FDA recommends new dosing for colchicine when co-administered with protease inhibitors

May 14, 2010

The FDA issued new label information on May 6 affecting all approved protease inhibitors for treatment of HIV when co-administered with colchicine (Colcrys, USP).

The FDA issued new label information on May 6 affecting all approved protease inhibitors for treatment of HIV when co-administered with colchicine (Colcrys, USP). These dosing guidelines are intended to avoid potentially fatal drug-drug interactions.

These new dosing recommendations were issued as a result of several clinical studies designed and conducted by URL Pharma that uncovered the risk of serious interactions when colchicine is taken along with certain other prescription medications. In addition to protease inhibitors, the URL Pharma studies discovered potentially dangerous interactions between colchicine and certain hypertension medications and antibiotics. URL Pharma conducted 17 clinical trials as part of its submissions to FDA in the three New Drug Applications (NDAs) filed for Colcrys.

“The drug-drug interaction studies we conducted for Colcrys have yielded new and critically important guidance for physicians on the safe and appropriate use of colchicine, particularly among special populations, and represent a significant public health milestone in the treatment of gout,” said Matthew W. Davis, MD, RPh, chief medical officer for URL Pharma. “Prior to our work, scientifically rigorous guidance on dosing colchicine to avoid drug interactions was virtually non-existent. We urge all healthcare providers to consult the new labeling for protease inhibitors prior to concomitant use with Colcrys.”The new dosing adjustment covers all approved protease inhibitors for the treatment of HIV-1 infection, including fosamprenavir calcium (Lexiva, GlaxoSmithKline) and ritonavir.

Patients with hepatic or renal impairment:
For the prevention or treatment of gout flares, or for familial Mediterranean fever (FMF), FDA has recommended against the co-administration of colchicine with protease inhibitors.

Acute gout flares:
The new recommended dosing for treatment is 0.6 mg (1 tablet) x 1 dose, followed by 0.3 mg (half tablet) 1 hour later; this dose to be repeated no earlier than 3 days.

For patients taking fosamprenavir calcium without ritonavir, the suggested dose is 1.2 mg (2 tablets) x 1 dose; this dose is to be repeated no earlier than 3 days.

Prophylaxis of gout flares:
In patients taking colchicine for the prophylaxis of gout flares, FDA recommends that if the original colchicine regimen was 0.6 mg twice a day, the regimen should be adjusted to 0.3 mg once a day. If the original colchicine regimen was 0.6 mg once daily, the regimen should be adjusted to 0.3 mg once every other day.

In patients taking fosamprenavir calcium without ritonavir, FDA recommends that if the original colchicine regimen was 0.6 mg twice daily, the regimen should be adjusted to 0.3 mg twice daily or 0.6 mg once daily. However, if the original colchicine regimen was 0.6 mg once daily, FDA recommends it be adjusted to 0.3 mg once daily.

Familial Mediterranean fever (FMF):
In patients with FMF, FDA recommends a maximum daily dose of colchicine of 0.6 mg (may be given as 0.3 mg twice daily) when co-administered with protease inhibitors.

However, in patients with FMF taking fosamprenavir calcium without ritonavir, the maximum daily dose of colchicine is recommended to be no more than 1.2 mg (may be given as 0.6 mg twice daily).

Additional information about the new label information affecting all approved protease inhibitors for the treatment of HIV may be found at www.fda.gov/ForConsumers/ByAudience/ForPatientAdvocates/HIVandAIDSActivities/ucm209920.htm.