Procedures for Working with MPTP (1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine) and MPTP Treated Animals I. INTRODUCTION MPTP (1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine) is a neurotoxin used to induce Parkinsonism symptoms in experimental models of Parkinson’s Disease (PD). MPTP can produce irreversible neurological damage indistinguishable from PD in humans and animals. The inappropriate handling of MPTP may result in exposure and irreversible neurological damage to research staff. MPTP is lipophilic which freely and rapidly crosses the blood-brain barrier. It is metabolized to MPDP+ which is oxidized to the active metabolite MPP+. MPP+ is the active metabolite that results in neuron cell death. Excretion of unmetabolized MPTP occurs mainly during first day post injection while MPTP metabolites are excreted up to four days post injection. Excretion is mainly in the urine; some has been found in the bile. MPTP metabolites in urine are expected to be ionized and not volatile and be absorbed by the bedding. Exposure to staff may occur via needle sticks, aerosolized droplets, skin exposure, or inhalation of aerosols from MPTP-contaminated bedding. Exposure potential is greatest during preparation, administration, and when handling the animal bedding during the first four days after administration. The purpose of this Standard Operating Procedure (SOP) is to define the safe work practices and appropriate medical management for staff working with MPTP in your research laboratory. A lab-specific SOP must be approved by EH&S prior to Institutional Animal Care and Use Committee (IACUC) approval. For questions or assistance in completing the SOP that is specific for your laboratory, contact EH&S at 206-221-7770. UW MPTP SOP Developed by: Environmental Health and Safety Department Department of Comparative Medicine Office of Animal Welfare Rev. 07/2005, 03/2008, 05/2010, 11/2013 Page 1 of 21 II. PRIOR TO BEGINNING WORK WITH MPTP (All of the following procedures are required for employees who plan to work with MPTP or enter MPTP work areas up to four days post administration and after first cage change) A. Medical Management: 1. Prior to initiating work with MPTP, the Principal Investigator (PI), , and his/her staff must contact the Employee Health Center (EHC) -UW Campus (UWC) at 206-685-1026 to schedule an appointment for evaluation and to receive the post-exposure prophylaxis (PEP) of Selegiline hydrochloride. The EHC-UWC will prescribe the Selegiline if indicated and there are no contraindications. The EHC MPTP handout is attached in Appendix 1. 2. Selegiline is obtained prior to beginning work with MPTP. Selegiline must be immediately available for use in room in case of exposure. It must be kept in the white capped container labeled “FOR MPTP USE ONLY.” Each staff person working with MPTP must have a medical clearance and prescription. The container must be regularly checked to ensure it is in its proper place and the use date has not expired. If expired, contact the EHCUWC (206-685-1026) for collection or instructions for proper disposal. 3. The PI, , must send all personnel who intend to work with MPTP to the EHC-UWC prior to beginning work and annually thereafter for evaluation and determination of their ability to successfully take Selegiline. B. Respiratory Protection: Respirators are required when working with MPTPtreated animals. You MUST be enrolled the University’s Respiratory Protection Program prior to wearing a respirator. The PI must complete a Respirator Request to initiate the process of respirator medical clearance, training and fit testing: http://www.ehs.washington.edu/ohsresp/index.shtm#supervisors. C. Laboratory Set-up: 1. Order PRE-WEIGHED injectable form MPTP from the manufacturer. MPTP must be purchased in hydrochloride or tartrate salt form rather than as a free base. The chemical must be stored in a secondary container in a lock-box in or adjacent to the fume hood. Only people who work with MPTP will have the key to the lock-box. Post Appendix 2 on the fume hood. 2. MPTP must be entered into the chemical inventory (MyChem) system for all laboratories and rooms where the chemical will be stored. 3. The protocol / procedures for new PIs and research staff who have not worked with MPTP in the past should be peer reviewed by another PI familiar with handling highly toxic chemicals. 4. It is very desirable to practice procedures using a surrogate before handling MPTP to ensure all necessary equipment is available. UW MPTP SOP Rev. 07/2005, 03/2008, 05/2010, 11/2013 Page 2 of 21 5. The PI or laboratory manager must identify, in writing, specific individuals authorized to handle MPTP and those who will be handling MPTP-treated animals within four days post treatment. 6. Check for proper operation of the eyewash and fume hood prior to handling MPTP. 7. Establish procedures for make-up of 1% bleach disinfectant solution on a daily basis. 8. Ensure receptacles and procedures for correct waste disposal (including hazardous waste and incineration waste) are in place prior to initiation of work. D. Employee Training and Notification: 1. The PI, , must ensure his/her staff are trained on this SOP, review the MPTP Material Safety Data Sheet / Safety Data Sheet (MSDS/SDS), the hazards of MPTP, and the proper use of equipment (syringes, fume hood, emergency eyewash, etc.) and personal protective equipment (PPE) prior to beginning work. This training must be documented in Appendix 4. For assistance, contact EH&S at 206-221-7770. 2. The following EH&S training must be taken and documented prior to beginning work: a. Online fume-hood training b. Managing laboratory chemicals c. Respirator training and fit testing E. III. EH&S Notification: Notify EH&S (206-221-7770) one week prior to beginning initial work for review of the final SOP and to check that training and pre-work actions have been completed. After the initial EH&S SOP approval, mock-work using surrogate materials or the first experiment may be observed by EH&S staff to evaluate work practices and procedures. Annual reviews may be conducted by EH&S staff. ACCIDENTS, INJURIES, AND POTENTIAL EXPOSURES (Post these procedures in the laboratory where the work will be conducted): A. In the event of a recognized percutaneous or mucous membrane exposure to MPTP: 1. Immediately take prescribed Selegiline as directed by the EHC-UWC. 2. Initiate first aid at the worksite: a. Contaminated skin should be washed with copious amounts of soap and UW MPTP SOP Rev. 07/2005, 03/2008, 05/2010, 11/2013 Page 3 of 21 water for 15 minutes. b. Contaminated eyes and mucous membranes should be irrigated for 15 minutes, using saline or water. 3. Go directly to the University of Washington Medical Center Emergency Room (ER). Be sure to give your name, your exact location, and that you were exposed to MPTP. 4. Notify the PI, at contact at as soon as possible. If he/she is not available, . 5. Report the incident on the UW Online Accident Reporting System (OARS): http://www.ehs.washington.edu/ohsoars/index.shtm B. In the event of a suspect exposure to MPTP: 1. Immediately initiate first aid at the worksite as outlined above. 2. Go directly to the University of Washington Medical Center Emergency Room (ER). Be sure to disclose your name, your exact location, and that you may have been exposed to MPTP. Based on the likelihood of exposure, Selegiline may be recommended. 3. Notify the PI, contact at at as soon as possible. If he/she is not available, . 4. Report the incident on the UW Online Accident Reporting System (OARS): http://www.ehs.washington.edu/ohsoars/index.shtm C. Fume-hood alarm: In the event the safety monitor is in alarm, lower sash until it returns to normal, then press the reset button. If monitor continues to alarm with the sash below 18”, cover caging, stop work, and call EH&S at 206-543-9510 to assess whether maintenance is needed. If fume-hood maintenance is required, follow procedures outlined in section VIII, Emergency Transport of MPTP-Treated Animals. IV. Spill procedures A. Spills inside a fume hood: 1. Close the fume hood sash. 2. Remove any contaminated PPE, wash hands for 15 minutes, and replace PPE. UW MPTP SOP Rev. 07/2005, 03/2008, 05/2010, 11/2013 Page 4 of 21 3. Clean up the spill with 1% bleach solution (made daily) and paper towels. 4. Remove and replace plastic backed pads. 5. Clean all exposed surfaces with 1% fresh bleach. 6. Dispose of all clean-up materials as hazardous chemical waste as described in Section X. B. Liquid Spills outside a fume hood: 1. Cordon off the area and restrict access. 2. Contact EH&S Environmental Programs (EP) at 206-543-0467 for advice as to whether a contractor should come in and clean up the spill. C. Bedding spills outside a fume hood: 1. Cordon off the area and restrict access. 2. Pour 1% bleach solution on the spill, allowing the liquid to flow into the bedding, taking care to not create dust. Allow the liquid to sit for 30 minutes. 3. Leave the room. Remove any contaminated PPE, wash hands for 15 minutes, and replace PPE. 4. Collect all the bedding using paper towels. Place the bedding in the container for incineration. 5. Wipe up the spill area with paper towels. Discard paper towels as hazardous chemical waste. 6. For further information, contact the EH&S EP at 206-543-0467 for advice as to whether a contractor should come in and clean up the spill. V. PERSONAL PROTECTIVE EQUIPMENT (PPE) A. PPE must be worn whenever working with MPTP or MPTP-treated animals and their waste within four days of last administration. These activities include preparing MPTP solutions, administering MPTP to animals, entering MPTPanimal room within first four days of administration, first cage change: Standard vivarium scrubs Rear-closing disposable water-proof gown Disposable liquid resistant sleeve covers (wrist guards) Double nitrile gloves Chemical safety goggles or faceshield N95 disposable respirator UW MPTP SOP Rev. 07/2005, 03/2008, 05/2010, 11/2013 Page 5 of 21 B. Cage changing: The cage changes must be done every seven days. When possible, cage changes should not be performed for the first four days postinjection. However, protocol-specific dosing schedules may require cages to be changed within four days post-injection. With the current dosing regimen, cages will be changed on days 1 (prior to the first MPTP injection), and days . Cage changes on days will involve MPTP-contaminated bedding. C. Frequent glove changes are recommended. Change gloves immediately if their integrity has been compromised (e.g., punctured, torn) or if contaminated. D. Protective clothing should be changed prior to entering non- MPTP designated areas. E. Remove PPE in the following order: 1. Outer gloves (place in MPTP-waste to be incinerated). 2. Put on a new pair of gloves. 3. Remove goggles/face shield. Spray goggles with 1% bleach. Wipe. 4. Sleeve covers (to non-contaminated regular trash). 5. Disposable gown (to non-contaminated regular trash). 6. N95 respirator (to non-contaminated regular trash). 7. Outer pair of gloves (to non-contaminated regular trash). 8. Exit the MPTP administration area, remove inner pair of gloves and wash hands. F. Dispose of protective clothing which is not contaminated into the regular trash. Dispose of contaminated clothing into hazardous solid waste container for collection. When waste bags are full, remove from the waste cans, tie shut with a label indicating either “MPTP-contaminated waste for incineration” (orange bags), or “Uncontaminated waste” (black bags), spray with 1% bleach and leave next to the door for disposal by Comparative Medicine staff. See Section X (Waste) for more details. UW MPTP SOP Rev. 07/2005, 03/2008, 05/2010, 11/2013 Page 6 of 21 Overview of MPTP Personal Protective Equipment and Room Restrictions Procedures MPTP Preparation and administration in approved fume hood PPE rear closing water proof gown, N95 respirator, double nitrile gloves, disposable sleeves covers, chemical safety goggles or face shield Restrictions Room : restricted to only those staff authorized to work with MPTP. N95 respirator, double-gloves, sleeves covers, chemical safety goggles or face shield Standard laboratory PPE: lab coat, gloves, Room : restricted to only those staff authorized to work with MPTP. Animal housing for one to four days post last injection in approved fume hood Animal housing after four days post last injection VI. Room : No restricted access RESEARCH STAFF ONLY: MPTP PREPARATION AND ADMINISTRATION TO ANIMALS A. As with all highly hazardous chemicals, two research staff must be available at all times when working with MPTP, administering MPTP, and working with MPTPadministered animals until four days post last administration. The second person does not have to be in the room during handling or administration but must be readily available in the event of an emergency. B. During preparation and administration of MPTP: All of Room to only those research staff authorized to work with MPTP. C. The approved fume hood in Room for MPTP work is restricted to staff authorized to work with MPTP and MPTP treated animals for a minimum of four days after last MPTP administration. PPE must be changed prior to exiting the room. The approved fume hood is the designated location for preparing, administering, and housing animals. D. All animal procedures and housing must be performed in a centralized animal facility. For the first four days post-injection, the door to the MPTP animal room and the approved fume hood must be posted with the appropriate MPTP signs so it is clear that the MPTP and treated animals are present. Appendix 2 must be posted on the fume hood when animals administered MPTP are present. The red MPTP sign in Appendix 3 must be posted on animal housing room UW MPTP SOP Rev. 07/2005, 03/2008, 05/2010, 11/2013 Page 7 of 21 is restricted door. E. Only trained animal husbandry and veterinary staff may enter the room up to four days after the final administration. F. MPTP and MPTP solutions must be stored in labeled, tightly capped containers. The container label must include the identity of the hazardous contents (i.e., MPTP) and the appropriate hazard warning (i.e., neurotoxin). G. MPTP, as received from the manufacturer/vendor in its original undiluted form, must be stored in a lock box inside or adjacent to a clutter free certified and approved chemical fume hood. Only people who work with MPTP will have the key to the lock-box. The box will be permanently attached to the side of the fume hood / to the wall adjacent to the fume hood. If the lock box is outside the hood, the MPTP must be kept in a secondary container inside the lock box and while moving it between the lock box and the fume hood. H. The fume hood must be posted with the red MPTP sign in Appendix 2. I. MPTP solutions must be prepared in a certified chemical fume hood. Appropriate PPE must be worn, as noted in Section III. All work surfaces must be covered with absorbent, plastic-backed, disposable absorbent pads. Make the 1% bleach solution and prepare the fume hood with all necessary materials (pads, paper towels, syringes, decapicones, syringe tray, etc.) prior to opening the lock box. J. When the lock box is adjacent to the fume hood, it is safer and more convenient if the back-up person opens the lock box, allowing the primary investigator to transfer the MPTP from the lock box to the fume hood. K. Use only needle-locking syringes or disposable syringe-needle units (i.e., needle is integral to the syringe). Used disposable needles must not be bent, sheared, broken, recapped, removed from disposable syringes, or otherwise manipulated before disposal. Never leave the tip exposed on work surface. After each injection, immediately place the syringe-needle unit in a sharps disposal container located in the fume hood or approved containment. L. Disposable labware should be used when preparing MPTP solutions. If nondisposable glassware is used, it must be triple rinsed in 1% bleach solution prior to washing. The rinsate must be collected and disposed by EH&S as hazardous chemical waste (see section X: MPTP Waste). M. When all work with MPTP is complete, place th MPTP vial in the lock box/secondary container. Change outer gloves, then spray the exterior surface with 1% bleach and wipe down. Carefully remove all absorbent pads and dispose as hazardous chemical waste. Wipe all surfaces with a 1% bleach solution and double bag the wipes or paper towels and discard with regular garbage. TURN THE HOOD LIGHT OFF. UW MPTP SOP Rev. 07/2005, 03/2008, 05/2010, 11/2013 Page 8 of 21 N. Tie the MPTP-contaminated waste bag closed, spray down the exterior surface with 1% bleach, then place in a second bag labeled as hazardous chemical waste. Tie the second bag closed and leave in the room for disposal. O. Change the non-contaminated waste bag. Tie the full non-contaminated waste bag closed and leave in the room for disposal. P. Remove PPEinto the non-contaminated waste located next to the door, and exit the room. Q. If emergency maintenance must be done during the first four days after the injection, stop all work and decontaminate the area. Ensure that all concentrated and dilute concentrations of MPTP are closed and properly stored. Please escort the worker into the space and remain in the room during the entire maintenance. If work needs to be done in the fume hood, the animals should be moved to another fume hood following the procedures outlined below. The sign should remain on the door and fume hood to inform other staff of the MPTP and MPTPtreated animals. After the four days post injection, no extra PPE is required in this space and any requirements for escorts will be determined by the Department of Comparative Medicine staff. VII. TRANSPORTING MPTP A. MPTP containers must be transported between rooms using the following method: 1. MPTP solutions must always be transported in a labeled, sealed, primary container within a sealed, leakproof, unbreakable secondary container. 2. The primary container must be placed inside a secondary container lined with a plastic-backed pad or other absorbent material. 3. If a spill does occur outside the lab, follow the spill procedures above; cordon off the area and restrict access until all of the MPTP has been cleaned up. 4. The secondary container must be cleaned with 1% bleach solution after each use. 5. All PPE must be removed prior to leaving the designated area. 6. PPE must be put on prior to handling the MPTP container in the new space. B. All locations where MPTP will be stored must be entered in MyChem. UW MPTP SOP Rev. 07/2005, 03/2008, 05/2010, 11/2013 Page 9 of 21 VIII. EMERGENCY TRANSPORT OF MPTP-TREATED ANIMALS A. In the event of an emergency requiring the treated animals be moved before the first cage change, contact EH&S (206-221-7770) and the Office of Animal Welfare. B. A new fume hood and room for procedures and animal housing must be approved by the Office of Animal Welfare and EH&S. C. in a fume hood, prepare animals for transport: 1. Secure the cage tops to the cage bottoms with tape. 2. Wipe down the cages with 1% fresh bleach solution made daily. 3. Pack up to four cages in the transport box. Transport boxes may be obtained from the Department of Comparative Medicine. 4. Secure the transport lid using the snaps. 5. Carefully transport the animals to the new fume hood or animal housing room. 6. Ensure no cage has opened during transport. 7. Remove cages from the transport box into the chemical fume hood. IX. ANIMAL HOUSING Research staff will be responsible for changing the animal cages during the course of the experiments and for the final cage change four days after the last injection. The Department of Comparative Medicine staff will ONLY care for the animals if there is a sick animal, flooded cage, or other special circumstances. A. Animals will be housed in room centralized animal facility. B. The animals will be housed in disposable cages; all bedding will remain in the cages and be disposed of at the same time/re-useable cages. C. For the first four days post-injection, the fume hood in room is the designated location for preparing, administering, and housing animals. The door to each MPTP-animal room must be posted in such a manner that it is clear that the fume hood contains MPTP-treated animals. The fume hood may only be used for the MPTP work (preparing, administering MPTP and housing animals). Post the sign in Appendix 2 on the chemical fume hood . D. The animal cages must also be properly labeled with cage cards stating “MPTP – neurotoxin.” UW MPTP SOP Rev. 07/2005, 03/2008, 05/2010, 11/2013 Page 10 of 21 , where the fume hood is located in a E. For the first four days post-injection, cover the cages with filter bonnets. Place the cages in a certified chemical fume hood. Ensure the lids are secured to the cage. F. No animal husbandry staff is allowed in the animal housing room during the animal procedures. G. When possible, cage changes should not be performed for the first four days post-injection. However, protocol-specific dosing schedules may require cages to be changed within four days post-injection. H. Four days after the final MPTP injection, the animals may be transferred to clean, standard caging and the MPTP door signs and cage tags may be removed. 1. Cage change should be performed wearing appropriate PPE (section V) and in a chemical fume hood. Work atop absorbent pads. The fume hood should be wiped down with 1% bleach solution and water after use. 2. Dirty reusable cages and reusable racks should be wiped down with 1% bleach solution for 10 minutes, rinsed with water, and covered with a full drape. 3. Dispose of bedding by misting the bedding with minimum 1% bleach solution, carefully place bedding into plastic bag, then into incineration container. Alternatively, bedding may be completely saturated with 1% bleach solution, allowed to sit for 10 minutes, and then double bagged and disposed with regular trash. 4. Reusable caging, cage racks and reusable water bottles can be sprayed with 1% bleach solution, allowed to sit for 10 minutes, wiped down with paper towels and then bagged for transport to facility cage wash. Any extra water in the water bottle should have 1% bleach added and allowed to sit for 10 minutes. I. X. The use of special PPE is not required after the animals have been transferred to clean cages (after four days post-injection). MPTP WASTE A. Unused concentrated MPTP (including empty vials) waste is managed as hazardous chemical waste through EH&S. See http://www.ehs.washington.edu/epowaste/chemwaste.shtm B. Spill cleanup materials, soiled PPE, and absorbent pads contaminated with MPTP should be double bagged and managed as hazardous chemical waste through EH&S as above. UW MPTP SOP Rev. 07/2005, 03/2008, 05/2010, 11/2013 Page 11 of 21 C. Grossly contaminated solids can be decontaminated with 0.1 N hydrochloric acid or 1% bleach. After decontamination, the solids can be disposed with regular garbage or reused. The liquid waste containing dilute MPTP and decontaminant should be managed as hazardous chemical waste through EH&S. D. All other solid waste, including gowns and gloves, believed not to have contact with MPTP can be double bagged and discarded with regular garbage. E. Animal bedding: Bedding from first change (four days after last administration) must be incinerated. Complete the UW Biomedical Waste Account Request Form to arrange for proper containers and pick-up. Specify that pick-up is for incineration. Bedding from subsequent cage changes can be double bagged and discarded with regular garbage. F. Animal carcasses: Carcasses that have received MPTP within the last four days must be incinerated. Complete the UW Recycling and Solid Waste Biomedical Waste Account Request Form to arrange for proper containers to be delivered and pick-up. Specify that pick-up is for incineration. Carcasses that have not received MPTP in the past four days can be double bagged and discarded with regular garbage. G. Sharps are collected in an appropriate sharps container, and picked up by the UW biomedical waste contractor for incineration. Principal Investigator Signature: Date: References: 1. Kopin, I.J. 1987. MPTP: An industrial chemical and contaminant of illicit narcotics stimulates a new era in research on Parkinson’s disease. Environmental Health Perspectives. 75, 45-51. 2. National Institutes of Health (NIH), Office of Research Services, Division of Occupational Health and Safety: Procedures for Working with MPTP or MPTP-Treated Animals. http://dohs.ors.od.nih.gov/pdf/Procedures_for_Working_with_MPTP_or_MPTP_Treated_Animals_july%202006.pdf 3. Przedborski, Serge, Jackson-Lewis , V., Naini, A.b., Jakowec , M., Petzinger , G., Miller, R., Akram , M. 2001. The parkinsonian toxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP): A technical review of its utility and safety. Journal of Neurochemistry. 76, 1265-1274. 4. Yang, S.C., Markey, S.P., Bankiewiez, K.S., London, W.T., Lunn, G. 1988. Recommended safe practices for using the neurotoxin MPTP in animal experiments. Laboratory Animal Science. 38, 563-567. UW MPTP SOP Rev. 07/2005, 03/2008, 05/2010, 11/2013 Page 12 of 21 Appendix 1: Employee Health Center (EHC) MPTP Handout MPTP Research Group Campus Health Services- UW Hall Health 206-685-1026 Background: MPTP (1-methyl-4-phenyl-1,2,5,6 tetrahydropyridine) and its analogues (ie., 2’-CH2-MPTP or 2’-NH2-MPTP) are neurotoxins used in animal models to simulate Parkinson’s syndrome. Low dose exposure (ie. 0.1mg/kg body weight) may cause irreversible neurological damage to dopamine neurons (exposure may result in Parkinson’s disease-like syndrome). Definition of Exposure: Skin puncture with materials contaminated with MPTP or analogues Ingestion of MPTP or analogues Mucous membrane exposure (ie nose, eyes, mouth) Inhalation of MPTP or analogues powder Cutaneous exposure if skin is broken (i.e. wound) Immediate Post-Exposure actions: Follow EH&S OHS Post exposure prophylaxis: initiate immediately following exposure 1. Treatment for significant exposures to MPTP is four (4) selegiline (Eldepryl) 5 mg capsules p.o. immediately. The employee should immediately initiate first aid at the worksite by washing the contaminated skin with copious amounts of soap and water for 15 minutes. Eyes and mucous membranes should be irrigated for 15 minutes with water or normal saline. 2. Alternate treatment for significant exposures to MPTP analogues (e.g. 2’-CH2-MPTP or 2’=NH2-MPTP) is phenelzine sulfate (Nardil) 15 mg, four tablets p.o. 3. Report to UWMC or Harborview Emergency Room for medical examination, assessment, and further treatment as needed. NOTE: treat percutaneous exposures as low as 0.001mg/kg. Treat ingestion/mucosal exposures and inhalation exposures as low as 0.1mg/kg. Consider treatment for any exposure especially if there is any burning or irritation at the site of exposure. Ongoing Post-Exposure treatment: Selegiline 5 mg, #18, three (3) tablets twice each day for significant exposure to MPTP Phenelzine sulfate 15 mg, #12, two (2) tablets twice each day is given for significant exposures to MPTP analogues (2’-CH2-MPTP or 2’-NH2-MPTP) Follow up with EHC-UW and possible referral to neurologist UW MPTP SOP Rev. 07/2005, 03/2008, 05/2010, 11/2013 Page 13 of 21 Per: Occupational Medical Service, DOHS National Institutes of Health 05/2008 http://dohs.ors.od.nih.gov/pdf/Procedures_for_Working_with_MPTP_or_MPTP_Treated_Animals.pdf Selegiline U.S. BRAND NAME- Eldepryl PHARMACOLOGIC CATEGORY Antidepressant, Monoamine Oxidase Inhibitor Anti-Parkinson's Agent, MAO Type B Inhibitor REASONS NOT TO TAKE THIS MEDICINE If you have an allergy to selegiline or any other part of this medicine If you are taking meperidine If you have taken isocarboxazid, phenelzine, or tranylcypromine in the last 14 days. Monoamine oxidase inhibitors (eg, isocarboxazid, phenelzine, and tranylcypromine) must be stopped 14 days before this medicine is started. Taking the two together could cause dangerously high blood pressure. How is it best taken? Avoid eating foods such as aged cheeses and meats, soy sauce, soy bean including paste, Miso soup, Italian green beans (fava beans), snowpea or broad bean pods, sauerkraut, kimchee, concentrated yeast extracts (Marmite), wine, beer including alcohol-free beer. Take this medicine with food. What do I do if I miss a dose? (This does not apply to patients in the hospital): Take a missed dose as soon as possible. If it is almost time for the next dose, skip the missed dose and return to your regular schedule. Do not take a double dose or extra doses. Do not change dose or stop medicine. Talk with healthcare provider. What are the precautions when taking this medicine? If you are taking a high dose (10 mg per day) of this medicine, avoid aged meats and cheeses, soy sauce, certain beans, sauerkraut, beer, concentrated yeast extracts, and others. Talk with healthcare provider. Check medicines with healthcare provider. This medicine may not mix well with other medicines. If you are taking this medicine and have high blood pressure, talk with healthcare provider before using over-the-counter products that may increase blood pressure. These include cough or cold remedies, diet pills, stimulants, ibuprofen or like products, and certain natural products or supplements. Avoid alcohol (includes wine, beer, and liquor). UW MPTP SOP Rev. 07/2005, 03/2008, 05/2010, 11/2013 Page 14 of 21 Tell healthcare provider if you are pregnant or plan on getting pregnant or if you are breastfeeding. What are some possible side effects of this medicine? Feeling lightheaded, sleepy, having blurred vision, or a change in thinking clearly. Avoid driving, doing other tasks or activities that require you to be alert or have clear vision until you see how this medicine affects you. Nausea or vomiting. Small frequent meals, frequent mouth care, sucking hard, sugar-free candy, or chewing sugar-free gum may help. PH ENELZINE- US BRAND NAME NARDIL PHARMACOLOGIC CATEGORY Antidepressant, Monoamine Oxidase Inhibitor REASONS NOT TO TAKE THIS MEDICINE If you have an allergy to phenelzine or any other part of this medicine. If you have any of the following conditions: Liver disease, pheochromocytoma, severely weakened heart, or uncontrolled high blood pressure. If you are taking any of these medicines: Citalopram, fluvoxamine, paroxetine, or sertraline (SSRI antidepressants). Do not use within two weeks of other antidepressants. Fluoxetine should be stopped for at least five weeks before starting this medicine. How is it best taken? Follow diet instructions. Certain foods and drinks taken with this medicine can cause very dangerous reactions such as sudden high blood pressure. To prevent these problems, get a list of foods to avoid from a nutritionist. Avoid eating foods such as aged cheeses and meats, soy sauce, soy bean including paste, Miso soup, Italian green beans (fava beans), snowpea or broad bean pods, sauerkraut, kimchee, concentrated yeast extracts (Marmite), wine, beer including alcohol-free beer. If medicine is stopped, follow diet for at least two more weeks. What do I do if I miss a dose? (does not apply to patients in the hospital) Take a missed dose as soon as possible. If it is almost time for the next dose, skip the missed dose and return to your regular schedule. Do not take a double dose or extra doses. Do not change dose or stop medicine. Talk with healthcare provider. UW MPTP SOP Rev. 07/2005, 03/2008, 05/2010, 11/2013 Page 15 of 21 What are the precautions when taking this medicine? If you have a weakened heart, talk with healthcare provider. Fluoxetine should be stopped for five weeks before starting this medicine. You may not be alert. Avoid driving, doing other tasks or activities until you see how this medicine affects you. Do not use over-the-counter medicines containing dextromethorphan or pseudoephedrine. Avoid alcohol (includes wine, beer, and liquor). Avoid caffeine (for example, tea, coffee, cola) and chocolate intake. Tell healthcare provider if you are pregnant or plan on getting pregnant. What are some possible side effects of this medicine? Feeling lightheaded, sleepy, having blurred vision, or a change in thinking clearly. Avoid driving, doing other tasks or activities that require you to be alert or have clear vision until you see how this medicine affects you. Feeling dizzy. Rise slowly over several minutes from sitting or lying position. Be careful climbing. Headache Constipation. More liquids, regular exercise, or a fiber-containing diet may help. Talk with healthcare provider about a stool softener or laxative. Inability to sleep High blood pressure can rarely occur. REASONS TO CALL HEALTHCARE PROVIDER IMMEDIATELY WHILE TAKING SELEGILINE OR PHENYLZINE Signs of a life-threatening reaction. These include wheezing; chest tightness; fever; itching; bad cough; blue skin color; fits; or swelling of face, lips, tongue, or throat. If you are planning to harm yourself or the desire to harm yourself increases. Chest pain or pressure, fast heartbeat, or passing out Confusion; very nervous; anger with sweating, shivering, stiffness, or shaking Severe nausea or vomiting Any rash UW MPTP SOP Rev. 07/2005, 03/2008, 05/2010, 11/2013 Page 16 of 21 No improvement in condition or feeling worse How should I store these medicines? Store at room temperature. Protect from moisture. Do not store in a bathroom or kitchen. Reference: Up-to-date; accessed 6/29/06 Information for the Patient: All patients, should be warned that the following foods, beverages and medications (Table II and III) must be avoided while taking selegiline or phenelzine, and for two weeks after discontinuing use. ------------------------------------------------------------------Table II Foods and Beverages to Avoid During Phenelzine Therapy Meat and Fish: Pickled herring, liver, dry sausage (including Genoa salami, hard salami, pepperoni, and Lebanon bologna) Vegetables: Broad bean pods (fava beans) Dairy Products: Cheese (cottage cheese and cream cheese are allowed), yogurt Beverages: Beer and wine, alcohol-free and reduced-alcohol beer and wine products Miscellaneous: Yeast extract (including brewer's yeast in large quantities), excessive amounts of chocolate or caffeine ------------------------------------------------------------------Patients being treated with selegiline or phenelzine should also avoid any spoiled or improperly refrigerated, handled or stored protein-rich foods such as meats, fish and dairy products, including foods that may have undergone protein breakdown by aging, pickling, fermentation, or smoking to improve flavor. ------------------------------------------------------------Table III OTC Medications to Avoid During Phenelzine Therapy 1. Cold and cough preparations (including those containing dextromethorphan) 2. Nasal decongestants (tablets, drops or spray) 3. Hay-fever medications 4. Sinus medications 5. Asthma inhalant medications UW MPTP SOP Rev. 07/2005, 03/2008, 05/2010, 11/2013 Page 17 of 21 6. Antiappetite medicines 7. Weight-reducing preparations 8. L-tryptophan containing preparations ------------------------------------------------------------Last revised Marguerite McCadden, ARNP 05/09/2008 UW MPTP SOP Rev. 07/2005, 03/2008, 05/2010, 11/2013 Page 18 of 21 Appendix 2: Post on fume hood MPTP NEUROTOXIN & MPTP-TREATED LIVE ANIMALS UW MPTP SOP Rev. 07/2005, 03/2008, 05/2010, 11/2013 Page 19 of 21 Appendix 3: Post on lab door until 4 days post last administration MPTP NEUROTOXIN ENTRY RESTRICTED TO AUTHORIZED* PERSONNEL *EH&S approved SOP, enrollment in respirator program, proper PPE, prescription selegeline in lab, documented training on SOP. UW MPTP SOP Rev. 07/2005, 03/2008, 05/2010, 11/2013 Page 20 of 21 Appendix 4: Documentation of MPTP SOP Training Name UW MPTP SOP Rev. 07/2005, 03/2008, 05/2010, 11/2013 MPTP SOP Training Date Page 21 of 21 Signature