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Gout Treatment Colchicine Gets Label Update for HIV Drug Interaction
 
 
  MedPage Today
Published: May 09, 2010
 
WASHINGTON -- The FDA updated the prescribing label of colchicine (Colcrys) to note the potential for adverse events ranging from serious infections to fatal drug interactions when colchicine is used while patients are also taking protease inhibitors to treat HIV.
 
The label change was due to a number of clinical studies performed by the drug's manufacturer, URL Pharma, which found the gout treatment may cause serious drug interactions when taken with protease inhibitors and certain other prescription medicines, such as some hypertension drugs and antibiotics.
 
The new label reflects a dosing adjustment for patients taking protease inhibitors or a combination of HIV treatments, such as fosamprenavir calcium (Lexiva) and ritonavir.
 
Colchicine is now contraindicated in patients with renal or hepatic impairment and prescribed protease inhibitors.
 
Those treating acute gout flares while using the fosamprenavir calcium/ritonavir drug combination should follow a new colchicine dosing regimen of 0.6 mg (one tablet) per dose followed by 0.3 mg (one half-tablet) an hour later.
 
Patients using fosamprenavir calcium without ritonavir should take 1.2 mg (two tablets) as an initial dose to treat acute gout flares.
 
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.
 
Colchicine is also contraindicated in patients taking P-gp and strong CYP3A4 inhibitors due to a potentially fatal toxicity in drug interaction.
 
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FDA Recommends New Dosing for Colcrys(R) (Colchicine, USP) when Co-Administered with Protease Inhibitors
 
Studies Undertaken by URL Pharma Discovered Previously Unknown Drug-Drug Interactions
 
PHILADELPHIA, May 6 /PRNewswire/ -- URL Pharma, Inc., today announced that the U.S. Food and Drug Administration (FDA) has issued new label information affecting all approved protease inhibitors for treatment of HIV when co-administered with Colcrys (colchicine, 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 the FDA in the 3 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, M.D., R.Ph., Chief Medical Officer. "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."
 
New Colcrys Dosing Guidance
 
The new dosing adjustment covers all approved protease inhibitors for the treatment of HIV-1 infection, including Lexiva (fosamprenavir calcium) and ritonavir.
 
* Patients with hepatic or renal impairment: For the prevention or treatment of gout flares, or for FMF, FDA has recommended against the co-administration of Colcrys with protease inhibitors.
 
* Acute gout flares: The new recommended dosing for the treatment of gout flares 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 Lexiva 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 Colcrys 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 a day, the regimen should be adjusted to 0.3 mg once every other day.
 
In patients taking Lexiva without ritonavir, FDA recommends that if the original Colcrys regimen was 0.6 mg twice a day, the regimen should be adjusted to 0.3 mg twice a day or 0.6 mg once a day. However, if the original Colcrys regimen was 0.6 mg once a day, FDA recommends it be adjusted to 0.3 mg once a day.
 
* Familial Mediterranean fever (FMF): In patients with FMF, FDA recommends a maximum daily dose of Colcrys of 0.6 mg (may be given as 0.3 mg twice a day) when co-administered with protease inhibitors.
 
However, in FMF patients taking Lexiva without ritonavir, the maximum daily dose of Colcrys is recommended to be no more than 1.2 mg (may be given as 0.6 mg twice a day).
 
Additional information about the new label information affecting all approved protease inhibitors for the treatment of HIV may be found at the FDA website: http://www.fda.gov/ForConsumers/ByAudience/ForPatientAdvocates/HIVandAIDSActivities/ucm209920.htm.
 
"At URL Pharma, patient safety is our primary concern," said Richard H. Roberts, M.D., Ph.D., President, Chief Executive Officer and Chairman of URL Pharma. "This is evidenced by the fact that our rigorous clinical program for Colcrys discovered these previously unknown drug-drug interactions. Patients and physicians should feel confident that they are prescribing and using a thoroughly tested, FDA-approved medication that meets all modern standards of safety, efficacy, purity, consistency and labeling."
 
Colcrys received approval from the U.S. Food and Drug Administration (FDA) on July 30, 2009 for use in treating acute gout flares at the first sign of a flare, and for the treatment of FMF. Colcrys received FDA approval for the prophylaxis of gout flares on October 19, 2009. It is the first and only single-agent colchicine treatment to receive FDA approval.
 
About Gout and Painful Gout Flares
 
Gout is a painful form of arthritis that affects an estimated 3 to 5 million Americans, most commonly adult men. It occurs when excess uric acid in the body is deposited as needle-like crystals, or tophi, in the joints or soft tissues, which cause inflammatory arthritis and can lead to gout flares typically lasting three to 10 days.
 
Gout flares are characterized by intermittent swelling, redness, heat, joint stiffness and pain, which are often excruciating and can be debilitating enough to significantly interfere with work, social activities and daily living. For many people, gout initially affects the joint of the big toe, though it can also affect other joint areas such as the ankles, heels, knees, wrists, fingers and elbows.
 
Important Safety Information
 
COLCRYS (colchicine, USP) tablets are indicated for the treatment of acute gout flares.
 
COLCRYS is contraindicated in patients with renal or hepatic impairment who are concurrently prescribed P-gp inhibitors or strong inhibitors of CYP3A4 as life-threatening or fatal toxicity has been reported. Dose adjustments of COLCRYS may be required when co-administered with P-gp or CYP3A4 inhibitors. The most common adverse events in clinical trials for the prophylaxis and treatment of gout were diarrhea and pharyngolaryngeal pain. Rarely, myelosuppression, thrombocytopenia, and leukopenia have been reported in patients taking colchicine. Rhabdomyolysis has been occasionally observed, especially when colchicine is prescribed in combination with other drugs known to cause this effect. Monitoring is recommended for patients with a history of blood dyscrasias or rhabdomyolysis.
 
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call 1-800-FDA-1088.
 
You may also report negative side effects to the manufacturer of COLCRYS by calling 1.888.351.3786.
 
For full Prescribing Information, please visit: http://www.colcrys.com/assets/pdf/COLCRYS_Full_Prescribing_Information.pdf
 
About URL Pharma
 
URL Pharma, Inc., headquartered in Philadelphia, PA, is a leading specialty pharmaceutical company with fully integrated technology development, product development, manufacturing, and commercialization capabilities. After a long history of generic pharmaceutical research, development, and manufacturing, the Company has successfully transitioned to a technology-driven, specialty pharmaceutical business. The Company seeks to develop and commercialize scientifically and medically innovative products that address unmet medical needs for improvements in safety and efficacy. The Company's profits are derived predominantly from its exclusive products and technologies. For additional information about the company, please visit www.urlpharma.com. For further information, please call 215-697-1900 or media@urlpharma.com.
 
Lexiva is a registered trademark of Vertex Pharmaceuticals, Inc.
 
SOURCE URL Pharma, Inc.
 
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FDA New label information affecting all approved protease inhibitors for treatment of HIV
 
HIV and AIDS Activities > New label information affecting all ... Apr 27, 2010 ... FDA, U S Food and Drug Administration. Enter Search terms ... The approved protease inhibitors for the treatment of HIV-1 infection now all ... New dosing recommendations for colchicine when prescribed for the treatment ... www.fda.gov/forconsumers/.../hivandaidsactivities/ucm209920.htm
 
The approved protease inhibitors for the treatment of HIV-1 infection now all include the following drug-drug interaction information:
 
· Revatio (sildenafil) as a contraindicated medication when prescribed for the treatment of pulmonary arterial hypertension
 
· Uroxatral (alfuzosin) as a contraindicated medication
 
· Recommendation that salmeterol should not be coadministered
 
· New dosing recommendation for Tracleer (bosentan) and Adcirca (tadalafil) when prescribed for the treatment of pulmonary arterial hypertension. Note, coadministration of bosentan and Reyataz (atazanavir) without ritonavir is not recommended.
 
· New dosing recommendations for colchicine when prescribed for the treatment of familial Mediterranean fever or gout
 
· New dosing recommendations for colchicine when prescribed for the prophylaxis of gout
 
· Recommendation that colchicine should not be coadministered with protease inhibitors in patients with hepatic or renal impairment
 
Below is an example of the new dosing recommendations for protease inhibitors and the following concomitant medications:
 
Colchicine:
 
Treatment of gout flares: 0.6 mg (1 tablet) x 1 dose, followed by 0.3 mg (half tablet) 1 hour later. Dose to be repeated no earlier than 3 days.
 
Note: Lexiva (fosamprenavir) without ritonavir: 1.2 mg (2 tablets) x 1 dose. Dose to be repeated no earlier than 3 days.
 
Prophylaxis of gout-flares: 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 a day, the regimen should be adjusted to 0.3 mg once every other day.
 
Note: Lexiva without ritonavir: if the original regimen was 0.6 mg twice a day, the regimen should be adjusted to 0.3 mg twice a day or 0.6 mg once a day. If the original regimen was 0.6 mg once a day, the regimen should be adjusted to 0.3 mg once a day
 
Treatment of familial Mediterranean fever (FMF): Maximum daily dose of 0.6 mg (may be given as 0.3 mg twice a day)
 
Note: Lexiva without ritonavir: maximum daily dose of 1.2 mg (may be given as 0.6 mg twice a day)
 
Bosentan: Treatment of pulmonary arterial hypertension
 
Coadministration of bosentan in patients already on a protease inhibitor for at least 10 days: Start at 62.5 mg once daily or every other day based upon individual tolerability
 
Coadministration of protease inhibitor in patients already on bosentan: Discontinue use of bosentan at least 36 hours prior to initiation of protease inhibitor. After at least 10 days following the initiation of the protease inhibitor, resume bosentan at 62.5 mg once daily or every other day based upon individual tolerability
 
Note: Coadministration of bosentan in patients on Crixivan (indinavir) or Viracept (nelfinavir) or coadministration of indinavir or nelfinavir in patients on bosentan. Start at or adjust bosentan to 62.5 mg once daily or every other day based upon individual tolerability.
 
Tadalafil (Adcirca): Treatment of pulmonary arterial hypertension
 
Coadministration of Adcirca in patients already on a protease inhibitor for at least one week: Start tadalafil at 20 mg once daily. Increase to 40 mg once daily based upon individual tolerability.
 
Coadministration of protease inhibitor in patients already on tadalafil: Avoid use of tadalafil during initiation of protease inhibitor. Stop tadalafil at least 24 hours prior to starting protease inhibitor. After at least one week following initiation of protease inhibitor, resume tadalafil at 20 mg once daily. Increase to 40 mg once daily based upon individual tolerability.
 
Note: Coadministration of Adcirca in patients already on nelfinavir or indinavir or coadministration of nelfinavir or indinavir in patients already on Adcirca: Start at or adjust Adcirca to 20 mg daily. Increase to 40 mg once daily based upon individual tolerability.
 
Richard Klein
Office of Special Health Issues
Food and Drug Administration
 
Kimberly Struble
Division of Antiviral Drug Products
Food and Drug Administration
 
 
 
 
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