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We’re at the U.S. Food and Drug Administration with the Division of Drug Information pharmacists
who answer hundreds of questions daily about drug products and FDA actions. Today they
are discussing important new information about colchicine. This is FDA Drug Info Rounds,
a program by pharmacists for pharmacists. We have been getting a lot of calls and emails
lately about colchicine. A drug that’s been used since the 1930s without FDA-approved
prescribing information, dosage recommendations, or drug interaction warnings. However, in
2009, FDA approved the first single-ingredient oral colchicine product, Colcrys, for the
treatment of familial Mediterranean fever and acute gout flares. This approval ensures,
for the first time that oral colchicine is safe, effective and properly labeled. This
wasn’t the case with the previously unapproved oral colchicine. One of the most common questions
patients are asking is “Why has the cost of my colchicine increased significantly ever
since Colcrys has been approved?” They say that for years they’ve been paying the same
low price everytime they pick up their colchicine prescription.
Of course we know that price affects access. However, unlike many countries around the
world, FDA has no statutory authority to control the prices charged for marketed drugs in the
United States. These prices are established by manufacturers, distributors, and retailers.
Right and besides price, there is the factor of whether a drug has FDA approval. Carefully
designed clinical trials have repeatedly demonstrated that the safety and effectiveness of drugs
cannot be adequately established from anecdotal evidence or consumer or prescriber preferences.
Plus drugs that have not been approved by the FDA may not be safe or effective;
may have been manufactured under sub-standard conditions; may contain too much or too little
(if any) active ingredients; and may not have the necessary labeling information and
warnings. If these oral colchicine products are unapproved, why are they allowed on the
market? There are a few products on the market that
pre-date existing FDA laws and regulations. Colchicine is one of these products. FDA has
not, to date, taken any regulatory action to remove unapproved oral colchicine from
the market. However, since FDA's Unapproved Drugs Initiative announced in June 2006, marketers
of unapproved drugs have been on notice that FDA is placing a high priority on addressing
risks from unapproved drugs. FDA is systematically and responsibly ensuring that all products
on the U.S. prescription drug market become compliant with current FDA approval requirements
for safety, efficacy and quality. The agency is aware of 21 firms that manufacture
and distribute unapproved oral colchicine. So far, only one, Mutual Pharmaceuticals has
chosen to take the responsible step of seeking FDA approval. Another issue that can be confusing
to patients is that many of them believe these unapproved products are generic versions of
Colcrys, and work just as well. To be clear, these unapproved colchicine products are not
generic versions of Colcrys. By definition, generic drugs are those evaluated and approved
by FDA to demonstrate bioequivalence to a brand name reference product. These unapproved
products have not been evaluated or approved by FDA. They are therefore unapproved drugs,
not generic medications, and neither their safety nor their efficacy can be ensured.
Why is FDA concerned about safety and efficacy when colchicine has been on the
market for years? Let’s look more closely at this issue.
During the drug review process for Mutual’s product Colcrys, FDA identified two previously
uncharacterized safety concerns associated with the use of colchicine.
First, FDA analyzed safety data 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 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. In addition, patients
receiving the lower dose experienced significantly fewer adverse events compared to the higher
dose. Because these new data provide actionable and important information for healthcare professionals
to guide dosing, and to reduce potential adverse events, FDA highlighted this in the approved
prescribing information for Colcrys. The unapproved products do not include this information.
To ensure the safe use of colchicine, FDA recommends that healthcare professionals:
Not use P-glycoprotein (P-gp) or strong CYP3A4 inhibitors in patients with renal or
hepatic impairment who are currently taking colchicine. 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. Prescribe the FDA-approved
Colcrys dose for the treatment of acute gout flares: which is 1.2 mg followed by 0.6mg
in 1 hour (for a total 1.8mg). Refer to Colcrys' approved prescribing information for
specific dosing recommendations and additional drug interaction information, and review
the Medication Guide for important safety information.
Without this review by FDA, outdated assumptions of what is safe and effective for treatment
with oral colchicine would have remained unchecked, and patients would have continued to suffer
from adverse reactions such as severe gastro-intestinal complications -- and even death -- needlessly.
Ok, if healthcare professionals want to switch their patients to approved Colcrys, the increase
in cost is still a major concern. What can pharmacists recommend to their patients?
The manufacturer of Colcrys, Mutual Pharmaceuticals, has started the Colcrys Patient Assistance
Program. The program helps patients with limited financial means save on Colcrys prescriptions.
Unlike other patients' assistance programs that may primarily target patients at or near the
poverty level, Mutual’s tiered program is designed to help patients in a variety of
socio-economic situations. By making healthcare professionals aware of
the differences between unapproved colchicine and the approved product, Colcrys, and by
giving them a plan to help off-set the cost, they can improve the health of their patients
while helping them save money. Thanks for joining the FDA pharmacists at
their Drug Info Rounds, the first of a series inside the FDA. This is our FDA program of
pharmacists helping pharmacists educate consumers, so they can make better medication
choices. To report medication adverse events call 1-800-332-1088 or go
online to www.fda.gov/medwatch. If you have any questions, you may reach FDA's Division
of Drug Information by calling 1-888-463-6332, or email us at druginfo@fda.hhs.gov.