Side Effects of Colcrys (colchicine)

Colcrys (colchicine) is used to treat acute gout flares and Familial Mediterranean fever (FMF), a genetic autoinflammatory disorder in adults and children 4 years and older.

Unapproved uses of Colcrys include treating pseudogout, amyloidosis, and scleroderma, but further evaluation is needed for these uses.

Common side effects of Colcrys include:

Serious side effects of Colcrys include:

Drug interactions of Colcrys include drugs that reduce its breakdown and elimination from the body. These drugs reduce the activity of enzymes that break down Colcrys, such as atazanavir, clarithromycin, indinavir, itraconazole, ketoconazole, lopinavir/ritonavir, nelfinavir, saquinavir, telithromycin, ritonavir, amprenavir, aprepitant, diltiazem, erythromycin, fluconazole, fosamprenavir, grapefruit juice, verapamil, cyclosporine, and ranolazine.

To avoid side effects, the dose of colchicine should be reduced when combined with or used within 14 days of drugs that reduce its elimination. Combining Colcrys with statins, such as atorvastatin, simvastatin, and lovastatin, gemfibrozil, or fenofibrate increases the risk of muscle-related adverse effects because these drugs also cause muscle-related side effects.

Available data from published literature on Colcrys use during pregnancy have not identified any drug-associated risks for major birth defects, miscarriage, or adverse maternal or fetal outcomes.

Colcrys passes into breast milk. Breastfeeding mothers should consider the developmental and health benefits of breastfeeding along with their clinical need for Colcrys and any potential adverse effects on the breastfed child.

Important side effects of Colcrys (colchicine)

The most common side effects of colchicine are dose-related and include:

• nausea
• vomiting
• abdominal pain
• diarrhea
• hair loss
• weakness
• nerve irritation

Colcrys (colchicine) side effects for healthcare professionals

Prophylaxis Of Gout Flares

• The most commonly reported adverse reaction in clinical trials of colchicine for gout prophylaxis was diarrhea.

Treatment Of Gout Flares

• The most common adverse reactions reported in the clinical trial of Colcrys for gout flares were diarrhea (23%) and pharyngolaryngeal pain (3%).

FMF

• The most frequent side effects in patients starting Colcrys for FMF are gastrointestinal tract adverse effects. These symptoms usually appear within 24 hours and occur in up to 20% of patients given therapeutic doses. Typical symptoms include:
• cramping
• nausea
• diarrhea
• abdominal pain
• vomiting

Clinical Trials Experience In Gout

Clinical studies of Colcrys have shown varying adverse reaction rates due to different conditions. In a randomized, double-blind, placebo-controlled trial in patients with a gout flare, 26% of patients using the recommended dose of Colcrys experienced gastrointestinal adverse reactions compared to 77% of patients using a nonrecommended high dose and 20% of patients taking placebo. Diarrhea was the most commonly reported drug-related gastrointestinal adverse event.

Severe diarrhea occurred in 19% of patients taking the nonrecommended high-dose regimen but did not occur in the recommended low-dose Colcrys regimen.

Table 3 shows the number of patients with at least one drug-related treatment-emergent adverse event, including diarrhea, associated with Colcrys treatment.

Postmarketing Experience

Serious toxic manifestations associated with colchicine include myelosuppression, disseminated intravascular coagulation, and injury to cells in the renal, hepatic, circulatory, and central nervous systems. These most often occur with excessive accumulation or overdosage.

Adverse reactions that have been identified with colchicine include:

• Neurological: sensory motor neuropathy
• Dermatological: alopecia, maculopapular rash, purpura, rash
• Digestive: abdominal cramping, abdominal pain, diarrhea, lactose intolerance, nausea, vomiting
• Hematological: leukopenia, granulocytopenia, thrombocytopenia, pancytopenia, aplastic anemia
• Hepatobiliary: elevated AST, elevated ALT
• Musculoskeletal: myopathy, elevated CPK, myotonia, muscle weakness, muscle pain, rhabdomyolysis
• Reproductive: azoospermia, oligospermia

Drug interactions with Colcrys (colchicine)

• Colcrys is a substrate of the efflux transporter P-glycoprotein (P-gp) and is mainly metabolized by CYP3A4.
• If Colcrys is administered with drugs that inhibit P-gp and CYP3A4, increased concentrations of colchicine are likely.
• Fatal drug interactions have been reported.
• Physicians should ensure that patients are suitable candidates for treatment with Colcrys and remain alert for signs and symptoms of toxicities related to increased colchicine exposure as a result of a drug interaction.
• Signs and symptoms of Colcrys toxicity should be evaluated promptly, and if toxicity is suspected, Colcrys should be discontinued immediately.
• Table 4 provides recommendations for other potentially significant drug interactions.
• Table 1 provides recommendations for strong and moderate CYP3A4 inhibitors and P-gp inhibitors.

Table 4 shows other potentially significant drug interactions.