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RHEUMATOLOGIC
DISORDERS Arthur A. Schuna, Section
Advisor
GASTROENTEROLOGIC DISORDERS C. Wayne Weart,
Section Advisor
Safer colchicine dosing regimen approved
Key point: FDA has approved colchicine
(Colcrys—Mutual) tablets with a much lower dosing regimen for gout
flares compared with historic dosing. The approval was accompanied by
warnings for potential serious and life-threatening drug interactions if
colchicine is coadministered with P-glycoprotein (P-gp) or strong
cytochrome P450 (CYP)3A4 inhibitors.
Finer points: In late July, FDA announced the
approval of colchicine tablets for the treatment of familial
Mediterranean fever in adults and children 4 years or older, in addition
to acute gout flares. The tablets were approved with a revised dosing
regimen of 1.2 mg (2 tablets) at the first sign of a gout flare followed
by 0.6 mg (1 tablet) 1 hour later. This revised regimen was based on
data from a multicenter, randomized, double-blind, placebo-controlled
trial that showed that similar percentages of patients with gout flare
given low-dose colchicine (n = 74, 1.2 mg, then 0.6 mg 1 hour later) and
high-dose colchicine (n = 52, 1.2 mg, then 0.6 mg hourly for 6 hours
[4.8 mg total]) achieved a 50% reduction in pain in the target joint
(38% and 33%, respectively). More important, the rates of
gastrointestinal adverse events such as diarrhea (23% vs. 77%), nausea
(4% vs. 17%), and vomiting (0% vs. 17%) were significantly less in the
low-dose group compared with the high-dose group. FDA reported that no
severe adverse events occurred in the low-dose group, while there were
10 events in patients given high-dose therapy.
During the approval process, FDA also analyzed a variety of safety
data on colchicine and noted that numerous deaths associated with
colchicine therapy occurred in patients on doses of 2 mg/day or less.
The agency reported that approximately 50% of these deaths involved
patients who were receiving clarithromycin concurrently. Based on this
analysis, FDA reported that alterations in the pharmacokinetics of
colchicine via inhibition of the efflux transporter P-gp or CYP3A4
increases the risk for colchicine toxicity. Therefore, detailed
information on medications that interact with colchicine and recommended
dosing adjustments were included in the approved label.
What you need to know: Educating patients and other
health care providers on the revised dosing regimen is needed because
many may not be aware of this change. In addition, screening for
potential drug interactions when dispensing prescriptions for colchicine
is essential. Assess patient profiles for medications that inhibit P-gp
such as cyclosporine and for strong CYP3A4 inhibitors such as
clarithromycin, erythromycin, nefazodone, azole antifungals, and HIV
protease inhibitors. If patients are receiving these agents, be sure
that the colchicine dosing regimen has been reduced as recommended in
the prescribing information. Use of colchicine is contraindicated for
patients with renal or hepatic impairment if they are already receiving
P-gp or strong CYP3A4 inhibitors. In addition, the dosage of colchicine
must be reduced for patients with severe renal impairment and in
patients undergoing dialysis. Colchicine toxicity has also been reported
in patients who consume large amounts of grapefruit juice daily. Careful
screening for potential drug interactions and provider and patient
education should help minimize the occurrence of colchicine
toxicity.
What your patients need to know: Give patients the
FDA-approved MedGuide and educate them on the new colchicine dosing
regimen by telling them to take two tablets at the first symptoms of a
gouty attack followed by one tablet 1 hour later. Emphasize that higher
doses have not been shown to be more effective and only increase their
risk of adverse events, especially gastrointestinal events. In addition,
tell patients that colchicine can interact with numerous medications.
Patients need to inform health care providers that they are receiving
colchicine before starting any new medications. Advise patients to avoid
consuming grapefruit and grapefruit juice while taking colchicine, as
they have been shown to increase the risk of colchicine toxicity.
Sources: Colcrys
[prescribing information]. Mutual: Philadelphia, PA; 2009.
Related resource on www.pharmacist.com
Joe Sheffer (jsheffer@aphanet.org)
Posted September 28, 2009
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