Protocols for Drug Allergy Desensitization

Protocols for Rapid and Slow Drug Allergy Desensitization

First EditionNovember, 2009

By

Timothy J. Sullivan, M.D.

Atlanta, Georgia

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Introduction

This short monograph is a compilation of representative protocols that have been used in our clinics to desensitize patients who met generally accepted criteria for a diagnosis of drug allergy. The purpose of presenting this information is to facilitate the design of protocols for use by other clinicians or investigators.

Approaches to patient specific diagnosis of drug allergy, assessment of relative risks, decisions about premedication, and other patient specific factors crucial to successful use of these protocols is beyond the scope of this monograph.

Rapid desensitization protocols have been used to allow use of medications in patients with IgE-mediated sensitivity to medications. The mechanism seems to be primariy acute antigen-specific mast cell desensitization. The general principles are to initiate desensitization with low microgram amounts of drug, doubling the dose every 15 minutes, and then careful observation for 2 hours after the administration of the last dose. Individual patients may require lower starting doses and longer intervals between doses. Representative oral desensitization and intravenous desensitization protocols are presented. Code 95180 per hour of the procedure to the nearest hour.

Slow desensitization protocols are used for management of patients with drug allergy involving

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mechanisms other than antigen-specific IgE. The best evidence at the moment is that gradually increasing doses allow metabolic adaptation to increasing need to clear reactive drug metabolites. This efficient metabolism of the drug minimizes the formation of the haptenated carrier molecules that induce immune responses and elicit allergic reactions. This process would not be expected to work with complete antigens such as insulin or aminoglycosides. Regardless of mechanism, the principles are to start at a low dose and increase over one to four weeks or more to reach therapeutic doses. Approximately 15% of patients will not be controlled with a one or two week protocol and may need slower increases in doses.

Modifications of the protocols to accommodate patient and drug issues are common in the published literature. As long as starting doses are low microgram doses, or lower, and the intervals between doses of antigen administration are not shortened the mast cell desensitization or metabolic adaptation has been reported to be successful with a wide variety of drug antigens.

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INTRODUCTION.............................................................................................................2Rapid desensitization.....................................................................................................2Slow desensitization.......................................................................................................2

ALENDRONATE (FOSAMAX) DESENSITIZATION................................................5AMOXICILLIN/CLAVULANATE DESENSITIZATION................................................6ANASTROZOLE (ARIMIDEX) DESENSITIZATION................................................7ASPIRIN DESENSITIZATION.......................................................................................8AZITHROMYCIN DESENSITIZATION......................................................................9CEFDINIR DESENSITIZATION.................................................................................10CEFPODOXIME DESENSITIZATION.......................................................................11CEPHALEXIN DESENSITIZATION...........................................................................12CIPROFLOXACIN DESENSITIZATION.......................................................................13CITALOPRAM (CELEXA) DESENSITIZATION..........................................................14CLINDAMYCIN DESENSITIZATION.......................................................................15CLONAZEPAM (KLONOPIN) DESENSITIZATION...............................................16CLOPIDOGREL (PLAVIX) DESENSITIZATION....................................................17COUMADIN DESENSITIZATION..............................................................................18COZAAR DESENSITIZATION....................................................................................19DEFERASIROX DESENSITIZATION........................................................................20ESTRADIOL DESENSITIZATION PROTOCOL......................................................21ESTRADIOL (ESTRACE) DESENSITIZATION.......................................................22FEBUXOSTAT (ULORIC) DESENSITIZATION...........................................................23GENTAMICIN INTRAVENOUS DESENSITIZATION...............................................24HYDROCHLOROTHIAZIDE DESENSITIZATION.................................................25INFLUENZA VACCINE DESENSITIZATION..........................................................26INSULIN DESENSITIZATION.......................................................................................27LEVOFLOXACIN DESENSITIZATION.....................................................................28METRONIDAZOLE DESENSITIZATION.................................................................29NITROFURANTOIN DESENSITIZATION................................................................30OPIATE SENSITIVITY.................................................................................................31PACLITAXEL (TAXOL) INTRAVENOUS DESENSITIZATION..............................32PENICILLIN DESENSITIZATION – ORAL..............................................................33PENICILLIN G INTRAVENOUS DESENSITIZATION - Materials.........................34PENICILLIN G INTRAVENOUS DESENSITIZATION PROTOCOL......................35PIPERACILLIN/TAZOBACTAM INTRAVENOUS DESENSITIZATION...............36SERTRALINE (ZOLOFT) DESENSITIZATION.......................................................37SULFASALAZINE (AZULFIDINE) DESENSITIZATION.......................................38TRIMETHOPRIM/SULFAMETHOXAZOLE DESENSITIZATION......................39VANCOMYCIN INTRAVENOUS DESENSITIZATION.........................................40

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ALENDRONATE (FOSAMAX) DESENSITIZATION

Need oral solutions prepared in the pharmacy:

75 mL of 70 mg/ 75 mL Fosamax

100 mL of 0.7 mg/75 mL (1:100 of 75 mg/75 mL)

This protocol will provide a cumulative 10 mg dose of Fosamax. Then conventional therapy with Fosamax 10 mg daily can begin. Place the indicated amount of the oral solution in a cup. Add at least

25 mL of water and swirl to make swallowing small doses feasible. Administer doses at least 15 minutes apart. Observe 2 hours after last

dose.

Dose Concentration Amount (mL)

Time Comments

1 0.7 mg/75 mL 0.1 mL2 0.7 mg/75 mL 0.23 0.7 mg/75 mL 0.44 0.7 mg/75 mL 0.85 0.7 mg/75 mL 1.66 0.7 mg/75 mL 3.27 0.7 mg/75 mL 68 0.7 mg/75 mL 129 0.7 mg/75 mL 25

10 70 mg/75 mL 0.511 70 mg/75 mL 112 70 mg/75 mL 213 70 mg/75 mL 314 70 mg/75 mL 4

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AMOXICILLIN/CLAVULANATE DESENSITIZATION

Augmentin Oral Suspension 600 mg amoxicillin/5 mL and 1 : 100 of that (6 mg/5 mL)


Time Comments

1 6 mg/5 mL 0.032 6 mg/5 mL 0.063 6 mg/5 mL 0.124 6 mg/5 mL 0.255 6 mg/5 mL 0.56 6 mg/5 mL 17 6 mg/5 mL 2

8 600 mg/5 mL 0.049 600 mg/5 mL 0.0810 600 mg/5 mL 0.1511 600 mg/5 mL 0.312 600 mg/5 mL 0.613 600 mg/5 mL 1.214 600 mg/5 mL 2.5

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ANASTROZOLE (ARIMIDEX) DESENSITIZATION

A slow desensitization (one that allows drug metabolism to keep up with the increasing doses, and also desensitizes mast cells) has been successful with Arimidex. We can use an oral suspension to deliver low doses. Since this is to start chronic therapy, we have used a protocol giving one dose once a day. We give the doses in the office to avoid errors by the patients. This would take ~2 weeks to reach full doses. Weekends provide logistical problems, but we prepare the weekend doses and give them to the patient to take at home on Fridays. We have started at 0.1 mcg (microgram) a day and doubled that amount every day. We reach full doses in about 2 weeks. The patient should be advised that if she stops the medication for more than 1 day, we would need to re-desensitize her. 0.1 mg Arimidex/mL Have a compounding pharmacy prepare an oral suspension.

0.001 mg Arimidex/mL Have a compounding pharmacy prepare a 1:100 dilution of the 0.1 mg/mL suspension.

Dose ConcentrationArimidex

Amount (mL)

Date Comments

1 0.001mg/mL 0.1 mL2 0.001mg/mL 0.2 mL3 0.001mg/mL 0.4 mL4 0.001mg/mL 0.8 mL5 0.001mg/mL 1.6 mL6 0.001mg/mL 3.2 mL7 0.001mg/mL 6.4 mL8 0.001mg/mL 13 mL9 0.001mg/mL 25 mL

10 0.1 mg/mL 0.5 mL11 0.1 mg/mL 1 mL12 0.1 mg/mL 2 mL13 0.1 mg/mL 4 mL14 0.1 mg/mL 8 mL

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ASPIRIN DESENSITIZATION

325 mg Alka-Seltzer tablets

One tablet in 100 mL water is ~3 mg/mL. Dissolve one tablet in 100 mL of water for each dose. The 0.3 mg/mL concentration is prepared immediately after preparing a 3 mg/mL solution by making a 1:10 dilution (e.g. 2 mL added to 18 mL of water)

Each dose is prepared fresh from one Alka-Seltzer tablet in 100 mL of water.

Give one dose every 15 minutes.

Dose Concentration Volume Given Comments

1 0.3 mg/mL 0.1 mL 2 0.3 mg/mL 0.2 mL 3 0.3 mg/mL 0.4 mL 4 3 mg/mL 0.08 mL 5 3 mg/mL 0.16 mL 6 3 mg/mL 0.3 mL 7 3 mg/mL 0.6 mL 8 3 mg/mL 1.2 mL 9 3 mg/mL 2.5 mL 10 3 mg/mL 4 mL 11 3 mg/mL 8 mL 12 3 mg/mL 16 mL 13 3 mg/mL 32 mL 14 3 mg/mL 64 mL

Then continue with aspirin therapy as desired, but one dose a day is needed to sustain desensitization.

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AZITHROMYCIN DESENSITIZATION

Azithromycin 200 mg/5 mL stock

Azithromycin 2 mg/5 mL (1 mL 200/5 + 99 mL water)

Dose Concentration Volume Time Comments

1 2 mg/5mL 0.06 mL 2 2 mg/5mL 0.12 mL 3 2 mg/5mL 0.25 mL 4 2 mg/5mL 0.5 mL 5 2 mg/5mL 1 mL 6 2 mg/5mL 2 mL

7 200 mg/5mL 0.04 mL 8 200 mg/5mL 0.08 mL 9 200 mg/5mL 0.16 mL 10 200 mg/5mL 0.32 mL 11 200 mg/5mL 0.64 mL 12 200 mg/5mL 1.25 mL 13 200 mg/5mL 2.5 mL

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CEFDINIR DESENSITIZATION

Cefdinir 250 mg/5 mL oral suspension

Also need a 1:100 dilution (e.g. 1 mL of 250 mg/5 mL plus 99 mL of water)


1 2.5 mg/5mL 0.06 mL 2 2.5 mg/5mL 0.12 mL 3 2.5 mg/5mL 0.25 mL 4 2.5 mg/5mL 0.5 mL 5 2.5 mg/5mL 1 mL 6 2.5 mg/5mL 2 mL


Doses given q15minutes. Then 300 mg b.i.d.

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CEFPODOXIME DESENSITIZATION

Cefpodoxime 50 mg/5 mL oral solution used as starting material

Cefpodoxime 0.5 mg/5 mL (1:100) used for initial doses


1 0.5 mg/5 mL 0.06 mL 2 0.5 mg/5 mL 0.12 mL 3 0.5 mg/5 mL 0.25 mL 4 0.5 mg/5 mL 0.5 mL 5 0.5 mg/5 mL 1 mL 6 0.5 mg/5 mL 2 mL

7 50 mg/5 mL 0.04 mL 8 50 mg/5 mL 0.08 mL 9 50 mg/5 mL 0.16 mL 10 50 mg/5 mL 0.32 mL 11 50 mg/5 mL 0.64 mL 12 50 mg/5 mL 1.25 mL 13 50 mg/5 mL 2.5 mL

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CEPHALEXIN DESENSITIZATION

Cephaexin oral suspension 250 mg/5 mL and 1:100 of that (2.5 mg/5 mL)


1 2.5 mg/5mL 0.06 mL 2 2.5 mg/5mL 0.12 mL 3 2.5 mg/5mL 0.25 mL 4 2.5 mg/5mL 0.5 mL 5 2.5 mg/5mL 1 mL 6 2.5 mg/5mL 2 mL


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CIPROFLOXACIN DESENSITIZATION

Ciprofloxacin Oral Solution 250 mg/mL: Need only about 25 mLCiprofloxacin Oral Solution 2.5 mg/mL: Need 1 part 250 mg/5mL diluted in 99 parts water.

Doses given at 15 minute intervals. Longer intervals OK, shorter are not.

The patient should be observed for at least 2 hours after the last dose to be sure no reaction occurs as the drug continues to be absorbed.

Once the first dose is given by desensitization, subsequent doses can be given in tablet form.


Time Comments

1 2.5 mg/5 mL 0.12 2.5 mg/5 mL 0.23 2.5 mg/5 mL 0.44 2.5 mg/5 mL 0.85 2.5 mg/5 mL 1.66 2.5 mg/5 mL 3.2

7 250 mg/5 mL 0.068 250 mg/5 mL 0.129 250 mg/5 mL 0.2410 250 mg/5 mL 0.511 250 mg/5 mL 112 250 mg/5 mL 213 250 mg/5 mL 414 250 mg/5 mL 8

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CITALOPRAM (CELEXA) DESENSITIZATION

Slow desensitization with 10 mg/5 mL and 1:100 of that (0.1 mg/5 mL)

Day Concentration Volume Comments1 0.1 mg/5 mL 0.06 mL Done2 0.1 mg/5 mL 0.12 mL Done3 0.1 mg/5 mL 0.25 mL Done4 0.1 mg/5 mL 0.5 mL Done5 0.1 mg/5 mL 1 mL Done6 0.1 mg/5 mL 2 mL Done7 10 mg/5 mL 0.05 mL Done8 10 mg/5 mL 0.1 mL Done9 10 mg/5 mL 0.2 mL Done10 10 mg/5 mL 0.4 mL Done11 10 mg/5 mL 0.8 mL Done12 10 mg/5 mL 1.6 mL Done13 10 mg/5 mL 3.2 mL Done14 10 mg/5 mL 5 mL Done

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CLINDAMYCIN DESENSITIZATIONSlow desensitization

Clindamycin oral suspension 75 mg/5 mL, & 1:100 (0.75 mg/5 mL).

Dose Concentration Volume Day

1 0.75 mg/5mL 0.05 mL AM Monday2 0.75 mg/5mL 0.1 mL PM Monday

3 0.75 mg/5mL 0.2 mL AM Tuesday4 0.75 mg/5mL 0.5 mL PM Tuesday

5 0.75 mg/5mL 1 mL AM Wednesday6 0.75 mg/5mL 2 mL PM Wednesday

7 75 mg/5mL 0.05 mL AM Thursday8 75 mg/5mL 0.1 mL PM Thursday

9 75 mg/5mL 0.2 mL AM Friday10 75 mg/5mL 0.4 mL PM Friday

11 75 mg/5mL 0.8 mL AM Saturday12 75 mg/5mL 1.5 mL PM Saturday

13 75 mg/5mL 3 mL AM Sunday14 75 mg/5mL 5 mL PM Sunday

15 75 mg/5mL 10 mL AM Monday16 75 mg/5mL 20 mL PM Monday

CLONAZEPAM (KLONOPIN) DESENSITIZATION

Materials:

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1. Prepare 25 mL of 0.2 mg/mL by making a suspension of 5 mg of Klonopin in 25 mL of syrup.

2. Prepare 20 mL of 0.02 mg/mL by placing 2 mL of 0.2 mg/mL in 18 mL of syrup.3. Prepare 20 mL of 0.002 mg/mL by placing 2 mL of 0.02 mg/mL in 18 mL of

syrup.4. Prepare 20 mL of 0.0002 mg/mL by placing 2 mL of 0.002 mg/mL in 18 mL of

syrup.

Date Dose Concentration Amount Comments1 0.0002 mg/mL ¼ tsp2 0.0002 mg/mL ½ tsp3 0.0002 mg/mL 1 tsp4 0.0002 mg/mL 2 tsp

5 0.002 mg/mL ½ tsp6 0.002 mg/mL 1 tsp7 0.002 mg/mL 2 tsp



14 Oral tablets at desired dose

Doses are in teaspoons measured with a medicine spoon Doses are administered once a day

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CLOPIDOGREL (PLAVIX) DESENSITIZATION

Need oral suspensions prepared in the pharmacy:

100 mL of 75 mg PLAVIX/5 mL 100 mL of 0.75 mg PLAVIX/5 mL (1:100 – 1 mL of the 75mg/5mL in 99 mL)

This protocol will provide a cumulative 75 mg dose of Plavix. Then conventional therapy with Plavix can begin. Place the indicated amount of the oral suspension in a cup. Add at least 25 mL of

water and swirl to make swallowing small doses feasible. Administer doses at least 15 minutes apart. Observe 2 hours after last dose.


Time Comments

1 0.75 mg/5 mL 0.04 mL2 0.75 mg/5 mL 0.083 0.75 mg/5 mL 0.154 0.75 mg/5 mL 0.35 0.75 mg/5 mL 0.66 0.75 mg/5 mL 1.27 0.75 mg/5 mL 2.58 0.75 mg/5 mL 59 0.75 mg/5 mL 10

10 75 mg/5 mL 0.211 75 mg/5 mL 0.412 75 mg/5 mL 0.713 75 mg/5 mL 0.1514 75 mg/5 mL 0.315 75 mg/5 mL 0.616 75 mg/5 mL 1.317 75 mg/5 mL 2.5

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COUMADIN DESENSITIZATION

Coumadin oral suspensions must be prepared:2 mg/mL and 1:100 (0.02 mg/mL)

Slow desensitization.

Dose Concentration Amount Day1 0.02 mg/mL 0.05 mL 1

2 0.02 mg/mL 0.1 mL 2

3 0.02 mg/mL 0.2 mL 3

4 0.02 mg/mL 0.4 mL 4

5 0.02 mg/mL 0.8 mL 5

6 0.02 mg/mL 1.6 mL 6

7 0.02 mg/mL 3 mL 7

8 0.02 mg/mL 6 mL 8

9 2 mg/mL 0.1 mL 9

10 2 mg/mL 0.2 mL 10

11 2 mg/mL 0.4 mL 11

12 2 mg/mL 0.8 mL 12

13 2 mg/mL 1.6 mL 13

14 2 mg/mL 2.5 mL 14

Administer one dose a day. The last few days you should begin obtaining INR values.

After finishing the desensitization you can begin the recommended dosage schedule.

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COZAAR DESENSITIZATION

REAGENTS:1. Cozaar Oral Suspension (0.1 and 10 mg/5mL )2. Tap water 3. Syringes and other measuring devices to measure doses from 0.1 mL

to 10 mL

PROCEDURE:1. Administer one dose every 15 minutes3. Follow the protocol below. Add extra water to doses less than 25 mL to make swallowing easier.

Dose Concentration AmountDate/Time

1 0.1 mg/5 mL 0.05 mL2 0.1 mg/5 mL 0.1 mL3 0.1 mg/5 mL 0.2 mL4 0.1 mg/5 mL 0.4 mL5 0.1 mg/5 mL 0.8 mL6 0.1 mg/5 mL 1.6 mL7 0.1 mg/5 mL 3.2 mL8 0.1 mg/5 mL 6.4 mL

9 10 mg/5 mL 0.12 mL10 10 mg/5 mL 0.25 mL11 10 mg/5 mL 0.5 mL12 10 mg/5 mL 1 mL13 10 mg/5 mL 2 mL14 10 mg/5 mL 4 mL

Then begin usual dosage regimen, one 25 mg tablet once a day.

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DEFERASIROX DESENSITIZATION

1 mg/mL Place one 125 mg tablet in 125 mL of water. Allow to dissassocaite and stir to make a suspension. Take the required dose and discard. Each dose should be prepared fresh. Administer on an empty stomach.

10 mg/mL Place on 500 mg tablet in 50 mL of water and proceed as above. The final dose will require two 500 mg tablets in 100 mL of water.


Time Comments

1 1 mg/mL 0.1 mL2 1 mg/mL 0.2 mL3 1 mg/mL 0.4 mL4 1 mg/mL 0.8 mL5 1 mg/mL 1.6 mL6 1 mg/mL 3.2 mL7 1 mg/mL 6.4 mL8 1 mg/mL 13 mL9 1 mg/mL 25 mL10 1 mg/mL 50 mL11 1 mg/mL 100 mL12 10 mg/mL 20 mL13 10 mg/mL 40 mL14 10 mg/mL 80 mL

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ESTRADIOL DESENSITIZATION PROTOCOL

REAGENTS:4. Estradiol Suspensions

a. 0.125 mg/5 mLb. 0.00125 mg/5mL

5. Tap water 6. Syringes and other measuring devices to measure doses from 0.05 mL

to 10 mL

PROCEDURE:2. Administer one dose every 24 hours3. Follow the protocol below. Add extra water to doses less than 25 mL

to make swallowing easier.

Day Concentration AmountDate/Time

1 0.00125 mg/5 mL 0.05 mL2 0.00125 mg/5 mL 0.1 mL3 0.00125 mg/5 mL 0.2 mL4 0.00125 mg/5 mL 0.4 mL5 0.00125 mg/5 mL 0.8 mL6 0.00125 mg/5 mL 1.6 mL7 0.00125 mg/5 mL 3.2 mL8 0.00125 mg/5 mL 6.4 mL

9 0.125 mg/5 mL 0.12 mL10 0.125 mg/5 mL 0.25 mL11 0.125 mg/5 mL 0.5 mL12 0.125 mg/5 mL 1 mL13 0.125 mg/5 mL 2 mL14 0.125 mg/5 mL 4 mL

Then begin usual dosage regimen, one 0.125 mg capsule once a day.

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ESTRADIOL (ESTRACE) DESENSITIZATION

Materials:

5. Estrace Cream #1: 0.000001%6. Estrace Cream #2: 0.0001%7. Estrace Cream #3: 0.01%

Procedure:

Using the Estrace applicator, draw up the amount of cream needed and apply intravaginally. The doses are to be administered ~8 hours apart for 3 days. Then the drug can be administered once a day in whatever doses the physician requires.

Date Dose Concentration Amount CommentsFirst day – Doses ~8 hours apart

1 Cream #1 1 gram2 Cream #1 2 gram3 Cream #1 4 gram

Second day – Doses ~8 hours apart4 Cream #2 1 gram5 Cream #2 2 gram6 Cream #2 4 gram

Third day – Doses ~8 hours apart7 Cream #3 1 gram8 Cream #3 2 gram9 Cream #3 4 gram

After this procedure, Estrace can be used as normally recommended. Estrace should not be stopped for more than one day, or we will need to desensitize again.

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FEBUXOSTAT (ULORIC) DESENSITIZATION

Uloric suspension 0.1 mg/mLUloric suspension 10 mg/mL

1. Shake the correct bottle to resuspend the medication 2. Measure out the amount of medication from the correct bottle

and put into a glass of water3. Take one dose once a day, then advance to the next dose4. Weekend doses are prepared and marked for the patient to

add to water and take at home. Other doses should be given in the office to assure correct doses and absence of reactions

5. Then start one 40 mg Uloric tablet once a day6. The dose can be adjusted as needed after that7. If the patient misses more than one dose, the desensitization

should be repeated.

Day Concentration Amount Date Comments1 0.1 mg/mL 0.1 mL2 0.1 mg/mL 0.2 mL3 0.1 mg/mL 0.4 mL4 0.1 mg/mL 0.8 mL5 0.1 mg/mL 1.6 mL6 0.1 mg/mL 3 mL7 0.1 mg/mL 6 mL8 0.1 mg/mL 12 mL9 0.1 mg/mL 24 mL

10 10 mg/mL 0.5 mL11 10 mg/mL 1 mL12 10 mg/mL 2 mL13 10 mg/mL 3 mL14 10 mg/mL 4 mL

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GENTAMICIN INTRAVENOUS DESENSITIZATION

Materials:

Gentamicin 40 mg/mL most concentrated solutionSerial 10 fold dilutions in normal saline

Can be prepared as follows:1:10 (4 mg/mL) – 20 mL of 40 mg/mL + 180 mL saline1:100 (0.4 mg/mL) - 20 mL of 4 mg/mL + 180 mL saline1:1000 (0.04 mg/mL) - 20 mL of 0.4 mg/mL + 180 mL saline

Procedure:

Infuse the indicated concentration of drug for 15 minutes at the flow rate indicated.Then change the flow rate, and if necessary the concentration of drug, and continue with increasing doses until the protocol has been completed.This will constitute the first dose.Usual doses and intervals can then be instituted.

Dose Concentration Flow rate

Time Amount given

Total given

Comments

1 0.04 mg/mL 10 mL/hr

15 min.

0.1 mg 0.1 mg

2 0.04 mg/mL 20 mL/hr

15 min.

0.2 mg 0.3 mg

3 0.04 mg/mL 40 mL/hr

15 min.

0.4 mg 0.7 mg

4 0.04 mg/mL 80 mL/hr

15 min.

0.8 mg 1.5 mg

5 0.04 mg/mL 160 mL/hr

15 min.

1.6 mg 3 mg

6 0.4 mg/mL 30 mL/hr

15 min.

3 mg 6 mg


15 min.

6 mg 12 mg

8 0.4 mg/mL 120 mL/hr

15 min.

12 mg 24 mg

9 0.4 mg/mL 240 mL/hr

15 min.

25 mg 50 mg

10 4 mg/mL 50 mL/hr

15 min.

50 mg 100 mg

11 4 mg/mL 100 mL/hr

15 min.

100 mg 200 mg


15 min.

200 mg 400 mg


15 min.

400 mg 800 mg

Then begin usual doses and intervals, assuming this to be the first dose.

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HYDROCHLOROTHIAZIDE DESENSITIZATION

REAGENTS:Hydrochlorothiazide oral suspension 50 mg/5 mL and a 1:100 dilution 0.5 mg/mLTap water Syringes and other measuring devices to measure doses from 0.1 mL to 100 mL

Dose Concentration Amount Time1 0.5 mg/mL 0.05 mL2 0.5 mg/mL 0.1 mL3 0.5 mg/mL 0.2 mL4 0.5 mg/mL 0.4 mL5 0.5 mg/mL 0.8 mL6 0.5 mg/mL 1.6 mL7 0.5 mg/mL 3.2 mL8 0.5 mg/mL 6.4 mL9 0.5 mg/mL 12.8 mL10 0.5 mg/mL 25 mL11 50 mg/mL 0.5 mL12 50 mg/mL 1 mL13 50 mg/mL 2 mL14 50 mg/mL 4 mL

Then begin usual daily dosage regimen.

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INFLUENZA VACCINE DESENSITIZATION

Undiluted1:10 = 0.5 mL vaccine + 4.5 mL diluent1:100 = 1:10 of 1:101:1000 = 1:10 of 1:100


1 1:1000 0.03 mL 2 1:1000 0.06 mL 3 1:1000 0.12 mL 4 1:1000 0.25 mL 5 1:1000 0.5 mL

6 1:100 0.1 mL 7 1:100 0.2 mL 8 1:100 0.4 mL

9 1:10 0.08 mL 10 1:10 0.16 mL 11 1:10 0.32 mL

12 Undiluted 0.05 mL 13 Undiluted 0.1 mL 14 Undiluted 3.5 mL

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INSULIN DESENSITIZATION For IgE mediated sensitivity

Lantus 100 u/mL

Dilutions needed:

1:10 (1 part INSULIN 100 U/mL + 9 parts saline) = 10 u/mL1:100 (1 part INSULIN 10 U/mL + 9 parts saline) = 1 u/mL1:1,000 (1 part INSULIN 1 U/mL + 9 parts saline) = 0.1 u/mL1:10,000 (1 part INSULIN 0.1 U/mL + 9 parts saline) = 0.01 u/mL

Doses are to be given every 15 minutes. Start at 0.05 mL SC of 0.01 mg/mL and build up to 0.8 mL SC of 10 u/mL. The cumulative dose will be 16 u. The final doses may have to be modified depending on how much insulin the patient needs.

Dose Concentration Amount ( SC)

Time Comments

1 0.01 u/mL 0.05 mL2 0.01 u/mL 0.1 mL3 0.01 u/mL 0.2 mL

4 0.1 u/mL 0.04 mL5 0.1 u/mL 0.08 mL6 0.1 u/mL 0.15 mL7 0.1 u/mL 0.3 mL

8 1 u/mL 0.06 mL9 1 u/mL 0.12 mL10 1 u/mL 0.25 mL

11 10 u/mL 0.05 mL12 10 u/mL 0.1 mL13 10 u/mL 0.2 mL14 10 u/mL 0.4 mL15 10 u/mL 0.8 mL

Cumulative dose ~16 u

Desensitization depends on the continuous presence of the drug antigen. Do not allow lapses in therapy after desensitization.

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LEVOFLOXACIN DESENSITIZATION

Levofloxacin Oral Solution 25 mg/mL, and 0.25 mg/mL (1:100)


Time Comments

1 0.25 mg/mL 0.12 0.25 mg/mL 0.23 0.25 mg/mL 0.44 0.25 mg/mL 0.85 0.25 mg/mL 1.66 0.25 mg/mL 3.2

7 25 mg/mL 0.068 25 mg/mL 0.129 25 mg/mL 0.2410 25 mg/mL 0.511 25 mg/mL 112 25 mg/mL 213 25 mg/mL 414 25 mg/mL 8

28

METRONIDAZOLE DESENSITIZATION

Need oral suspensions:

100 mL of 500 mg metronidazole/5mL (100 mg/mL)100 mL of 5 mg metronidazole/5 mL (1 mg/mL)

Administer doses at least 15 minutes apart. Observe 2 hours after last dose.


Time Comments

1 5 mg/5 mL 0.04 mL2 5 mg/5 mL 0.083 5 mg/5 mL 0.154 5 mg/5 mL 0.35 5 mg/5 mL 0.66 5 mg/5 mL 1.27 5 mg/5 mL 2.58 5 mg/5 mL 59 5 mg/5 mL 10

10 500 mg/5 mL 0.211 500 mg/5 mL 0.412 500 mg/5 mL 0.713 500 mg/5 mL 0.1514 500 mg/5 mL 0.315 500 mg/5 mL 0.616 500 mg/5 mL 1.317 500 mg/5 mL 2.5

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NITROFURANTOIN DESENSITIZATION

Nitrofurantoin oral suspension 100 mg/5 mL

Nitrofurantoin oral suspension 1 mg/5 mL


Time Comments

1 1 mg/5 mL 0.12 1 mg/5 mL 0.23 1 mg/5 mL 0.44 1 mg/5 mL 0.85 1 mg/5 mL 1.66 1 mg/5 mL 3.2

7 100 mg/5 mL 0.068 100 mg/5 mL 0.129 100 mg/5 mL 0.2410 100 mg/5 mL 0.511 100 mg/5 mL 112 100 mg/5 mL 213 100 mg/5 mL 414 100 mg/5 mL 8

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OPIATE SENSITIVITY: SUGGESTIONS FOR MANAGEMENT

Allergy-like reactions to opiates appear to be the result of pharmacologically-induced cutaneous mast cell mediator release (Tharp MD, Kagey-Sabotka A, Fox CC, Maroni G, Lichtenstein LM, Sullivan TJ. Functional heterogeneity of human mast cells from different anatomical sites: in vitro responses to morphine sulfate. J Allergy Clin Immunol 1987;79:646-652.).

Patients differ in their degree of opiate sensitivity over time, and which opiates they tolerate better than others.

Fentanyl appears to be the best tolerated of the opiates, for most patients.

Premedication with antihistamines, and perhaps antileukotrienes can be very helpful.

Suggested approach to perioperative use of opiates in patients with a history of “pseudoallergic” reactions to opiates:

When feasible use non-opiate medications or approaches to pain control to avoid the need, or reduce the dose of opiates. This includes NSAIDs such as Toradol, local anesthetics, epidural blocks, etc.

When feasible use PCA pumps for opiate administration. This avoids the high blood levels that come from intermittent doses that in turn exaggerate the mast cell stimulation.

When feasible use fentanyl. This can be used in PCA pumps, but in some hospitals the logistics are a problem.

Premedication with diphenhydramine 1 mg/kg q4-6h can help. We also use Singulair 10 mg PO b.i.d., but there are no data regarding

effectiveness. If blood pressure is a problem we can add an H2 antihistamine such as

cimetidine 4 mg/kg q6h. Peripheral opiate antagonists such as methylnaltrexone or alvimopan

may be beneficial without interfering with central pain control..

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PACLITAXEL (TAXOL) INTRAVENOUS DESENSITIZATION

Materials:

Taxol 300 mg in 500 mL normal saline – 0.6 mg/mL (Full strength) You may want to add a little more Taxol to make up for the 2% we will use for the dilutions.

Put 10 mL of Taxol 300 mg/500 mL into 100 mL of normal saline. This is Taxol 1:10 (0.06 mg/mL)

Put 10 mL of Taxol 1:10 into 100 mL normal saline. This is Taxol 1:100 (0.006 mg/mL)

*Make sure we use the dilute 1:100 first, then the more

concentrated 1:10 next, and then the full strength last.

Procedure:

Infuse the indicated concentration of drug for 15 minutes at the flow rate indicated. Then change the flow rate, and if necessary the concentration of drug, and continue with the increasing doses until the protocol has been completed.


Time Comments

1 Taxol 1:100 2 mL/hr 15 min.2 Taxol 1:100 5 mL/hr 15 min.3 Taxol 1:100 10 mL/hr 15 min.4 Taxol 1:100 20 mL/hr 15 min.

5 Taxol 1:10 5 mL/hr 15 min.6 Taxol 1:10 10 mL/hr 15 min.7 Taxol 1:10 20 mL/hr 15 min.8 Taxol 1:10 40 mL/hr 15 min.

9 Full Strength 10 mL/hr 15 min.10 Full Strength 20 mL/hr 15 min.11 Full Strength 40 mL/hr 15 min.12 Full Strength 80 mL/hr Until infusion of the remaining 300 mg in 500 mL is

completed

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PENICILLIN DESENSITIZATION – ORAL

Penicillin 500 mg/5 mL and 1:100 (5 mg/5 mL)

For rapid desensitization doses are administered at 15 minute intervals


1 5 mg/5mL 0.03 mL 2 5 mg/5mL 0.06 mL 3 5 mg/5mL 0.12 mL 4 5 mg/5mL 0.25 mL 5 5 mg/5mL 0.5 mL 6 5 mg/5mL 1 mL 7 5 mg/5mL 2 mL


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PENICILLIN G INTRAVENOUS DESENSITIZATION - Materials

Penicilin G aqueous 1,000,000 units/50 mL (20,000units/mL)Serial 10 fold dilutions in normal saline can be prepared as follows:

1:10 (2,000units/mL) – 20 mL of 20,000 units/mL + 180 mL saline

1:100 200units/mL) - 20 mL of 2,000 units/mL + 180 mL saline

1:1000 (20units/mL) - 20 mL of 200 units/mL + 180 mL saline

Procedure:

Infuse the indicated concentration of drug for 15 minutes at the flow rate indicated.

Then change the flow rate, and if necessary the concentration of drug, and continue with the increasing doses until the protocol has been completed.

This will constitute the first dose. Usual doses and intervals can then be instituted.

For the treatment of latent syphilis, long acting bicillin is administered IM 2 hours after the last IV dose, if no reaction is evident. Subsequent weekly doses can be given without need for a repeat of the desensitization procedure.

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PENICILLIN G INTRAVENOUS DESENSITIZATION PROTOCOL

Desensitization Protocol


Time Amount given

Total given

Comments

1 20 units/mL 10 mL/hr

15 min.

50 units 50


15 min.

100 units 150


15 min.

200 units 350


15 min.

400 units 750


15 min.

800 units 1,550


15 min.

1,500 units

3,050


15 min.

3,000 units

6,050


15 min.

6,000 units

12,050


15 min.

12,000 units

24,050

10 2,000 units/mL

50 mL/hr

15 min.

25,000 units

49,050

11 2,000 units/mL

100 mL/hr

15 min.

50,000 units

99,050

12 2,000 units/mL

200 mL/hr

15 min.

100,000 units

199,050

13 20,000 units/mL

40 mL/hr

15 min.

200,000 units

399,050

14 20,000 units/mL

80 mL/hr

15 min.

400,000 units

799,050

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PIPERACILLIN/TAZOBACTAM INTRAVENOUS DESENSITIZATION (ZOSYN))

Materials:Zosyn (2 gm/0.25 gm) in 50 mL (eqivalent of 40 mg/mL piperacillin)

Serial 10 fold dilutions in normal salineCan be prepared as follows:

1:10 (4 mg/mL) – 20 mL of 40 mg/mL + 180 mL saline1:100 (0.4 mg/mL) - 20 mL of 4 mg/mL + 180 mL saline1:1000 (0.04 mg/mL) - 20 mL of 0.4 mg/mL + 180 mL saline

Procedure:

Infuse the indicated concentration of drug for 15 minutes at the flow rate indicated.Then change the flow rate, and if necessary the concentration of drug, and continue with the increasing doses until the protocol has been completed.This will constitute the first dose.Usual doses and intervals can then be instituted.


Time Amount given

Total given

Comments

1 0.04 mg/mL 10 mL/hr

15 min.

0.1 mg 0.1 mg

2 0.04 mg/mL 20 mL/hr

15 min.

0.2 mg 0.3 mg

3 0.04 mg/mL 40 mL/hr

15 min.

0.4 mg 0.7 mg

4 0.04 mg/mL 80 mL/hr

15 min.

0.8 mg 1.5 mg

5 0.04 mg/mL 160 mL/hr

15 min.

1.6 mg 3 mg


15 min.

3 mg 6 mg


15 min.

6 mg 12 mg

8 0.4 mg/mL 120 mL/hr

15 min.

12 mg 24 mg

9 0.4 mg/mL 240 mL/hr

15 min.

25 mg 50 mg

10 4 mg/mL 50 mL/hr

15 min.

50 mg 100 mg


15 min.

100 mg 200 mg


15 min.

200 mg 400 mg


15 min.

400 mg 800 mg


15 min.

800 mg 1600 mg

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SERTRALINE (ZOLOFT) DESENSITIZATION

Zoloft 20 mg mL oral solution used as starting materialZoloft 0.2 mg mL used for initial doses


1 0.2 m mL 0.06 mL 2 0.2 mg mL 0.12 mL 3 0.2 mg mL 0.25 mL 4 0.2 mg mL 0.5 mL 5 0.2 mg mL 1 mL 6 0.2 mg mL 2 mL

7 20 mg/5 mL 0.04 mL 8 20 mg/5 mL 0.08 mL 9 20 mg/5 mL 0.16 mL 10 20 mg/5 mL 0.32 mL 11 20 mg/5 mL 0.64 mL 12 20 mg/5 mL 1.25 mL 13 20 mg/5 mL 2.5 mL

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SULFASALAZINE (AZULFIDINE) DESENSITIZATION

Azulfidine 10 mg/100 mL oral solutionAzulfidine 0.1 mg/100 mL used for initial doses


1 0.1 gm/100 mL 0.05 mL 2 0.1 gm/100 mL 0.1 mL 3 0.1 gm/100 mL 0.2 mL 4 0.1 gm/100 mL 0.4 mL 5 0.1 gm/100 mL 0.8 mL 6 0.1 gm/100 mL 1.6 mL

7 10 gm/100 mL 0.03 mL 8 10 gm/100 mL 0.06 mL 9 10 gm/100 mL 0.12 mL 10 10 gm/100 mL 0.25 mL 11 10 gm/100 mL 0.5 mL 12 10 gm/100 mL 1 mL 13 10 gm/100 mL 2 mL 14 10 gm/100 mL 4 mL

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TRIMETHOPRIM/SULFAMETHOXAZOLE DESENSITIZATION

REAGENTS for pediatric patients. Adults will need higher final dosesl

Bactrim Pediatric Suspension (80 mg trimethoprim/400 mg sulfamethoxazole per 5 mL)Tap water Syringes and other measuring devices to measure doses from 0.1 mL to 100 mL

Dose Concentration Amount Time1 1:100 0.05 mL2 1:100 0.1 mL3 1:100 0.2 mL4 1:100 0.4 mL5 1:100 0.8 mL6 1:100 1.6 mL7 1:100 3.2 mL8 1:100 6.4 mL9 1:100 12.8 mL10 1:100 25 mL11 Undiluted 0.5 mL12 Undiluted 1 mL13 Undiluted 2 mL14 Undiluted 4 mL

Then begin usual dosage regimen, considering this the first dose of 5 mL.

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VANCOMYCIN INTRAVENOUS DESENSITIZATION

Materials:

Vancomycin 40 mg/mL most concentrated solutionSerial 10 fold dilutions in normal saline

Can be prepared as follows:1:10 (4 mg/mL) – 20 mL of 40 mg/mL + 180 mL saline1:100 (0.4 mg/mL) - 20 mL of 4 mg/mL + 180 mL saline1:1000 (0.04 mg/mL) - 20 mL of 0.4 mg/mL + 180 mL saline

Procedure:

Infuse the indicated concentration of drug for 15 minutes at the flow rate indicated.Then change the flow rate, and if necessary the concentration of drug, and continue with the increasing doses until the protocol has been completed.This will constitute the first dose.Usual doses and intervals can then be instituted.


Time Amount given

Total given

Comments

1 0.04 mg/mL 10 mL/hr

15 min.

0.1 mg 0.1 mg

2 0.04 mg/mL 20 mL/hr

15 min.

0.2 mg 0.3 mg

3 0.04 mg/mL 40 mL/hr

15 min.

0.4 mg 0.7 mg

4 0.04 mg/mL 80 mL/hr

15 min.

0.8 mg 1.5 mg

5 0.04 mg/mL 160 mL/hr

15 min.

1.6 mg 3 mg


15 min.

3 mg 6 mg


15 min.

6 mg 12 mg

8 0.4 mg/mL 120 mL/hr

15 min.

12 mg 24 mg

9 0.4 mg/mL 240 mL/hr

15 min.

25 mg 50 mg

10 4 mg/mL 50 mL/hr

15 min.

50 mg 100 mg


15 min.

100 mg 200 mg


15 min.

200 mg 400 mg


15 min.

400 mg 800 mg

Then begin usual doses and intervals, assuming this to be the first dose.

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Protocols for Drug Allergy Desensitization

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