Redesign of Cisplatin Packaging Could Signal New Era of Safer Medication Packaging

If all pharmaceutical and medical device manufacturers used error prevention analysis (EPA) - a trouble-shooting process introduced to the health care community by ISMP and now encouraged by the US Food and Drug Administration (ISMP Medication Safety Alert!, Oct 9, 1996) - they would save money and lives. For pharmaceutical products, the method examines how and where the item might be misused. Consideration is given to product nomenclature, labeling, packaging, user instructions and practice-related issues. When failures are likely and are predicted to have serious consequences, the item is redesigned to make errors less likely or inconsequential. Since practitioners are familiar with how the products will be used in actual practice, companies should involve them in EPA. The process, also known as failure mode and effect analysis (FMEA), has been of benefit in preventing accidents in other industries and is expected to have a similar effect in health care.

Although error potential analysis should be done before a new product is launched, it can also address product-related medication errors should they arise after a drug is marketed. That is exactly what Bristol-Myers Squibb Oncology has done in the case of Platinol-AQ (cisplatin injection). Since its launch in the 1980s, the drug has occasionally been associated with accidental overdoses when daily doses are confused with the total dose for a course of therapy. The drug has also been confused with Paraplatin (carboplatin). Doses appropriate for carboplatin usually exceed the maximum dose of cisplatin. Severe toxicity and death has been associated with accidental cisplatin overdose.

As a result of the ongoing error reports, the company decided to utilize EPA to consider what, if anything, needed to be done to prevent medication errors. In conjunction with ISMP, an advisory panel of oncology specialists in pharmacy, medicine and nursing was appointed to conduct the analysis. Recognized problems were discussed. Labeling and packaging changes were proposed, accepted by the company, and later approved by FDA. The new package helps prevent inadvertent confusion with carboplatin and potential overdose by encouraging health professionals to verify, clarify and certify that patients receive the correct platinum-containing product at the correct dose. The following changes were made:

• The generic name is depicted using bold, upper case, red characters for the letters "CIS" in cisplatin to help differentiate it from carboplatin

• A red STOP! sign warns people to stop and verify the drug name and dose

• A boxed warning notes that cisplatin doses greater than 100 mg/m2 once every 3 to 4 weeks are rarely used and that the package insert should be consulted for further information

• Information is on more than one box flap. No matter how the product is oriented on the shelf, the warnings can be seen

• Lyophilized cisplatin was removed from market. Only PlatinolO- AQ, a solubilized product remains. This helps differentiate cisplatin from carboplatin, available only in powder form as a lyophilized product

• Vial seals and closures call attention to the maximum dose of cisplatin

• Cisplatin safety stickers are included in the box to certify that cisplatin has been prepared at the proper dosage

• An extensive advertising campaign is being conducted to educate health professionals about the changes and proper drug dose

ISMP congratulates Bristol-Myers Squibb Oncology for their actions. Practitioners should welcome the changes and expect that other companies will begin using similar processes - before and after product launch - to help assure patient safety.