Protocols For Drug Allergy Desensitization

Protocols for Rapid and Slow Drug Allergy
Desensitization
First Edition
November, 2009
By
Timothy J. Sullivan, M.D.
Atlanta, Georgia
1
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
2
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.
3
INTRODUCTION...............................................................................................................2
Rapid desensitization.......................................................................................................2
Slow desensitization.........................................................................................................2
ALENDRONATE (FOSAMAX) DESENSITIZATION....................................................5
AMOXICILLIN/CLAVULANATE DESENSITIZATION................................................6
ANASTROZOLE (ARIMIDEX) DESENSITIZATION.....................................................7
ASPIRIN DESENSITIZATION..........................................................................................8
AZITHROMYCIN DESENSITIZATION...........................................................................9
CEFDINIR DESENSITIZATION.....................................................................................10
CEFPODOXIME DESENSITIZATION...........................................................................11
CEPHALEXIN DESENSITIZATION..............................................................................12
CIPROFLOXACIN DESENSITIZATION.......................................................................13
CITALOPRAM (CELEXA) DESENSITIZATION..........................................................14
CLINDAMYCIN DESENSITIZATION...........................................................................15
CLONAZEPAM (KLONOPIN) DESENSITIZATION....................................................16
CLOPIDOGREL (PLAVIX) DESENSITIZATION.........................................................17
COUMADIN DESENSITIZATION.................................................................................18
COZAAR DESENSITIZATION.......................................................................................19
DEFERASIROX DESENSITIZATION............................................................................20
ESTRADIOL DESENSITIZATION PROTOCOL...........................................................21
ESTRADIOL (ESTRACE) DESENSITIZATION............................................................22
FEBUXOSTAT (ULORIC) DESENSITIZATION...........................................................23
GENTAMICIN INTRAVENOUS DESENSITIZATION.................................................24
HYDROCHLOROTHIAZIDE DESENSITIZATION......................................................25
INFLUENZA VACCINE DESENSITIZATION..............................................................26
INSULIN DESENSITIZATION.......................................................................................27
LEVOFLOXACIN DESENSITIZATION........................................................................28
METRONIDAZOLE DESENSITIZATION.....................................................................29
NITROFURANTOIN DESENSITIZATION....................................................................30
OPIATE SENSITIVITY....................................................................................................31
PACLITAXEL (TAXOL) INTRAVENOUS DESENSITIZATION................................32
PENICILLIN DESENSITIZATION – ORAL..................................................................33
PENICILLIN G INTRAVENOUS DESENSITIZATION - Materials..............................34
PENICILLIN G INTRAVENOUS DESENSITIZATION PROTOCOL..........................35
PIPERACILLIN/TAZOBACTAM INTRAVENOUS DESENSITIZATION .................36
SERTRALINE (ZOLOFT) DESENSITIZATION............................................................37
SULFASALAZINE (AZULFIDINE) DESENSITIZATION............................................38
TRIMETHOPRIM/SULFAMETHOXAZOLE DESENSITIZATION.............................39
VANCOMYCIN INTRAVENOUS DESENSITIZATION.............................................40
4
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 Time Comments

(mL)
1 0.7 mg/75 mL 0.1 mL
2 0.7 mg/75 mL 0.2
3 0.7 mg/75 mL 0.4
4 0.7 mg/75 mL 0.8
5 0.7 mg/75 mL 1.6
6 0.7 mg/75 mL 3.2
7 0.7 mg/75 mL 6
8 0.7 mg/75 mL 12
9 0.7 mg/75 mL 25
10 70 mg/75 mL 0.5
11 70 mg/75 mL 1
12 70 mg/75 mL 2
13 70 mg/75 mL 3
14 70 mg/75 mL 4
5
AMOXICILLIN/CLAVULANATE DESENSITIZATION
Augmentin Oral Suspension 600 mg amoxicillin/5 mL and 1 : 100 of that (6 mg/5 mL)
Dose Concentratio Amount Time Comments

n (mL)
1 6 mg/5 mL 0.03
2 6 mg/5 mL 0.06
3 6 mg/5 mL 0.12
4 6 mg/5 mL 0.25
5 6 mg/5 mL 0.5
6 6 mg/5 mL 1
7 6 mg/5 mL 2
8 600 mg/5 mL 0.04

9 600 mg/5 mL 0.08
10 600 mg/5 mL 0.15
11 600 mg/5 mL 0.3
12 600 mg/5 mL 0.6
13 600 mg/5 mL 1.2
14 600 mg/5 mL 2.5
6
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 Concentratio Amount Date Comments

n (mL)
Arimidex
1 0.001mg/mL 0.1 mL
2 0.001mg/mL 0.2 mL
3 0.001mg/mL 0.4 mL
4 0.001mg/mL 0.8 mL
5 0.001mg/mL 1.6 mL
6 0.001mg/mL 3.2 mL
7 0.001mg/mL 6.4 mL
8 0.001mg/mL 13 mL
9 0.001mg/mL 25 mL
10 0.1 mg/mL 0.5 mL

11 0.1 mg/mL 1 mL
12 0.1 mg/mL 2 mL
13 0.1 mg/mL 4 mL
14 0.1 mg/mL 8 mL
7
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.
8
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
9
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
7 250 mg/5mL 0.04 mL

8 250 mg/5mL 0.08 mL
9 250 mg/5mL 0.16 mL
10 250 mg/5mL 0.32 mL
11 250 mg/5mL 0.64 mL
12 250 mg/5mL 1.25 mL
13 250 mg/5mL 2.5 mL
Doses given q15minutes. Then 300 mg b.i.d.
10
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
11
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
7 250 mg/5mL 0.04 mL

8 250 mg/5mL 0.08 mL
9 250 mg/5mL 0.16 mL
10 250 mg/5mL 0.32 mL
11 250 mg/5mL 0.64 mL
12 250 mg/5mL 1.25 mL
13 250 mg/5mL 2.5 mL
12
CIPROFLOXACIN DESENSITIZATION
Ciprofloxacin Oral Solution 250 mg/mL: Need only about 25 mL

Ciprofloxacin 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.

n (mL)
1 2.5 mg/5 mL 0.1
2 2.5 mg/5 mL 0.2
3 2.5 mg/5 mL 0.4
4 2.5 mg/5 mL 0.8
5 2.5 mg/5 mL 1.6
6 2.5 mg/5 mL 3.2
7 250 mg/5 mL 0.06

8 250 mg/5 mL 0.12
9 250 mg/5 mL 0.24
10 250 mg/5 mL 0.5
11 250 mg/5 mL 1
12 250 mg/5 mL 2
13 250 mg/5 mL 4
14 250 mg/5 mL 8
13
CITALOPRAM (CELEXA) DESENSITIZATION
Slow desensitization with 10 mg/5 mL and 1:100 of that (0.1 mg/5

mL)
Day Concentration Volume Comments

1 0.1 mg/5 mL 0.06 mL Done
2 0.1 mg/5 mL 0.12 mL Done
3 0.1 mg/5 mL 0.25 mL Done
4 0.1 mg/5 mL 0.5 mL Done
5 0.1 mg/5 mL 1 mL Done
6 0.1 mg/5 mL 2 mL Done
7 10 mg/5 mL 0.05 mL Done
14 10 mg/5 mL 5 mL Done
14
CLINDAMYCIN DESENSITIZATION
Slow 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 Monday

2 0.75 mg/5mL 0.1 mL PM Monday
3 0.75 mg/5mL 0.2 mL AM Tuesday

4 0.75 mg/5mL 0.5 mL PM Tuesday
5 0.75 mg/5mL 1 mL AM Wednesday

6 0.75 mg/5mL 2 mL PM Wednesday
7 75 mg/5mL 0.05 mL AM Thursday

8 75 mg/5mL 0.1 mL PM Thursday
9 75 mg/5mL 0.2 mL AM Friday

10 75 mg/5mL 0.4 mL PM Friday
11 75 mg/5mL 0.8 mL AM Saturday

12 75 mg/5mL 1.5 mL PM Saturday
13 75 mg/5mL 3 mL AM Sunday
14 75 mg/5mL 5 mL PM Sunday
15 75 mg/5mL 10 mL AM Monday
16 75 mg/5mL 20 mL PM Monday
15
CLONAZEPAM (KLONOPIN) DESENSITIZATION
Materials:
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 Concentratio Amount Comments

n
1 0.0002 mg/mL ¼ tsp
2 0.0002 mg/mL ½ tsp
3 0.0002 mg/mL 1 tsp
4 0.0002 mg/mL 2 tsp
5 0.002 mg/mL ½ tsp

6 0.002 mg/mL 1 tsp
7 0.002 mg/mL 2 tsp
8 0.02 mg/mL ½ tsp

9 0.02 mg/mL 1 tsp
10 0.02 mg/mL 2 tsp
11 0.2 mg/mL ½ tsp

12 0.2 mg/mL 1 tsp
13 0.2 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
16
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.

n (mL)
1 0.75 mg/5 mL 0.04 mL
2 0.75 mg/5 mL 0.08
3 0.75 mg/5 mL 0.15
4 0.75 mg/5 mL 0.3
5 0.75 mg/5 mL 0.6
6 0.75 mg/5 mL 1.2
7 0.75 mg/5 mL 2.5
8 0.75 mg/5 mL 5
9 0.75 mg/5 mL 10
10 75 mg/5 mL 0.2
11 75 mg/5 mL 0.4
12 75 mg/5 mL 0.7
13 75 mg/5 mL 0.15
14 75 mg/5 mL 0.3
15 75 mg/5 mL 0.6
16 75 mg/5 mL 1.3
17 75 mg/5 mL 2.5
17
COUMADIN DESENSITIZATION
Coumadin oral suspensions must be prepared:

2 mg/mL and 1:100 (0.02 mg/mL)
Slow desensitization.
Dose Concentration Amount Day

1 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.
18
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 minutes
3. Follow the protocol below. Add extra water to doses less than 25 mL
to make swallowing easier.
Date/
Dose Concentration Amount Time
1 0.1 mg/5 mL 0.05 mL
2 0.1 mg/5 mL 0.1 mL
3 0.1 mg/5 mL 0.2 mL
4 0.1 mg/5 mL 0.4 mL
5 0.1 mg/5 mL 0.8 mL
6 0.1 mg/5 mL 1.6 mL
7 0.1 mg/5 mL 3.2 mL
8 0.1 mg/5 mL 6.4 mL
9 10 mg/5 mL 0.12 mL
10 10 mg/5 mL 0.25 mL
11 10 mg/5 mL 0.5 mL
12 10 mg/5 mL 1 mL
13 10 mg/5 mL 2 mL
14 10 mg/5 mL 4 mL
Then begin usual dosage regimen, one 25 mg tablet once a day.
19
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.

n (mL)
1 1 mg/mL 0.1 mL
2 1 mg/mL 0.2 mL
3 1 mg/mL 0.4 mL
4 1 mg/mL 0.8 mL
5 1 mg/mL 1.6 mL
6 1 mg/mL 3.2 mL
7 1 mg/mL 6.4 mL
8 1 mg/mL 13 mL
9 1 mg/mL 25 mL
10 1 mg/mL 50 mL
11 1 mg/mL 100 mL
12 10 mg/mL 20 mL
13 10 mg/mL 40 mL
14 10 mg/mL 80 mL
20
ESTRADIOL DESENSITIZATION PROTOCOL
REAGENTS:
4. Estradiol Suspensions
a. 0.125 mg/5 mL
b. 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 hours
3. Follow the protocol below. Add extra water to doses less than 25 mL
to make swallowing easier.
Date/
Day Concentration Amount Time
1 0.00125 mg/5 mL 0.05 mL
2 0.00125 mg/5 mL 0.1 mL
3 0.00125 mg/5 mL 0.2 mL
4 0.00125 mg/5 mL 0.4 mL
5 0.00125 mg/5 mL 0.8 mL
6 0.00125 mg/5 mL 1.6 mL
7 0.00125 mg/5 mL 3.2 mL
8 0.00125 mg/5 mL 6.4 mL
9 0.125 mg/5 mL 0.12 mL

10 0.125 mg/5 mL 0.25 mL
11 0.125 mg/5 mL 0.5 mL
12 0.125 mg/5 mL 1 mL
13 0.125 mg/5 mL 2 mL
14 0.125 mg/5 mL 4 mL
Then begin usual dosage regimen, one 0.125 mg capsule once a day.
21
ESTRADIOL (ESTRACE) DESENSITIZATION
Materials:
5. Estrace Cream #1: 0.000001%

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 Concentratio Amount Comments

n
First day – Doses ~8 hours apart
1 Cream #1 1 gram
2 Cream #1 2 gram
3 Cream #1 4 gram
Second day – Doses ~8 hours apart
4 Cream #2 1 gram
5 Cream #2 2 gram
6 Cream #2 4 gram
Third day – Doses ~8 hours apart
7 Cream #3 1 gram
8 Cream #3 2 gram
9 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.
22
FEBUXOSTAT (ULORIC) DESENSITIZATION
Uloric suspension 0.1 mg/mL

Uloric 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 water
3. Take one dose once a day, then advance to the next dose
4. 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 day
6. The dose can be adjusted as needed after that
7. If the patient misses more than one dose, the desensitization
should be repeated.
Day Concentration Amount Date Comments

1 0.1 mg/mL 0.1 mL
2 0.1 mg/mL 0.2 mL
3 0.1 mg/mL 0.4 mL
4 0.1 mg/mL 0.8 mL
5 0.1 mg/mL 1.6 mL
6 0.1 mg/mL 3 mL
7 0.1 mg/mL 6 mL
8 0.1 mg/mL 12 mL
9 0.1 mg/mL 24 mL
10 10 mg/mL 0.5 mL
11 10 mg/mL 1 mL
12 10 mg/mL 2 mL
13 10 mg/mL 3 mL
14 10 mg/mL 4 mL
23
GENTAMICIN INTRAVENOUS DESENSITIZATION
Materials:
Gentamicin 40 mg/mL most concentrated solution

Serial 10 fold dilutions in normal saline
Can be prepared as follows:
1:10 (4 mg/mL) – 20 mL of 40 mg/mL + 180 mL saline
1:100 (0.4 mg/mL) - 20 mL of 4 mg/mL + 180 mL saline
1:1000 (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 Concentratio Flow Time Amount Total Comments

n rate given giv
en
1 0.04 mg/mL 10 15 0.1 mg 0.1 mg
mL/hr min.
2 0.04 mg/mL 20 15 0.2 mg 0.3 mg
mL/hr min.
3 0.04 mg/mL 40 15 0.4 mg 0.7 mg
mL/hr min.
4 0.04 mg/mL 80 15 0.8 mg 1.5 mg
mL/hr min.
5 0.04 mg/mL 160 15 1.6 mg 3 mg
mL/hr min.
6 0.4 mg/mL 30 15 3 mg 6 mg
mL/hr min.
7 0.4 mg/mL 60 15 6 mg 12 mg
mL/hr min.
8 0.4 mg/mL 120 15 12 mg 24 mg
mL/hr min.
9 0.4 mg/mL 240 15 25 mg 50 mg
mL/hr min.
10 4 mg/mL 50 15 50 mg 100 mg
mL/hr min.
11 4 mg/mL 100 15 100 mg 200 mg
mL/hr min.
12 4 mg/mL 200 15 200 mg 400 mg
mL/hr min.
13 40 mg/mL 40 15 400 mg 800 mg
mL/hr min.
Then begin usual doses and intervals, assuming this to be the first dose.
24
HYDROCHLOROTHIAZIDE DESENSITIZATION
REAGENTS:
Hydrochlorothiazide oral suspension 50 mg/5 mL and a 1:100 dilution 0.5
mg/mL
Tap water
Syringes and other measuring devices to measure doses from 0.1 mL to 100
mL

1 0.5 mg/mL 0.05 mL
2 0.5 mg/mL 0.1 mL
3 0.5 mg/mL 0.2 mL
4 0.5 mg/mL 0.4 mL
5 0.5 mg/mL 0.8 mL
6 0.5 mg/mL 1.6 mL
7 0.5 mg/mL 3.2 mL
8 0.5 mg/mL 6.4 mL
9 0.5 mg/mL 12.8 mL
10 0.5 mg/mL 25 mL
11 50 mg/mL 0.5 mL
12 50 mg/mL 1 mL
13 50 mg/mL 2 mL
14 50 mg/mL 4 mL
Then begin usual daily dosage regimen.
25
INFLUENZA VACCINE DESENSITIZATION
Undiluted
1:10 = 0.5 mL vaccine + 4.5 mL diluent
1:100 = 1:10 of 1:10
1:1000 = 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
26
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/mL

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

n ( SC)
1 0.01 u/mL 0.05 mL
2 0.01 u/mL 0.1 mL
3 0.01 u/mL 0.2 mL
4 0.1 u/mL 0.04 mL

5 0.1 u/mL 0.08 mL
6 0.1 u/mL 0.15 mL
7 0.1 u/mL 0.3 mL
8 1 u/mL 0.06 mL
9 1 u/mL 0.12 mL
10 1 u/mL 0.25 mL
11 10 u/mL 0.05 mL
12 10 u/mL 0.1 mL
13 10 u/mL 0.2 mL
14 10 u/mL 0.4 mL
15 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.
27
LEVOFLOXACIN DESENSITIZATION
Levofloxacin Oral Solution 25 mg/mL, and 0.25 mg/mL (1:100)

(mL)
1 0.25 mg/mL 0.1
2 0.25 mg/mL 0.2
3 0.25 mg/mL 0.4
4 0.25 mg/mL 0.8
5 0.25 mg/mL 1.6
6 0.25 mg/mL 3.2
7 25 mg/mL 0.06
8 25 mg/mL 0.12
9 25 mg/mL 0.24
10 25 mg/mL 0.5
11 25 mg/mL 1
12 25 mg/mL 2
13 25 mg/mL 4
14 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.

n (mL)
1 5 mg/5 mL 0.04 mL
2 5 mg/5 mL 0.08
3 5 mg/5 mL 0.15
4 5 mg/5 mL 0.3
5 5 mg/5 mL 0.6
6 5 mg/5 mL 1.2
7 5 mg/5 mL 2.5
8 5 mg/5 mL 5
9 5 mg/5 mL 10
10 500 mg/5 mL 0.2

11 500 mg/5 mL 0.4
12 500 mg/5 mL 0.7
13 500 mg/5 mL 0.15
14 500 mg/5 mL 0.3
15 500 mg/5 mL 0.6
16 500 mg/5 mL 1.3
17 500 mg/5 mL 2.5
29
NITROFURANTOIN DESENSITIZATION
Nitrofurantoin oral suspension 100 mg/5 mL
Nitrofurantoin oral suspension 1 mg/5 mL

(mL)
1 1 mg/5 mL 0.1
2 1 mg/5 mL 0.2
3 1 mg/5 mL 0.4
4 1 mg/5 mL 0.8
5 1 mg/5 mL 1.6
6 1 mg/5 mL 3.2
7 100 mg/5 mL 0.06

8 100 mg/5 mL 0.12
9 100 mg/5 mL 0.24
10 100 mg/5 mL 0.5
11 100 mg/5 mL 1
12 100 mg/5 mL 2
13 100 mg/5 mL 4
14 100 mg/5 mL 8
30
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.
.
31
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.
Dose Concentratio Flow Time Comments

n rate
1 Taxol 1:100 2 mL/hr 15 min.

9 Full Strength 10 mL/hr 15 min.

12 Full Strength 80 mL/hr Until infusion of the remaining 300 mg in 500 mL is
completed
32
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
8 500 mg/5mL 0.04 mL

9 500 mg/5mL 0.08 mL
10 500 mg/5mL 0.16 mL
11 500 mg/5mL 0.32 mL
12 500 mg/5mL 0.64 mL
13 500 mg/5mL 1.25 mL
14 500 mg/5mL 2.5 mL
33
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.
34
PENICILLIN G INTRAVENOUS DESENSITIZATION PROTOCOL
Desensitization Protocol
Dose Concentration Flow Time Amount Total Comments

rate given give
n
1 20 units/mL 10 15 50 units 50
mL/hr min.
2 20 units/mL 20 15 100 units 150
mL/hr min.
3 20 units/mL 40 15 200 units 350
mL/hr min.
4 20 units/mL 80 15 400 units 750
mL/hr min.
5 20 units/mL 160 15 800 units 1,550
mL/hr min.
6 200 units/mL 30 15 1,500 3,050

mL/hr min. units
7 200 units/mL 60 15 3,000 6,050
mL/hr min. units
8 200 units/mL 120 15 6,000 12,050
mL/hr min. units
9 200 units/mL 240 15 12,000 24,050
mL/hr min. units
10 2,000 50 15 25,000 49,050

units/mL mL/hr min. units
11 2,000 100 15 50,000 99,050
12 2,000 200 15 100,000 199,050
13 20,000 40 15 200,000 399,050

14 20,000 80 15 400,000 799,050
35
PIPERACILLIN/TAZOBACTAM INTRAVENOUS
DESENSITIZATION (ZOSYN))
Materials:
Zosyn (2 gm/0.25 gm) in 50 mL (eqivalent of 40 mg/mL piperacillin)
Procedure:
the increasing doses until the protocol has been completed.

n rate given giv
en
1 0.04 mg/mL 10 15 0.1 mg 0.1 mg
mL/hr min.
2 0.04 mg/mL 20 15 0.2 mg 0.3 mg
mL/hr min.
3 0.04 mg/mL 40 15 0.4 mg 0.7 mg
mL/hr min.
4 0.04 mg/mL 80 15 0.8 mg 1.5 mg
mL/hr min.
5 0.04 mg/mL 160 15 1.6 mg 3 mg
mL/hr min.
6 0.4 mg/mL 30 15 3 mg 6 mg
mL/hr min.
7 0.4 mg/mL 60 15 6 mg 12 mg
mL/hr min.
8 0.4 mg/mL 120 15 12 mg 24 mg
mL/hr min.
9 0.4 mg/mL 240 15 25 mg 50 mg
mL/hr min.
10 4 mg/mL 50 15 50 mg 100 mg
mL/hr min.
11 4 mg/mL 100 15 100 mg 200 mg
mL/hr min.
12 4 mg/mL 200 15 200 mg 400 mg
mL/hr min.
13 40 mg/mL 40 15 400 mg 800 mg
mL/hr min.
14 40 mg/mL 80 15 800 mg 1600
mL/hr min. mg
36
SERTRALINE (ZOLOFT) DESENSITIZATION
Zoloft 20 mg mL oral solution used as starting material

Zoloft 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
37
SULFASALAZINE (AZULFIDINE) DESENSITIZATION
Azulfidine 10 mg/100 mL oral solution

Azulfidine 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
38
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

1 1:100 0.05 mL
2 1:100 0.1 mL
3 1:100 0.2 mL
4 1:100 0.4 mL
5 1:100 0.8 mL
6 1:100 1.6 mL
7 1:100 3.2 mL
8 1:100 6.4 mL
9 1:100 12.8 mL
10 1:100 25 mL
11 Undiluted 0.5 mL
12 Undiluted 1 mL
13 Undiluted 2 mL
14 Undiluted 4 mL
Then begin usual dosage regimen, considering this the first dose of 5 mL.
39
VANCOMYCIN INTRAVENOUS DESENSITIZATION
Materials:
Vancomycin 40 mg/mL most concentrated solution

Procedure:
the increasing doses until the protocol has been completed.

n rate given giv
en
1 0.04 mg/mL 10 15 0.1 mg 0.1 mg
mL/hr min.
2 0.04 mg/mL 20 15 0.2 mg 0.3 mg
mL/hr min.
3 0.04 mg/mL 40 15 0.4 mg 0.7 mg
mL/hr min.
4 0.04 mg/mL 80 15 0.8 mg 1.5 mg
mL/hr min.
5 0.04 mg/mL 160 15 1.6 mg 3 mg
mL/hr min.
6 0.4 mg/mL 30 15 3 mg 6 mg
mL/hr min.
7 0.4 mg/mL 60 15 6 mg 12 mg
mL/hr min.
8 0.4 mg/mL 120 15 12 mg 24 mg
mL/hr min.
9 0.4 mg/mL 240 15 25 mg 50 mg
mL/hr min.
10 4 mg/mL 50 15 50 mg 100 mg
mL/hr min.
11 4 mg/mL 100 15 100 mg 200 mg
mL/hr min.
12 4 mg/mL 200 15 200 mg 400 mg
mL/hr min.
13 40 mg/mL 40 15 400 mg 800 mg
mL/hr min.
Then begin usual doses and intervals, assuming this to be the first dose.
40

Protocols For Drug Allergy Desensitization

Transféré par

Informations du document

Titre original

Copyright

Formats disponibles

Partager ce document

Partager ou intégrer le document

Options de partage

Avez-vous trouvé ce document utile ?

Ce contenu est-il inapproprié ?

Droits d'auteur :

Formats disponibles

Protocols For Drug Allergy Desensitization

Transféré par

Droits d'auteur :

Formats disponibles

Protocols for Rapid and Slow Drug Allergy

Timothy J. Sullivan, M.D.

This short monograph is a compilation of

Approaches to patient specific diagnosis of drug

Rapid desensitization protocols have been used

Slow desensitization protocols are used for

Modifications of the protocols to accommodate patient

Need oral solutions prepared in the pharmacy:

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.

Dose Concentration Amount Time Comments

Dose Concentratio Amount Time Comments

8 600 mg/5 mL 0.04

0.1 mg Arimidex/mL Have a compounding pharmacy prepare an oral

0.001 mg Arimidex/mL Have a compounding pharmacy prepare a 1:100

Dose Concentratio Amount Date Comments

10 0.1 mg/mL 0.5 mL

325 mg Alka-Seltzer tablets

One tablet in 100 mL water is ~3 mg/mL. Dissolve one tablet in

Each dose is prepared fresh from one Alka-Seltzer tablet in 100

Give one dose every 15 minutes.

Dose Concentration Volume Given Comments

1 0.3 mg/mL 0.1 mL

Azithromycin 200 mg/5 mL stock

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

Dose Concentration Volume Time Comments

7 200 mg/5mL 0.04 mL

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

Dose Concentration Volume Time Comments

1 2.5 mg/5mL 0.06 mL

7 250 mg/5mL 0.04 mL

Cefpodoxime 50 mg/5 mL oral solution used as starting

Dose Concentration Volume Time Comments

1 0.5 mg/5 mL 0.06 mL

Cephaexin oral suspension 250 mg/5 mL

Dose Concentration Volume Time Comments

1 2.5 mg/5mL 0.06 mL

7 250 mg/5mL 0.04 mL

Ciprofloxacin Oral Solution 250 mg/mL: Need only about 25 mL

Dose Concentratio Amount Time Comments

7 250 mg/5 mL 0.06

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

Day Concentration Volume Comments

Clindamycin oral suspension 75 mg/5 mL,

Dose Concentration Volume Day

1 0.75 mg/5mL 0.05 mL AM Monday

3 0.75 mg/5mL 0.2 mL AM Tuesday

5 0.75 mg/5mL 1 mL AM Wednesday

7 75 mg/5mL 0.05 mL AM Thursday

9 75 mg/5mL 0.2 mL AM Friday

11 75 mg/5mL 0.8 mL AM Saturday

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

Date Dose Concentratio Amount Comments

5 0.002 mg/mL ½ tsp

8 0.02 mg/mL ½ tsp

11 0.2 mg/mL ½ tsp

14 Oral tablets at desired dose

• Doses are in teaspoons measured with a medicine spoon

• This protocol will provide a cumulative 75 mg dose of Plavix.

Dose Concentratio Amount Time Comments

Coumadin oral suspensions must be prepared:

Dose Concentration Amount Day