Quinine is a natural cinchona alkaloid that has been used for centuries in the prevention and therapy of malaria. Quinine is also used for idiopathic muscle cramps. Quinine therapy has been associated with rare instances of hypersensitivity reactions which can be accompanied by hepatitis and mild jaundice.


Quinine (kwye' nine) is the major alkaloid contained in the powered bark of the South American cinchona tree. The powder of the cinchona tree bark was used by native Quechna Indians in Peru to treat fever and was introduced into Western medicine when Jesuit priests took samples to Europe. The major effect of the cinchona tree bark was against malaria. Quinine acts against the asexual erythrocytic forms of malaria, including Plasmodium vivax, malariae and falciparum and is gametosidal to P. vivax and malariae. The use of quinine for malaria has been largely replaced by chloroquine, which is more potent and better tolerated. However, quinine is still used intravenously in some instances of drug resistant P. falciparum. In addition, quinine has been used frequently for nocturnal leg cramps, although the data in support of its efficacy is controversial, and quinine by prescription is no longer approved for this use. Quinine is available in multiple generic forms in low doses as an over-the-counter medication and as tablets of 324 mg for therapy of malaria. The use and dosage for malaria treatment and prevention requires higher doses than are used for leg cramps. Regularly updated recommendations on the therapy of malaria including specific details on diagnosis, management, drug dosage and safety are available at the CDC website: http://www.cdc.gov/malaria/. Common side effects of quinine include headache, dizziness, blurred vision, gastrointestinal upset, thrombocytopenia and hypersensitivity reactions.


There is little evidence that chronic quinine therapy is associated with elevations in serum enzymes, although it has not been carefully assessed. However, there have been several reports of acute hypersensitivity reactions to quinine that include hepatic involvement. The reactions usually arise after 1 to 2 weeks of therapy, but can appear within 24 hours of restarting quinine or with rechallenge. The clinical features are marked by fatigue, nausea, vomiting, diffuse muscle aches, arthralgias and high fever. Blood testing at an early stage shows increases in serum aminotransferase and alkaline phosphatase levels as well as mild jaundice, which can deepen for a few days even after stopping quinine. The pattern of serum enzymes elevations is typically cholestatic or mixed. Rash is uncommon and eosinophilia is not typical, despite the presence of other signs of hypersensitivity (fever, arthralgias). Autoantibodies are not typically found. Liver biopsies usually show mild injury and small epithelioid granulomas, as are typically found in many organs during systemic hypersensitivity reactions. A similar clinical signature of liver injury occurs with quinidine, an optical isomer of quinine that is used predominantly as an antiarrhythmic.

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

Mechanism of Injury

The hepatotoxicity of quinine is clearly due to a hypersensitivity reaction and there is no evidence for a direct hepatotoxic effect. There is likely to be a genetic predisposition to this hypersensitivity.

Outcome and Management

The hepatotoxicity of quinine is usually mild and resolves within 1 to 4 weeks of stopping. In many instances, jaundice and liver test abnormalities may worsen for a few days after stopping quinine, but fatalities have not been reported, and recovery is usually rapid. Because of the rapidity of recovery, therapy with corticosteroids is best avoided. There is cross reactivity to quinidine (the optical isomer of quinine which is used as an antiarrhythmic agent) and other exposures to quinine should be avoided. Because quinine is in tonic water as well as many over-the-counter medications, medicinal foods and herbal preparations, patients with quinine sensitivity should make sure that they are not inadvertently exposed.

Drug Class: Antimalarial Agents


Case 1. Acute hypersensitivity and cholestatic jaundice due to quinine.

[Modified from: Farver DK, Lavin MN. Quinine-induced hepatotoxicity. Ann Pharmacother 1999: 33: 32-4. PubMed Citation]

A 57 year old woman was given quinine for nocturnal leg cramps and developed high fever, chills, fatigue, muscle aches and nausea necessitating hospital admission within 24 hours of starting quinine. She had a history of hypertension, diabetes, hyperlipidemia and coronary artery disease for which she was taking insulin, lisinopril, amlodipine, aspirin, furosemide and multivitamins. She used acetaminophen occasionally. She did not drink alcohol and had no risk factors for acquiring viral hepatitis. On examination, she was febrile (39.5 oC), but without rash, lymphoadenopathy or signs of acute or chronic liver disease. Laboratory testing showed normal blood counts, but elevations in alkaline phosphatase and aminotransferase levels without hyperbilirubinemia (Table). Tests for hepatitis A and B were negative as were autoantibodies. Her serum enzymes remained elevated and several days later she became jaundiced. Endoscopic retrograde cholangiopancreatography showed that the biliary tree was normal and the gallbladder was without gallstones. Quinine had been continued during the hospitalization, but was stopped on day 6, whereupon her symptoms began to improve. Hyperbilirubinemia resolved within a few days of stopping quinine and serum enzymes were normal or near normal 2 weeks later.

Key Points

Laboratory Values


A dramatic hypersensitivity reaction with jaundice, following a single dose of quinine in a patient without a known history of previous exposure. Improvement was prompt once quinine was stopped.



Quinine – Generic, Qualaquin®


Antimalarial Agents


Product labeling at DailyMed, National Library of Medicine, NIH



References updated: 15 May 2018

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