Colchicine Drug-Drug Interactions; HIV Protease Inhibitors Increase Colchicine Levels (see tables below) FDA label pdf attached
FULL PRESCRIBING INFORMATION
1 INDICATIONS AND USAGE
1.1 Gout Flares
COLCRYSTM (colchicine, USP) tablets are indicated for treatment of acute gout flares when taken at the first sign of a flare.
Patients with renal or hepatic impairment should not be given COLCRYS in conjunction with P-gp or strong CYP3A4 inhibitors (5.3). In these patients, life-threatening and fatal colchicine toxicity has been reported with colchicine taken in therapeutic doses (7).
Gout Flares: For treatment of gout flares in patients with mild (estimated creatinine clearance Clcr 50 - 80 mL/min) to moderate (Clcr 30 - 50 mL/min) renal function impairment, adjustment of the recommended dose is not required, but patients should be monitored closely for adverse effects of colchicine. However, in patients with severe impairment, the dose does not need to be adjusted, but a treatment course should be repeated no more than once every 2 weeks. For these patients, requiring repeated courses, consideration should be given to alternate therapy. For patients undergoing dialysis, the total recommended dose for gout flares should be reduced to a single dose of 0.6 mg (1 tablet). For these patients, a treatment course should not be repeated more than once every 2 weeks [See Clinical Pharmacology (12.3) and Renal Impairment (8.6)].
Colchicine is a P-gp and CYP3A4 substrate. Life-threatening and fatal drug interactions have been reported in patients treated with colchicine given with P-gp and strong CYP3A4 inhibitors. If treatment with a P-gp or strong CYP3A4 inhibitor is required in patients with normal renal and hepatic function, the patient's dose of colchicine may need to be reduced or interrupted [See DRUG INTERACTIONS (7)]. Use of COLCRYS in conjunction with P-gp or strong CYP3A4 inhibitors is contraindicated in patients with renal or hepatic impairment. [See CONTRAINDICATIONS (4)].
WARNINGS AND PRECAUTIONS ------------------------
· Fatal overdoses have been reported with colchicine in adults and children. Keep COLCRYS out of the reach of children (5.1, 10).
· Blood dyscrasias: myelosuppression, leukopenia, granulocytopenia, thrombocytopenia, and aplastic anemia have been reported.
· Monitor for toxicity and if present consider temporary interruption or discontinuation of colchicine (5.2, 5.3, 5.4, 6, 10).
· Drug interaction P-gp and/or CYP3A4 inhibitors: Coadministration with P-gp and/or strong CYP3A4 inhibitors has resulted in life-threatening interactions and death (5.3, 7).
· Neuromuscular toxicity: Myotoxicity including rhabdomyolysis may occur, especially in combination with other drugs known to cause this effect. Consider temporary interruption or discontinuation of COLCRYS. (5.4, 7).
USE IN SPECIFIC POPULATIONS -----------------------
· In patients with severe hepatic or renal impairment, close monitoring is recommended in both gout flares and FMF patients; a dose reduction may not be needed in gout flares but should be considered in FMF patients, based on the patient's estimated creatinine clearance. (2.5, 2.6, 8.6, 8.7)
· In the presence of renal impairment, dosing for gout flares should be repeated no more than once every two weeks, whereas dosing for FMF should be continued but adjusted based upon the patients estimated creatinine clearance. (2.5, 8.6).
Drug Interactions: Pharmacokinetic Parameters for Colchicine in the Presence of the Co-Administered Drug
COLCRYS Dose Adjustment for Co-administration with Interacting Drugs if no Alternative Available1
(colchicine, USP) tablets
Read the Medication Guide that comes with COLCRYS before you start taking it and each time you get a refill. There may be new information. This Medication Guide does not take the place of talking to your healthcare provider about your medical condition or treatment. You and your healthcare provider should talk about COLCRYS when you start taking it and at regular checkups.
What is the most important information I should know about COLCRYS?
COLCRYS can cause serious side effects or even death if COLCRYS levels are too high in your body. Keep COLCRYS out of the reach of children.
Tell your healthcare provider about all your medical conditions, including if you have kidney or liver problems. Your dose of COLCRYS may need to be changed.
Certain medicines when taken with COLCRYS can cause the levels of COLCRYS to be too high in your body. It is important for you to tell your healthcare provider about all the medicines you take, including prescription and non-prescription medicines, vitamins and herbal supplements. COLCRYS and other medicines may affect each other causing serious side effects or even death. Do not start taking a new medicine without telling your healthcare provider or pharmacist.
Even medications that you might take for a short period of time, such as antibiotics, can interact with COLCRYS and cause serious side effects or death.
Especially tell your healthcare provider if you take:
· clarithromycin (Biaxin®)
· telithromycin (Ketek®)
· cyclosporine (Neoral®, Gengraf®, Sandimmune®)
· ketoconazole (Nizoral®)
· itraconazole (Sporanox®)
· HIV protease inhibitors
· nefazodone (Serzone®)
This is not a complete list of all the medicines that can interact with COLCRYS. Talk to your healthcare provider or pharmacist to find out if taking COLCRYS with the other medicines you are taking could be dangerous.
Colchicine (marketed as Colcrys) Information
FDA ALERT [07-30-09]: FDA has now approved the first single-ingredient oral colchicine product, Colcrys, for the treatment of familial Mediterranean fever (FMF) and acute gout flares. Oral colchicine has been used for many years as an unapproved drug with no FDA-approved prescribing information, dosage recommendations, or drug interaction warnings.
During the drug application review, FDA identified two previously uncharacterized safety concerns associated with the use of colchicine (marketed as Colcrys).
First, FDA analyzed safety data for colchicine from adverse events reported to the Agency, the published literature, and company-sponsored pharmacokinetic and drug interaction studies. This analysis revealed cases of fatal colchicine toxicity reported in certain patients taking standard therapeutic doses of colchicine and concomitant medications that interact with colchicine, such as clarithromycin. These reports suggest that drug interactions affecting the gastrointestinal absorption and/or hepatic metabolism of colchicine play a central role in the development of colchicine toxicity.
Second, data submitted supporting the safety and efficacy of Colcrys in acute gout flares demonstrated that a substantially lower dose of colchicine was as effective as the higher dose traditionally used. Moreover, patients receiving the lower dose experienced significantly fewer adverse events compared to the higher dose.
Based on this information, FDA is highlighting important safety considerations found in the approved prescribing information to assure safe use of Colcrys.
· Healthcare professionals not use P-glycoprotein (P-gp) or strong CYP3A4 inhibitors in patients with renal or hepatic impairment who are currently taking colchicine.
· Healthcare professionals consider a dose reduction or interruption of colchicine treatment in patients with normal renal and hepatic function if treatment with a P-gp or a strong CYP3A4 inhibitor is required.
· Healthcare professionals prescribe the FDA-approved Colcrys dose for the treatment of acute gout flares: 1.2 mg followed by 0.6mg in 1 hour (total 1.8mg).
· Healthcare professionals refer to Colcrys' approved prescribing information for specific dosing recommendations and additional drug interaction information.
· Patients review the Medication Guide for important safety information