Side Effects of Colcrys (colchicine)

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

Other unapproved uses of Colcrys include treatment of pseudogout, amyloidosis, and scleroderma. These unapproved uses of Colcrys require further evaluation.

Common side effects of Colcrys include

• nausea,
• vomiting,
• abdominal pain, and
• diarrhea. 

Serious side effects of Colcrys include

• hair loss,
• weakness, and
• nerve irritation.

Drug interactions of Colcrys include drugs that reduce the breakdown and elimination of Colcrys from the body by reducing the activity of enzymes that breakdown 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.

In order to avoid side effects from Colcrys the dose of colchicine should be reduced when it is combined with or used within 14 days of drugs that reduce its elimination. Combining Colcrys with statins, for example 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 in pregnancy over several decades have not identified any drug-associated risks for major birth defects, miscarriage, or adverse maternal or fetal outcomes. 

Colcrys passes into breast milk. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Colcrys and any potential adverse effects on the breastfed child from Colcrys or from the underlying maternal condition.

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

• nausea,
• vomiting,
• abdominal pain, and
• diarrhea. Colchicine also may
• cause hair loss,
• weakness, and
• nerve irritation.

Prophylaxis Of Gout Flares

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

Treatment Of Gout Flares

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

FMF

• Gastrointestinal tract adverse effects are the most frequent side effects in patients initiating Colcrys, usually presenting within 24 hours, and occurring in up to 20% of patients given therapeutic doses.
• Typical symptoms include
  • cramping,
  • nausea,
  • diarrhea,
  • abdominal pain and
  • vomiting.
• These events should be viewed as dose-limiting if severe, as they can herald the onset of more significant toxicity.

Clinical Trials Experience In Gout

Because clinical studies are conducted under widely varying and controlled conditions, adverse reaction rates observed in clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not predict the rates observed in a broader patient population in clinical practice.

• In a randomized, double-blind, placebo-controlled trial in patients with a gout flare, gastrointestinal adverse reactions occurred in 26% of patients using the recommended dose (1.8 mg over one hour) of Colcrys compared to 77% of patients taking a nonrecommended high dose (4.8 mg over six hours) of colchicine and 20% of patients taking placebo.
• Diarrhea was the most commonly reported drug-related gastrointestinal adverse event.
• As shown in Table 3, diarrhea is associated with Colcrys treatment.
• Diarrhea was more likely to occur in patients taking the high-dose regimen than the low-dose regimen.
• Severe diarrhea occurred in 19% and vomiting occurred in 17% of patients taking the nonrecommended high-dose colchicine regimen but did not occur in the recommended low-dose Colcrys regimen.

Table 3: Number (%) of Patients with at Least One Drug-Related Treatment-Emergent Adverse Event with an Incidence of ≥2% of Patients in Any Treatment Group

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.

The following adverse reactions have been identified with colchicine. These have been generally reversible upon temporarily interrupting treatment or lowering the dose of colchicine. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

• 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

• Colcrys (colchicine) is a substrate of the efflux transporter P-glycoprotein (P-gp). Of the cytochrome P450 enzymes tested, CYP3A4 was mainly involved in the metabolism of colchicine.
• If Colcrys is administered with drugs that inhibit P-gp, most of which also inhibit 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 as a result of other potentially significant drug interactions.
• Table 1 provides recommendations for strong and moderate CYP3A4 inhibitors and P-gp inhibitors.

Table 4: Other Potentially Significant Drug Interactions

Drug Abuse And Dependence

• Tolerance, abuse or dependence with colchicine has not been reported.