NEWS: FDA Safety Labeling Changes: Bextra, Phenergan, Cosmegen

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FDA Safety Labeling Changes: Bextra, Phenergan, Cosmegen

Jan. 26, 2005 ‹ The U.S. Food and Drug Administration (FDA) approved in

November 2004 revisions to safety labeling to advise healthcare

professionals of the following changes: valdecoxib use is contraindicated

for pain management immediately after coronary artery bypass graft surgery,

and valdecoxib may cause serious adverse skin reactions; use of promethazine

HCl tablets and suppositories is contraindicated in pediatric patients

younger than two years, and promethazine HCl is associated with

sometimes-fatal respiratory depression and sleep apnea in pediatric

patients; use of dactinomycin injection is contraindicated in patients with

hypersensitivities to dactinomycin or mannitol, and dactinomycin therapy may

cause delayed gastrointestinal adverse events.

Valdecoxib (Bextra) Contraindicated for Post-CABG Pain

On Nov. 24, the FDA approved revisions to the safety labeling for valdecoxib

(Bextra tablets, made by Pfizer, Inc.) to advise of contraindications and

warnings associated with its use.

Valdecoxib is contraindicated for the management of postoperative pain

immediately after coronary artery bypass graft (CABG) surgery. Results of a

recent study have demonstrated that use of valdecoxib in this setting is

associated with increased risk of cardiovascular and thromboembolic adverse

events (including myocardial infarction, cerebrovascular accident, deep vein

thrombosis, and pulmonary embolism), deep surgical infections, and sternal

wound complications.

The FDA has received reports of serious and sometimes fatal skin reactions

(toxic epidermal necrolysis, s- syndrome, and erythema

multiforme) in patients receiving valdecoxib. The incidence of these

reactions has been higher with use of valdecoxib than with other

cyclooxygenase-2 (COX-2) inhibitors or traditional nonsteroidal

anti-inflammatory drugs (NSAIDs).

The FDA notes that while adverse skin reactions are most likely to occur

within the first two weeks of valdecoxib therapy, they may occur at any

time. Patients with a history of allergic reactions to sulfa may be at

increased risk.

Valdecoxib should be discontinued immediately if skin rash, mucosal lesions,

or other signs of hypersensitivity reaction occur.

Valdecoxib is indicated for the relief of signs and symptoms of

osteoarthritis and adult rheumatoid arthritis, and for the treatment of

primary dysmenorrhea.

Promethazine (Phenergan) May Cause Fatal Pediatric Respiratory Depression,

Apnea

On Nov. 8, the FDA approved revisions to the safety labeling for

promethazine HCl tablets and suppositories (Phenergan, made by Wyeth

Pharmaceuticals, Inc.) to advise of contraindications and warnings

associated with their use in pediatric patients.

Promethazine is contraindicated for use in pediatric patients younger than

two years due to the potential for fatal respiratory depression. The

contraindication is based on postmarketing reports received by the FDA of

respiratory depression and apnea (including fatalities) associated with a

wide range of weight-based promethazine doses in this population.

Because these adverse events are not directly related to individualized

weight-based dosing, promethazine should be administered with caution and at

the lowest effective dose for pediatric patients aged two years and older.

Concurrent administration of other drugs with the potential for respiratory

depression should be avoided.

Promethazine is indicated for use in treating hypersensitivity reactions and

as an antiemetic and/or sedative in various settings. It may also be used as

an adjunct to meperidine or other analgesics for control of postoperative

pain.

Dactinomycin May Cause Delayed Gastrointestinal Adverse Events

On Nov. 30, the FDA approved revisions to the safety labeling for

dactinomycin for injection (Cosmegen, made by Merck & Co., Inc.), advising

of its contraindication in patients with hypersensitivities to its

components and of adverse gastrointestinal events associated with its use.

Dactinomycin injection is contraindicated for use in patients with

hypersensitivity to dactinomycin or mannitol.

Nausea and vomiting may occur early during the first few hours after

administration of dactinomycin injection and can be treated with

antiemetics. Other toxic effects most often occur two to four days after the

end of a therapeutic cycle and may not peak until one to two weeks have

elapsed.

Gastrointestinal adverse effects include anorexia, abdominal pain,

gastrointestinal ulceration, and liver toxicity, including ascites,

hepatomegaly, hepatic veno-occlusive disease associated with intravascular

clotting disorder and multi-organ failure, hepatitis, and liver function

test abnormalities.

Dactinomycin injection is indicated for use with other agents in the

treatment of Wilms' tumor, childhood rhabdomyosarcoma, Ewing's sarcoma, and

metastatic nonseminomatous testicular cancer. It may be used as monotherapy

or with other agents in the treatment of gestational trophoblastic

neoplasias, and as a component of regional perfusion palliative and/or

adjunctive treatment for locally recurring or locoregional solid

malignancies.

Reviewed by D. Vogin, MD

http://www.medscape.com/viewarticle/498181