What are the major contraindications to colchicine (anti-gout medication)?

From the Guidelines

Colchicine is contraindicated in patients with severe renal impairment, severe hepatic dysfunction, and concurrent use of strong CYP3A4 inhibitors or P-glycoprotein inhibitors in patients with renal or hepatic impairment, as well as in patients with blood dyscrasias and known hypersensitivity to the medication. The contraindications to colchicine are primarily due to its narrow therapeutic window and the potential for toxic accumulation, which can lead to serious adverse effects such as bone marrow suppression, neuromyopathy, and multiorgan failure 1.

Some key points to consider when prescribing colchicine include:

• Severe renal impairment (creatinine clearance <30 mL/min) is a contraindication to colchicine use, as it can lead to toxic accumulation of the drug 1.
• Severe hepatic dysfunction is also a contraindication, as colchicine is metabolized by the liver and impaired liver function can lead to increased levels of the drug 1.
• Concurrent use of strong CYP3A4 inhibitors (such as clarithromycin, ketoconazole, and ritonavir) or P-glycoprotein inhibitors in patients with renal or hepatic impairment is a contraindication, as these drugs can increase colchicine levels and lead to toxicity 1.
• Blood dyscrasias, such as thrombocytopenia, anemia, and leukopenia, are contraindications to colchicine use, as the drug can exacerbate these conditions 1.
• Known hypersensitivity to colchicine is a contraindication, as it can lead to severe allergic reactions 1.

It is essential to carefully evaluate patients for these contraindications before prescribing colchicine and to monitor them closely for signs of toxicity or adverse effects. Dose adjustments may be necessary for patients with moderate renal impairment or those taking moderate CYP3A4 inhibitors 1.

From the FDA Drug Label

Patients with renal or hepatic impairment should not be given Colchicine Tablets, USP in conjunction with P-gp or strong CYP3A4 inhibitors (this includes all protease inhibitors except fosamprenavir). Use of Colchicine Tablets, USP in conjunction with P-gp or strong CYP3A4 inhibitors (this includes all protease inhibitors except fosamprenavir) is contraindicated in patients with renal or hepatic impairment [see Contraindications (4)].

The major contraindications to colchicine are:

• Renal impairment in patients taking P-gp or strong CYP3A4 inhibitors
• Hepatic impairment in patients taking P-gp or strong CYP3A4 inhibitors
• Concomitant use of P-gp or strong CYP3A4 inhibitors (including all protease inhibitors except fosamprenavir) in patients with renal or hepatic impairment 2 2

From the Research

Major Contraindications to Colchicine

The major contraindications to colchicine include:

• Combined renal and hepatic disease 3
• Creatinine clearances below 10 cc/min 3
• Extrahepatic biliary obstruction 3
• Patients with severe renal impairment, as they are at a higher risk of myelosuppression 4
• Patients taking cytochrome P450 3A4 (CYP3A4) inhibitors and P-glycoprotein (P-gp) efflux transporter inhibitors, as they may increase the risk of myelosuppression 4

Special Considerations

Special considerations should be taken when prescribing colchicine to:

• Older patients with apparently normal renal function, as they may require reduced doses 3
• Patients with hepatic disease, as they may require reduced doses 3
• Patients with renal disease, as they may require reduced doses and close monitoring 5

Adverse Events

Adverse events associated with colchicine use include:

• Diarrhea and gastrointestinal events 6
• Adverse liver events 6
• Muscle events 6
• Haematology events 6
• Myelosuppression, particularly in patients with renal impairment or taking CYP3A4 or P-gp inhibitors 4