02-17-2011] The U.S. Food and Drug Administration (FDA) is warning the public that injectable terbutaline should not be used in pregnant women for prevention or prolonged treatment (beyond 48-72 hours) of preterm labor in either the hospital or outpatient setting because of the potential for serious maternal heart problems and death. The agency is requiring the addition of a Boxed Warning and Contraindication to the terbutaline injection label to warn against this use. In addition, oral terbutaline should not be used for prevention or any treatment of preterm labor because it has not been shown to be effective and has similar safety concerns. The agency is requiring the addition of a Boxed Warning and Contraindication to the terbutaline tablet label to warn against this use.
Terbutaline is approved to prevent and treat bronchospasm (narrowing of airways) associated with asthma, bronchitis, and emphysema. The drug is sometimes used off-label (an unapproved use) for acute obstetric uses, including treating preterm labor and treating uterine hyperstimulation. Terbutaline has also been used off-label over longer periods of time in an attempt to prevent recurrent preterm labor.
Although it may be clinically deemed appropriate based on the healthcare professional's judgment to administer terbutaline by injection in urgent and individual obstetrical situations in a hospital setting, the prolonged use of this drug to prevent recurrent preterm labor can result in maternal heart problems and death. Terbutaline should not be used in the outpatient or home setting.
The decision to require the addition of a Boxed Warning and Contraindication is based on new safety information received and reviewed by the FDA. Specifically, FDA has reviewed postmarketing safety reports of terbutaline used for obstetrical indications (see Data Summary below), as well as data from the medical literature.1-6 These label changes are consistent with statements from the American College of Obstetricians and Gynecologists (ACOG).6
Additional Information for Patients
Be aware that serious side effects, including maternal heart problems and death, have been reported after prolonged use of terbutaline to manage preterm labor.
There are serious situations where a healthcare professional may decide that the short-term use of injectable terbutaline in the hospital setting may benefit a pregnant woman.
Oral terbutaline should not be used either to treat preterm labor or prevent recurrent preterm labor.
If you are taking terbutaline for another medical condition (e.g., asthma), talk to your healthcare professional if you are pregnant or become pregnant to determine whether terbutaline is still right for you.
FDA encourages patients to talk to their healthcare professional if they have concerns about any treatment they are receiving.
Report any side effects from the use of oral or injectable terbutaline to the FDA MedWatch program, using the information in the "Contact Us" box at the bottom of the page.
Additional Information for Healthcare Professionals
Be aware that death and serious adverse reactions, including increased heart rate, transient hyperglycemia, hypokalemia, cardiac arrhythmias, pulmonary edema, and myocardial ischemia have been reported after prolonged administration of oral or injectable terbutaline to pregnant women.
Treatment with terbutaline administered by injection or by continuous infusion pump should not be used beyond 48 to 72 hours. In particular, injectable terbutaline should not be used in the outpatient or home setting.
There are certain obstetrical conditions where the healthcare professional may decide that the benefit of terbutaline injection for an individual patient in a hospital setting clearly outweighs the risk.
Oral terbutaline is contraindicated for the treatment or prevention of preterm labor.
Report adverse events involving terbutaline to the FDA MedWatch program using the information in the "Contact Us" box at the bottom of this page.
Data Summary
In November 1997, FDA issued a Dear Colleague letter to notify healthcare professionals about concerns regarding the safety of long-term subcutaneous administration of terbutaline. The Precautions section of the labeling was revised to warn about serious adverse reactions, including cardiovascular adverse events that may occur after administration of terbutaline to women in labor.
Publications in the medical literature have reported a lack of safety and efficacy of terbutaline for the treatment of recurrent preterm labor.2-5 Despite labeling changes, FDA's communication to the public, and professional association recommendations, prolonged use of terbutaline continues, with serious and sometimes fatal consequences.
FDA reviewed postmarketing reports of maternal death and serious cardiovascular adverse events submitted to the Adverse Event Reporting System (AERS) associated with obstetric use of terbutaline.
A search of AERS identified 16 maternal deaths that were reported since initial marketing of the drug in 1976 until 2009. Three of the 16 cases reported outpatient use of terbutaline administered by a subcutaneous pump, while nine cases reported use of oral terbutaline alone or in addition to subcutaneous or intravenous terbutaline. Of these nine cases, two reported use of oral terbutaline on an outpatient basis and seven cases involved inpatient use of oral terbutaline. The routes of administration in the remaining four cases were subcutaneous, intravenous, or unknown.
FDA identified 12 maternal cases of serious cardiovascular events associated with use of terbutaline that were reported to AERS between January 1, 1998 (after FDA issued the Dear Colleague letter) and July 2009. These events included cardiac arrhythmias, myocardial infarction, pulmonary edema, hypertension, and tachycardia. Three of the 12 cases reported use of the terbutaline administered by subcutaneous pump. Five cases involved use of oral terbutaline alone or in addition to subcutaneous terbutaline. Of these five cases, three cases involved use of oral terbutaline on an outpatient basis and two cases involved inpatient use of oral terbutaline.
In summary, based on this information, FDA has concluded that the risk of serious adverse events outweighs any potential benefit to pregnant women receiving prolonged treatment with terbutaline injection (beyond 48-72 hours), or acute or prolonged treatment with oral terbutaline. FDA is requiring the addition of a new Boxed Warning and Contraindication to the terbutaline drug labels to warn healthcare professionals about these risks.
References
1. National Asthma Education and Prevention Program (NAEPP). Working Group Report on Managing Asthma During Pregnancy: Recommendations for Pharmacologic Treatment—Update 2004. NIH Publication No. 05-5236. Bethesda, MD: U.S. Department of Health and Human Services; National Institutes of Health; National Heart, Lung, and Blood Institute, 2004. Available from: http://www.nhlbi.nih.gov/health/prof/lung/asthma/astpreg/astpreg_full.pdf 1. Accessed November 19, 2010.
2. Wenstrom KD, Weiner CP, Merrill D, et al. A placebo-controlled randomized trial of the terbutaline pump for prevention of preterm delivery. Am J Perinatol. 1997;14:87-91.
3. Guinn DA, Goepfert AR, Owen J, et al. Terbutaline pump maintenance therapy for prevention of preterm delivery: a double-blind trial. Am J Obstet Gynecol. 1998;179:874-878.
4. Sanchez-Ramos L, Kaunitz AM, Gaudier FL, et al. Efficacy of maintenance therapy after acute tocolysis: a meta-analysis. Am J Obstet Gynecol. 1999;181:484-490.
5. Berkman ND, Thorp JM, Lohr KN, et al. Tocolytic treatment for the management of preterm labor: a review of the evidence. Am J Obstet Gynecol. 2003;188:1648-1659.
6. American College of Obstetricians and Gynecologists (ACOG). ACOG Practice Bulletin. Clinical management guidelines for obstetrician-gynecologist. No. 43. Management of preterm labor. Obstet Gynecol. 2003;101:1039-1047.
Related Information
FDA Response to Citizen Petition on Terbutaline (PDF - 151KB)2
2/17/2011
FDA warns against certain uses of asthma drug terbutaline for preterm labor3
Press Release - 2/17/2011
Terbutaline Information4
NDA Terbutaline Safety Labeling Change Letter (Injection) (PDF - 75KB)5
NDA Terbutaline Safety Labeling Change Letter (Oral) (PDF - 72KB)6
ANDA Terbutaline Safety Labeling Change Letter (Oral) (PDF - 50KB)7
ANDA Terbutaline Safety Labeling Change Letter (Injection) (PDF - 41KB)8
FDA Drug Safety Podcast for Healthcare Professionals: New warnings against use of terbutaline to treat preterm labor9
-
Contact Us
· Report a Serious Problem
1-800-332-1088
1-800-FDA-0178 Fax
MedWatch Online10
Regular Mail: Use postage-paid FDA Form 350011
Mail to: MedWatch 5600 Fishers Lane
Rockville , MD 20857
-
No comments:
Post a Comment