INTRODUCTION 45-year-old man with resected Stage III colorectal cancer was to receive 12

cycles of FOLFOX (leucovorin, 5-fluorouracil, oxaliplatin).

During the 7th FOLFOX treatment, the patient experienced a grade III

hypersensitivity reaction after 2 minutes of oxaliplatin infusion.

Generalized erythema, rash on torso, diaphoresis, hypotension,

O2 desaturation. Patient received medications, IV fluids, supplemental O2

and was discharged home in stable condition after several hours.

Due to curative intent of chemotherapy and increased efficacy of oxaliplatin-

based chemotherapy, the oncologist wished to continue FOLFOX.

Immunology was consulted to determine whether patient can receive

oxaliplatin despite having had a hypersensitivity reaction.

As per recommendation from allergist, patient would require oxaliplatin

desensitization at each subsequent FOLFOX treatment.

No prior platinum chemotherapy desensitization had been performed at

St. Michael’s Hospital.

Despite published oxaliplatin desensitization protocols and case reports,

limited details exist in literature regarding preparation, handling and

administration considerations.1, 2

Patient’s chemotherapy was stopped after 1 oxaliplatin desensitization

treatment due to worsening neuropathy attributed to oxaliplatin.

St. Michael’s Hospital REB approval was obtained for publication of this case.

OBJECTIVE To identify practical considerations and solutions to enable safe administration

of oxaliplatin desensitization in an intensive-care unit at a tertiary hospital

METHODS Contacted Dr. Mariana Castells and team at Brigham and Women’s College

Hospital Drug Hypersensitivity and Desensitization Centre in Boston, Massachusetts due to their expertise in high risk desensitization3

Established interdisciplinary team because multiple services involved Table 1

Team used meetings and emails to identify challenges, propose and

implement solutions

RESULTS

Challenge Solution

Lack of stability data for very

low concentrations of

oxaliplatin in IV bags used in

desensitization protocol

Oxaliplatin stability data on product

monograph extrapolated to apply to

concentrations in the protocol

Rationale: oxaliplatin not known to leach or

adhere to polyvinyl PL 146 plastic IV bags

Need for standardized

prescribing, and clear

communication of steps for

preparation and infusion of

oxaliplatin IV bags

Stakeholder input

Pharmacy department developed:

1. Pharmacy worksheet for IV bag

preparation Figure 3

2. Physician’s Orders template Figure 4

3. Nursing MAR with detailed instructions for

execution of protocol Figure 5

Need to satisfy safety

requirements for handling

cytotoxic drug during

preparation and infusion of

oxaliplatin IV bags

IV line primed with D5W to avoid exposure to

cytotoxic medication

IV line measured to have 15 mL volume,

hence first 15 mL at the beginning of each

new IV bag rapidly infused into an empty IV

bag before connecting to patient’s IV access

and starting infusion at rate as per protocol.

Instruction for RN outlined in MAR Figure 5

D5W in drip chamber

inappropriately diluting the

oxaliplatin solution

Drip chamber and line primed with D5W

Invert drip chamber and squeeze content

back into IV bag

Spike oxaliplatin bag with line. Fill drip

chamber to fill line with IV bag contents.

Instruction for RN outlined in MAR Figure 5

Appropriate and adequate

staffing

Compounding pharmacist and pharmacy

technician work hours adjusted to enable

oxaliplatin bags compounded and delivered

to ICU by 0800h on day of treatment

Chemotherapy-certified ICU nurse assigned

to care for patient in ICU

ICU nurse educator, managers, oncology

pharmacist on standby to assist during

administration

Oncologist and allergist available by pager

DISCUSSION Attempting a high-risk procedure such as a cytotoxic drug desensitization is a

team effort, and requires communication with multidisciplinary team to define

roles, identify practical considerations and develop strategies to address

challenges

Frequent and open communication amongst all involved team members is

essential to success

Collaboration with external expertise may be necessary to devise patient-

specific protocol

Site-specific drug handling policies and occupational safety guidelines govern

how and when the drug is stored and handled during the desensitization

Adequate staffing, bed availability and arrangements for post-desensitization

care must be planned well in advance

All worksheets and paper orders must be finalized and made available to the

responsible staff prior to the day of the procedure

RESULTS (continued)

Figure 5. Page 1 (left) and page 2 (right) of nursing Medication Administration Record. Detailed instructions provided for steps to be taken before, during and after infusion of each IV bag.

a.Detailed instructions to avoid dilution in drip chamber.

b.Repeating same instructions for each step

Ph

arm

acy

Pharmacy managers

Oncology pharmacist

ICU pharmacist

Compounding pharmacist

Pharmacy students

Nu

rsin

g

ICU clinical leader manager

ICU clinical nurse educator

ICU clinical nurse specialist

ICU nurse

Oncology nurse

Med

ical Oncologist

Allergist

ICU attending

3

Table 1. Team members involved in planning and

preparation of the desensitization protocol

Table 2. Identified challenges and implemented solutions

Figure 4. Page 1 (left) and page 2 (right) of physician order template of desensitization protocol

Preprinted order for pre-medications

Preprinted order for

management of emergent

hypersensitivity reaction

RESULTS (continued)16-step oxaliplatin desensitization protocol based on patient’s calculated oxaliplatin dose from Castells et al. Figure 2

Figure 2. 16-step oxaliplatin desensitization protocol

REFERENCES

ACKNOWLEDGEMENTS

CONTACT INFORMATION Ruth Law, PharmDClinical Pharmacy Practitioner, St. Michael’s Hospital, Toronto.lawr@smh.ca

We thank Dr. Mariana Castells (Director, Drug Hypersensitivity and

Desensitization Center) and Donna-Marie Lynch (Nurse Practitioner) at Brigham

and Women’s Hospital, Boston, Massachusetts for providing the desensitization

protocol, and valued guidance

1. Madrigal-Burgaleta R, Berges-Gimeno MP, Angel-Pereira D, et al.

Hypersensitivity and desensitization to antineoplastic agents: outcomes of 189

procedures with a new short protocol and novel diagnostic tools assessment.

Allergy, 2013; 68(7): 853-861.

2. Limsuwan T, & Castells MC. Outcomes and safety of rapid desensitization for

chemotherapy hypersensitivity. Expert Opin Drug Saf. 2010; 9(1): 39-53.

3. Castells M. Rapid desensitization for hypersensitivity reactions to

chemotherapy agents. Curr Opin Allergy Clin Immunol 2006; 6:271–277.

The authors have no conflict of interest to declare.

A multidisciplinary team approach to ensuring safe administration of a desensitization protocol involving a cytotoxic medication

Arpit Chhabra1,2, BSc, Alexandra Kourkounakis1,2, BSc, Ruth Law1, PharmD1. St. Michael’s Hospital, Toronto 2. Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto

Figure 1. Milestones in the planning and execution of the desensitization protocol

Appropriate protocol specific to patient’s

oxaliplatin dose received from Castells et al

Pharmacy Worksheet, IV bag label set, MD

Order, nursing MAR generated by Pharmacy

Department

Team meetings and email communication to

(1) identify issues concerning staffing and

administration procedure, and

(2) ensure clarity of documents and roles

Team debriefing after completion of

desensitization protocol

Inset: IV bag labels designed to include key messages

Labels prepared for IV bags 1 and 2

Figure 3. Pharmacy worksheet for preparation of oxaliplatin IV bags

Independent double check by

pharmacist

Detailed step-wise

instructions