Oxaliplatin desensitization protocol

Section editor
	Austin Fitts, PharmD National Cancer Institute Silver Springs, MD, USA LinkedIn

This desensitization protocol is one example of what is used in clinical practice for patients who require treatment with Oxaliplatin (Eloxatin), yet have a history of hypersensitivity to it, and for which there are no equally effective alternatives. Desensitization will not affect the incidence of non-IgE mediated reactions such as serum sickness, Stevens-Johnson syndrome, exfoliative dermatitis, hemolytic anemia, maculopapular rash, drug fever, or interstitial nephritis.

Preparation & setting

1. The provider should obtain an complete allergy history of the prior allergic reaction(s), ensure that the previous reaction was not a type of erythema multiforme, and clarify whether the reaction was consistent with an anaphylaxis or a less well-described rash.
2. Patients are generally admitted to an area, such as an intensive care unit (ICU), where there can be 1:1 nursing supervision of the infusion. Patients who have successfully tolerated previous desensitizations may be considered by physician discretion on a case-by-case basis for lower acuity settings such as the inpatient oncology floor or outpatient infusion center.
3. A signed consent for the chemotherapy regimen should be obtained from the patient.
4. Patients who are using beta-blockers or ACE (angiotensin converting enzyme) inhibitors should ideally have these discontinued prior to desensitization, since they can lower the threshold for anaphylaxis or blunt treatment effects.
5. A blood pressure cuff should be at the bedside, and a peak flow meter should be available if needed.
6. A qualified physician or nurse must be in the patient room for the first 15 minutes after the first dose during the protocol and for 5 minutes after each subsequent dose. A physician must be available by page during the protocol.

Concentrations of Oxaliplatin (Eloxatin) & administration parameters

Five different solutions containing Oxaliplatin (Eloxatin) at different concentrations are to be prepared as described below.

• This Oxaliplatin desensitization spreadsheet can be used to to calculate the necessary solutions based on the target dose of Oxaliplatin (Eloxatin).
• In the tables below, x is the target dose, in milligrams (calculated based on the mg/m² dosage from the chemotherapy regimen) of Oxaliplatin (Eloxatin) to be administered.

Solution #	Dilution	Total amount of drug in solution	Volume	Concentration
1	1/10,000th dilution	x/10,000 mg	100 mL	x/1,000,000 mg/mL
2	1/1000th dilution	x/1000 mg	100 mL	x/100,000 mg/mL
3	1/100th dilution	x/100 mg	100 mL	x/10,000 mg/mL
4	1/10th dilution	x/10 mg	100 mL	x/1000 mg/mL
5	standard concentration	x*0.9 mg	500 mL	(x*0.9)/500 mg/mL

These five solutions are to be administered as follows:

Step #	Solution #	Rate	Time per step	Volume per step	Dose/step	Cumulative dose
1	1	100 mL/H	60 min	100 mL	x/10,000 mg	x/10,000 mg
2	2	100 mL/H	60 min	100 mL	x/1000 mg	(x/10,000 mg) + (x/1000 mg)
3	3	100 mL/H	60 min	100 mL	x/100 mg	(x/10,000 mg) + (x/1000 mg) + (x/100 mg)
4	4	100 mL/H	60 min	100 mL	x/10 mg	(x/10,000 mg) + (x/1000 mg) + (x/100 mg) + (x/10 mg)
5	5	125 mL/H	237.04 min	493.83 mL	x*0.88889999 mg	x mg

• The total time of solution 5 is calculated to use slightly less than the full bag, which takes into account the small amounts of medication administered in the more dilute solutions, so that the correct total dose is administered, not slightly more than the intended amount.
• Total time to administer: 477.04 minutes
• Total dose: x mg

Supportive medications

• Diphenhydramine (Benadryl) 25 mg IV 30-60 minutes prior to the start of chemotherapy
• Famotidine (Pepcid) 40 mg PO or 20 mg IV 30-60 minutes prior to the start of chemotherapy
• Lorazepam (Ativan) 1 mg PO prn nausea, anxiety 30-60 minutes prior to the start of chemotherapy
• Montelukast (Singulair) 10 mg PO 60 minutes prior to the start of chemotherapy; some providers also give an earlier dose 12 hours prior to the start of chemotherapy
• Methylprednisolone (Solumedrol) 40 mg IV 30-60 minutes prior to the start of chemotherapy
• Standard premedications typically used with oxaliplatin, such as calcium gluconate and magnesium sulfate; see example orders.
• Diphenhydramine (Benadryl) 25-50 mg IV or PO prn allergic reaction and Epinephrine (Epipen) 0.3 mg IM prn allergic reaction as noted below:
  • If the patient develops a mild reaction, such as fever, self-limiting rash, itching, mild chest tightness, abdominal or back pain, nausea, another dose of Diphenhydramine (Benadryl) 25-50 mg IV or PO may be given. Observe until the reaction improves, then resume the infusion at the point where it was stopped. If the reaction does not improve within 30 minutes, contact the allergist on call.
  • If the patient develops a moderate to severe reaction, such as acute dyspnea or angioedema, and/or acute hypotension, stop protocol, follow ACLS guidelines to treat, use Epinephrine (Epipen) 0.3 mg IM for hypotension or glottic edema, and nebulized albuterol for bronchospasm. Discuss the event with the attending allergy physician on call. When the patient is stable, the protocol may be resumed (with allergist's guidance regarding the rate at which to restart and with revisions if necessary).

Example orders

Example orders for Oxaliplatin (Eloxatin) desensitization protocol

References

1. Gammon D, Bhargava P, McCormick MJ. Hypersensitivity reactions to oxaliplatin and the application of a desensitization protocol. Oncologist. 2004;9(5):546-9. link to original article contains dosing details in abstract PubMed
2. Nozawa H, Muto Y, Yamada Y. Desensitization to oxaliplatin with two stages of premedication in a patient with metastatic rectal cancer. Clin Ther. 2008 Jun;30(6):1160-5. link to original article PubMed
3. Mis L, Fernando NH, Hurwitz HI, Morse MA. Successful desensitization to oxaliplatin. Ann Pharmacother. 2005 May;39(5):966-9. Epub 2005 Mar 22. link to original article PubMed
4. Rosique-Robles D, Vicent Verge JM, Borrás-Blasco J, Giner-Marco V, Casterá E, Galan-Brotons A, Abad J. Successful desensitization protocol for hypersensitivity reactions caused by oxaliplatin. Int J Clin Pharmacol Ther. 2007 Nov;45(11):606-10. link to original article PubMed