Is colchicine safe to initiate in a patient with mild elevation of alanine transaminase (ALT)?

From the Guidelines

Starting colchicine with a mildly elevated ALT of 51 is generally considered safe for most patients. Colchicine can be initiated at standard dosing (typically 0.6 mg once or twice daily for gout flares, or 0.6 mg daily for prophylaxis) with this level of liver enzyme elevation, as recommended by the American College of Physicians 1. However, patients should be monitored with periodic liver function tests during treatment, especially during the first few months. If ALT levels increase significantly during treatment (typically more than 3 times the upper limit of normal), dose reduction or discontinuation may be necessary. Colchicine is primarily metabolized by the liver and excreted through biliary pathways, which explains why severe liver impairment can increase drug exposure and toxicity risk, as noted in the guidelines 1. Patients with mild ALT elevation should be advised to avoid alcohol while taking colchicine, stay well-hydrated, and report any symptoms like unusual fatigue, abdominal pain, nausea, vomiting, or yellowing of skin/eyes. Dose adjustments are more critical for patients with moderate to severe liver disease or those taking medications that interact with colchicine through the CYP3A4 pathway or P-glycoprotein.

Some key points to consider when starting colchicine in patients with mild liver enzyme elevation include:

• Monitoring liver function tests regularly, especially in the first few months of treatment
• Advising patients to avoid alcohol and stay well-hydrated
• Being aware of potential interactions with other medications that may affect colchicine metabolism
• Considering dose adjustments or alternative treatments in patients with moderate to severe liver disease or significant elevations in liver enzymes.

It's also important to note that the American College of Physicians recommends using low-dose colchicine when treating acute gout, as it is associated with fewer gastrointestinal adverse effects 1. Overall, the benefits of colchicine in managing gout symptoms should be weighed against the potential risks, and patients should be closely monitored for any signs of liver toxicity or other adverse effects.

From the FDA Drug Label

For prophylaxis of gout flares in patients with mild to moderate hepatic function impairment, adjustment of the recommended dose is not required, but patients should be monitored closely for adverse effects of colchicine Dose reduction should be considered for the prophylaxis of gout flares in patients with severe hepatic impairment For treatment of gout flares in patients with mild to moderate hepatic function impairment, adjustment of the recommended dose is not required, but patients should be monitored closely for adverse effects of colchicine

Colchicine can be started with mild elevation in ALT of 51, but patients should be monitored closely for adverse effects of colchicine 2.

• Mild hepatic impairment does not require dose adjustment, but close monitoring is necessary.
• Dose reduction should be considered in patients with severe hepatic impairment. It is essential to exercise caution and monitor the patient's condition closely when initiating colchicine therapy in patients with hepatic impairment 2.

From the Research

Colchicine and Elevated ALT Levels

• There is no direct evidence in the provided studies that addresses the safety of starting colchicine with a mild elevation in ALT of 51.
• However, study 3 discusses the clinical characteristics and health care utilization patterns in patients with gout who were newly prescribed colchicine, but it does not specifically address the issue of elevated ALT levels.
• Studies 4, 5, 6, and 7 provide information on the causes and evaluation of elevated liver enzymes, including ALT, but do not directly relate to the use of colchicine in patients with elevated ALT levels.

Evaluation of Elevated ALT Levels

• Study 7 suggests that a true healthy normal ALT level ranges from 29 to 33 IU/l for males and 19 to 25 IU/l for females, and levels above this should be assessed.
• Study 6 found that intensive muscular exercise, such as weightlifting, can cause highly pathological liver function tests in healthy men, including elevated ALT levels.
• Study 4 presents a case of an asymptomatic healthy male who had elevated transaminase levels after vigorous exercise, which returned to normal after discontinuation of exercise.
• Study 5 discusses the differential diagnostic work-up of elevated serum transaminase levels and highlights the importance of considering extrahepatic causes, such as muscular injury, in the evaluation of elevated ALT levels.

Considerations for Starting Colchicine

• In the absence of direct evidence, it is unclear whether a mild elevation in ALT of 51 is a contraindication to starting colchicine.
• Studies 3 and 7 suggest that patients with gout often have multiple comorbidities, including liver disease, and that the evaluation of abnormal liver chemistries is an important part of clinical practice.
• Therefore, it is likely that the decision to start colchicine in a patient with a mild elevation in ALT should be made on a case-by-case basis, taking into account the patient's overall clinical profile and the potential risks and benefits of treatment 3, 7.