[Federal Register Volume 77, Number 135 (Friday, July 13, 2012)]
[Notices]
[Pages 41412-41413]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2012-17091]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA-2011-P-0081]
Determination That CHLOROMYCETIN (Chloramphenicol) Capsules, 250
Milligrams, Were Withdrawn From Sale for Reasons of Safety or
Effectiveness
AGENCY: Food and Drug Administration, HHS.
ACTION: Notice.
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SUMMARY: The Food and Drug Administration (FDA) has determined that
CHLOROMYCETIN (chloramphenicol) Capsules, 250 milligrams (mg), were
withdrawn from sale for reasons of safety or effectiveness. The Agency
will not accept or approve abbreviated new drug applications (ANDAs)
for chloramphenicol capsules, 250 mg.
FOR FURTHER INFORMATION CONTACT: Nikki Mueller, Center for Drug
Evaluation and Research, Food and Drug Administration, 10903 New
Hampshire Ave., Bldg. 51, Rm. 6312, Silver Spring, MD 20993-0002, 301-
796-3601.
SUPPLEMENTARY INFORMATION: In 1984, Congress enacted the Drug Price
Competition and Patent Term Restoration Act of 1984 (Pub. L. 98-417)
(the 1984 amendments), which authorized the approval of duplicate
versions of drug products under an ANDA procedure. ANDA applicants
must, with certain exceptions, show that the drug for which they are
seeking approval contains the same active ingredient in the same
strength and dosage form as the ``listed drug,'' which is a version of
the drug that was previously approved. ANDA applicants do not have to
repeat the extensive clinical testing otherwise necessary to gain
approval of a new drug application (NDA). The only clinical data
required in an ANDA are data to show that the drug that is the subject
of the ANDA is bioequivalent to the listed drug.
The 1984 amendments include what is now section 505(j)(7) of the
Federal Food, Drug, and Cosmetic Act (21 U.S.C. 355(j)(7)), which
requires FDA to publish a list of all approved drugs. FDA publishes
this list as part of the ``Approved Drug Products With Therapeutic
Equivalence Evaluations,'' which is known generally as the ``Orange
Book.'' Under FDA regulations, drugs are removed from the list if the
Agency withdraws or suspends approval of the drug's NDA or ANDA for
reasons of safety or effectiveness or if FDA determines that the listed
drug was withdrawn from sale for reasons of safety or effectiveness (21
CFR 314.162).
A person may petition the Agency to determine, or the Agency may
determine on its own initiative, whether a listed drug was withdrawn
from sale for reasons of safety or effectiveness. This determination
may be made at any time after the drug has been withdrawn from sale,
but must be made prior to approving an ANDA that refers to the listed
drug (Sec. 314.161 (21 CFR 314.161)). FDA may not approve an ANDA that
does not refer to a listed drug.
CHLOROMYCETIN (chloramphenicol) Capsules, 250 mg, are the subject
of ANDA 60-591, held by Parkedale Pharmaceuticals, and initially
approved on December 8, 1950. CHLOROMYCETIN is an antibiotic indicated
to treat only serious infections for which less potentially dangerous
drugs are ineffective or contraindicated.
In a letter dated October 9, 2007, Parkedale Pharmaceuticals
requested withdrawal of ANDA 60-591 for CHLOROMYCETIN (chloramphenicol)
Capsules, 50 mg, 100 mg and 250 mg. In the Federal Register of February
11, 2009 (74 FR 6896), FDA announced that it was withdrawing approval
of ANDA 60-591, effective March 13, 2009, and moved the drug to the
``Discontinued Drug Product List'' section of the Orange Book.
Armenpharm, Ltd., submitted a citizen petition dated February 7,
2011 (Docket No. FDA-2011-P-0081), under 21 CFR 10.30, requesting that
the Agency determine whether CHLOROMYCETIN (chloramphenicol) Capsules,
250 mg, were withdrawn from sale for reasons of safety or
effectiveness.
After considering the citizen petition, and based on the
information we have at this time, FDA has determined under Sec.
314.161 that CHLOROMYCETIN (chloramphenicol) Capsules, 250 mg, were
withdrawn for reasons of safety or effectiveness. We have carefully
reviewed Agency records concerning the withdrawal of CHLOROMYCETIN
(chloramphenicol) Capsules, 250 mg, from sale. We have also
independently evaluated relevant literature and data for possible
postmarketing adverse events. At the time of the approval of
CHLOROMYCETIN (chloramphenicol) Capsules, 250 mg, there was significant
unmet medical need. With the approval of additional therapies with less
severe adverse drug effects, FDA has determined that the risks
associated with CHLOROMYCETIN (chloramphenicol) Capsules, 250 mg, as
currently labeled, outweigh the benefits. Most importantly,
CHLOROMYCETIN
[[Page 41413]]
(chloramphenicol) Capsules, 250 mg, may cause a number of adverse
reactions, the most serious being bone marrow depression (anemia,
thrombocytopenia, and granulocytopenia temporally associated with
treatment). A boxed warning in the prescribing information for both
chloramphenicol sodium succinate injection and chloramphenicol capsules
states that serious hypoplastic anemia, thrombocytopenia, and
granulocytopenia are known to occur after administration of
chloramphenicol. The drug product labeling recommends extensive safety
monitoring, including baseline blood studies followed by periodic blood
studies approximately every 2 days during therapy. The boxed warning
also describes fatal aplastic anemia associated with administration of
the drug and aplastic anemia attributed to chloramphenicol that later
terminated in leukemia. There is published literature which suggests
that the risk of fatal aplastic anemia associated with the oral
formulation of chloramphenicol may be higher than the risk associated
with the intravenous formation.
FDA has also reviewed the latest approved labeling for the product
and has determined that this labeling is inadequate and a Risk
Evaluation and Mitigation Strategy (REMS) would be required to ensure
that the benefits of the drug outweigh its risks. The REMS may include
Elements to Assure Safe Use, including restricted distribution, and a
Medication Guide could be required as part of the labeling. FDA has
determined that additional nonclinical and possibly clinical studies of
safety and efficacy would be necessary before CHLOROMYCETIN
(chloramphenicol) Capsules, 250 mg, could be considered for
reintroduction to the market.
Accordingly, the Agency will remove CHLOROMYCETIN (chloramphenicol)
Capsules, 250 mg, from the list of drug products published in the
Orange Book. FDA will not accept or approve ANDAs that refer to this
drug product.
Dated: July 10, 2012.
Leslie Kux,
Assistant Commissioner for Policy.
[FR Doc. 2012-17091 Filed 7-12-12; 8:45 am]
BILLING CODE 4160-01-P