# Determination That DEMEROL (Meperidine Hydrochloride) Tablet, 100 Milligrams, and Other Drug Products Were Not Withdrawn From Sale for Reasons of Safety or Effectiveness
**AGENCY:**
Food and Drug Administration, HHS.
**ACTION:**
Notice.
**SUMMARY:**
The Food and Drug Administration (FDA or Agency) has determined that the drug products listed in this document were not withdrawn from sale for reasons of safety or effectiveness. This determination means that FDA will not begin procedures to withdraw approval of abbreviated new drug applications (ANDAs) that refer to these drug products, and it will allow FDA to continue to approve ANDAs that refer to the products as long as they meet relevant legal and regulatory requirements.
**FOR FURTHER INFORMATION CONTACT:**
Stacy Kane, Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 51, Rm. 6236, Silver Spring, MD 20993-0002, 301-796-8363, *[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 generally known as the “Orange Book.” Under FDA regulations, a drug is 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of the drug's NDA or ANDA for reasons of safety or effectiveness, or if FDA determines that the listed drug was withdrawn from sale for reasons of safety or effectiveness (21 CFR 314.162).
Under § 314.161(a) (21 CFR 314.161(a)), the Agency must determine whether a listed drug was withdrawn from sale for reasons of safety or effectiveness: (1) before an ANDA that refers to that listed drug may be approved, (2) whenever a listed drug is voluntarily withdrawn from sale and ANDAs that refer to the listed drug have been approved, and (3) when a person petitions for such a determination under 21 CFR 10.25(a) and 10.30. Section 314.161(d) provides that if FDA determines that a listed drug was withdrawn from sale for safety or effectiveness reasons, the Agency will initiate proceedings that could result in the withdrawal of approval of the ANDAs that refer to the listed drug.
FDA has become aware that the drug products listed in table 1 are no longer being marketed.
| Application No. | Drug name | Active ingredient(s) | Strength(s) | Dosage form/route | Applicant |
| --- | --- | --- | --- | --- | --- |
| NDA 005010 | DEMEROL | Meperidine Hydrochloride | 100 Milligrams (mg) | Tablet; Oral | Quagen Pharmaceuticals LLC. |
| NDA 009402 | DELESTROGEN | Estradiol Valerate | 40 mg/Milliliter (mL) | Injectable; Injection | Endo Operations Ltd. |
| NDA 011338 | FLUOTHANE | Halothane | 99.99% | Liquid; Inhalation | Wyeth-Ayerst Laboratories. |
| NDA 017354 | LOESTRIN FE 1/20 | Ethinyl Estradiol, Norethindrone Acetate | 0.02 mg, 1 mg | Tablet; Oral | Teva Branded Pharmaceutical Products R&D Inc. |
| NDA 018063 | CORGARD | Nadolol | 20 mg; 40 mg; 80 mg | Tablet; Oral | US WorldMeds, LLC. |
| NDA 019429 | FIORINAL W/CODEINE | Aspirin, Butalbital, Caffeine, Codeine Phosphate | 325 mg, 50mg, 40 mg, 30mg | Capsule; Oral | Allergan. |
| NDA 019758 | CLOZARIL | Clozapine | 50 mg; 200 mg | Tablet; Oral | Heritage Life Sciences Barbados Inc. |
| NDA 020496 | AMARYL | Glimepiride | 1 mg; 2 mg; 4 mg | Tablet; Oral | Sanofi-Aventis U.S. LLC. |
| NDA 020768 | ZOMIG | Zolmitriptan | 2.5 mg; 5 mg | Tablet; Oral | IPR Pharmaceuticals, Inc. |
| NDA 020933 | VIRAMUNE | Nevirapine | 50 mg/5 mL | Suspension; Oral | Boehringer Ingelheim Pharmaceuticals Inc. |
| NDA 021123 | ULTRACET | Acetaminophen, Tramadol Hydrochloride | 325 mg, 37.5 mg | Tablet; Oral | Janssen Pharmaceuticals Inc. |
| NDA 021142 | OLUX | Clobetasol Propionate | 0.05% | Aerosol, Foam; Topical | Norvium Bioscience, LLC. |
| NDA 021231 | ZOMIG-ZMT | Zolmitriptan | 2.5 mg; 5 mg | Orally Disintegrating Tablet; Oral | AstraZeneca Pharmaceuticals LP. |
| NDA 021368 | CIALIS | Tadalafil | 2.5 mg | Tablet; Oral | Eli Lilly and Co. |
| NDA 021497 | ALINIA | Nitazoxanide | 500 mg | Tablet; Oral | Romark Laboratories. |
| NDA 021636 | ZEGERID | Omeprazole, Sodium Bicarbonate | 20 mg/Packet, 1.68 grams (g)/Packet; 40 mg/Packet, 1.68 g/Packet | For Suspension; Oral | Salix Pharmaceuticals Inc. |
| NDA 021689 | NEXIUM IV | Esomeprazole Sodium | EQ 40 mg Base/Vial | Injectable; Intravenous | AstraZeneca Pharmaceuticals LP. |
| NDA 021799 | QUALAQUIN | Quinine Sulfate | 324 mg | Capsule; Oral | Sun Pharmaceutical Industries, Inc. |
| NDA 021937 | ATRIPLA | Efavirenz, Emtricitabine, Tenofovir Disoproxil Fumarate | 600 mg, 200 mg, 300 mg | Tablet; Oral | Gilead Sciences, Inc. |
| NDA 021963 | ALLEGRA | Fexofenadine Hydrochloride | 30 mg/5 mL | Suspension; Oral | Chattem Inc., DBA Sanofi Consumer Healthcare. |
| NDA 022331 | KAPVAY | Clonidine Hydrochloride | 0.1 mg | Extended-Release Tablet; Oral | Concordia Pharmaceuticals, Inc. |
| NDA 022352 | COLCRYS | Colchicine | 0.6 mg | Tablet; Oral | Takeda Pharmaceuticals USA, Inc. |
| NDA 050682 | COSMEGEN | Dactinomycin | 0.5 mg/Vial | Injectable; Injection | Recordati Rare Diseases Inc. |
| NDA 050717 | MONUROL | Fosfomycin Tromethamine | EQ 3 g Base/Packet | For Solution; Oral | Zambon Company S.p.A. |
| ANDA 086162 | BUTALBITAL, ASPIRIN AND CAFFEINE | Aspirin, Butalbital, Caffeine | 325 mg, 50 mg, 40 mg | Tablet; Oral | Hikma International Pharmaceuticals LLC. |
| ANDA 087056 | CYPROHEPTADINE HYDROCHLORIDE | Cyproheptadine Hydrochloride | 4 mg | Tablet; Oral | Avet Pharmaceuticals. |
| ANDA 088763 | PROMETHAZINE HYDROCHLORIDE AND CODEINE PHOSPHATE | Codeine Phosphate, Promethazine Hydrochloride | 10mg/5mL, | Syrup; Oral | Actavis Mid-Atlantic, LLC. |
FDA has reviewed its records and, under § 314.161, has determined that the drug products listed were not withdrawn from sale for reasons of safety or effectiveness. Accordingly, the Agency will continue to list the drug products in the “Discontinued Drug Product List” section of the Orange Book. The “Discontinued Drug Product List” identifies, among other items, drug products that have been discontinued from marketing for reasons other than safety or effectiveness.
Approved ANDAs that refer to the drug products listed are unaffected by the discontinued marketing of the products subject to these applications. Additional ANDAs that refer to these products may also be approved by the Agency if they comply with relevant legal and regulatory requirements. If FDA determines that labeling for these drug products should be revised to meet current standards, the Agency will advise ANDA applicants to submit such labeling.
Lowell M. Zeta,
Acting Deputy Commissioner for Policy, Legislation, and International Affairs.