FDA Safety Changes: Catapres-TTS, Noroxin, and Synarel

August 23, 2006 — The US Food and Drug Administration (FDA) has approved safety labeling revisions to advise that use of clonidine patches during magnetic resonance imaging may cause skin burns; concomitant use of nonsteroidal anti-inflammatory drugs and quinolones such as norfloxacin may be linked to an increased risk for convulsive seizures; and use of nafarelin nasal spray during pregnancy is contraindicated.
Use of Clonidine Patch (Catapres-TTS) During MRI Procedures May Lead to Burns

On April 13, the FDA approved safety labeling revisions for clonidine 0.1-, 0.2-, and 0.3-mg transdermal therapeutic system (Catapres-TTS 1, 2, and 3, made by Boehringer Ingelheim Pharmaceuticals, Inc) to warn of the risk for skin burns associated with their use during magnetic resonance imaging (MRI) procedures.

The FDA has received several reports of skin burns at the patch site in patients wearing an aluminized transdermal system during MRI scanning. Because the clonidine patch contains aluminum, its removal prior to the procedure is recommended.

Clonidine transdermal systems are indicated for use alone or with other agents in the treatment of hypertension.
Concomitant Use of NSAIDs With Norfloxacin (Noroxin) May Increase Seizure Risk

On May 16, the FDA approved safety labeling revisions for norfloxacin (Noroxin tablets, made by Merck and Co, Inc) to advise caution with concomitant use of nonsteroidal anti-inflammatory drugs (NSAIDs).

According to the FDA, concurrent administration of NSAIDs, such as ibuprofen and naproxen, with a quinolone, such as norfloxacin, may increase the risk for central nervous system stimulation and convulsive seizures.

Norfloxacin is indicated for the treatment of adults with urinary tract infections, sexually transmitted diseases, and prostatitis caused by susceptible strains of designated microorganisms.
Nafarelin Acetate Nasal Spray (Synarel) Contraindicated in Pregnancy

On April 12, the FDA approved safety labeling revisions for nafarelin acetate nasal solution (Synarel, made by Pfizer, Inc) to include warnings related to a new indication that allows its use for the management of endometriosis (including pain relief and lesion reduction) in women aged 18 years and older; the maximum duration of therapy is 6 months.

The recommended daily dose of nafarelin for endometriosis is 1 spray (200 µg) into one nostril in the morning and another 200-µg spray into the other nostril in the evening. Treatment should be initiated between days 2 and 4 of the menstrual cycle.

The FDA warned that because safe use of nafarelin during pregnancy has not been established clinically, pregnancy must be ruled out prior to initiation of treatment.

The warning was based on data from animal studies, showing that administration of nafarelin to pregnant rats during fetal organogenesis yielded major fetal abnormalities, dose-related increases in fetal mortality, and dose-related decreases in fetal weight. According to the FDA, these effects are expected consequences of nafarelin-related hormonal changes.

The FDA notes that despite nafarelin's inhibitory effects on ovulation and menstruation, contraception is not ensured, particularly when successive doses are missed. Patients should be counseled regarding use of nonhormonal contraceptives during therapy; those who conceive must discontinue treatment and be apprised of potential risks to the fetus.

As with other drugs that stimulate the release of gonadotropins or induce ovulation, ovarian cysts may occur during the first 2 months of nafarelin therapy. Many, but not all, of these events have been reported in women with polycystic ovarian disease. Although spontaneous resolution of the enlargements generally occurs within 4 to 6 weeks of treatment, some cases may require discontinuation of therapy and/or surgical intervention.

Gonadotropin-releasing hormone agonists such as nafarelin have also been linked to rare postmarketing reports of pituitary apoplexy secondary to infarction of the gland. A majority of these cases yielded a diagnosis of pituitary adenoma, mainly occurring within 2 weeks of the first nafarelin dose and some within the first hour. Symptoms included sudden headache, vomiting, visual changes, ophthalmoplegia, altered mental status, and sometimes cardiovascular collapse.

Nafarelin acetate nasal solution was approved previously for the treatment of central precocious puberty (also known as gonadotropin-dependent precocious puberty) in children of both sexes.

http://www.fda.gov/medwatch/safety/2006/apr06.htm

http://www.fda.gov/medwatch/safety/2006/may06.htm
Learning Objectives for This Educational Activity
Upon completion of this activity, participants will be able to:

* Describe the potential for burns in patients wearing clonidine patches during magnetic resonance image scanning.
* Identify the potential for convulsive seizures in patients receiving nonsteroidal anti-inflammatory drugs and norfloxacin tablets.
* Describe the appropriate use of nafarelin nasal spray for the treatment of endometriosis.

Pearls for Practice

* As with other aluminized transdermal systems, use of clonidine patches during magnetic resonance imaging for patients with hypertension may cause local burns. Patches should be removed prior to the procedure.
* Concurrent use of nonsteroidal anti-inflammatory drugs with norfloxacin or other quinolones may increase the risk for central nervous stimulation and convulsive seizures in adult patients with urinary tract infections, sexually transmitted diseases, and prostatitis caused by susceptible strains of designated microorganisms. Caution is advised when prescribing this drug combination.
* Because its safety has not been established, use of nafarelin therapy for endometriosis is contraindicated in women who are or may become pregnant. Pregnancy should be ruled out prior to initiation of therapy. Patients should be counseled regarding use of nonhormonal contraceptives during therapy; those who conceive must discontinue treatment and be apprised of potential risks to the fetus. In animal studies, nafarelin use during organogenesis was linked to major fetal abnormalities, dose-related increases in fetal mortality, and dose-related decreases in fetal weight. The FDA also warned of the risk for ovarian cysts and postmarketing reports of pituitary apoplexy related to nafarelin use.

FDA Safety Changes: Catapres-TTS, Noroxin, and Synarel
http://www.medscape.com/viewarticle/543557