The Institute for Safe Medication Practices (ISMP) is calling for the FDA to examine the product labeling of promethazine (PHENERGAN) and consider eliminating the IV route of administration.

Promethazine is available in oral, rectal, and injectable forms and possesses antihistamine, sedative, anti-motion sickness, and antiemetic effects.

Deep injection into large muscle is the preferred route of administration, but many hospitals give the drug by slow IV push, a practice that is also supported by the product labeling. However, the drug is known to be highly caustic to blood vessels, and can damage veins and surrounding tissue when not administered properly.

A growing number of error reports involving IV promethazine administration and serious post-injection tissue damage have been submitted to ISMP, the United States Pharmacopeia, FDA, and the Pennsylvania Patient Safety Reporting System.

Errors reported on by the media include a 2005 incident where a 19-year-old woman had to have fingers amputated after damage to blood vessels in her hand, and a 2004 incident where a professional guitar player suffered progressive circulatory problems and gangrene that necessitated amputation of her arm in stages.

Although the promethazine package insert does include some safety recommendations, ISMP believes that the long-standing hazards surrounding administration of the drug by IV require even further action on the part of healthcare providers, the Food and Drug Administration (FDA), and manufacturers.

In addition to the manufacturer recommendations, ISMP recommends the following strategies to help prevent tissue damage when giving IV promethazine.  

Limit concentration. Stock only 25 mg/mL of the drug, since it is the highest concentration that should be given IV.
Limit the dose. Consider 6.25 to 12.5 mg of promethazine as the starting IV dose, especially for elderly patients, since hospitals have reported that these smaller doses are effective.
Dilute the drug. Require further dilution of the 25 mg/mL strength to reduce caustic effects and enable slow administration. Leakage into surrounding tissue also can be recognized more quickly when promethazine is diluted than if the drug is given in a smaller volume.
Use large patient veins. Give the medication only through a large-bore vein, preferably a central venous access vein, and never through the hand or wrist. Check patency of the access site before administration; note that aspiration of dark blood does not indicate proper placement, since blood can discolor upon contact with the drug.
Inject into the furthest port. Administer IV promethazine through a running IV line at the port furthest from the patient's vein.
Administer slowly. Consider requiring IV administration of promethazine over 10-15 minutes.
Educate patients. Before administration of the drug, tell patients to let you know immediately if burning or pain occurs during or after the injection.
Create alerts. Build an alert to appear on computer-generated medication administration records (MARs), electronic MARs, and automated dispensing cabinet screens for nurses to view each time they access and administer promethazine, reminding them that the drug should be diluted and administered slowly through an IV.
Use alternatives. Consider safer alternatives to IV promethazine. For example, 5-hydroxytryptamine3 receptor antagonists may be used for both prophylaxis and as a rescue antiemetic.

ISMP is a nonprofit organization that works closely with health care practitioners, consumers, hospitals, regulatory agencies and professional organizations to provide education about preventing medication errors. ISMP is recognized as the premier international resource in all matters pertaining to safe medication practices in healthcare organizations.