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
| MedDRA System Organ Class MedDRA Preferred Term | COLCRYS Dose | Placebo (N=59) n (%) |
|
| High (N=52) n (%) |
Low (N=74) n (%) |
||
| Number of Patients with at Least One Drug-Related TEAE | 40 (77) | 27 (37) | 16 (27) |
| Gastrointestinal Disorders | 40 (77) | 19 (26) | 12 (20) |
| Diarrhea | 40 (77) | 17 (23) | 8 (14) |
| Nausea | 9 (17) | 3 (4) | 3 (5) |
| Vomiting | 9 (17) | 0 | 0 |
| Abdominal Discomfort | 0 | 0 | 2 (3) |
| General Disorders and Administration Site Conditions | 4 (8) | 1 (1) | 1 (2) |
| Fatigue | 2 (4) | 1 (1) | 1 (2) |
| Metabolic and Nutrition Disorders | 0 | 3 (4) | 2 (3) |
| Gout | 0 | 3 (4) | 1 (2) |
| Nervous System Disorders | 1 (2) | 1 (1.4) | 2 (3) |
| Headache | 1 (2) | 1 (1) | 2 (3) |
| Respiratory Thoracic Mediastinal Disorders | 1 (2) | 2 (3) | 0 |
| Pharyngolaryngeal Pain | 1 (2) | 2 (3) | 0 |
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 [see OVERDOSAGE].
The following adverse reactions have been reported with colchicine. These have been generally reversible upon temporarily interrupting treatment or lowering the dose of colchicine.
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