Sterile Water Shortages

Transcription

1 This Clinical Resource gives subscribers additional insight related to the Recommendations published in March 2018 ~ Resource # Sterile Water Shortages Shortages of small volume parenterals have shifted the administration of many meds from intermittent IV infusion to IV push. 1,2 This practice change has put additional pressure on sterile water for injection (SWFI) supplies for diluting IV push meds. 1-3 Coupled with manufacturing delays this increase in demand has created a nationwide shortage of SWFI bags and vials. 2,3 This chart provides conservation strategies to preserve existing SWFI supplies, and offers recommendations for safe use of alternative sterile diluents. Abbreviations: D5W = dextrose 5% in water; IV = intravenous; IVPB = intravenous piggyback; NS = normal saline; SWFI = sterile water for injection What strategies can Reserve SWFI for use in diluting lyophilized powder meds that cannot be reconstituted with another diluent. 2,3 be used to conserve For example, other sterile diluents cannot be used to reconstitute injectable olanzapine or carfilzomib (Kyprolis). 4-6 SWFI? Centralize prep of IV push meds to pharmacy to better control inventory of SWFI vials. 2 Prepare meds requiring sterile water for reconstitution in batches using large-volume SWFI bags to limit waste: 3 Label SWFI bags being used for med reconstitution with date and time of first entry and beyond-use time. 3 Typical in-use time is 4 hours for SWFI bags labeled Pharmacy Bulk Package (2 to 3 L bags). 3,7 For SWFI bags without this designation, in-use time should not exceed 6 hours. 3 Any unused SWFI must be discarded once the specified in-use time has been reached. 3 Stock commercially available products that don t require further dilution, such as premixes or dual-chamber containers. 2,3 Consider stocking premade 3% saline rather than compounding it from concentrated sodium chloride and SWFI. Substitute Activase 50 to 100 mg kits for Cathflo to eliminate need for SWFI diluent vials in alteplase mixing. 2 Activase kits come with diluent vials and can be batched into smaller line-clearing doses, then frozen. 3,8,9 Consider transitioning some IV push meds back to IVPB administration if possible to help reduce need for SWFI. 3 IVPB bag systems (ADD-Vantage, etc) and adapters (addease, etc) allow mixing without SWFI. 2,10-12 Consider switching to products requiring less SWFI to prepare, such as Ryanodex instead of older dantrolene products. Ryanodex requires 5 ml SWFI per vial for dilution versus 60 ml per vial for other dantrolene formulations Excess SWFI vials from malignant hyperthermia kits/carts can be pulled back to the main pharmacy. Consider diluting select IV meds with an alternative sterile diluent when possible (see next section). 2,3 For example, D5W or 0.45% NS can be used in place of SWFI when making sodium bicarbonate infusions.

2 (Clinical Resource #340321: Page 2 of 5) What risks are Package insert labeling for most meds specifies that SWFI must be used for reconstitution. 3 associated with the Stability and compatibility of meds reconstituted with alternative sterile diluents is often unknown and/or untested. 3 use of alternative Use of alternative sterile diluents may lead to: sterile diluents? Incomplete or slow dissolution of lyophilized powder meds, and/or precipitation upon dilution. 3 For example, cefazolin reconstitution with NS causes crystallization when concentrations exceed 330 mg/ml. 3,32 Change in composition of product that results in loss of med activity prior to administration. 3 Use of NS or D5W results in higher final product osmolarity than when SWFI is used for IV push med preparation. 16 Osmolarity may exceed safe limit (<600 mosmol/l) for peripheral administration leading to phlebitis and increased injury risk if extravasation occurs. 16,17,22,26 This limitation can sometimes be overcome by using larger NS or D5W diluent volumes than SWFI. 26. For example, 560 mosmol/l is achieved when diluting cefazolin or cefotaxime 1 gram with NS 15 ml or 7 ml SWFI. 26 Similarly, cefoxitin or oxacillin 1 gram diluted with 20 ml NS or 10 ml SWFI results in 560 mosmol/l. 26 Ceftriaxone 1 gram diluted with NS 20 ml results in an osmolarity of 364 mosmol/l vs 423 mosmol/l when diluted with 10 ml SWFI. 33,34 Unasyn can be safely prepared with equal volumes of NS, D5W, or SWFI for IV push administration. 18 Consider limiting use of IV push medications of unknown final osmolarity to patients with central venous access. 26 Use of bacteriostatic water in place of SWFI may cause toxicity related to the preservative(s) it contains. 3,19,20 Bacteriostatic water is contraindicated for preparation of meds that will be given to newborns, and/or via intrathecal, epidural, or ocular routes. 19,20 Sterile water for irrigation should NOT be used in place of SWFI due to less stringent testing for particulate matter. 3 What medications can be safely prepared with alternative sterile diluents? Stability data with alternative sterile diluents may be available despite not being included in the package labeling: Infliximab (Remicade) 100 mg vials can be dissolved with NS 10 ml with similar stability as when SWFI is used (both 24 hours). 2,9,21 This information should not be extrapolated to biosimilar infliximab products (Inflectra, Ixifi, Renflexis). Rarely package insert labeling provides information about alternative sterile diluents that can be used instead of SWFI: Cubicin RF can be reconstituted with either SWFI or bacteriostatic water but NOT with NS due to hypertonicity. 23 Cefepime, cefoxitin, and ceftriaxone can be reconstituted with SFWI, bacteriostatic water, NS, or D5W. 9,24,25 Meropenem (Merrem) can be reconstituted with NS when given via IVBP. 27

3 (Clinical Resource #340321: Page 3 of 5) How should enteral and parenteral nutrition be compounded when SWFI is not available? Enteral Nutrition (tube feed preparation, free water supplementation): Use of sterile water is NOT necessary. 28 Safe alternatives may include purified, distilled, or potable tap water. 28,29 Parenteral Nutrition: Consider maximally concentrating (similar to fluid-restricted formulas) to limit SWFI needed during compounding. 30 Provide additional IV fluid (NS, 0.45% NS, D5W, etc) separately to meet fluid requirements if needed. 30 Adjust parenteral nutrition formula for electrolytes and/or carbohydrate calories provided by these IV fluids. Alternative sterile diluents could potentially be used instead, but compounding equipment may require re-programming. 31 Users of this resource 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.

4 (Clinical Resource #340321: Page 4 of 5) Project Leader in preparation of this clinical resource (340321): Leslie Gingo, PharmD, BCPS References 1. ASHP. Small-volume parenteral solutions shortages suggestions for management and conservation. October 18, /media/assets/drug-shortages/docs/drug-shortagessvp-shortages-suggestions-for-management conservation.ashx?la=en&hash=d6bb06db8ad589 1E7EAE628E3B B75. (Accessed January 31, 2018). 2. Thompson CA. Even sterile water for injection becomes hard for hospitals to obtain. January 30, ASHP. (Accessed February 1, 2018). 3. ASHP. Sterile water for injection shortage FAQ. Jan 31, Shortages/Shortage-Resources/Sterile-Water-for- Injection-FAQ. (Accessed February 1, 2018). 4. Product information for Bacteriostatic water. Hospira, Inc. Lake Forest, IL December Product information for Kyprolis. Onyx Pharmaceuticals, Inc. Thousand Oaks, CA January Personal communication (written). Onyx Pharmaceuticals, Inc. Thousand Oaks, CA January 25, FDA. Repackaging of certain human drug products by pharmacies and outsourcing facilities: guidance for industry. U.S. Department of Health and Human Services. January M pdf. (Accessed January 31, 2018). 8. Product information for Activase. Genentech, Inc. South San Francisco, CA January Clinical Pharmacology powered by Clinical Key. Tampa (FL): Elsevier (Accessed January 31, Product information for Sodium Chloride Injection ADD-Vantage Diluent. Hospira, Inc. Lake Forest, IL September Baxter Healthcare Corporation. Mini-Bag Plus container systems. May ug-delivery/minibag.html. (Accessed January 31, 2018). 12. Product information for addease binary connector. B. Braun Medical, Inc. Bethlehem, PA July Product information for Ryanodex. Eagle Pharmaceuticals, Inc. Woodcliff Lake, NJ September Product information for Dantrolene. West-Ward Pharmaceuticals Corp. Eatontown, NJ October Product information for Revonto. US WorldMeds. Louisville, KY October McLaughlin JM, Scott RA, Koenig SL, Mueller SW. Intravenous push cephalosporin antibiotics in the emergency department: a practice improvement project. Adv Emerg Nurs J 2017;39: Clinical Resource, Management of Non-Chemo Extravasation. Pharmacist s Letter/Prescriber s Letter. October Product information for Unasyn. Pfizer Inc. New York, NY August Clinical Resource, Water for Pharmacy Use. Pharmacist s Letter/Prescriber s Letter. July Product information for Bacteriostatic water. Hospira, Inc. Lake Forest, IL December Personal communication (written). Murphy R, Medical Information Specialist. Janssen Scientific Affairs, LCC. Janssen Biotech, Inc. Titusville, NJ January 25, Stranz M, Kastango ES. A review of ph and osmolarity. Int J Pharm Compd 2002;6: Product information for Cubicin RF. Merck & Co., Inc. Whitehouse Station, NJ March Product information for Cefoxitin. Sagent Pharmaceuticals. Schaumburg, IL May Product information for Ceftriaxone. Sagent Pharmaceuticals. Schaumburg, IL October Robinson DC, Cookson TL, Grisafe JA. Concentration guidelines for parenteral antibiotics in fluid-restricted patients. Drug Intell Clin Pharm. 1987;21: Product information for Merrem. AstraZeneca. Wilmington, DE January Rice TW. Sterile water and enteral feeding: fear over logic. October Practical Gastroenterology. content/uploads/sites/199/2014/06/parrish-october pdf. (Accessed February 5, 2018). 29. Bankhead R, Boullata J, Brantley S, et al. Enteral nutrition practice recommendations. JPEN J Parenter Enteral Nutr 2009;33: Wolk R, Moore E, Foulks C. Renal Disease. In: The A.S.P.E.N. Nutrition Support Core Curriculum: A Case-Based Approach The Adult Patient. 2 nd printing. Silver Spring, MD: American Society of Parenteral and Enteral Nutrition, 2007: Holcombe B. Strategies for managing parenteral nutrition component shortages. July 14, Pharmacy Times. (Accessed February 13, 2018). 32. McEvoy GK Ed. Handbook on Injectable Drugs. 19 th ed. Bethesda, MD: American Society of Health- System Pharmacists, Inc, 2017;216.

5 (Clinical Resource #340321: Page 5 of 5) 33. McEvoy GK, Ed. Handbook of Injectable Drugs. 19 th ed. Bethesda, MD: American Society of Heath- System Pharmacists, Inc. 2017; Spaulding A. Trick of the trade: IV-push antibiotics in the ED. May 11, Academic Life in Emergency Medicine. (Accessed February 21, 2018). Cite this document as follows: Clinical Resource, Sterile Water Shortages. Pharmacist s Letter/Prescriber s Letter. March Evidence and Recommendations You Can Trust 3120 West March Lane, Stockton, CA ~ TEL (209) ~ FAX (209) Copyright 2018 by Therapeutic Research Center Subscribers to the Letter can get clinical resources, like this one, on any topic covered in any issue by going to PharmacistsLetter.com, PrescribersLetter.com, PharmacyTechniciansLetter.com, or NursesLetter.com