Released by FDA: 7/20/00.  Posted by FDA:  8/2/00

Donna M. Dea 
Assistant Manager, Marketed Products 
AstraZeneca Pharmaceuticals 
1800 Concord Pike 
Wilmington, DE 19850-5437

Re:    Nolvadex® (tamoxifen citrate) 
         NDA 17-970 
         MACMIS ID# 9075

Dear Ms. Dea:

As part of its routine monitoring and surveillance program, the Division of Drug Marketing, Advertising, and Communications (DDMAC) has become aware that AstraZeneca Pharmaceuticals (Zeneca) is promoting its product, Nolvadex, in violation of the Federal Food, Drug, and Cosmetic Act (the Act) and its implementing regulations.  Reference is made to the following promotional materials:

1.  Journal advertisements (ZN09031, NL1297, NL1329)
2.  Mailed consumer brochure (“Are you a helpless female?”)

We have reviewed these materials and have determined that they are false or misleading for the following reasons:

Misleading Efficacy Claims

The promotional materials are misleading because they do not provide adequate context for efficacy information for Nolvadex, thereby implying greater efficacy than demonstrated by substantial evidence.  For example, the following statements are presented in the mailed consumer brochure and journal advertisements, respectively:

Nolvadex is a medicine that has been used for decades to keep women who have had breast cancer from having a recurrence.  But recently, a landmark study showed that it could also reduce the chance of a first occurrence of breast cancer by as much as 44% in women over 35 who were at high risk.

For the first time, there is a clinically proven way for many women at high risk of developing breast cancer to significantly reduce that risk: Nolvadex Tablets.  The proof? I n a landmark study of women 35 and older at high risk for breast cancer, women who took Nolvadex had 44% fewer breast cancers than women taking sugar pills.

Promoting a “44% reduction in the risk of breast cancer” without additional context is misleading because it overstates the efficacy of Nolvadex in reducing the incidence of breast cancer in women at high risk.  This percentage is not further qualified with the number of cases of breast cancer annually/1000 women who took Nolvadex versus those who took placebo.  Zeneca’s promotional materials do not provide this, or similar, context.

In addition, the mailed consumer brochure is misleading because it does not provide adequate context for the personal risk score calculated from the Gail Model Risk Assessment.  The following statements are presented in this brochure:

Your doctor calculates your personal risk, which estimates your chances of developing breast cancer over the next 5 years.  If you’re 35 or older and your score is 1.7 or higher, you are considered at high risk for developing breast cancer.  And if you’re at high risk, now there’s a new option: Nolvadex Tablets.

Zeneca does not adequately communicate that women who achieve a score of 1.7 or higher will not necessarily develop breast cancer.  In addition, these statements do not adequately convey that a score of 1.7 translates to a 1.7% chance of developing breast cancer in five years; rather, it implies that women with a score of > 1 .7 should take Nolvadex to reduce their chances of developing breast cancer.  Again, Zerieca’s promotional materials are misleading because they do not provide adequate context to allow evaluation of the potential benefits versus the risks of treatment with Nolvadex and they overstate the efficacy of the drug.

Lack of Fair Balance

These advertisements are also misleading because they minimize the severity of adverse effects (AE’s) in high risk women who received Nolvadex for reduction in breast cancer incidence.  As stated in the approved product labeling:

Hot flashes of any severity occurred in 68% of women on placebo and in 80% of women on Nolvadex.  Severe hot flashes occurred in 28% of women on placebo and 45% of women on Nolvadex.  Vaginal discharge occurred in 35% and 55% of women on placebo and Nolvadex, respectively, and was severe in 4.5% and 12.3%, respectively. 

Zeneca undermines the significance of these AE’s in these promotional materials by presenting the following statement:

Women may experience some level of hot flashes and vaginal discharge.

An 80% incidence of hot flashes and a 55% incidence of vaginal discharge is not consistent with the phrase “some level of hot flashes and vaginal discharge,” especially when these severe AE’s occurred at a much higher incidence in women who received Nolvadex as compared to those who received placebo.

Failure to Comply with 314.81(b)(3)(i)

The mailed consumer brochure was not submitted on Form FDA 2253 at the time of initial dissemination, in violation of the post-marketing reporting requirements of the Act.

Requested Actions

Zeneca should immediately cease dissemination of promotional materials that contain these or similar claims.  Zeneca should submit in writing, on or before August 3, 2000, a description of the steps that will be taken to comply with the above request.  Zeneca should also include a list of all similarly violative materials being discontinued, as well as the date of discontinuation.

Zeneca should direct its response to me by facsimile at (301) 594-6771, or by written communication at the Food and Drug Administration; Division of Drug Marketing, Advertising, and Communications, HFD-42; Room 17B-20; 5600 Fishers Lane; Rockville, MD 20857.  DDMAC reminds Zeneca that only written communications are considered official.

In all future correspondence regarding this matter, please refer to MACMIS lD# 9075 and NDA 17-970.

Sincerely,

Jean-Ah Choi, Pharm.D. 
Regulatory Review Officer 
Division of Drug Marketing, 
     Advertising, and Communications

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