JANUARY 2003

WEEK ENDING JANUARY 10

The Food and Drug Administration (FDA) today is advising women and health care professionals about important new safety changes to labeling of all estrogen and estrogen with progestin products for use by postmenopausal women. These changes reflect FDA's analysis of data from the Women's Health Initiative study (WHI), a landmark study sponsored by the National Institutes of Health that raised concern about risks of using these products.

FDA's labeling revisions are part of a series of actions to provide risk management information to women and advice to health care providers who prescribe these estrogen and estrogen with progestin-containing drug products for postmenopausal women. FDA will also be issuing updated guidances for manufacturers of estrogen and estrogen with progestin products regarding labeling of those products and development of new products for use in postmenopausal women. FDA's new labeling changes include a new boxed warning that reflects new risk information and changes to the approved indications to emphasize individualized decisions that appropriately balance the benefits and the potential risks of these products.

FDA Commissioner Mark McClellan, M.D, Ph.D., said, "The Women's Health Initiative Study provided valuable information about the use of estrogen and progestin therapies for postmenopausal women. A woman who is using or considering estrogens or estrogen-progestin treatment should consult with her health care provider about the implications of the new information on risks and benefits in her case.

He added, "In many cases, women will still want to rely on these products to deal with the effects of menopause. In other cases, alternative treatments will be appropriate. FDA's actions today will help inform health care providers and their patients so that they can appropriately balance the benefits and risks to make the best possible decisions about use of these drugs."

The WHI study has several components, one of which was designed to assess the effects of Prempro, a combination of estrogens plus a progestin, on the risk of developing heart disease. The Prempro arm of the WHI was halted early in July 2002 because the overall health risks, particularly the risks of invasive breast cancer and cardiovascular disease, exceeded the benefits of the drug. Estrogen and progestin hormones have never been approved by FDA for prevention of heart disease, although physicians could prescribe them "off-label" for this use.

FDA's approval for new physician prescribing information and patient information leaflets for Prempro and Premphase (containing estrogens with a progestin) and Premarin (containing estrogens) highlight this important new safety information.

FDA has also requested that all other manufacturers of estrogen and estrogen with progestin drug products for use in postmenopausal women make similar changes to the labeling for their products.

It is estimated that about ten million postmenopausal women in the United States currently use estrogen and combination estrogen with progestin products for relief of menopausal symptoms and prevention of postmenopausal osteoporosis. Estrogen products are approved for use in relieving vasomotor symptoms of menopause such as "hot flashes" and night sweats; symptoms of vulvar and vaginal atrophy such as dryness, itching, and burning; and prevention of postmenopausal osteoporosis. Because there are few alternatives for the relief of severe vasomotor symptoms and severe symptoms of vulvar vaginal atrophy, estrogens and estrogens with progestins have an important role in women's health.

The revisions for the Premarin, Prempro, and Premphase labeling build on revisions to the labeling that Wyeth Pharmaceuticals (the products' manufacturer) made in August 2002, shortly after the release of the findings from WHI. Since August, FDA has carefully reviewed the data from the WHI study and has worked with Wyeth to develop the new labeling approved today for these products.

The new boxed warning, the highest level of warning information in labeling, highlights the increased risks for heart disease, heart attacks, strokes, and breast cancer. This warning also emphasizes that these products are not approved for heart disease prevention. FDA has also modified the approved indications for Premarin, Prempro, and Premphase to clarify that these drugs should only be used when the benefits clearly outweigh risks. Of the three indications, two have been revised to include consideration of other therapies:

Treatment of moderate to severe vasomotor symptoms (such as "hot flashes") associated with the menopause. (This indication has not changed.)

Treatment of moderate to severe symptoms of vulvar and vaginal atrophy (dryness and irritation) associated with the menopause. When these products are being prescribed solely for the treatment of symptoms of vulvar and vaginal atrophy, topical vaginal products should be considered.

Prevention of postmenopausal osteoporosis (weak bones). When these products are being prescribed solely for the prevention of postmenopausal osteoporosis, approved non-estrogen treatments should be carefully considered, and estrogens and combined estrogen-progestin products should only be considered for women with significant risk of osteoporosis that outweighs the risks of the drug.

To minimize the potential risks and to accomplish the desired treatment goals, the new labeling also advises
health care providers to prescribe estrogen and combined estrogen with progestin drug products at the lowest dose and for the shortest duration for the individual woman. Women who choose to take estrogens or combined estrogen and progestin therapies after discussing their treatment with their doctor should have yearly breast exams by a health care provider, perform monthly breast self-examinations, and receive periodic mammography examinations scheduled based on their age and risk factors. Women should also talk to their health care provider about other ways to reduce their risk factors for heart disease (e.g., high blood pressure, poor diet, tobacco use) and osteoporosis (e.g., an appropriate diet, use of Vitamin D and Calcium supplements, weight-bearing exercise).

FDA will update guidances to provide advice on studies needed to demonstrate safety and effectiveness of new products for these indications and provide recommendations on labeling for estrogen and estrogen with progestin products used in postmenopausal women.

FDA's review of the WHI findings leads to some important research questions for the medical community. These questions include whether lower doses of estrogen and progestin will have lower risks, if other types of estrogens and progestins or other ways of administering these drugs, such as through patches, have different risks, and how best to stop taking estrogens and progestins. FDA intends to work with researchers, sponsors and product manufacturers to encourage this further research.

Wyeth Pharmaceuticals, a division of Wyeth of St. Davids, Pa., manufactures Premarin (conjugated estrogens), and Prempro and Premphase (conjugated estrogens/medroxyprogesterone).

WEEK ENDING JANUARY 17

Herbsland Inc. is recalling all 100 tablet bottles of Ancom Anti-Hypertensive Compound Tablets, an unapproved new drug labeled to contain several prescription drug ingredients, including reserpine, diazepam, promethiazine, and hydrochlorothiazide. The sale of a product with this combination of ingredients poses possible serious health risks including sedation, depression, and potentially life-threatening abnormalities of the blood.

This recall includes all lot codes of the product remaining on the market.

Ancom Tablets were sold without prescriptions to consumers through distributors and retail stores located in the New York City metropolitan area, specifically Manhattan, Brooklyn, and Queens. Nationwide sales are also possible as this product was sold via the Internet.

Ancom Tablets are labeled for anti-hypertensive use and are packaged in white plastic bottles of 100 tablets bearing blue and white lettered labeling. Each bottle is sold in an outer cardboard holding carton. Both the carton and immediate container label bear the product name as Ancom tablets, Anti-hypertensive Compound, and display the manufacture's name as Shanghai Pharmaceutical Industry Corp., Shanghai, China. The labeling also bears Chinese markings, which appear to be dual declarations. The holding carton is white with a pink and blue vertical stripe bearing blue and white lettering. The product carton also includes a pre-printed insert labeled with an ingredient statement and directions for use.

No illnesses have been reported to date. Consumers who have used this product and are experiencing any adverse reactions should seek advice from their physician for appropriate evaluation and treatment of their hypertension.

Consumers who purchased Ancom Anti-Hypertensive Compound Tablets are urged to immediately discontinue use of the product and return it to the place of purchase for a full refund. Consumers with questions may contact the company at

1-917-480-9107.

New warnings for the labels of over-the-counter vaginal contraceptive drugs that contain the spermicide nonoxynol 9. The warning would state that vaginal contraceptives containing nonoxynol 9 do not protect against infection from HIV (human immunodeficiency virus, the AIDS virus) or other sexually transmitted diseases (STDs).

The proposed label warnings would also advise consumers that the use of vaginal contraceptives containing nonoxynol 9 can increase vaginal irritation, which may actually increase the possibility of transmitting the AIDS virus and other STDs from infected partners.

FDA's proposed labeling statements are based on recent studies using nonoxynol 9, including data from a four-year World Health Organization study of 991 HIV-negative sex workers in Africa and Thailand. The study, whose final results were recently published, showed nonoxynol 9 to be ineffective in the prevention of HIV infection.

Nonoxynol 9 works as a vaginal contraceptive by damaging the cell membrane of sperm. It has been shown in laboratory studies to damage the cell walls of certain organisms that cause STDs and to be active against some STD-causing bacteria and viruses. On the basis of data that are described in the labeling proposal, FDA believes that this same membrane-damaging effect can harm the cell lining of the vagina and cervix, thereby increasing the risk of STD transmission.

PRODUCT
a) Garamycin Ophthalmic Ointment, USP (Gentamicin Sulfate) 0.3%, 3.5g tube, Rx only. Recall # D-069-3;b) Celestone Phosphate Injection, USP(Betamethasone sodium phosphate) 3 mg/mL, 5mL Multiple-Dose Vial, Rx only, NDC-0085-0879-05. Recall # D-070-3;c) Solganal Injectable Suspension , USP(Aurothioglucose), 500 mg, 50 mg/mL, 10 mL Multiple-Dose Vial, Rx only, NDC-0085-0460-03. Recall # D-071-3;
d) Trilafon Injection, USP (Perphenazine), 5 mg, 1 mL Ampule, NDC-0085-0012-04, Rx only. Recall # D-072-3;e) Sterile Diluent (Bacteriostatic Water for Injection with benzyl alcohol 0.945% w/v), 1 mL, NDC-0009-0780-46, Rx only. Recall # D-073-3;f) Bacteriostatic Water for Injection, USP., 2 mL syringe. Recall # D-074-3.
CODE
a) All lots within expiry: 0-HJ-1, March 2003; 0-HG-2, March 2003.
b) All lots within expiry: 0-AKP-3, August 2003; 0-AKP-2, June 2003; 0-AKP-1, May 2003. 0-AKP-4, September 2003.
c) All lots within expiry: 0-WS-4, November 2002; 0-WS-5,December 2002; 1-WS-1, March 2003.
d) All lots within expiry: 1-AEC-1, April 2004; 1-AEC-2, April 2004; 9-AEC-9, November 2002.
e) All lots within expiry: 0-BEX-501, Mar-21-2003; 0-BEX-502, Mar-25-2003; 0-BEX-503, Apr-02-2003; 0-BEX-504,
Apr-26-2003; 0-BEX-505, Jun-27-2003; 0-BEX-506, Jul-12-2003; 0-BEX-507, Jul-12-2003; 0-BEX-508, Nov-18-2003;
0-BEX-509, Dec-01-2003; 0-BEX-510, Dec-27-2003; 1-BEX-501, Feb-11-2004; 1-BEX-502, Feb-12-2004; 1-BEX-503,
Feb-22-2004; 1-BEX-505, Mar-22-2004; 1-BEX-506, Mar-29-2004; 1-BEX-507, May-28-2004; 1-BEX-508, May-29-2004;
1-BEX-509, May-30-2004; 1-BEX-511, Aug-15-2004; 1-BEX-512, Aug-20-2004; 1-BEX-513, Aug-27-2004; 1-BEX-514,
Aug-30-2004; 1-BEX-515, Oct-29-2004; 1-BEX-517, Nov-14-2004.
f) All lots within expiry: 1-BEX-701, Mar-2003; 1-BEX-702, Dec-2003; 2-BEX-701, Jan-14-2004.
RECALLING FIRM/MANUFACTURER
Schering Corp., Kenilworth, NJ, by letter dated November 8, 2002. Firm initiated recall is ongoing.
REASON
Lack of assurance of sterility.
VOLUME OF PRODUCT IN COMMERCE
4,047,706 units.
DISTRIBUTION
Nationwide and Caribbean islands: Bahamas, Curacao, Trinidad, Jamaica, St. Kitts and Aruba.

RECALLS AND FIELD CORRECTIONS: DRUGS -- CLASS III

****CORRECTION****

The expiration date for the codes in Recall D-096/D-097-3 should be 7/03 not 7/04.

PRODUCT
a) Nabumetone Tablets, 500 mg, 100 count bottles, Rx only, NDC 0185-0145-01. Recall # D-065-3;
b) Nabumetone Tablets, 750 mg, 100 count bottles, Rx only,NDC 0185-0146-01. Recall # D-066-3.
CODE
a) and b) Lot 021159, expiration date 10/2004.
RECALLING FIRM/MANUFACTURER
Eon Labs Manufacturing Inc., Laurelton, NY, by letter and fax on November 13, 2002. Firm initiated recall is ongoing.
REASON
Mislabeling - some bottles labeled to contain Nabumetone 750 mg tablets actually contain Nabumetone 500 mg tablets.
VOLUME OF PRODUCT IN COMMERCE
1533 bottles total lot.
DISTRIBUTION
Nationwide.

PRODUCT
a) Premphase Tablets, (conjugated estrogens 0.625mg and medroxyprogesterone 5mg) dial dispenser containing 28 tablets, Rx only. Recall # D-067-3.
b) Premarin Tablets (conjugated estrogens) 0.625 mg, Rx only, unit dose packages of 100 (NDC 0046-0867-99), bottles of 100 (NDC 0046-0867-81) and bottles of 5000 (NDC 0046-0867-95), Recall # D-068-3.

Enforcement Report 03-03, January 15, 2003, Recall # D-068-3, under code information, section b, the lot number for unit dose 100's were missing. It should read: lot # 9000846.
CODE
a) 9001385, Exp. 2/03; 9001386, Exp. 2/03
b) 100''s - lot #9001216, exp 5/03 5000''s - lot #9000986,
exp 5/05 unit dose 100''s - lot #.
RECALLING FIRM/MANUFACTURER
Robins, A.H./Division of American Home Products, Richmond, VA, by letter issued November 18, 2002, via certified mail. Firm initiated recall is ongoing.
REASON
Dissolution; failure to meet specifications at the 24 month/2-hour timepoint.
VOLUME OF PRODUCT IN COMMERCE
239,896 various size dispensers.
DISTRIBUTION
Nationwide.

PRODUCT
Pulmicort Turbuhaler (budesonide inhalation powder) 200mcg, 200 Metered Doses, Rx only, Professional Sample. Recall # D-075-3.
CODE
Lot Number: DA1625 Exp. Date: July 2003.
RECALLING FIRM/MANUFACTURER
Astra Zeneca Pharmaceuticals LP, Wilmington, DE, by letter to notify physicians, 11/18/02. Firm initiated recall is ongoing.
REASON
Fine particle size out of specification; patient may not receive full dose to lungs
VOLUME OF PRODUCT IN COMMERCE
23232 units (50 each).
DISTRIBUTION
Nationwide.

WEEK ENDING JANUARY 24

PRODUCT
Fluoxetine Capsules USP, 20 mg, 500 and 1000 count bottles, Rx only. Recall # D-061-3.
CODE
Lot 105458, Exp. 2/2004, 500 Count---NDC #00172-4356-70 Lot 104926, Exp. 2/2004, 1000 Count--NDC #00172-4356-80.
RECALLING FIRM/MANUFACTURER
Ivax Pharmaceuticals, Northvale, NJ, by letters on July 16, 2002. Firm initiated recall is ongoing.
REASON
Product exceeded specification for impurity level (1 month stability).
VOLUME OF PRODUCT IN COMMERCE
2991 bottles.
DISTRIBUTION
Nationwide and Puerto Rico.

PRODUCT
a) Premphase Tablets, (conjugated estrogens 0.625mg and medroxyprogesterone 5mg) dial dispenser containing 28
tablets, Rx only. Recall # D-067-3;

b) Premarin Tablets (conjugated estrogens) 0.625 mg, Rx only, unit dose packages of 100 (NDC 0046-0867-99),
bottles of 100 (NDC 0046-0867-81) and bottles of 5000 (NDC 0046-0867-95). Recall # D-068-3.

CODE
a) Lot 9001385, Exp 2/2003; Lot 9001386, Exp 2/2003
b) Lot 9001216, Exp 5/03; Lot 9000986, Exp 5/05; Lot 9000846, Exp 5/05.
RECALLING FIRM/MANUFACTURER
A.H. Robins, Richmond, VA, by letter dated 11/18/02. Firm initiated recall is ongoing.
REASON
Dissolution; failure to meet specifications at the 24 month/2-hour timepoint.
VOLUME OF PRODUCT IN COMMERCE
a) Premphase - 41,220 units
b) Premarin - 198,676 units.
DISTRIBUTION
Nationwide.

PRODUCT
Clemastine Fumarate Syrup, 0.5mg/5mL, Each teaspoonful (5mL) contains clemastine 0.5 mg (present as clemastine fumarate 0.67 mg) and alcohol 5.5%, 4 fluid ounces (118 mL) bottles, Rx only. Recall # D-108-3.
CODE
Lot number 1A950, exp. 02 2003.
RECALLING FIRM/MANUFACTURER
Novex Pharma, Richmond Hill, CA, by letter on November 19, 2002. Firm initiated recall is ongoing.
REASON
Degradation; product exceeds specification at 18 month timepoint.
VOLUME OF PRODUCT IN COMMERCE
2,083 bottles.
DISTRIBUTION
Nationwide.

WEEK ENDING JANUARY 31

STUDY OF ASTHMA-DRUG HALTED

The Food and Drug Administration (FDA) today announced that an interim analysis of a large safety study of the approved asthma drug Serevent (salmeterol xinafoate) Inhalation Aerosol suggests that the drug may be associated with an increased risk of life-threatening asthma episodes or asthma-related deaths, particularly in some patients.

The interim analysis did not show a statistically significant result for the primary endpoint - a combination of respiratory-related deaths or intubations (or ventilatory failure). There was a trend, however, towards increases in asthma deaths and serious asthma episodes when all patients in the study were considered, though again this did not reach statistical significance. A further analysis of the data from the study suggested that the risk might be greater in African-American patients. Also, further analyses showed that patients not taking inhaled corticosteroids at study entry appeared to have greater risk for serious outcomes than those who were taking inhaled corticosteroids.

This study was designed to further investigate the safety of Serevent, particularly whether it might rarely cause serious asthma-related adverse events. It was begun in 1996, after FDA received post-marketing reports of several asthma deaths associated with the use of Serevent Inhalation Aerosol and following publication of studies raising concern about the regular use of short-acting and long-acting beta agonists, including Serevent. Because asthma patients can sometimes suffer sudden, serious life-threatening episodes of bronchospasm as a consequence of their disease, the deaths and serious adverse events reported for Serevent could neither be clearly attributed to use of this product, nor could it be excluded as a cause. This study was undertaken to try to help provide better information on the safety of this product.

Today, the manufacturer of Serevent Inhalation Aerosol, GlaxoSmithKline (GSK), notified investigators that it is stopping this study, mostly due to difficulties in enrollment and the likelihood the study would not give a clear result, even if fully enrolled. The Glaxo Data Safety Monitoring Board overseeing this trial conducted the interim data analyses that led to today's action. Approximately 26,000 subjects, representing more than 4.3 million patient-days of exposure to the drug, had participated in the study. The study was intended to enroll 60,000 patients.

FDA routinely monitors adverse event reports as part of its continuing efforts to reduce adverse events. Drug safety and risk management are among FDA Commissioner Dr. Mark B. McClellan's top priorities.

FDA approved Serevent Inhalation Aerosol in 1994 to treat asthma, and later this approval was extended to use for treatment of chronic obstructive pulmonary disease (COPD). The drug belongs to the class of asthma medications known as beta2-receptor agonists (commonly called beta agonists). The active drug in Serevent, salmeterol, is also contained in the asthma drugs Serevent Diskus and Advair Diskus, also manufactured by Glaxo.

FDA plans to meet with Glaxo shortly to obtain more details about the data from the interim analyses of the study and to determine what steps are warranted to address this important new risk information. FDA is particularly interested in further evaluating the question of whether certain patients may be at a greater risk for rare, but potentially serious adverse events due to Serevent use and use of other related drugs.

FDA emphasizes that based on available data, the benefits of Serevent for the asthma population continue to outweigh the risks and that the serious adverse events reported in the trial were rare. FDA strongly advises patients that they should NOT stop taking Serevent, or any other medication, for asthma or COPD, without first talking to their physicians. Abruptly stopping drugs for the treatment of asthma and COPD can result in serious exacerbations of these diseases that could be life-threatening. FDA further emphasizes that all asthma drugs, including Serevent, should be a given as a part of a comprehensive treatment plan that takes into account the patient's asthma severity and fully educates the patient in the disease and its proper treatment.

An estimated 16 million patients in the U.S. now have asthma, and the number of asthmatics has increased significantly in the recent decades. In addition to the beta2-receptor family of medications, other drugs approved for asthma include leukotriene blockers, inhaled corticosteroids and theophylline.

PRODUCT
ESTRACE tablets (estradiol tablets, USP), 2 mg, 100 and 500 count bottles, Rx Only. Recall # D-116-3.
CODE
100 Count bottles - Lot no. 0K28404, Exp. Date Oct-2003, 500 Count bottles - Lot no. 0J41630, Exp. Date Oct-2003.
RECALLING FIRM/MANUFACTURER
Bristol-Myers Squibb Company, New Brunswick, NJ, by letters on November 11, 2002. Firm initiated recall is ongoing.
REASON
Dissolution Failure.
VOLUME OF PRODUCT IN COMMERCE
4,587 bottles.
DISTRIBUTION
Nationwide and Canada.

PRODUCT
a) MEGACE tablets (megestrol acetate, USP), 20 mg,100 count bottles, Rx Only. Recall # D-114-3;
b) MEGACE tablets (megestrol acetate, USP), 40 mg, 100 count bottles, Rx Only. Recall # D-115-3.
CODE
a) Megace 20 mg TABLETS

Lot no. Exp. date

OB31296 1/2003

1A42693 1/2004

1D47119 5/2004

1L55188 10/2004

b) Megace 40 mg TABLETS

Lot no. Exp. date

1B37102 1/2004

1F39749 5/2004

1D47154 5/2004

1J56964 5/2004

1D47155 6/2004

1L55181 10/2004

2H56553 10/2004

1L55141 11/2004

1L55142 11/2004

2H56552 8/2004

RECALLING FIRM/MANUFACTURER
Bristol-Myers Squibb Company, New Brunswick, NJ, by letters on November 5, 2002. Firm initiated recall is ongoing.
REASON
Dissolution Failure; tablets are below specification.
VOLUME OF PRODUCT IN COMMERCE
44,779 bottles (20 and 40 mg).
DISTRIBUTION
United States and the following countries Buenos Aires, Argentina, Seoul, Korea, Rep. Of South Africa, Santiago, Chile, Phillipines, and Vietnam.