Probenecid and Colchicine Disease Interactions

The use of colchicine should be used with caution in patients with bone marrow suppression. Patients on long term therapy may require periodic blood counts.

The use of colchicine should be used with caution in patients with cardiac dysfunction. The possibility of cumulative effects of colchicine is increased in these patients.

Colchicine should be used with caution in patients with disseminated intravascular coagulation. Debilitated patients have an increased risk of developing colchicine toxicity.

Electrolyte imbalances including hypokalemia and hyponatremia may worsen in patients taking colchicine as the most common adverse effects of colchicine include nausea and vomiting. Therapy with colchicine should be administered with caution in patients with electrolyte imbalances. Monitoring serum electrolytes is recommended in these patients.

The clearance of colchicine may be significantly reduced and plasma half-life prolonged in patients with chronic hepatic impairment compared to healthy subject. No pharmacokinetic data are available for patients with severe hepatic impairment (Child-Pugh C). Caution is recommended when prescribing colchicine to these patients.

Colchicine is significantly excreted in urine in healthy subjects. Clearance of colchicine is decreased in patients with impaired renal function. Colchicine dosing must be individualized according to the patient's renal function. Caution must be exercised when colchicine therapy is instituted in these patients. Monitoring creatinine function is recommended in patients on long term therapy.

The manufacturer does not recommend the use of probenecid in patients with known blood dyscrasias. Aplastic anemia, leukopenia, hemolytic anemia and other anemia have been reported infrequently during administration of probenecid. Glucose-6-phosphate dehydrogenase (G-6-PD) deficiency may increase the risk of probenecid-induced hemolytic anemia.

Probenecid may promote lithiasis by increasing uric acid concentration in the renal tubules. Adequate hydration is necessary during therapy. Patients who are dehydrated (e.g., due to severe diarrhea or vomiting) may be at increased risk for the development of uric acid kidney stones and should be encouraged to consume additional amounts of liquid or given intravenous fluid. In general, fluid intake sufficient to yield a daily urinary output of at least 2 liters is recommended. Maintenance of a slightly alkaline or neutral urine is also desirable.

The use of probenecid is not recommended in patients with a history of uric acid nephrolithiasis or a urinary urate excretion greater than 750 mg/24 hr. Probenecid may promote lithiasis by increasing uric acid concentration in the renal tubules. Adequate hydration is necessary during treatment. In general, a fluid intake sufficient to yield a daily urinary output of at least 2 liters is recommended. Maintenance of a slightly alkaline urine is also desirable.

Colchicine-induced neuromuscular toxicity and rhabdomyolysis have been reported with chronic treatment in therapeutic doses. Patients with renal dysfunction and elderly patients, even those with normal renal and hepatic function, are at increased risk. Caution must be exercised when colchicine therapy is instituted in these patients.

The manufacturer states that probenecid should be used with caution in patients with a history of peptic ulcer. Uricosuric agents can cause upper gastrointestinal irritation and aggravate or reactivate peptic ulcer. However, these effects have primarily been reported with another uricosuric agent, sulfinpyrazone. GI effects associated with probenecid are usually limited to nausea, vomiting, and anorexia.

Probenecid may not be effective in patients with chronic renal insufficiency, particularly when glomerular filtration rate is 30 mL/min or less. Probenecid has been used in patients with some renal impairment but dosage requirements may be increased.