Notice: Determination That AVALIDE (Hydrochlorothiazide and Irbesartan), 
Oral Tablets, 25 Milligrams/300 Milligrams and 12.5 Milligrams/75 
Milligrams, Were Not Withdrawn From Sale for Reasons of Safety or 
Effectiveness

Federal Register: Volume 77, Number 7 (Wednesday, January 11, 2012)
                  Pages 1695-1696

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

SUMMARY: The Food and Drug Administration (FDA) has determined that 
AVALIDE (hydrochlorothiazide and irbesartan), oral tablets, 25 
milligrams (mg)/300 mg and 12.5 mg/75 mg, were not withdrawn from sale 
for reasons of safety or effectiveness. This determination will allow 
FDA to approve abbreviated new drug applications (ANDAs) for 
hydrochlorothiazide and irbesartan, oral tablets, 25 mg/300 mg and 12.5 
mg/75 mg, if all other legal and regulatory requirements are met.

FOR FURTHER INFORMATION CONTACT: Jane Inglese, Center for Drug 
Evaluation and Research, Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 51, rm. 6210, 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drug was withdrawn from sale for reasons of safety or effectiveness (21 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.
    AVALIDE (hydrochlorothiazide and irbesartan), oral tablets, 25 mg/
300 mg and 12.5 mg/75 mg, are the subject of NDA 20-758, held by 
Sanofi-Aventis, and initially approved on September 30, 1997. AVALIDE 
is indicated for treatment of hypertension in patients whose blood 
pressure is not adequately controlled on monotherapy. AVALIDE is also 
indicated for initial therapy for hypertension in patients who are 
likely to need multiple drugs to achieve their blood pressure goals.
    AVALIDE (hydrochlorothiazide and irbesartan), oral tablets, 25 mg/
300 mg and 12.5 mg/75 mg are currently listed in the ``Discontinued 
Drug Product List'' section of the Orange Book.
    EAS Consulting Group, LLC on behalf of Aurobindo Pharmaceuticals, 
Ltd. submitted a citizen petition dated October 11, 2011 (Docket No. 
FDA-2011-P-0743), under Sec.  10.30 (21 CFR 10.30), requesting that the 
Agency

[[Page 1696]]

determine whether AVALIDE (hydrochlorothiazide and irbesartan), oral 
tablets, 25 mg/300 mg, were withdrawn from sale for reasons of safety 
or effectiveness. In addition, Lupin Pharmaceuticals, Inc. submitted a 
citizen petition dated November 10, 2011 (Docket No. FDA-2011-P-0822), 
under Sec.  10.30, also requesting that the Agency determine whether 
AVALIDE (hydrochlorothiazide and irbesartan), oral tablets, 25 mg/300 
mg, were withdrawn from sale for reasons of safety or effectiveness. 
Although the citizen petitions did not address the 12.5 mg/75 mg 
strength, that strength has also been discontinued. On our own 
initiative, we have also determined whether that strength was withdrawn 
for safety or effectiveness reasons.
    After considering the citizen petitions and reviewing Agency 
records, and based on the information we have at this time, FDA has 
determined under Sec.  314.161 that AVALIDE (hydrochlorothiazide and 
irbesartan), oral tablets, 25 mg/300 mg and 12.5 mg/75 mg were not 
withdrawn for reasons of safety or effectiveness. The petitioners have 
identified no data or other information suggesting that AVALIDE 
(hydrochlorothiazide and irbesartan), oral tablets, 25 mg/300 mg and 
12.5 mg/75 mg were withdrawn for reasons of safety or effectiveness. We 
have carefully reviewed our files for records concerning the withdrawal 
of AVALIDE (hydrochlorothiazide and irbesartan), oral tablets, 25 mg/
300 mg and 12.5 mg/75 mg from sale. We have also independently 
evaluated relevant literature and data for possible postmarketing 
adverse events. We have reviewed the available evidence and determined 
that AVALIDE (hydrochlorothiazide and irbesartan), oral tablets, 25 mg/
300 mg and 12.5 mg/75 mg were not withdrawn from sale for reasons of 
safety or effectiveness.
    Accordingly, the Agency will continue to list AVALIDE 
(hydrochlorothiazide and irbesartan), oral tablets, 25 mg/300 mg and 
12.5 mg/75 mg, in the ``Discontinued Drug Product List'' section of the 
Orange Book. The ``Discontinued Drug Product List'' delineates, among 
other items, drug products that have been discontinued from marketing 
for reasons other than safety or effectiveness. ANDAs that refer to 
AVALIDE (hydrochlorothiazide and irbesartan), oral tablets, 25 mg/300 
mg and 12.5 mg/75 mg, may be approved by the Agency as long as they 
meet all other legal and regulatory requirements for the approval of 
ANDAs. If FDA determines that labeling for this drug product should be 
revised to meet current standards, the Agency will advise ANDA 
applicants to submit such labeling.

    Dated: January 5, 2012.
Leslie Kux,
Acting Assistant Commissioner for Policy.
[FR Doc. 2012-312 Filed 1-10-12; 8:45 am]
BILLING CODE 4160-01-P