PL Detail-Document #280513 This PL Detail-Document gives subscribers additional insight related to the Recommendations published in PHARMACIST S LETTER / PRESCRIBER S LETTER May 2012 Drugs with Handling Concerns Due to Reproductive Risk Drugs that are considered hazardous can be helpful and even lifesaving for the sickest patients. 1 However, these drugs can pose risks to individuals who are exposed to them in a nontherapeutic manner, such as by inhalation or absorption through the skin in the workplace. 1-3 Hazardous drugs may also cause reproductive toxicities such as increased risk of spontaneous abortion, reduced fertility, and fetal harm. 3 Some drugs such as dutasteride and finasteride only have the potential to pose reproductive risks to exposed individuals, and are not otherwise hazardous. Reproductive toxicities may only be demonstrated when a drug is ingested, and sometimes only in animal studies. The risks of occupational exposure may not be clear. Proper hand hygiene is also key. Ingestion of hazardous drugs in the workplace can occur via the hand to mouth route. 2,4 Keep in mind there are a lack of good data on the reproductive risks of handling hazardous drugs using the currently recommended practices and personal protective equipment. 5 The following chart presents suggestions on drug handling for individuals with reproductive concerns. This chart may not be all-inclusive of drugs with reproductive toxicities or exactly reflective of classifications and policies of various pharmacies and organizations. Refer to your pharmacy s policies, consult with your health care provider, and notify your supervisor for further guidance about drug handling. 2,5 Any individual who handles hazardous drugs should receive proper training. 2,3,6 Hazardous Drugs 7,8 (Listed drugs are hazardous to all individuals, in addition to possible reproductive hazards) Antivirals (some) Chemotherapy and A higher risk of (e.g., cidofovir-u.s. other hazardous handle drugs in original packaging or packaged for delivery to spontaneous abortion and [Vistide], entecavir drugs may not only a patient or patient care unit with gloves. 2,7 Use powder-free birth defects has been [Baraclude], ganciclovir harm an individual chemotherapy gloves. 2,4 Double gloving is recommended. 2 seen in nurses who [Cytovene], ribavirin [e.g., who is exposed, but administer Copegus-U.S., Rebetol-U.S., may also cause birth chemotherapy. 1,2,5 Virazole], valganciclovir defects and increase Pregnant should [Valcyte]) the risk of wear powder-free chemotherapy gloves and an N95 surgical generally avoid direct care spontaneous mask when repackaging hazardous drugs (e.g., placing caps or of patients who are abortion, birth tabs from a bulk bottle into prescription bottle, unit-dosing caps receiving aerosolized defects, and or tabs). 2,4,7 Double gloving is recommended. 2 ribavirin (Virazole). 24,25 Chemotherapy infertility. 2,8,9 Refer to U.S. product labeling for specific recommendations. Some institutions may Continued Continued subcategorize hazardous
(PL Detail-Document #280513: Page 2 of 5) Hazardous Drugs, 7,8 continued (Listed drugs are hazardous to all individuals, in addition to possible reproductive hazards) Immunosuppressants (e.g., azathioprine [e.g., Imuran], everolimus [e.g., Afinitor], mycophenolate [e.g., only manipulate (e.g., crush or split tablets, reconstitute powders, etc) or compound hazardous drugs in a biological safety cabinet (vertical flow hood) with appropriate garb CellCept]) Miscellaneous (e.g., chloramphenicol, sorafenib, sunitinib, thalidomide) (e.g., gloves, gown, mask) as required for ALL individuals handling these drugs. 2,7 Check your pharmacy s policy. requesting an alternate work assignment is reasonable. 2 drugs. High-risk hazardous and low-risk hazardous is an example. This categorization may depend on the risk of exposure and toxicity. For example, oral dosage forms may be considered low-risk and injectable dosage forms high-risk. 7 Drugs with only reproductive toxicity concerns (and WITH specific handling instructions in product labeling) Ambrisentan 9,11 Letairis-U.S., Volibris-Canada Bosentan 10 Tracleer Endothelin receptor antagonists can cause serious birth defects. The manufacturer of bosentan recommends pregnant not handle crushed or broken tabs or liquid suspension. This information is not included in product labeling. Gloves and a mask should be worn when handling these dosage forms. 10 The manufacturer of ambrisentan does not have the same information, but the same precautions are likely prudent considering the similar reproductive toxicities of the drugs. Dutasteride 12-15 Avodart, Jalyn Antiandrogenic effect could feminize male fetus Absorbed across skin Women who are or may become pregnant: do not handle capsules. If contact is made with leaking capsules, wash the area immediately with soap and water. 12-15
(PL Detail-Document #280513: Page 3 of 5) Drugs with only reproductive toxicity concerns (and WITH specific handling instructions in product labeling), continued Finasteride 16-19 Propecia, Proscar Antiandrogenic effect could feminize male fetus Absorbed across skin Women who are or may become pregnant: do not handle crushed or broken tablets. (Finasteride tablets are coated and will prevent contact with the active ingredient during normal handling provided that the tablets have not been broken or crushed.) 16-19 Testosterone, Topical 20-22 Androderm, AndroGel, Axiron (U.S.), Fortesta (U.S.), Testim, others Testosterone may cause fetal harm Pregnant : avoid skin contact with gel application sites in men. If unwashed or unclothed skin to which gel has been applied (or unwashed clothing exposed to testosterone gel) comes in direct contact with the skin of a pregnant woman, wash the general area of contact on the woman with soap and water as soon as possible. (In vitro studies show that residual testosterone is removed from the skin surface by washing with soap and water.) 21,22 Pregnant : avoid exposure to used packets, patches, pumps, etc. 22 A study evaluated dermal exposure in female partners of men using AndroGel. Women had skin contact with the application site for 15 min, two to 12 h after application. Serum testosterone levels doubled over baseline. Transfer was prevented by the wearing of a shirt. 21
(PL Detail-Document #280513: Page 4 of 5) Drugs with only reproductive toxicity concerns (and WITHOUT specific handling instructions in product labeling) Other Pregnancy Category D and X drugs (e.g., ACE inhibitors, angiotensin receptor blockers, misoprostol, statins, estrogen, etc) Reproductive toxicities with Pregnancy Category D and X drugs vary widely. In addition, their toxicities can vary depending on the stage of pregnancy. Check your pharmacy s policy to find out if there are special handling precautions in place for drugs with the potential to cause reproductive toxicity. Practices that generally reduce exposure to drugs include: Category D and X drugs can cause fetal harm when ingested. However, the risks with occupational exposure (other than those already mentioned) may not be known. 5 Frequent handwashing to prevent hand to mouth exposure to drugs. Wearing chemotherapy gloves when handling capsules, tablets, etc. 4 Adding an N95 mask when crushing tablets, splitting tablets, reconstituting powders, etc. 4 Requesting an alternate work assignment. Topical dosage forms increase the risk for exposure compared with oral dosage forms. 7 Coated tabs or caps pose a lower risk for exposure than uncoated tabs or liquids. 1,5,23 Keep drugs that are unitdosed or available in bottles with quantities for dispensing (e.g., isotretinoin, misoprostol) in their original packaging to reduce exposure. Users of this PL Detail-Document are cautioned to use their own professional judgment and consult any other necessary or appropriate sources prior to making clinical judgments based on the content of this document. Our editors have researched the information with input from experts, government agencies, and national organizations. Information and internet links in this article were current as of the date of publication.
(PL Detail-Document #280513: Page 5 of 5) Project Leader in preparation of this PL Detail- Document: Stacy A. Hester, R.Ph., BCPS, Assistant Editor References 1. CDC. Preventing occupational exposures to antineoplastic and other hazardous drugs in health care settings. September 2004. http://www.cdc.gov/niosh/docs/2004-165/pdfs/2004-165.pdf. (Accessed April 16, 2012). 2. American Society of Health-System Pharmacists. ASHP guidelines on handling hazardous drugs. January 12, 2006. http://www.ashp.org/doclibrary/bestpractices/prepg dlhazdrugs.aspx. (Accessed March 20, 2012). 3. Pharmaceutical compounding-sterile preparations. In: The United States Pharmacopeia, 35th rev., and The National Formulary, 30th ed. Rockville, MD: The United States Pharmacopeial Convention, 2012. 4. CDC. Personal protective equipment for health care workers who work with hazardous drugs. October 2008. http://www.cdc.gov/niosh/docs/wpsolutions/2009-106/pdfs/2009-106.pdf. (Accessed April 16, 2012). 5. United States Department of Labor. Controlling Occupational Exposure to Hazardous Drugs. January 1999. http://www.osha.gov/dts/osta/otm/otm_vi/otm_vi_2.ht ml. (Accessed April 16, 2012). 6. Pharmaceutical compounding-nonsterile preparations. In: The United States Pharmacopeia, 35th rev., and The National Formulary, 30th ed. Rockville, MD: The United States Pharmacopeial Convention, 2012. 7. University HealthSystem Consortium. UHC consensus statement: model hazardous drug safety plan for institutions. January 2011. 8. CDC. NIOSH list of antineoplastic and other hazardous drugs in healthcare settings 2010. September 2010. http://www.cdc.gov/niosh/docs/2010-167/pdfs/2010-167.pdf. (Accessed April 13, 2012). 9. Product information for Letairis. Gilead. Foster City, CA 94404. February 2012. 10. Personal communication (written). T. White, Pharm.D. Medical Information Department. Actelion Pharmaceuticals. South San Francisco, CA 94080. April 13, 2012. 11. Product monograph for Volibris. GlaxoSmithKline. Mississauga, ON L5N 6L4. December 2011 12. Product information for Avodart. Research Triangle Park, NC 27709. October 2011. 13. Product information for Jalyn. GlaxoSmithKline. Research Triangle Park, NC 27709. June 2011. 14. Product monograph for Avodart. GlaxoSmithKline. Mississauga, ON L5N 6L4. November 2011. 15. Product monograph for Jalyn. GlaxoSmithKline. Mississauga, ON L5N 6L4. February 2012. 16. Product information for Propecia. Merck. Whitehouse Station, NJ 08889. June 2011. 17. Product information for Proscar. Merck. Whitehouse Station, NJ 08889. January 2012. 18. Product monograph for Propecia. Merck Canada. Kirkland, QC H9H 4M7. November 2011. 19. Product monograph for Proscar. Merck Canada. Kirkland, QC H9H 4M7. November 2011. 20. PL Detail-Document, Secondary Exposure to Topical Hormones. Pharmacist s Letter/Prescriber s Letter. July 2009. 21. Product information for AndroGel. Abbott. North Chicago, IL 60064. December 2011. 22. Product monograph for AndroGel. Abbott. Saint- Laurent, QC H4S 1Z1. January 2011. 23. Conner T. Safe handling of hazardous drugs: risks and practical considerations. November 2010. http://www.proce.com/safehandling_ondemand.html (Accessed April 13, 2012). 24. Product information for Virazole. Valeant. Aliso Viejo, CA 92656. November 2008. 25. Product monograph for Virazole. Valeant Canada. Montreal, QC H4R 2P9. February 2005. Cite this document as follows: PL Detail-Document, Drugs with Handling Concerns Due to Reproductive Risk. Pharmacist s Letter/Prescriber s Letter. May 2012. Evidence and Recommendations You Can Trust 3120 West March Lane, P.O. Box 8190, Stockton, CA 95208 ~ TEL (209) 472-2240 ~ FAX (209) 472-2249 Subscribers to the Letter can get PL Detail-Documents, like this one, on any topic covered in any issue by going to www.pharmacistsletter.com, www.prescribersletter.com, or www.pharmacytechniciansletter.com