FDA Safety Labeling Changes: Vistaril, Estraderm, Nolvadex

Yael Waknine

March 02, 2005

March 2, 2005 — The U.S. Food and Drug Administration (FDA) approved in December 2004 revisions to safety labeling to advise healthcare professionals of the following changes: use of hydroxyzine pamoate capsules and oral solution is contraindicated in patients with prior history of hypersensitivity to their components; use of the estradiol transdermal system is associated with risks of dementia, cardiovascular disorders, and breast cancer, and is contraindicated in patients with liver disorder or disease; use of tamoxifen citrate tablets may be associated with an increased risk of uterine malignancies.

Hydroxyzine Pamoate (Vistaril) Contraindicated in Patients With Hypersensitivity to Components

On Dec. 24, the FDA approved revisions to the safety labeling for hydroxyzine pamoate capsules and oral solution (Vistaril, made by Pfizer, Inc.), advising that their use is contraindicated in patients who have demonstrated prior hypersensitivity to the active moiety or components of the products.

Inert components of the capsule include hard gelatin (may contain Yellow 10, Green 3, Yellow 6, Red 33, and other dyes), magnesium stearate, sodium lauryl sulfate, starch, and sucrose.

Inert components of the oral solution include carboxymethylcellulose sodium, lemon flavor, propylene glycol, sorbic acid, and sorbitol solution.

Hydroxyzine pamoate is indicated for the symptomatic relief of anxiety and tension associated with psychoneurosis and as an adjunct in organic disease states in which anxiety is manifested. It is also indicated for the management of pruritus due to allergic conditions and as pre-anesthetic adjunctive therapy for sedation.

Estradiol Transdermal System (Estraderm) Linked to Dementia, Cardiovascular Disorders, Breast Cancer

On Dec. 17, the FDA approved revisions to the safety labeling for estradiol transdermal system (Estraderm, made by Novartis Pharmaceuticals Corp.) to advise of contraindications and warnings associated with its use.

Use of estrogens, including the estradiol patch, is contraindicated in individuals with liver dysfunction or disease.

The FDA also warned of the increased risk of developing probable dementia associated with the use of conjugated estrogen (CE) plus medroxyprogesterone acetate (MPA) therapy compared with placebo in postmenopausal women aged 65 years and older. The FDA notes that it is unknown whether the warning applies to younger postmenopausal women or to those taking estrogen-only therapy.

The warning was based on results of the Women's Health Initiative (WHI) Memory Study, demonstrating that after four years the number of women diagnosed with probable dementia was significantly higher in the CE plus MPA group compared with the placebo group (1.8% vs 0.9%; probable risk, 2.05; absolute risk per 10,000 women-years, 45 vs 22 cases).

Results of the WHI also showed increased risks of myocardial infarction, stroke, invasive breast cancer, pulmonary emboli, and deep vein thrombosis in postmenopausal women (aged 50-79 years) during five years of treatment with CE plus MPA.

Although use of the estradiol transdermal patch was not evaluated in the WHI, the FDA assumes the risks to be similar.

The FDA advises appropriate management of risk factors for arterial vascular disease and/or venous thromboembolism in patients using the estradiol patch. Estrogens should be discontinued in patients who present with papilledema or retinal vascular lesions.

Estradiol transdermal systems are indicated for the treatment of moderate to severe vasomotor symptoms and symptoms of vulvovaginal atrophy associated with menopause. Secondary indications include hypoestrogenism due to hypogonadism, castration, or primary ovarian failure, and the prevention of postmenopausal osteoporosis.

Tamoxifen (Nolvadex) Linked to Risk of Uterine Malignancies

On Dec. 14, the FDA approved revisions to the safety labeling for tamoxifen citrate tablets (Nolvadex, made by AstraZeneca Pharmaceuticals, LP) to warn of the risk of uterine malignancies that may be associated with its use.

The warning was based on results of the Breast Cancer Prevention Trial that demonstrated increased risks of endometrial adenocarcinoma and uterine sarcoma in patients receiving tamoxifen compared with placebo (incidence rates per 1,000 women-years, 2.20 vs 0.71 and 0.17 vs 0.04, respectively).

The FDA recommends that abnormal vaginal bleeding be promptly evaluated in patients receiving tamoxifen or who have a prior history of use. All patients receiving or who have previously received tamoxifen therapy should have regular gynecological examinations and should be advised to promptly report abnormal symptoms such as menstrual irregularities, abnormal vaginal bleeding, changes in discharge, or pelvic pain or pressure.

Tamoxifen is indicated for the treatment of metastatic breast cancer and ductal carcinoma in situ, and for the reduction of breast cancer incidence in women at high risk.

Reviewed by Gary D. Vogin, MD

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