New Drug Update 2009-2010 - LAFP

The AGREE (Acute Gout Flare Receiving Colchicine Evaluation) a mulitcenter, randomized, doubleblind,
placebo-controlled, parallel-group study compared self-administered low-dose colchicine (1.8 mg total
over 1 hour) and high-dose colchicine (4.8 mg total over 6 hours) with placebo. The primary end point
was >50% pain reduction at 24 hours without rescue medication. Results: There were 184 patients in the
intent-totreat analysis. Responders included 28 of 74 patients (37.8%) in the low-dose group, 17 of 52
patients (32.7%) in the high-dose group, and 9 of 58 patients (15.5%) in the placebo group (P= 0.005 and
P = 0.034, respectively versus placebo). Rescue medication was taken within the first 24 hours by 23
patients (31.1%) in the low-dose group (P = 0.027 versus placebo), 18 patients (34.6%) in the high-dose
group (P = 0.103 versus placebo), and 29 patients (50.0%) in the placebo group. The low-dose group had
an adverse event (AE) profile similar to that of the placebo group, with an odds ratio (OR) of 1.5 (95%
confidence interval [95% CI] 0.7–3.2). High-dose colchicine was associated with significantly more
diarrhea, vomiting, and other AEs compared with low-dose colchicine or placebo. With high-dose
colchicine, 40 patients (76.9%) had diarrhea (OR 21.3 [95% CI 7.9–56.9]), 10 (19.2%) had severe
diarrhea, and 9 (17.3%) had vomiting. With low-dose colchicine, 23.0% of the patients had diarrhea (OR
1.9 [95% CI 0.8–4.8]), none had severe diarrhea, and none had vomiting. (ARTHRITIS & RHEUMATISM
Vol. 62, No. 4, April 2010, pp 1060–1068)
Based on this information, FDA is highlighting important safety considerations found in the approved
prescribing information to assure safe use of Colcrys.
FDA recommends:
• 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
For treatment of prophylaxis of gout flares, the FDA recommended that patients taking an HIV drug
combination cut their initial dose of colchicine by three-fourths, from 0.6 mg twice a day to 0.3 mg
once a day, or, if they're taking 0.6 mg once a day, to 0.3 mg once every other day. For patients
taking fosamprenavir calcium alone, cutting the colchicine dosage in half -- from 0.6 mg twice a day to
0.3 mg twice a day, or from 0.6 mg once a day to 0.3 mg once daily -- is recommended.
As a treatment for familial Mediterranean fever, the FDA recommended a maximum dose of 0.6 mg
colchicine per day in patients taking both protease inhibitors and 1.2 mg daily in patients taking the
single drug.
November 2, 2009 FDA Alert Byetta (exenatide) – Renal Failure
FDA notified healthcare professionals of revisions to the prescribing information for Byetta (exenatide) to
include information on post-marketing reports of altered kidney function, including acute renal failure and
insufficiency. Byetta, an incretin-mimetic, is approved as an adjunct to diet and exercise to improve
glycemic control in adults with type 2 diabetes mellitus.
From April 2005 through October 2008, FDA received 78 cases of altered kidney function (62 cases of
acute renal failure and 16 cases of renal insufficiency), in patients using Byetta. Some cases occurred in
patients with pre-existing kidney disease or in patients with one or more risk factors for developing kidney
problems. Labeling changes include:
• Information regarding post-market reports of acute renal failure and insufficiency, highlighting that
Byetta should not be used in patients with severe renal impairment (creatinine clearance