Physical Incompatibilities of Antineoplastics
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Henry, 1/e, ISBN 978-1-4160-3183-3 Chapter 012 (edited file)—“Tables 12B-1 and 12B-2” 4/10/2020, Page 1 of 12, 0 Figure(s), 2 Table(s), 0 Box(es) Physical Incompatibilities of Antineoplastics Agent BCNU (Carmustine) Cyclophosphamide Dacarbazine (DTIC) Drug Incompatibilities Comments ALKYLATING AGENTS Allopurinol sodium12 Gas evolves immediately Sodium bicarbonate Decomposition of drug with sodium bicarbonate or solutions2,8,12 solutions with pH >6.02 Dextrose 5% in water2,12 PVC containers2,12 Inactivates agent2 Inactivates agent; recommend glass containers2 Amphotericin B cholesteryl sulfate complex12 Increased turbidity immediately Benzyl alcohol7,11 Decomposition of drug in contact with benzyl alcohol; avoid in vitro contact Allopurinol sodium12 Cefepime HCl12 Small particles within 1 hr Cloudy solution immediately Dextrose 5% in water12 Some degradation of drug with increased contact Heparin1,3,12 Drug precipitates at 25 mg/ml dacarbazine and 100 U/ml heparin; no precipitation at lower DTIC concentrations12 Hydrocortisone sodium succinate1,2,5,7,8,11 Physically incompatible2; avoid in vitro combination; immediate pink precipitate5 Lidocaine1 Physically incompatible Light 1,5 50% deactivation when left in room light >4 hr Piperacillin sodiumtazobactam sodium12 Drug precipitates Ifosfamide Cefepime HCl12 Methotrexate sodium12 Precipitates in <1 hr Precipitates in 4 hr Mechlorethamine Acidic solutions2,8 Alkaline or neutral solutions2,3,12 Immediate decomposition of agent2 Agent is highly unstable in these solutions2; avoid with sodium thiosulfate or sodium bicarbonate solutions Allopurinol sodium12 Immediate precipitation 12 Cefepime HCl Dextrose 5% in water12 Immediate precipitation Degradation of agent Methohexital sodium9,12 Physically incompatible Henry, 1/e, ISBN 978-1-4160-3183-3 Chapter 012 (edited file)—“Tables 12B-1 and 12B-2” 4/10/2020, Page 2 of 12, 0 Figure(s), 2 Table(s), 0 Box(es) Melphalan Sodium chloride 0.9%12 Degradation of agent within several hours Amphotericin B12 Precipitation in sodium chloride solution Chlorpromazine HCl12 Dextrose 5% in water12 Precipitation in <1 hr Degradation of agent within <2 hr Ringer’s injection, lactated12 Degradation within hours Sodium chloride 0.9% Procarbazine Streptozocin Actinomycin D (Dactinomycin, DACT) Bleomycin Daunorubicin 12 Degradation within <1 hr 5 Aqueous solution Degradation of agent to toxic compounds5 5 Light Inactivation Allopurinol sodium12 Haze within 1 hr Aztreonam12 Color change within 1 hr Cefepime HCl12 Haze immediately and color change Piperacillin sodiumParticle formation within 1 hr tazobactam sodium12 ANTI-TUMOR ANTIBIOTICS Diluents with preservatives5,8,12 Precipitation Filgrastin12 Immediate precipitatation Filters1,8,11,12 Do not use filters, which remove drug from solution, particularly cellulose8,11,12 Amino acids7 Aminophylline7,8,12 Ascorbic acid2,5,7-9,12 Carbenicillin8 Cefazolin8,12 Cephalothin7,8 Copper (or other ionic solutions)7,8,11 Physically incompatible 50% loss of activity in 1 week12 Loss of all activity over 1 week12 Physically incompatible 43% loss of activity in 1 week12 Physically incompatible Bleomycin chelates with divalent and trivalent anions; do not mix Dexamethasone7 Dextrose 5% in water2,12 Diazepam7,8,12 Droperidol7 Furosemide7 Hydrocortisone sodium succinate7,8,12 Physically incompatible Inactivation of agent Physically incompatible Physically incompatible Physically incompatible Loss of activity in 1 week12 Hydrogen peroxide5,9 Methotrexate7,8,12 Mitomycin C7,8,12 Nafcillin8,12 Physically incompatible Loss of activity in 1 week12 Loss of activity in 1 week12 Loss of activity in 1 week12 Penicillin7,8,12 Riboflavin2,7 Sulfhydryl-group containing compounds5,7,9 Terbutaline7,8,12 Aluminum12 Allopurinol12 Loss of activity in 1 week12 Physically incompatible Physically incompatible Loss of activity in 1 week12 Results in color change Color change Henry, 1/e, ISBN 978-1-4160-3183-3 Chapter 012 (edited file)—“Tables 12B-1 and 12B-2” 4/10/2020, Page 3 of 12, 0 Figure(s), 2 Table(s), 0 Box(es) Doxorubicin Doxorubicin (liposome encapsulated; Doxil) Aztreonam12 Cefepime HCl12 Dexamethasone sodium phosphate2,5,8,9,12 Haze immediately Haze immediately Gross precipitate Fludarabine phosphate12 Heparin1,2,4,5,8,9,11,12 Haze formation Precipitate Solutions with pH >8.02 Piperacillin sodiumtazobactam sodium12 Color change Turbidity immediately Aluminum11,12 Aluminum hubs may inactivate drug Allopurinol12 Aminophylline1,5,7-9,12 Precipitate Decomposition of agent, solution darkening12 Amphotericin B12 Cefepime HCl12 Cephalothin5,7-9 Combination ondansetron and dacarbazine Cyclosporine1 Dexamethasone sodium phosphate1,5,7-9 Precipitate formation Precipitate formation Precipitate formation Inactivation of doxorubicin and ondansetron Diazepam1,5,7,9,12 Fluorouracil2,5,7-9,12 Furosemide1,7,8,12 Ganciclovir sodium12 Heparin1,2,4,5,7-9,11,12 Hydrocortisone sodium phosphate9 Hydrocortisone sodium succinate5,7,9 Immediate precipitate Color change Precipitate formation Color change Precipitate formation Precipitate formation Piperacillin sodiumtazobactam sodium12 Propofol12 Streptozocin1 Precipitate formation TPN (212-215)12 Vinblastine12 Physically incompatible Suspected to be incompatible Amphotericin B12 Buprenorphine HCl12 Cefoperazone sodium12 Ceftazidime12 Docetaxel12 Filters12 Precipitate within 4 hr Loss of turbidity Loss of turbidity Loss of turbidity Loss of turbidity Removes liposome; do not use filters Hydroxyzine HCl12 Mannitol12 Meperidine HCl12 Precipitate in 4 hr Loss of turbidity Increase in turbidity Physically incompatible Precipitate formation Precipitate formation Emulsion breaks Physically incompatible Henry, 1/e, ISBN 978-1-4160-3183-3 Chapter 012 (edited file)—“Tables 12B-1 and 12B-2” 4/10/2020, Page 4 of 12, 0 Figure(s), 2 Table(s), 0 Box(es) Metoclopramide12 Mitoxantrone HCl12 Morphine sulfate12 Paclitaxel12 Piperacillin sodiumtazobactam sodium12 Increase in turbidity Loss of turbidity Loss of turbidity Loss of turbidity Loss of turbidity Promethazine HCl12 Increase in turbidity 12 Epirubicin Idarubicin Mitomycin C Sodium bicarbonate Alkaline solutions Combination ifosfamide and mesna12 Fluorouracil12 Acyclovir8,12 Alkaline solutions1,3 Allopurinol sodium12 Ampicillin8,12 Loss of turbidity Hydrolyzes agent Loss of 50% epirubicin by 7 days Cefazolin8,12 Cefepime12 Ceftazidime8,12 Precipitate within 1 hr Precipitate within 4 hr Haze forms within 1 hr Cilastin8 Clindamycin8,12 Haze formation Precipitate within hours Precipitate within 12 min Precipitation Precipitate within 1 hr Immediate precipitate Dexamethasone8,12 Etoposide8,12 Furosemide8,12 Gentamicin8,12 Heparin1,2,3,8,12 Hydrocortisone sodium succinate8,12 Imipenim8 Lorazepam8,12 Immediate precipitate Immediate gas formation Immediate precipitate Immediate color change Immediate precipitate Immediate precipitate Meperidine8,12 Methotrexate8,12 Mezlocillin8 Immediate color change Immediate color change Immediate precipitate Piperacillin sodiumtazobactam sodium12 Immediate precipitate Sodium bicarbonate8,12 Teniposide (VM-26)12 Vancomycin8,12 Immediate precipitate Immediate color change Immediate color change Vincristine8,12 Acidic solutions12 Alkaline solutions12 Aztreonam12 Bleomycin sulfate12 Cefepime HCl Dextrose solutions12 Immediate color change Decomposition Decomposition Color change within 4 hr Loss of activity in 1 week Color change within 1 hr Incompatible at some concentrations Etoposide (VM-16)12 Filgrastim12 Color change within 1hr Color change within 1 hr Immediate color change Immediate color change Henry, 1/e, ISBN 978-1-4160-3183-3 Chapter 012 (edited file)—“Tables 12B-1 and 12B-2” 4/10/2020, Page 5 of 12, 0 Figure(s), 2 Table(s), 0 Box(es) Mitoxantrone Antimetabolites Azathioprine Cytosine arabinoside (Cytarabine) Gemcitabine12 Piperacillin sodiumtazobactam sodium12 Color change within 1 hr Color change within 4 hr Sagramostim12 Sodium chloride 0.9%12 Precipitate in 30 min At 50 mg/L mitomycin, incompatible; however, not at other concentrations Vinorelbine12 Color change in 1 hr Amphotericin B cholesteryl sulfate complex12 Gross precipitate forms Aztreonam12 Cefepime HCl12 Heavy precipitate in 1 hr Haze immediately Doxorubicin HCl liposome injection12 Fluorouracil7 Loss of turbidity Heparin2,3,7,8 Hydrocortisone sodium phosphate12 Precipitate formation 100–200 g hydrocortisone with 50–200 mg mitoxantrone in D5W in PVC; this did not occur with same concentrations in glass container Paclitaxel12 Piperacillin sodiumtazobactam sodium12 Propofol12 TPN (212–215)12 Decreased natural haze of paclitaxel Haze immediately Alkaline pH solutions8,11,12 Azathioprine is metabolized to mercaptopurine at alkaline pH Cysteine (or other sulfhydrylcontaining compounds)12 Hydrolysis to mercaptopurine occurs in presence of cysteine Allopurinol sodium12 Particles within 4 hr Amphotericin B cholesteryl sulfate complex12 Gross precipitate Alkaline solutions12 Increased rate of decomposition Benzyl alcohol2 Bacteriostatic water containing benzyl alcohol should not be used for reconstitution Carbenicillin8 Cephalothin7 Particles form immediately Loss of natural turbidity Henry, 1/e, ISBN 978-1-4160-3183-3 Chapter 012 (edited file)—“Tables 12B-1 and 12B-2” 4/10/2020, Page 6 of 12, 0 Figure(s), 2 Table(s), 0 Box(es) Fluorouracil5,7,9,11,12 Ganciclovir sodium12 Gentamicin sulfate7,8,12 Heparin7,8,12 Hydrocortisone sodium succinate7,12 Insulin, regular7,8,12 Methotrexate7,9,11 Methylprednisolone sodium succinate7,12 Nafcillin sodium8,12 12 Fluorouracil Change in spectrophotometry of cytarabine5,9,12 Turbidity within 30 min Physically incompatible, but compatible for 24 hr at 80 mg/L gentamicin and 300 mg/L cytarabine Haze formation Physically incompatible Fine precipitate formation Change in spectrophotometry of methotrexate9 At 250 mg/L MPSS and 360 mg/L cytarabine 12 Heavy precipitate Oxacillin sodium pH outside stability range for oxacillin Penicillin sodium7,12 TPN (#212–215)12 pH outside stability range for penicillin Loss of natural turbidity Amino acids7,8,11 Amphotericin B cholesteryl sulfate complex12 Carboplatin12 Cisplatin12 Cytarabine5,7,9,12 Microprecipitate immediately >20% carboplatin loss in 24 hr Loss of cisplatin within 4 hr Change in spectrophotometry of cytarabine Dextrose solutions7 10% loss of fluorouracil in 7 hr at room temperature Diazepam5,7,8,9,11,12 Doxorubicin5,8,9,11,12 Droperidol7,12 Epirubicin HCl12 Fentanyl citrate12 Filgrastim12 Precipitate Color change Immediate precipitation Precipitate within hrs Loss of fentanyl Particles in 1 hr Insulin7,8,11 Leucovorin calcium12 Particulate formation Methotrexate5,7,8,9,11 Metoclopramide12 Change in spectrophotometry of both Loss of both drugs Morphine sulfate12 Multivitamins7,8,11 Ondansetron12 Precipitate Immediate precipitation 7,8,11 Gemcitabine Penicillin Tetracycline7,8,11 TPN (#212–215)12 Vinorelbine tartrate12 Acyclovir sodium12 Amphotericin B12 Cefoperazone sodium12 Cefotaxime sodium12 Turbidity formation Precipitate immediately Precipitate immediately Precipitate immediately Precipitate immediately Haze formation Furosemide12 Precipitate immediately Henry, 1/e, ISBN 978-1-4160-3183-3 Chapter 012 (edited file)—“Tables 12B-1 and 12B-2” 4/10/2020, Page 7 of 12, 0 Figure(s), 2 Table(s), 0 Box(es) Mercaptopurine Ganciclovir sodium12 Imipenem-cilastatin sodium12 Precipitate immediately Color change within 1 hr Methotrexate12 Methylprednisolone sodium succinate12 Precipitate immediately Precipitate immediately Mitomycin12 Piperacillin sodium12 Piperacillin sodiumtazobactam sodium12 Prochlorperazine edixylate12 Allopurinol sodium8,9 Allopurinol sodium in D5W5,7,9 Color change Cloudiness immediately Cloudiness immediately Prednisolone sodium succinate8,9 Physical incompatibility Haze immediately Physical incompatibility Prednisolone sodium succinate and D5W5,7 Methotrexate Aluminum12 Bleomycin sulfate12 Orange crystal formation with aluminum needles 60% loss of bleomycin activity in 1 week Chlorpromazine12 Cytarabine5,8,9,11 Dexamethasone sodium phosphate12 Droperidol7,12 Turbidity and precipitate immediately Change in spectrophotometry of methotrexate8,9 Dark precipitate in 4 hr 5,7,8,9,11 Immediate precipitate Fluorouracil Gemcitabine12 Idarubicin12 Change in spectrophotometry of both8,9 Precipitate immediately Color change immediately Ifosfamide12 Metoclopramide7,12 Yellow precipitate in 4 hr Incompatible; if mixed, use immediately Midazolam12 Nalbuphine HCl12 Yellow precipitate immediately Yellow precipitate immediately Prednisolone sodium phosphate7,8,9,11 Change in spectrophotometry of both8,9 Promethazine HCl12 Turbidity in 30 min Propofol 12 Precipitate in 1 hr 7 Ranitidine HCl TPN (#212–215)12 Vancomycin12 Etoposide (VP-16) Loss of natural turbidity Precipitate within 4 hr PLANT ALKALOIDS Alkaline solutions8,12 Inactivates drug (hydrolysis) Amphotericin B12 Cefepime HCl12 Chlorpromazine12 Precipitate with etoposide phosphate Haze formation Precipitate with etoposide phosphate Dextrose solutions7,9 Filgrastim12 Precipitate formation9 Particles immediately Henry, 1/e, ISBN 978-1-4160-3183-3 Chapter 012 (edited file)—“Tables 12B-1 and 12B-2” 4/10/2020, Page 8 of 12, 0 Figure(s), 2 Table(s), 0 Box(es) Idarubicin12 Imipenem-cilastatin sodium12 Gas forms immediately Discoloration with etoposide phosphate Methylprednisolone sodium succinate12 Mitomycin12 Haze formation with etoposide phosphate Prochlorperazine edisylate Paclitaxel 12 Leaches diethylhexyl phthalate (DEHP) plasticizer Precipitate Amphotericin B2,12 Aqueous solutions12 Decreased natural turbidity Unpredictable precipitate formation Chlorpromazine HCl2,12 Normal paclitaxel haze decreases Cisplatin Dextrose 5% in water12 Doxorubicin liposome injection12 Hydroxyzine HCl2,12 Methylprednisolone sodium succinate2,12 Mitoxantrone HCl2,12 PVC containers1,2,8,12 Vincristine Subvisual particulates after 3–5 days At some concentrations Loss of natural turbidity Normal paclitaxel haze decreases Normal paclitaxel haze decreases Cefepime12 Doxorubicin12 Furosemide7,12 Normal paclitaxel haze decreases PVC can leach out plasticizer DHEP when exposed to Cremophor-containing solutions Haze immediately Questionable compatibility; assays erratic Immediate precipitation Heparin sodium7,12 Solutions with pH <3.5, >5.53 Turbidity within minutes Inactivate drug Alkaline solutions12 Precipitation 12 Vinorelbine Precipitate immediately with etoposide phosphate PVC containers12 Sodium chloride 0.9%7,12 12 Vinblastine Color change with etoposide phosphate Cefepime Furosemide7,12 Light2,12 Immediate precipitate Immediate precipitate Inactivated in light Idarubicin12 Sodium bicarbonate12 Solutions with pH <3.5, >5.53 Color change immediately White precipitate Incompatible Acyclovir sodium12 Precipitates immediately Allopurinol sodium Aminophylline 12 12 Precipitates immediately Light haze immediately Amphotericin B12 Amphotericin B cholesteryl complex12 Immediate yellow precipitate Gross precipitate Ampicillin sodium12 Precipitates immediately Henry, 1/e, ISBN 978-1-4160-3183-3 Chapter 012 (edited file)—“Tables 12B-1 and 12B-2” 4/10/2020, Page 9 of 12, 0 Figure(s), 2 Table(s), 0 Box(es) Cefazolin sodium12 Cefotetan disodium12 Ceftriaxone sodium12 Turbidity increases Precipitates immediately Precipitates immediately Cefuroxime sodium12 Turbidity increases Fluorouracil12 Precipitates immediately Furosemide 12 Ganciclovir sodium12 Precipitates immediately Methylprednisolone sodium succinate12 Mitomycin12 Precipitates immediately Piperacillin sodium Carboplatin Cisplatin Precipitates immediately 12 Color change within 1 hr Increased turbidity Sodium bicarbonate12 Precipitates immediately Thiotepa12 Precipitates immediately Trimethoprimsulfamethoxazole12 Precipitates immediately PLATINUM AGENTS Alkaline solutions (pH >6)12 Increased degradation Aluminum1,2,3,8,12 Do not use aluminum needles; displaces platinum from agent2 Amphotericin B cholesteryl Turbidity increases sulfate complex12 Fluorouracil12 Mesna12 >20% carboplatin loss in 24 hr >10% carboplatin loss in 24 hrs Sodium bicarbonate12 Sodium chloride2,5,12 200-nM solution has 13% loss in 24 hr Controversial; converts carboplatin to cisplatin at rate of <10% per day12 Increased hydrolysis12 Alkaline solutions12 Aluminum1,2,12 Do not use aluminum needles; displaces platinum from agent2 Amifostine12 Amphotericin B cholesteryl sulfate complex12 Cefepime HCl12 Subvisual haze in 4 hr Gross precipitate formation Dextrose 5% in water 5,7,8,12 Haze formation in 1 hr Breakdown after 2 hr in solution7 Fluorouracil12 Cisplatin loss within several hours Light2,12 Mannitol2,5,7,8,9 Degradation of drug Time-dependent degradation of cisplatin9; can store together for less than 2–3 days8 Cisplatin not detectable after 1 hr Mesna8,12 Metoclopramide Paclitaxel12 Particulate formation after 3–5 days Henry, 1/e, ISBN 978-1-4160-3183-3 Chapter 012 (edited file)—“Tables 12B-1 and 12B-2” 4/10/2020, Page 10 of 12, 0 Figure(s), 2 Table(s), 0 Box(es) L-Asparaginase Piperacillin sodiumtazobactam sodium12 Refrigeration12 Haze and particles in 1 hr Sodium bicarbonate 5%2,4,5,7 Sodium bisulfite2,7,11 Sodium chloride <0.2%2 Enhanced decomposition of agent; gold precipitate Cisplatin inactivated Decomposition of agent Sodium thiosulfite2,8 Inactivates agent Thiotepa12 TPN (#212–215)12 White cloudiness in 4 hr Discoloration in 1-4 hr Filters <0.2 m 12 Particle formation MISCELLANEOUS Filters 5 m are fine12; filters bind asparaginase8 Henry, 1/e, ISBN 978-1-4160-3183-3 Chapter 012 (edited file)—“Tables 12B-1 and 12B-2” 4/10/2020, Page 11 of 12, 0 Figure(s), 2 Table(s), 0 Box(es) REFERENCES 1. Baquiran DC and Gallagher J: Lippincott’s Cancer Chemotherapy Handbook, Philadelphia, 1998, Lippincott-Raven. A handbook on general management of chemotherapy reactions in human patients, drug administration, and individual drug information including drug interactions. 2. Dorr RT and Fritz WL: Drug Interactions. In Cancer Chemotherapy Handbook. New York, 1980, Elsevier. A textbook on general chemotherapy principles in human medicine, individual chemotherapy information and drug interactions. 3. Dorr RT and Von Hoff DD: Cancer Chemotherapy Handbook, ed 2, Norwalk, 1994, Appleton & Lange. A textbook on administration of chemotherapy in human patients and individual drug information including drug interactions for each drug. 4. Henry CJ and Brewer WJ: Drug Interactions with Antineoplastic Agents. In Current Veterinary Therapy XII, Philadelphia, 1995, WB. Saunders. This chapter lists chemotherapy agents and drugs with which they interact in vivo as well as in vitro incompatibilities focusing on drugs more commonly used in veterinary medicine. 5. Hansten PD and Horn JR: Hansten and Horn’s Managing Clinically Important Drug Interactions, Vancouver, 1998, Applied Therapeutics, Inc. A manual of specific drug interactions listed by individual drug, and how to manage the toxicities and interactions, not limited to chemotherapy agents. 6. McEvoy GK(editor): Antineoplastic Agents. In American Hospital Formulary Services (AHFS) Drug Information, Bethesda, 2005, American Society of Health-System Pharmacists, Henry, 1/e, ISBN 978-1-4160-3183-3 Chapter 012 (edited file)—“Tables 12B-1 and 12B-2” 4/10/2020, Page 12 of 12, 0 Figure(s), 2 Table(s), 0 Box(es) Inc. A pharmaceutical manual providing details of individual drug information including pharmacology, use, toxicities, drug interactions, incompatibilities, stability, and chemistry of agents. 7. Olin BR (ed): Drug Interactions. In Drug Facts and Comparisons, St. Louis, 1992, Wolters Kluwer Company. A manual of pharmacologic information on drugs. 8. Fisher DS, Knobf M Tish and Durivage HJ: Drug Interactions with Antineoplastic Agents. In The Cancer Chemotherapy Handbook, ed 4, St. Louis, 1993, Mosby. A manual on chemotherapy principles, administration, and drug interactions. 9. Griffin JP and D’arcy PF: Antineoplastic Agents. A Manual of Adverse Drug Interactions, ed 3, Bristol, 1984, Wright. A textbook on drug interactions not limited to chemotherapy. 10. Chabner BA and Longo DL: Cancer Chemotherapy and Biotherapy: Principles and Practice, ed 3. Philadelphia, 2001, Lippincott Williams & Wilkins. A textbook on principles of chemotherapy and chemotherapy drug information. 11. Dorr RT: Incompatibilities with Parenteral Anticancer Drugs. In the American Journal of Intravenous Therapy. 6(2):44, 1979. A review of in vitro chemotherapy drug interactions. 12. Trissel LA: Handbook on Injectable Drugs, ed 11, Bethesda, 2001, American Society of Health-System Pharmacists, Inc. A textbook providing detailed information regarding in vitro drug interactions, stability, and pharmacology of individual drugs based on in vitro studies.
