FDA Safety Labeling Changes: Celexa, Lexapro,
Premarin, and Others
July 14, 2004 — The U.S. Food and Drug Administration (FDA)
approved revisions in April to drug safety labeling, informing
healthcare professionals of the following changes: citalopram
hydrobromide and escitalopram oxalate adversely interact with
linezolid, 8% amino acid injection can cause aluminum toxicity in
patients with impaired kidney function, and conjugated estrogens,
alone or with medroxyprogesterone, are associated with malignant
Citalopram (Celexa) and Escitalopram (Lexapro) Interact With
On April 20, the FDA approved a revision to the safety labeling
for citalopram hydrobromide and escitalopram oxalate (Celexa and
Lexapro, respectively, made by Forest Laboratories) in tablet and
oral formulations, advising that serotonin syndrome has been
reported in two patients receiving concomitant doses of the
antibiotic linezolid, a reversible nonselective monoamine oxidase
Citalopram and escitalopram are indicated for the treatment of
8% Amino Acid Injection (HepatAmine) May Cause Aluminum
Toxicity in Patients with Impaired Kidney Function
On April 29, the FDA approved revisions to the safety labeling
for 8% amino acid injection (HepatAmine, made by B. Braun), warning
that the product contains aluminum that may reach toxic levels with
prolonged parenteral administration in patients with impaired kidney
Premature neonates are particularly at risk because they have
immature kidneys and require large amounts of calcium and phosphate
solutions that contain aluminum.
The FDA recommends frequent clinical and laboratory monitoring in
The 8% amino acid injection is indicated as a source of
nutritional support to patients with hepatic encephalopathy
requiring parenteral nutrition and who are unable to receive general
purpose amino acid injections.
Conjugated Estrogen Alone (Premarin) or With
Medroxyprogesterone (Prempro, Premphase) Associated With Risk of
On April 20, the FDA approved extensive revisions to the safety
labeling for conjugated estrogen tablets and vaginal cream
(Premarin) and conjugated estrogen/medroxyprogesterone acetate
tablets (Prempro, Premphase), advising of increased health risks
associated with their use. The products are made by Wyeth
The FDA warned that estrogen with or without progestin should not
be used for the prevention of cardiovascular disease.
Use of conjugated estrogen in women with intact uteri is
associated with an increased risk of endometrial cancer, the
greatest risk occurring with prolonged use (15- to 24-fold increased
risk for 5-10 years of use or more) and persisting for at least 8 to
15 years after discontinuation.
Use of conjugated estrogen is also associated with an increased
risk of breast cancer. Results of the Million Women Study in Europe
showed an increased risk of mortality due to breast cancer among
current users of estrogen alone or with progestin compared with
Results of the Women's Health Initiative (WHI) study showed
increased risks of myocardial infarction, stroke, invasive breast
cancer, pulmonary emboli, and deep vein thrombosis in postmenopausal
women aged 50 to 79 years during five years of treatment with
conjugated estrogens (0.625 mg) combined with medroxyprogesterone
acetate (2.5 mg), compared with placebo.
The WHI Memory Study showed an increased risk of probable
dementia in postmenopausal women aged 65 years and older treated
with combined conjugated estrogen and medroxyprogesterone acetate
over four years.
The FDA notes that although other combinations and doses were not
studied in the WHI clinical trials, the risks should be assumed to
be similar. Estrogen with or without progestin should be prescribed
at the lowest effective dose and for the shortest duration
consistent with treatment goals.
The FDA recommends close clinical monitoring of women taking
these products, including diagnostic measures such as endometrial
sampling to rule out malignancies in all cases of undiagnosed
persistent or recurring abnormal vaginal bleeding.
Conjugated estrogen vaginal cream is indicated in the treatment
of atrophic vaginitis and lichen sclerosus et atrophicus of the
vulva (also known as kraurosis vulvae).
Reviewed by Gary D. Vogin, MD
is a freelance writer for Medscape.
Medical News is edited by Deborah Flapan, assistant managing
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