Determination That Oxandrin (Oxandrolone) Tablets, 2.5 Milligrams and 10 Milligrams, Were Withdrawn From Sale for Reasons of Safety or Effectiveness, 62799-62800 [2023-19796]
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Federal Register / Vol. 88, No. 176 / Wednesday, September 13, 2023 / Notices
62799
ESTIMATED RECORDKEEPING TIME
Instrument
Respondent
Total number
of respondents
Total number
of responses
per
respondent
Average
burden hours
per response
Total burden
hours
Annual burden
hours
SMR Form .....
Care Provider Program Staff ...................
250
1.38
.08
27.6
9
Comments: The Department
specifically requests comments on (a)
whether the proposed collection of
information is necessary for the proper
performance of the functions of the
agency, including whether the
information shall have practical utility;
(b) the accuracy of the agency’s estimate
of the burden of the proposed collection
of information; (c) the quality, utility,
and clarity of the information to be
collected; and (d) ways to minimize the
burden of the collection of information
on respondents, including through the
use of automated collection techniques
or other forms of information
technology. Consideration will be given
to comments and suggestions submitted
within 60 days of this publication.
Authority: 6 U.S.C 279: Exhibit 1, part
A.2 of the Flores Settlement Agreement
(Jenny Lisette Flores, et al., v. Janet
Reno, Attorney General of the United
States, et al., Case No. CV 85–4544–RJK
[C.D. Cal. 1996])
Mary B. Jones,
ACF/OPRE Certifying Officer.
[FR Doc. 2023–19795 Filed 9–12–23; 8:45 am]
BILLING CODE 4184–45–P
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA–2022–P–0558]
Determination That Oxandrin
(Oxandrolone) Tablets, 2.5 Milligrams
and 10 Milligrams, Were Withdrawn
From Sale for Reasons of Safety or
Effectiveness
AGENCY:
Food and Drug Administration,
HHS.
ACTION:
Notice.
The Food and Drug
Administration (FDA, Agency, or we)
has determined that Oxandrin
(oxandrolone) tablets, 2.5 milligrams
(mg) and 10 mg, were withdrawn from
sale for reasons of safety or
effectiveness. The Agency will not
accept or approve abbreviated new drug
applications (ANDAs) for Oxandrin
(oxandrolone) tablets, 2.5 mg and 10 mg.
FOR FURTHER INFORMATION CONTACT:
Alexandria Fujisaki, Center for Drug
ddrumheller on DSK120RN23PROD with NOTICES1
SUMMARY:
VerDate Sep<11>2014
17:37 Sep 12, 2023
Jkt 259001
Evaluation and Research, Food and
Drug Administration, 10903 New
Hampshire Ave., Bldg. 51, Rm. 6222,
Silver Spring, MD 20993–0002, 301–
796–3600, Alexandria.Fujisaki@
fda.hhs.gov.
SUPPLEMENTARY INFORMATION: Section
505(j) of the Federal Food, Drug, and
Cosmetic Act (FD&C Act) (21 U.S.C.
355(j)) allows the submission of an
ANDA to market a generic version of a
previously approved drug product. To
obtain approval, the ANDA applicant
must show, among other things, that the
generic drug product: (1) has the same
active ingredient(s), dosage form, route
of administration, strength, conditions
of use, and (with certain exceptions)
labeling as the listed drug, which is a
version of the drug that was previously
approved, and (2) is bioequivalent to the
listed drug. ANDA applicants do not
have to repeat the extensive clinical
testing otherwise necessary to gain
approval of a new drug application
(NDA).
Section 505(j)(7) of the FD&C Act
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
(§ 314.162 (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 (§ 314.161 (21 CFR 314.161)).
FDA may not approve an ANDA that
does not refer to a listed drug.
The anabolic steroid Oxandrin
(oxandrolone) tablets, 2.5 mg and 10 mg,
is the subject of NDA 013718, held by
Gemini Laboratories LLC (Gemini), and
initially approved on July 21, 1964 (for
the 2.5 mg strength) and November 5,
PO 00000
Frm 00030
Fmt 4703
Sfmt 4703
2001 (for the 10 mg strength). Oxandrin
is indicated as follows: ‘‘as adjunctive
therapy to promote weight gain after
weight loss following extensive surgery,
chronic infections, or severe trauma,
and in some patients who without
definite pathophysiologic reasons fail to
gain or to maintain normal weight, to
offset the protein catabolism associated
with prolonged administration of
corticosteroids, and for the relief of the
bone pain frequently accompanying
osteoporosis.’’ 1
In a letter dated March 26, 2019,
Gemini requested that FDA withdraw
approval of NDA 013718 for Oxandrin
(oxandrolone) tablets, 2.5 mg and 10 mg,
under § 314.150(c) (21 CFR 314.150(c)),
stating that the product was no longer
being marketed. Subsequently, on
December 16, 2022, FDA notified
Gemini that the Agency believes a
potential problem associated with
oxandrolone tablets is sufficiently
serious that the drug product should be
removed from the market, and to enable
withdrawal of approval of its
application under § 314.150(d). After
FDA notified Gemini that it believes the
potential problems associated with the
drug are sufficiently serious that the
drug should be removed from the
market pursuant to § 314.150(d), Gemini
requested in a letter dated December 19,
2022, that FDA withdraw approval of
NDA 013718 for Oxandrin
(oxandrolone) tablets, 2.5 mg and 10 mg
under § 314.150(d). In the Federal
Register of June 28, 2023 (88 FR 41970),
FDA announced that it was
withdrawing approval of NDA 013718,
effective June 28, 2023.
Novitium Pharma LLC submitted a
citizen petition dated April 6, 2022
(Docket No. FDA–2022–P–0558), under
21 CFR 10.30, requesting that the
Agency determine whether Oxandrin
(oxandrolone) tablets, 2.5 mg and 10 mg,
were withdrawn from sale for reasons of
safety or effectiveness. The petitioner
has identified no data or other
information suggesting that Oxandrin
(oxandrolone) tablets, 2.5 mg and 10 mg,
1 See Oxandrin (oxandrolone) tablets product
labeling (NDA 013718, supplement 023), approved
on June 20, 2005, available at https://
www.accessdata.fda.gov/drugsatfda_docs/label/
2005/013718s023lbl.pdf.
E:\FR\FM\13SEN1.SGM
13SEN1
ddrumheller on DSK120RN23PROD with NOTICES1
62800
Federal Register / Vol. 88, No. 176 / Wednesday, September 13, 2023 / Notices
were withdrawn from sale for reasons of
safety or effectiveness.
After considering the citizen petition
and reviewing Agency records and
based on the information we have at this
time, FDA has determined under
§ 314.161 that Oxandrin (oxandrolone)
tablets, 2.5 mg and 10 mg, were
withdrawn for reasons of safety or
effectiveness. We have carefully
reviewed our files for records
concerning the withdrawal of Oxandrin
(oxandrolone) tablets, 2.5 mg and 10 mg,
from sale. We have also independently
evaluated relevant literature and data
for possible postmarketing adverse
events.
Our records show that FDA’s
Endocrinologic and Metabolic Drugs
Advisory Committee met and discussed
anabolic steroids in January 1984. The
advisory committee unanimously
concluded that there was no evidence of
efficacy for oxandrolone.2
As communicated in the product
labeling for Oxandrin (oxandrolone)
tablets, 2.5 mg and 10 mg, multiple
safety warnings and precautions are
associated with the use of this product
including peliosis hepatis, sometimes
associated with liver failure and intraabdominal hemorrhage; liver cell
tumors, sometimes fatal; and blood lipid
changes that are known to be associated
with increased risk of atherosclerosis.3
Per the product labeling, additional
warnings with using this product
include the risks associated with
cholestatic hepatitis, hypercalcemia in
patients with breast cancer, and
increased risk for the development of
prostatic hypertrophy and prostatic
carcinoma in geriatric patients.4
Considering the safety concerns
associated with the use of oxandrolone
noted in the labeling, the Agency
concluded that the benefit-risk profile of
the drug product is unfavorable without
substantial evidence to support
effectiveness.
Based on a thorough evaluation of the
information we have available to us and
an evaluation of the latest version of the
drug products’ approved labeling, we
have determined that the drug products
would not be considered safe and
effective if they were reintroduced to
the market today. New clinical studies
would first need to be conducted to
address the concerns described above.
Thus, after considering the citizen
petition and reviewing Agency records
and based on the information we have
2 See minutes from the January 24 to 25, 1984,
advisory committee meeting discussing anabolic
steroids, at pg. 7.
3 See footnote 1.
4 See footnote 1.
VerDate Sep<11>2014
17:37 Sep 12, 2023
Jkt 259001
at this time, FDA has determined under
§ 314.161 that Oxandrin (oxandrolone)
tablets, 2.5 mg and 10 mg, were
withdrawn for reasons of safety or
effectiveness. Accordingly, the Agency
will remove Oxandrin (oxandrolone)
tablets, 2.5 mg and 10 mg, from the list
of drug products published in the
Orange Book per § 314.162. FDA will
not accept or approve ANDAs that refer
to this drug product.
Dated: September 8, 2023.
Lauren K. Roth,
Associate Commissioner for Policy.
[FR Doc. 2023–19796 Filed 9–12–23; 8:45 am]
BILLING CODE 4164–01–P
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
Office of the Secretary
Findings of Research Misconduct
Office of the Secretary, HHS.
Notice.
AGENCY:
ACTION:
Findings of research
misconduct have been made against
Kotha Subbaramaiah, Ph.D.
(Respondent), who was a Professor of
Biochemistry Research in Medicine,
Department of Medicine, Weill Cornell
Medical College (WCMC). Respondent
engaged in research misconduct in
research supported by U.S. Public
Health Service (PHS) funds, specifically
National Cancer Institute (NCI),
National Institutes of Health (NIH),
grants P01 CA077839, P01 CA106451,
R01 CA108773, R01 CA154481, T32
CA009685, R25 CA105012, and N01
CN43302, National Institute on Deafness
and Other Communication Disorders
(NIDCD), NIH, grant T32 DC000027, and
National Center for Advancing
Translational Sciences (NCATS), NIH,
grant UL1 TR000457. The
administrative actions, including
debarment for a period of seven (7)
years, were implemented beginning on
August 16, 2023, and are detailed
below.
SUMMARY:
FOR FURTHER INFORMATION CONTACT:
Sheila Garrity, JD, MPH, MBA, Director,
Office of Research Integrity, 1101
Wootton Parkway, Suite 240, Rockville,
MD 20852, (240) 453–8200.
SUPPLEMENTARY INFORMATION: Notice is
hereby given that the Office of Research
Integrity (ORI) has taken final action in
the following case:
Kotha Subbaramaiah, Ph.D., Weill
Cornell Medical College: Based on the
report of an investigation conducted by
WCMC and additional analysis
conducted by ORI in its oversight
PO 00000
Frm 00031
Fmt 4703
Sfmt 4703
review, ORI found that Kotha
Subbaramaiah, Ph.D., former Weill
Cornell Medical College, WCMC,
engaged in research misconduct in
research supported by PHS funds,
specifically NCI, NIH, grants P01
CA077839, P01 CA106451, R01
CA108773, R01 CA154481, T32
CA009685, R25 CA105012, and N01
CN43302, NIDCD, NIH, grant T32
DC000027, and NCATS, NIH, grant UL1
TR000457.
ORI found that Respondent engaged
in research misconduct by intentionally,
knowingly, or recklessly falsifying and/
or fabricating data included in the
following twelve (12) published papers:
• Increased levels of COX–2 and
prostaglandin E2 contribute to elevated
aromatase expression in inflamed breast
tissue of obese women. Cancer Discov.
2012 Apr;2(4):356–65. doi: 10.1158/
2159–8290.CD–11–0241 (hereafter
referred to as ‘‘Cancer Discov. 2012’’).
Retraction in: Cancer Discov. 2021
May;11(5):1306. doi: 10.1158/2159–
8290.CD–21–0224.
• EP2 and EP4 receptors regulate
aromatase expression in human
adipocytes and breast cancer cells.
Evidence of a BRCA1 and p300
exchange. J Biol Chem. 2008 Feb
8;283(6):3433–44. doi: 10.1074/
jbc.M705409200 (hereafter referred to as
‘‘J Biol Chem. 2008’’). Retraction in: J
Biol Chem. 2020 Jan 3; 295(1):295. doi:
10.1074/jbc.W119.012140.
• HDAC6 modulates Hsp90
chaperone activity and regulates
activation of aryl hydrocarbon receptor
signaling. J Biol Chem. 2009 Mar 20;
284(12):7436–45. doi: 10.1074/
jbc.M808999200 (hereafter referred to as
‘‘J Biol Chem. 2009’’). Retraction in: J
Biol Chem. 2020 Jan 3; 295(1):297. doi:
10.1074/jbc.W119.012142.
• p53 protein regulates Hsp90
ATPase activity and thereby Wnt
signaling by modulating Aha1
expression. J Biol Chem. 2014 Mar
7;289(10):6513–25. doi: 10.1074/
jbc.M113.532523 (hereafter referred to
as ‘‘J Biol Chem. 2014’’). Retraction in:
J Biol Chem. 2020 Jan 3; 295(1):289. doi:
10.1074/jbc.W119.012134.
• Hsp90 and PKM2 drive the
expression of aromatase in Li-Fraumeni
syndrome breast adipose stromal cells. J
Biol Chem. 2016 Jul 29;291(31):16011–
23. doi: 10.1074/jbc.M115.698902
(hereafter referred to as ‘‘J Biol Chem.
2016’’). Retraction in: J Biol Chem. 2020
Jan 3; 295(1):290. doi: 10.1074/
jbc.W119.012135.
• Heat shock protein 90 inhibitors
suppress aryl hydrocarbon receptormediated activation of CYP1A1 and
CYP1B1 transcription and DNA adduct
formation. Cancer Prev Res (Phila). 2008
E:\FR\FM\13SEN1.SGM
13SEN1
]]>Agencies
[Federal Register Volume 88, Number 176 (Wednesday, September 13, 2023)]
[Notices]
[Pages 62799-62800]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2023-19796]
-----------------------------------------------------------------------
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA-2022-P-0558]
Determination That Oxandrin (Oxandrolone) Tablets, 2.5 Milligrams
and 10 Milligrams, Were Withdrawn From Sale for Reasons of Safety or
Effectiveness
AGENCY: Food and Drug Administration, HHS.
ACTION: Notice.
-----------------------------------------------------------------------
SUMMARY: The Food and Drug Administration (FDA, Agency, or we) has
determined that Oxandrin (oxandrolone) tablets, 2.5 milligrams (mg) and
10 mg, were withdrawn from sale for reasons of safety or effectiveness.
The Agency will not accept or approve abbreviated new drug applications
(ANDAs) for Oxandrin (oxandrolone) tablets, 2.5 mg and 10 mg.
FOR FURTHER INFORMATION CONTACT: Alexandria Fujisaki, Center for Drug
Evaluation and Research, Food and Drug Administration, 10903 New
Hampshire Ave., Bldg. 51, Rm. 6222, Silver Spring, MD 20993-0002, 301-
796-3600, [email protected].
SUPPLEMENTARY INFORMATION: Section 505(j) of the Federal Food, Drug,
and Cosmetic Act (FD&C Act) (21 U.S.C. 355(j)) allows the submission of
an ANDA to market a generic version of a previously approved drug
product. To obtain approval, the ANDA applicant must show, among other
things, that the generic drug product: (1) has the same active
ingredient(s), dosage form, route of administration, strength,
conditions of use, and (with certain exceptions) labeling as the listed
drug, which is a version of the drug that was previously approved, and
(2) is bioequivalent to the listed drug. ANDA applicants do not have to
repeat the extensive clinical testing otherwise necessary to gain
approval of a new drug application (NDA).
Section 505(j)(7) of the FD&C Act 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 (Sec. 314.162 (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.
The anabolic steroid Oxandrin (oxandrolone) tablets, 2.5 mg and 10
mg, is the subject of NDA 013718, held by Gemini Laboratories LLC
(Gemini), and initially approved on July 21, 1964 (for the 2.5 mg
strength) and November 5, 2001 (for the 10 mg strength). Oxandrin is
indicated as follows: ``as adjunctive therapy to promote weight gain
after weight loss following extensive surgery, chronic infections, or
severe trauma, and in some patients who without definite
pathophysiologic reasons fail to gain or to maintain normal weight, to
offset the protein catabolism associated with prolonged administration
of corticosteroids, and for the relief of the bone pain frequently
accompanying osteoporosis.'' \1\
---------------------------------------------------------------------------
\1\ See Oxandrin (oxandrolone) tablets product labeling (NDA
013718, supplement 023), approved on June 20, 2005, available at
https://www.accessdata.fda.gov/drugsatfda_docs/label/2005/013718s023lbl.pdf.
---------------------------------------------------------------------------
In a letter dated March 26, 2019, Gemini requested that FDA
withdraw approval of NDA 013718 for Oxandrin (oxandrolone) tablets, 2.5
mg and 10 mg, under Sec. 314.150(c) (21 CFR 314.150(c)), stating that
the product was no longer being marketed. Subsequently, on December 16,
2022, FDA notified Gemini that the Agency believes a potential problem
associated with oxandrolone tablets is sufficiently serious that the
drug product should be removed from the market, and to enable
withdrawal of approval of its application under Sec. 314.150(d). After
FDA notified Gemini that it believes the potential problems associated
with the drug are sufficiently serious that the drug should be removed
from the market pursuant to Sec. 314.150(d), Gemini requested in a
letter dated December 19, 2022, that FDA withdraw approval of NDA
013718 for Oxandrin (oxandrolone) tablets, 2.5 mg and 10 mg under Sec.
314.150(d). In the Federal Register of June 28, 2023 (88 FR 41970), FDA
announced that it was withdrawing approval of NDA 013718, effective
June 28, 2023.
Novitium Pharma LLC submitted a citizen petition dated April 6,
2022 (Docket No. FDA-2022-P-0558), under 21 CFR 10.30, requesting that
the Agency determine whether Oxandrin (oxandrolone) tablets, 2.5 mg and
10 mg, were withdrawn from sale for reasons of safety or effectiveness.
The petitioner has identified no data or other information suggesting
that Oxandrin (oxandrolone) tablets, 2.5 mg and 10 mg,
[[Page 62800]]
were withdrawn from sale for reasons of safety or effectiveness.
After considering the citizen petition and reviewing Agency records
and based on the information we have at this time, FDA has determined
under Sec. 314.161 that Oxandrin (oxandrolone) tablets, 2.5 mg and 10
mg, were withdrawn for reasons of safety or effectiveness. We have
carefully reviewed our files for records concerning the withdrawal of
Oxandrin (oxandrolone) tablets, 2.5 mg and 10 mg, from sale. We have
also independently evaluated relevant literature and data for possible
postmarketing adverse events.
Our records show that FDA's Endocrinologic and Metabolic Drugs
Advisory Committee met and discussed anabolic steroids in January 1984.
The advisory committee unanimously concluded that there was no evidence
of efficacy for oxandrolone.\2\
---------------------------------------------------------------------------
\2\ See minutes from the January 24 to 25, 1984, advisory
committee meeting discussing anabolic steroids, at pg. 7.
---------------------------------------------------------------------------
As communicated in the product labeling for Oxandrin (oxandrolone)
tablets, 2.5 mg and 10 mg, multiple safety warnings and precautions are
associated with the use of this product including peliosis hepatis,
sometimes associated with liver failure and intra-abdominal hemorrhage;
liver cell tumors, sometimes fatal; and blood lipid changes that are
known to be associated with increased risk of atherosclerosis.\3\ Per
the product labeling, additional warnings with using this product
include the risks associated with cholestatic hepatitis, hypercalcemia
in patients with breast cancer, and increased risk for the development
of prostatic hypertrophy and prostatic carcinoma in geriatric
patients.\4\ Considering the safety concerns associated with the use of
oxandrolone noted in the labeling, the Agency concluded that the
benefit-risk profile of the drug product is unfavorable without
substantial evidence to support effectiveness.
---------------------------------------------------------------------------
\3\ See footnote 1.
\4\ See footnote 1.
---------------------------------------------------------------------------
Based on a thorough evaluation of the information we have available
to us and an evaluation of the latest version of the drug products'
approved labeling, we have determined that the drug products would not
be considered safe and effective if they were reintroduced to the
market today. New clinical studies would first need to be conducted to
address the concerns described above. Thus, after considering the
citizen petition and reviewing Agency records and based on the
information we have at this time, FDA has determined under Sec.
314.161 that Oxandrin (oxandrolone) tablets, 2.5 mg and 10 mg, were
withdrawn for reasons of safety or effectiveness. Accordingly, the
Agency will remove Oxandrin (oxandrolone) tablets, 2.5 mg and 10 mg,
from the list of drug products published in the Orange Book per Sec.
314.162. FDA will not accept or approve ANDAs that refer to this drug
product.
Dated: September 8, 2023.
Lauren K. Roth,
Associate Commissioner for Policy.
[FR Doc. 2023-19796 Filed 9-12-23; 8:45 am]
BILLING CODE 4164-01-P
