therapy. Higher doses are recommended for more severe cases of gastrointestinal reflux and peptic ulcer disease, and doses of up to 120 mg daily for Zollinger-Ellison syndrome. Combinations of lansoprazole with antibiotics for 10 to 14 days are effective and recommended for eradication of H. pylori infection. Dexlansoprazole is available by prescription only in capsules of 30 or 60 mg under the brand name Dexilant. The recommended dose of dexlansoprazole is 30 to 60 mg once daily. Both lansoprazole and dexlanscprazole are very well tolerated. Side effects are uncommon and usually mild: they can include diarrhea, nausea, vomiting, abdominal discomfort, flatulence, skin rash, headaches and dizziness. Severe adverse events are rare but can include hypersensitivity reactions. Long-term use may be associated with bone fractures, acute interstitial nephritis, lupus erythematosus, vitamin B12 deficiency and hypomagnesemia.


Despite its wide use, lansoprazole has only rarely been associated with hepatic injury. In large scale, long term trials of lansoprazole, serum ALT elevations have occurred in less than 1% of patients and at rates similar to those that occur with placebo or comparator drugs. Only a small number of cases of clinically apparent liver disease due to lansoprazole or dexlansoprazole have been published and most have been anicteric and mild. In most instances, the time to onset was within 2 to 4 weeks and the pattern of enzyme elevations was hepatocellular or mixed. Hypersensitivity reactions with fever, rash and eosinophilia have been described due to dexlansoprazole and lansoprazole, and these reactions may be accompanied by minor serum enzyme elevations and thus qualify for DRESS syndrome (drug-rash with eosinophilia and systemic symptoms). Autoantibody formation is rare. Recovery is usually rapid (within a month) and complete upon stopping lansoprazole. Recurrence on reexposures has been reported.

Likelihood score: C (probable rare cause of clinically apparent liver injury).

Mechanism of Injury

Several features of the hepatic injury with lansoprazole suggest a hypersensitivity reaction, but may merely reflect altered metabolism or acute toxicity of a metabolic byproduct. Lansoprazole is metabolized by the hepatic P450 system, but has little effect on the activity of the drug-metabolizing enzymes.

Outcome and Management

The mild and asymptomatic elevations in serum aminotransferase that have been observed during lansoprazole therapy are usually transient and usually resolve even without dose modification. Clinically apparent liver injury due to dexlansoprazole and lansoprazole, however, generally calls for prompt withdrawal of the agent. Severe injury is uncommon and most cases resolve promptly upon withdrawal. Cases of acute liver failure due proton pump inhibitors have been described, but they are exceedingly rare. There is no information about cross reactivity among the various PPIs after lansoprazole hepatotoxicity, but the PPIs all share a benzimidazole structure, and caution should be used in attempting to reintroduce another PPI after clinically apparent PPI-associated hepatic injury.

Drug Class: Antiulcer Agents

Other Drugs in the Subclass, Proton Pump Inhibitors: Esomeprazole, Omeprazole, Pantoprazole, Rabeprazole


Case 1. Acute hepatitis attributed to lansoprazole.

[Modified from: Viana de Miguel C, Alvarez García M, Sánchez Sánchez A, Carvajal García-Pando A. [Lansoprazole-induced hepatitis]. Med Clin (Barc) 1997; 108: 599. Spanish. PubMed Citation]

A 62 year old man with gastroesophageal reflux disease developed fatigue and jaundice 25 days after switching from omeprazole (20 mg daily for 3 months) to lansoprazole (30 mg daily). He had no history of drug reactions, liver disease, jaundice, alcohol abuse or risk factors for viral hepatitis. Laboratory testing showed marked elevations in serum bilirubin (26.0 mg/dL) and aminotransferase levels (ALT 1498 U/L, AST 952 U/L), and mild elevations in alkaline phosphatase (346 U/L: normal values not given). Tests for hepatitis A, B, and C were negative and abdominal ultrasound showed a single gallstone without evidence of biliary obstruction. A liver biopsy was compatible with acute toxic hepatitis. Lansoprazole was discontinued promptly upon admission and he improved rapidly, all liver tests being normal when he was seen 50 days later.

Key Points


This brief letter to the editor describes one of the few cases of lansoprazole associated liver injury in the literature. The onset of injury was within 4 weeks of starting lansoprazole, which is typical of proton-pump inhibitor associated acute liver injury, as was the hepatocellular pattern of serum enzyme elevations. Symptoms of hypersensitivity were not mentioned nor were autoantibody test results given, but the pattern otherwise resembles the clinically apparent liver injury associated with PPIs. Interestingly, this patient had tolerated omeprazole therapy for 3 months without problems, suggesting that there is little cross reactivity to hepatic injury among the proton pump inhibitors. Unfortunately, this cannot be assumed for all such agents and caution should be used in restarting another proton pump inhibitor after clinical apparent liver injury due to another.



Lansoprazole – Generic, Prevacid®


Antiulcer Agents


Product labeling at DailyMed, National Library of Medicine, NIH



References updated: 15 April 2019

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