Questions and Answers about FDA's Enforcement Action Regarding Unapproved Topical Drug Products Containing Papain
FDA has developed these questions and answers to help consumers, health care practitioners, and the general public understand FDA's actions regarding unapproved topical drug products containing papain. This document is not intended to be used, and cannot be used, to determine whether a particular product is covered by the action that is the subject of this document or to determine how to comply with the law and FDA policies regarding topical drug products containing papain.
1. What action is FDA taking concerning topical drug products containing papain?
The U.S. Food and Drug Administration (FDA) has ordered companies to stop marketing unapproved drug products that contain papain in a topical dosage form. Under today's notice firms marketing any unapproved topical papain products must stop manufacturing these products by November 24, 2008. Companies or others engaged in shipping these products must stop shipping them by by January 21, 2009. After these dates, all topical products containing papain must have FDA approval to be manufactured or shipped interstate.
2. What is papain?
Papain is a protein-cleaving enzyme derived from papaya fruit (Carica papaya) and certain other plants. Topical drug products containing papain are used for the removal of dead or contaminated tissue in acute and chronic lesions, such as diabetic ulcers, pressure ulcers, varicose ulcers, and traumatic infected wounds. These products combine papain with other active ingredients, such as urea, chlorophyllin copper complex, and copper sodium chlorophyllin, which are intended to promote removal of unhealthy skin tissue, control local inflammation, reduce wound odors, and rehydrate skin.
3. Why is FDA taking this action?
Topical drug products containing papain have historically been marketed without approval; there are no approved topical drug products containing papain. FDA is taking this action because adverse events with use of topical papain drug products reported to the agency raise serious safety concerns regarding these products. These drugs can produce harmful or near fatal effects including hypersensitivity resulting in anaphylactic reactions. Such cases have required emergency rooms visits, some requiring treatment with epinephrine. Hypersensitivity manifestations have also resulted in cardiovascular symptoms such as hypotension (low blood pressure) and tachycardia (rapid heart rate). Additionally, reports in the medical literature suggest that patients who are allergic to latex may also be allergic to papaya, the source of papain. Furthermore, the effectiveness of these products is not supported by scientifically sound studies in the medical literature.
4. What are the names of these products?
Most papain-containing drugs are marketed under trade names. These include Accuzyme, Allanfil, Allanzyme, Ethezyme, Gladase, Kovia, Panafil, Pap Urea, and Ziox Some are marketed under the names of the active ingredients, for instance papain-urea ointment. There are approximately 35 unapproved topical products containing papain on the market.
5. Will drug products containing papain remain on the market?
This action affects all topical products containing papain because no product currently has FDA approval. Under today's action, previously manufactured unapproved topical papain products may still be found on pharmacy shelves for a short period of time. Consumers should talk to their health care provider about whether or not to use an unapproved topical papain product.
6. What are the alternatives for consumers currently using topical drug products containing papain?
In addition to standard medical care of wounds and ulcers, which involves management of wound infection, wound closure, nutritional support, and pain control, there are approved topical products which are effective for care of many types of wounds, such as Regranex gel, which is indicated for the treatment of diabetic foot ulcers; and Santyl ointment, which is indicated for the debridement of chronical dermal ulcers and severely burned areas. Consumers should consult a healthcare professional for detailed guidance on other treatment options that are right for them.
Federal Register Notice (PDF)