… from the Drugs and Therapeutics Committee ______

Inside this Issue… Issue # 66: May 15, 2019 Additions to Hospital Formulary liposomal, AmBisome® Caspofungin, Cancidas® Cefepime I. Additions to Hospital Formulary Cefoxitin Cefprozil A NSHA Systemic Antimicrobial Formulary with Cidofovir Protected Antimicrobials Stoplight System has been ® Imipenem/ cilastatin, Primaxin approved. The NSHA Formulary has been updated to reflect these recommendations including the addition of the following systemic antimicrobials (refer to Section VI): ® Moxifloxacin ophthalmic solution, Vigamox Amphotericin B liposomal*, AmBisome® Removal from Hospital Formulary ® Amphoteracin B lipid complex, Abelcet® Caspofungin*, Cancidas Cefepime Famciclovir Cefoxitin Itraconazole Cefprozil Ketoconazole Cidofovir Micafungin ® Moxifloxacin Imipenem/ cilastatin, Primaxin Piperacillin Minocycline Revised Guidelines * refer to Appendix 1 for further details Oxaliplatin Expanded Guidelines Neomycin Pembrolizumab, Keytruda® Neomycin (Mycifradin®), an oral , was removed RITUXimab subcut, Rituxan® SC from the Canadian market several years ago; therefore, neomycin Therapeutic Interchange was not included on the Hospital Formulary. Systemic Antimicrobial Formulary Other - Systemic Antimicrobial Formulary with Surgical site (SSIs) following surgical procedures are Protected Antimicrobial Stoplight System amongst the most common healthcare-associated infections and Medication Policies represent a tremendous burden both for patient recovery and the Pre-Printed Orders overall healthcare system cost. To decrease the rates of SSIs, the IV Manual preoperative use of oral neomycin in combination with other (e.g., , ) and other treatment modalities (e.g., mechanical bowel preparation) has been The following policies were approved by the Medical Advisory encouraged in patients undergoing elective colorectal procedures. Committee (Oct18, Jan19, Feb19) on the recommendation of the Since neomycin is not marketed in Canada, it is obtained from a Drugs and Therapeutics Committee (Sept18, Oct18, Nov18, compounding pharmacy. Dec18). There are an extensive number of published cohort studies, RCTs and systematic reviews that have evaluated numerous types and combinations of oral antibiotics for reducing SSIs. It is difficult to determine the best single preoperative combination given the heterogeneity of antibiotic use in trials; however, evidence does favour the overall use of oral antibiotic prophylaxis, regardless of choice, assuming it has appropriate bacterial coverage and is administered appropriately based upon the current evidence and best practice guidelines. Approved Use: For inpatients receiving elective colorectal surgery.

III. Revised Guidelines

Moxifloxacin ophthalmic solution, Vigamox® Oxaliplatin Moxifloxacin ophthalmic solution (Health Canada approved for the Oxaliplatin injection has been restricted on the NSHA Formulary treatment of conjunctivitis) has been used in an off-label manner for the indications of colorectal cancer and advanced/metastatic intracamerally for the prophylaxis of endophthalmitis. pancreatic cancer only. The cost of oxaliplatin has reduced dramatically and oxaliplatin is used in standard treatment protocols Endophthalmitis, an of the interior cavities of the eye, is for gastric/gastroesophageal cancer, in the adjuvant treatment of a rare but serious complication of cataract surgery. pancreatic cancer and in HIPEC protocols for colorectal cancer Endophthalmitis occurs when bacteria from the conjunctiva, carcinomatosis (for this indication there is substantial cost savings eyelids or general environment are introduced via the surgical and equivalent efficacy over the alternate drug mitomycin C); incision into the anterior chamber and is considered a medical therefore, the current formulary restrictions for oxaliplatiin are emergency requiring immediate attention as it may result in removed substantial vision loss. Methods for prevention include the use of pre-operative , and post-operative antibiotics either applied topically, subconjunctivally, or intracamerally (directly into IV. Expanded Guidelines the anterior chambers of the eye). The intracameral route is attractive as it provides antibiotic directly to the site of infection and Pembrolizumab, Keytruda® has minimal systemic exposure. Two new Guidelines have been approved for pembrolizumab.

In order to be safe for intracameral use, an antibiotic formulation A new Guideline for the role of pembrolizumab for locally should be free of preservative and formulated to an appropriate advanced/ metastatic non-small cell lung cancer (NSCLC) first line concentration, pH and osmolarity. For most antibiotics this treatment has been approved by the Drugs and Therapeutics requires multi-step dilution, with or without the involvement of a Committee. sterile compounding pharmacy, and can be prone to compounding Approved Restriction errors. The National Institute for Health and Care Excellence As a single agent treatment option for the treatment of locally (NICE) endorsed the use of commercially or pharmacy-prepared advanced (Stage IIIB, not eligible for potentially curative intracameral antibiotic solutions to prevent dilution errors. concurrent chemoradiotherapy) or previously untreated metastatic Moxifloxacin 0.5% solution is preservative free and the contents of non-small cell lung cancer (NSCLC) in patients whose tumours the commercially available bottle requires only a single step express PD-L1 Tumour Proportion Score (TPS) ≥ 50% as dilution to obtain an appropriate concentration for intracameral determined by a validated test and who do not harbor a sensitizing administration. epidermal growth factor receptor (EGFR) mutation or anaplastic Approved Restriction: lymphoma kinase (ALK) translocation. Patients should have a Restricted to the Division of Ophthalmology for intracameral use good performance status. Treatment should continue until immediately after cataract surgery confirmed disease progression or unacceptable toxicity, or to a maximum of two years (35 cycles), whichever comes first.

A new Guideline for the role of pembrolizumab for advanced/ metastatic non-small cell lung cancer (NSCLC) second or II. Removal from Hospital Formulary subsequent line treatment has been approved by the Drugs and Therapeutics Committee. A NSHA Systemic Antimicrobial Formulary with Approved Restriction Protected Antimicrobials Stoplight System has been As a single agent treatment option for the treatment of metastatic approved. The NSHA Formulary has been updated to reflect these non-small cell lung cancer (NSCLC) in patients whose tumours recommendations including the removal of the following systemic express PD-L1 (Tumour Proportion Score (TPS) ≥ 1%) as antimicrobials (refer to Section VI): determined by a validated test and who have disease progression on or after cytotoxic and targeted therapy for Amphoteracin B lipid complex*, Abelcet® mutations of either epidermal growth factor receptor (EGFR) or Chloramphenicol anaplastic lymphoma kinase (ALK) for those patients whose tumours express these genomic aberrations. Patients should have Famciclovir a good performance status. Treatment should continue until Itraconazole confirmed disease progression or unacceptable toxicity, or to a Ketoconazole maximum of two years (35 cycles), whichever comes first. Micafungin*

Moxifoxacin* RITUXimab subcut, Rituxan® SC Piperacillin Approved Restriction * refer to Appendix 1 for further details The treatment of diffuse large B cell lymphoma (DLBCL).

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V. Therapeutic Interchange Antimicrobial order Interchange* , oral: Erythromycins, oral - Base The process to develop a NSHA Systemic Antimicrobial Base (enteric/particle - (conventional release) Formulary, includes approval of the following therapeutic coated tab) 250mg interchanges that provide therapeutically equivalent alternative to Erythromycins, oral: Erythromycins, oral: Stearate tablets non-formulary antimicrobials or address common dosing issues to Estolate tablets 250mg expedite and simplify clarifications. Previous formulary systemic 250mg antimicrobial interchanges are removed from the formulary. Erythromycins, oral: Erythromycins, oral: Base Tablet Ethylsuccinate tablets 250mg Antimicrobial order Interchange* 400mg Meropenem 1g or 2g* Meropenem 500mg IV q6h *dose Cefazolin* 1 g IV any Cefazolin 2 g IV same frequency IV q8h is not interchanged if treating CNS, frequency cystic fibrosis, or endophthalmitis Cefazolin* __g IV q6h Cefazolin 2g IV q8h infections Cefazolin 500mg PO Cephalexin 500mg PO q6h Metronidazole _ mg IV Metronidazole _ mg IV q12h q6h q 6-8h (Exception: Clostridium difficile Cefoxitin 1g IV q6-8h Cefazolin 2g IV q8h and infection, subdural empyema or metronidazole 500 mg IV q12h brain abscess) Exceptions: Pelvic inflammatory Metronidazole 250 mg Metronidazole 500 mg PO/IV q12h disease (PID), postpartum x 1 dose PO/IV q12h rd th for 3 or 4 degree tears, and Micafungin* Caspofungin 70mg IV on day 1 , surgical prophylaxis for gynecologic followed by 50mg IV q24h procedures. Nitrofurantoin regular Nitrofurantoin Macrocrystals Cefoxitin 2g IV q6-8h Cefazolin 2 g IV q8h and as follows: 50 mg PO (Macrobid®): 100 mg PO daily metronidazole 500 mg IV q12h bid 100 mg PO bid Exceptions: Pelvic inflammatory 50 mg PO qid Exceptions include: Tube and disease (PID), postpartum x 1 dose crushing administration, patients rd th for 3 or 4 degree tears, and with gut absorption issues i.e. surgical prophylaxis for gynecologic ileostomy, short gut syndrome procedures. oral Nystatin oral suspension 500,000 Ceftriaxone Ceftriaxone 1 g IV q24h suspension 100,000 units/mL (5mL) same (Rocephin®) 1 g IV Exceptions: meningitis or CNS units/mL, doses frequency/schedule-if no frequency q12h or 2 g IV q24h infections, necrotizing fasciitis, written for 1mL, any written will be dispensed as periorbital/orbital cellulitis, frequency/schedule 5mL QID for 10 days Exception – osteomyelitis, joint infections, Palliative Care typhoid, Lyme disease and Penicillins Penicillins endocarditis. - Penicillin G 500 000 - Penicillin V potassium 300 mg, oral 400 mg Ciprofloxacin 500 mg tablet IU (300 mg), oral tablet - Penicillin G IV - Penicillin G sodium IV Ciprofloxacin 500 mg Ciprofloxacin 400 mg IV - Penicillin G - Penicillin G sodium IV IV potassium IV Ciprofloxacin Ciprofloxacin regular release - Penicillin V - Penicillin V potassium 300 mg extended release product, same dose PO potassium 250 mg (500 000 IU) (Cipro® XL) PO (400 000 IU) _ mg IV q Clindamycin _ mg IV q 8h (total - Penicillin V - Penicillin V potassium 600 mg 6h daily dosage no more than 1800 potassium 500 mg mg), Exception: Gynecology - Penicillin V 300 mg - Penicillin V potassium 300 mg patients being treated for PID, necrotizing fasciitis, and toxic shock * refer to Appendix 1 for further details syndrome may receive 900 mg IV q8h ** The dosing recommendations are for adults. For pediatrics, Cloxacillin* IV any Cloxacillin 2g IV q4h please refer to IWK Spectrum app. or other resource. dose q4-6 hours Erythromycin IV (all 500 mg IV daily regimens) Exception: erythromycin IV used as motility agent

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VI. Other Protection A NSHA Systemic Antimicrobial Formulary with Drug Status has been Protected Antimicrobials Stoplight System Clindamycin yellow developed by the NSHA Antimicrobial Stewardship Program (ASP) with input from Infectious Disease experts and the Cloxacillin green Antimicrobial Subcommittee. yellow

Dapsone yellow The NSHA Formulary has been updated to reflect these recommendations. Since this review did not include non-systemic Daptomycin red antimicrobials, anti-parasitic, antiretroviral, or direct acting antiviral green (hepatitis C) medications, the formulary status of these Ertapenem yellow medications remain as previously approved. Ethambutol green Former formulary restrictions for systemic antimicrobials have Erythromycin yellow been removed and replaced with the Stoplight Guiding System to red preserve certain antimicrobials and/or provide alerts for adverse effects: Fluconazole green NSHA Systemic Antimicrobial Formulary with Protected Fosfomycin yellow Antimicrobial Stoplight System Green - No restrictions. Ganciclovir yellow Yellow - Protected antimicrobial. Defined criteria for use and/or yellow important safety considerations. Imipenem/Cilastatin red Red - Protected antimicrobial. Requires ASP review within 72 hours. Isoniazid green Levofloxacin yellow Protection red Drug Status Meropenem yellow Acyclovir green Metronidazole green yellow Minocycline green Amoxicillin green Neomycin yellow Amoxicillin/ Clavulanate yellow Nitrofurantoin green Amphotericin B deoxycholate yellow Nystatin green Amphotericin B liposomal (Ambisome) yellow Oseltamivir yellow Ampicillin green Penicillin G Benzathine green Azithromycin yellow Penicillin G Sodium green Caspofungin yellow Penicillin V Potassium green CeFAZolin green Isethionate yellow Cefepime red Piperacillin-Tazobactam yellow CeFIXime yellow Pyrazinamide green CefoTAXime yellow Pyrimethamine yellow Cefoxitin yellow RifABUTin green Cefprozil green RifAMPin green CeftAZIDime yellow Ceftolozane - Tazobactam red green red CefTRIAXone yellow yellow CefUROXime Axetil green Trimethoprim yellow CefUROXime Sodium green Trimethoprim/ Sulfamethoxazole yellow CephALEXin yellow ValACYclovir green Cidofovir yellow ValGANCIclovir yellow Ciprofloxacin yellow yellow yellow Voriconazole yellow 4

As part of this process, Antimicrobial Stewardship Guidelines for PPO 0633 Nivolumab/ Ipilimumab – Advanced Renal Cell Antimicrobial Use were approved to guide appropriate use and Carcinoma safety precautions for the yellow and red antimicrobials. These PPO 0343 Pre-op Gynecological High Dose Rate Guidelines can be accessed on the Antimicrobial Stewardship Brachytherapy website: PPO 0504 PERTuzumab/TRAStuzumab (with Taxane) – http://www.cdha.nshealth.ca/nsha-antimicrobial- Metastatic Breast Cancer stewardship/antimicrobial-formulary. PPO 0639 Linker Induction 1A Acute Lymphoblastic Leukemia (age greater than 50 years) PPO 0640 Linker Consolidation 1B 2B Acute Lymphoblastic Leukemia (age greater than 50 years) VII. Medication Policies PPO 0641 Linker Consolidation 1C 2C 3C Acute Lymphoblastic Leukemia (age greater than 50 The following hospital policies have been approved by the Medical years) Advisory Committee on the recommendation of the Drugs and PPO 0642 Linker – Consolidation 2A Acute Lymphoblastic Therapeutics Committee. These policies will be added to the Leukemia (age greater than 50 years) Medication Policy and Procedure Manual. PPO 0643 Linker- Maintenance Acute Lymphoblastic Leukemia (age greater than 50 years) BEL-MM-001 Dalteparin for Anticoagulation in the Extracorporeal PPO 0655 TRAStuzumab (every 21 days) – Adjuvant or Circuit during Hemodialysis Metastatic Breast MM-NC-010 Nova Scotia Antidote Program PPO 0044 Allogenic Bu (12.8) Cy (120) Transplant Orders MM-SR-045 Preprinted Orders (PPOs) PPO 0080 Admission Orders – Hematology Inpatient Orders PPO 0140 Subcutaneous Insulin Orders PPO 0394 Management of Confirmed Pathogen Peritonitis Associated With Peritoneal Dialysis VIII. Pre-Printed Orders PPO 0557 Obinutuzumab and Chlorambucil – Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic The following pre-printed orders have been approved by the Lymphoma (SLL) – Cycle 1 Medical Advisory Committee on the recommendation of the Drugs PPO 0596 BENDAmustine/RITUXimab and Therapeutics Committee. PPO 0618 NIVOLumab Single Agent – 14 Day Cycle PPO 0619 PEMBROlizumab Single Agent – 21 Day Cycle PPO 0620 NIVOLumab Single Agent – 28 Day CycleP PPO 0333 Intrathecal Chemotherapy Protocol PPO 0632 NIVOLumab/Ipilimumab – Advanced Melanoma PPO 0493 Folfirinox – Advanced Pancreatic Adenocarcinoma PPO 0633 NIVOLumab/Ipilimumab – Advanced Renal Cell PPO 0560 Gynecology Post-Operative Orders Carcinoma PPO 0603 Psychiatry Inpatient Admission – Acute Care and PPO 0659 Carfilzomib/CycloPHOSPHAMIDE/ Short Stay Relapsed Multiple Myeloma PPO 0611 High Risk APL – Induction – The Iland Protocol PPO 0660 Carfilzomib/Lenalidomide/Dexamethasone PPO 0612 High Risk APL – Consolidation I – The Iland Relapsed Multiple Myeloma Protocol PPO 0613 High Risk APL – Consolidation II – The Iland Protocol PPO 0614 High Risk APL – Maintenance – The Iland Protocol PPO 0627 MiniBeam Protocol PPO 0628 PACLitaxel Weekly – Breast Regmen PPO 0629 DOCEtaxel/OXALiplatin/Fluorouracil/Leucovorin – IX. IV Manual GI Regimen PPO 0635 Lumbar Drain Management Post Cardiovascular New Monographs: Surgery Cabazitaxel PPO 0637 Haploidentical Donor Transplant Orders Famotidine PPO 0638 Reduced Intensity Transplant Orders Nanoparticle Albumin Bound (NAB) PACLitaxel PPO 0644 IVIG Dermatology Adult and Pediatric Pemetrexed PPO 0645 IVIG Hematology Pediatric PERTuzumab PPO 0646 IVIG Infectious Diseases Adult and Pediatric PPO 0647 IVIG Rheumatology Adult and Pediatric Amphotericin B liposomal (Ambisome) PPO 0648 IVIG Solid Organ Transplant Adult and Pediatric Caspofungin PPO 0649 IVIG Immunology Adult and Pediatric Cefepime PPO 0650 IVIG Neurology Adult and Pediatric Ceftolozane Tazobactam PPO 0651 IVIG Hematology Adult Cefoxitin PPO 0652 SCIG Adult and Pediatric Cidofovir PPO 0632 Nivolumab/ Ipilimumab – Advanced Melanoma

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Revised Monographs: Acyclovir Ceftazidime Cetuximab Danaparoid DilTIAZem DimenhyDRINATE DOBUTamine Epoetin Alfa Estrogens, conjugated Fluorescein Ibutilide InFLIXimab Irinotecan Linezolid Lymphocyte immune globulin, anti-thymocyte globulin (equine) Sulfate Meperidine Methotrimeprazine Metoprolol Nitroglycerin 200 mcg/mL Infusion Table Oxaliplatin Protamine Remifentanil Rocuronium Salbutamol Tenecteplase

Adenosine Alteplase Ceftriaxone Dextrose 50%

Removed Monographs: Bortezomib Bretylium Chloramphenicol Quinupristin/ dalfopristin Sodium acetate

Aprotinin Amphotericin B lipid complex (Abelcet) Micafungin Piperacillin

The information contained in this newsletter may also be accessed online: http://cdhaintra/departmentservices/pharmacy/Formulary/index.cfm

Published by the Pharmacy Department Editor: Deborah MacIntyre, B.Sc. (Pharm.), ACPR Drug Information Pharmacist Central Zone

Tel: (902) 473-4248 Email: [email protected]

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Appendix 1 NSHA Antimicrobial Stewardship Program

There is a NEW antimicrobial formulary for NSHA Effective May 1, 2019 Change Reason Implications  Green: No restrictions Antimicrobials  Protect broad-spectrum  Yellow: Clinical guideline available classified into antimicrobials (see website) stoplight system:  Optimize safe antimicrobial  Red: Antimicrobial stewardship green, yellow, red use team review within 72 hours

 Oral levofloxacin is less expensive Levofloxacin  Levofloxacin is narrower-spectrum replacing  Moxifloxacin has poor anaerobic activity so should not be used for moxifloxacin gastrointestinal infections

Dosing: Caspofungin  More evidence for - 70mg IV on day 1, then 50mg IV replacing pediatric patients q24h micafungin  Same spectrum of activity - New orders for micafungin will be changed to caspofungin

Ensure adequate dosing for Orders for cefazolin1g will be changed Cefazolin Dosing serious Gram-positive to 2g. infections like S. aureus (frequency adjusted for renal function)

Ensure adequate dosing for Orders for any dose of cloxacillin IV Cloxacillin Dosing serious Gram-positive will be changed to cloxacillin 2g IV infections like S. aureus q4h

- Amphotericin B liposomal (Ambisome®) o formulation of choice in most situations Amphotericin - Amphotericin B deoxycholate/conventional: formulations: o for compounded preparations (ex: irrigation solutions) o preparation of choice in neonates - See guideline for indications and safety considerations

Questions or comments: [email protected] or [email protected]

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