1. BAD THINGS IN SMALL PACKAGES, ANTINEOPLASTIC AND CYTOTOXIC DRUGS Daryl Lance, Pharm D, BCOP, Susan Eisberg

2. INTRODUCTION What is the problem?

3. INTRODUCTION Communication is important.

4. WHAT ARE THESE CHEMICALS AND HOW ARE THEY USED?

5. Bone marrow suppression Hair loss (alopecia) Mucositis (mouth sores)

6. ALKYLATING AGENTS First chemotherapy drug to be produced Alkylation to the DNA base pairs

7. ALKYLATING AGENTS Secondary tumors Mutagenicity Sterility

8. ALKYLATING AGENTS Side effects: –Bone marrow suppression –Nausea and vomiting –Hemorrhagic cystitis –Sterility

9. ALKYLATING AGENTS Cyclophosphamide, Ifosfamide Cisplatin, Carboplatin Dacarbazine, Chlorambucil Busulfan, Chlorozotocin Streptozocin, Carmustine Semustine, Lomustine Melphalan, Mechlorethamine Procarbazine, Gemcitabine

10. ANTIMETABOLITES Inhibition of enzymatic processes False substrates

11. ANTIMETABOLITES This was the second chemotherapy agent to be produced –Antifolates Special applications

12. ANTIMETABOLITES Side effects –Hair loss –Mucositis –Bone marrow suppression

13. ANTIMETABOLITES Azathioprine, Cyclosporin Cytarabine, Floxuridine Fluorouracil, Capcitabine Ganciclovir, Hydroxyurea Mercaptopurine Methotrexate Ribavirin, Thioguanine Fludarabine, Zidovudine

14. ANTI-TUMOR ANTIBIOTICS Intercalation Alkylation

15. ANTI-TUMOR ANTIBIOTICS Highly colored. Important clinically

16. ANTI-TUMOR ANTIBIOTICS Side effects –Bone marrow suppression –Mucositis –Alopecia –Cardiac toxicity –Tissue vesicant agents –Nausea, vomiting

17. ANTI-TUMOR ANTIBIOTICS Doxorubicin, Daunamycin Idamycin, Dactinomycin Mitomycin Plicamycin Bleomycin, Mitoxantrone

18. SPINDLE POISONS AND NATURAL PRODUCTS Natural plant products Microtubule inhibition Mitosis inhibition Asparaginine inhibition

19. SPINDLE POISONS AND NATURAL PRODUCTS Tumor types Special applications

20. SPINDLE POISONS AND NATURAL PRODUCTS Side effects –Alopecia –Bone marrow suppression –Peripheral neuropathy –Vesicants –Diabetes, Coagulopathies

21. SPINDLE POISONS AND NATURAL PRODUCTS Vinca Alkyloids- Vincristine, Vinblastine, Vinorelbine Podophyllotoxins- etoposide, teniposide Taxanes- paclitaxol (taxol), Docetaxel Enzymes- L-asparaginase

22. HEALTH CARE RISK Risks to health care workers- Difficulties of relative risk –measurement of exposure –Long latent period –Identification of risk groups

23. BIOLOGIC RISKS WITH EXPOSURE Reproductive outcomes Chromosomal changes Urine mutagenicity Acute symptoms

24. LITERATURE DOCUMENTATION Study by Falck et al –Nurses were found to have mutagenic substances in their urine

25. LITERATURE DOCUMENTATION Study by Hemminki et al. –Spontaneous abortions and malformations in the offspring –of nurses exposed to anaesthetic gases, cytostatic drugs –and other potential hazards in hospitals based on –registerd information of outcome.

26. LITERATURE DOCUMENTATION Study by Kilmodin-Hedman, et al, Urine mutagenicity –Study comparing 2 groups one group utilizing personal protection one group not using personal protection

27. LITERATURE DOCUMENTATION Study by Selevan, et al. –Study of occupational exposure to antineoplastic drugs –and fetal loss in nurses.

28. LITERATURE DOCUMENTATION Study by Benhaamou, et al. –Mutagenicity in urine from nurses handling cytostatic agents

29. LITERATURE DOCUMENTATION Study by Conner, et al –Study of surface contamination with antineoplastic –agents in six cancer treatment centers in Canada –and the United States.

30. CHEMO/CYTOTOXIC EXPOSURE Absorption Inhalation Ingestion

31. ABSORPTION Can happen during preparation, administration or disposal of equipment OR while handling contaminated excreta or body fluids. Know that body fluids and excreta can remain contaminated up to 48 hours after the last dose.

32. ABSORPTION Prevention Measures Through skin, eyes, mucous membranes –Wear chemo gloves –Wash hands before & after gloves are used –If skin contact, wash ASAP –If eye contact, flush with normal saline liberally

33. INHALATION Inhalation of aerosols can be very subtle and can occur without awareness from: –opening vials of the medication –clipping needles –expelling air from a syringe –splash effect when discarding contaminated excreta or body fluids into the toilet or measuring container.

34. INHALATION Prevention Measures Use gauze pads when breaking vials Don’t clip or remove needles or re-cap, dispose as a whole in the sharps containers Use masks and/or goggles when there is a chance of creating an aerosol Empty waste products into the toilet close to the water to minimize splashing

35. INGESTION Eating, drinking, chewing gum, smoking or applying cosmetics or contact lenses may increase possible exposure

36. INGESTION Prevention Measures Keep all foods and utensils away from drugs Wash hands before and after contact with drug Avoid hand to eye or hand to mouth contact

37. GENERAL PRECAUTIONS Place waste in appropriate containers “Chemotherapy Precautions” should begin when chemotherapy is initiated and continue for 48 hrs. after completion. Staff should wear special chemotherapy gloves and gown whenever handling or administering IV, IM or subcutaneous AND whenever emptying body fluids of patients who are under “Chemo Precautions”

38. OSHA GUIDELINES Basics of the guidelines - Handling CD’s –Drug Preparation –Drug Administration –Caring for Patients –Waste Disposal –Spills –Medical Surveillance –Storage & Transport –Training & Information

39. OSHA GUIDELINES Basics of the guidelines - Handling CD’s –Drug Preparation –Drug Administration –Caring for Patients –Waste Disposal –Spills –Medical Surveillance –Storage & Transport –Training & Information

40. OSHA GUIDELINES Basics of the guidelines - Handling CD’s –Drug Preparation –Drug Administration –Caring for Patients –Waste Disposal –Spills –Medical Surveillance –Storage & Transport –Training & Information

41. OSHA GUIDELINES Basics of the guidelines - Handling CD’s –Drug Preparation –Drug Administration –Caring for Patients –Waste Disposal –Spills –Medical Surveillance –Storage & Transport –Training & Information

42. OSHA GUIDELINES Basics of the guidelines - Handling CD’s –Drug Preparation –Drug Administration –Caring for Patients –Waste Disposal –Spills –Medical Surveillance –Storage & Transport –Training & Information

43. OSHA GUIDELINES Basics of the guidelines - Handling CD’s –Drug Preparation –Drug Administration –Caring for Patients –Waste Disposal –Spills –Medical Surveillance –Storage & Transport –Training & Information

44. OSHA GUIDELINES Basics of the guidelines - Handling CD’s –Drug Preparation –Drug Administration –Caring for Patients –Waste Disposal –Spills –Medical Surveillance –Storage & Transport –Training & Information

45. OSHA GUIDELINES Website and OSHA information –www.osha.gov

46. EXPOSURE PREVENTION Having A Written Plan Standard Operating Procedures Criteria to determine and implement control measures –Engineering controls –PPE –Work Practices Requirement that protective equipment (i.e. ventilation) functions properly

47. Having a Written Plan Information & Training Medical Surveillance Designation of Responsible Person for Program Designation of handling area Use of BSC’s Procedures for safe removal of contaminated waste Decontamination Procedures

48. CHEMO WASTE Bulk Waste (i.e.-unadministered doses) should be disposed of as hazardous waste and picked up by licensed waste hauler. Trace Waste (empty IV bags, syringes, etc.) should be disposed of in containers specially marked for chemotherapy waste to be incinerated.

49. SPILL PREVENTION Staff education Handling techniques –Storage –Transport –Administration –Caring for Patients

50. SPILLS, UNAVOIDABLE, SO HOW DO YOU CLEAN THEM UP? Steps in clean up Who to contact The spill kit and its contents Personnel protection kits

51. SPILLS, UNAVOIDABLE, SO HOW DO YOU CLEAN THEM UP? Getting dirty (or how to avoid getting dirty!) Demonstration

52. STEPS IN CLEANUP What to do immediately –Control Traffic –Rinse exposed body parts –Send someone for spill kit –Mark spill with caution sign Containing the spill –Place spill pillows to prevent spread –Place absorbent towel over spill without touching spill

53. STEPS IN CLEANUP Clean –Put on PPE (gown, gloves, mask and goggles) –Pick up towel and pillows and place in chemo waste container –Sweep any glass fragments with scoop and brush - place in chemo waste container –Wash all surfaces, including furniture –Absorb rinse water with 2nd towel and place in chemo waste container –If on carpet, must be extracted

54. STEPS IN CLEANUP Follow Up –Immediately Wash hands and all exposed skin areas with soap and water –Notify EVS for further clean-up with detergent and rinse water –Notify Pharmacy and Safety Department of spill –Order new spill kit

55. STEPS IN CLEANUP Document –On Incident Report: Date, time, location, amount of spill and drug involved Area of body, personnel involved and action taken Notification of Pharmacy and Safety Office –On Patient’s Chart Amount of spill and the drug MD notified

56. MEDICAL SURVEILLANCE Types of questions How frequent to survey? Who keeps these records? Where do you report the records?

57. SUMMARY AND QUESTIONS What we said What you missed What else do you want to know.