What are the side effects of Pyrazinamide (PZA)?

From the Guidelines

Pyrazinamide commonly causes side effects including joint pain, arthralgia, and gout due to decreased uric acid excretion, as well as gastrointestinal disturbances and hepatotoxicity, which can be severe in some cases, as reported in studies such as 1 and 1. The medication works by converting to pyrazinoic acid inside Mycobacterium tuberculosis, disrupting bacterial metabolism and membrane transport. Patients may experience:

• Gastrointestinal disturbances such as nausea, vomiting, and loss of appetite
• Hepatotoxicity, with liver enzyme elevations occurring in approximately 10% of patients, sometimes progressing to severe liver injury, as noted in 1
• Joint pain, arthralgia, and gout due to decreased uric acid excretion
• Skin rash, photosensitivity, fever, and malaise
• Rarely, pyrazinamide can cause sideroblastic anemia or thrombocytopenia Regular liver function monitoring is essential during treatment, especially in patients with known chronic liver disease, as recommended in 1. Patients should avoid alcohol while taking pyrazinamide to reduce liver stress and should report symptoms like yellowing of skin/eyes, dark urine, or severe abdominal pain immediately. Typical dosing is 15-30 mg/kg daily (maximum 2g) as part of a multi-drug tuberculosis treatment regimen, usually for the first 2 months of therapy, as outlined in 1.

From the FDA Drug Label

Pyrazinamide inhibits renal excretion of urates, frequently resulting in hyperuricemia which is usually asymptomatic. If hyperuricemia is accompanied by acute gouty arthritis, pyrazinamide should be discontinued. Patients should be instructed to notify their physicians promptly if they experience any of the following: fever, loss of appetite, malaise, nausea and vomiting, darkened urine, yellowish discoloration of the skin and eyes, pain or swelling of the joints Pyrazinamide should be discontinued and not be resumed if signs of hepatocellular damage or hyperuricemia accompanied by an acute gouty arthritis appear.

The side effects of pyrazinamide include:

• Hyperuricemia (usually asymptomatic)
• Acute gouty arthritis
• Hepatocellular damage
• Fever
• Loss of appetite
• Malaise
• Nausea and vomiting
• Darkened urine
• Yellowish discoloration of the skin and eyes
• Pain or swelling of the joints 2 2

From the Research

Side Effects of Pyrazinamide

The side effects of pyrazinamide include:

• Hepatotoxicity, which is a significant concern when using this medication 3, 4, 5, 6
• Hyperuricemia, which can lead to arthralgia (joint pain) in some patients 7
• Arthralgia, which can occur even in the absence of hyperuricemia 7
• Gout, although this is relatively rare 7
• Jaundice, which can occur in some cases of pyrazinamide-associated hepatotoxicity 6

Hepatotoxicity

Hepatotoxicity is a well-documented side effect of pyrazinamide, with studies suggesting that the risk of hepatotoxicity is increased when pyrazinamide is used in combination with other medications such as isoniazid and rifampin 3. The exact mechanisms of pyrazinamide-induced hepatotoxicity are not fully understood, but it is thought to be related to the biotransformation of pyrazinamide in the liver 5.

Clinical Characteristics of Pyrazinamide-Associated Hepatotoxicity

Studies have characterized the clinical presentation of pyrazinamide-associated hepatotoxicity, including:

• Median time to onset of 14 days 6
• Jaundice in approximately 40% of cases 6
• Radiological patterns including hepatocellular, mixed, and cholestatic patterns 6
• Mild presentation in approximately 60% of cases, with moderate presentation in approximately 30% of cases 6