Desensitization Protocol -12 Step For Immediate Hypersensitivity

Desensitization 12-step Calculator (Beta)

Patient Name (optional):

Enter Drug Name:

Target (final - maintenance) dose: mg

Standard Volume: mL (Usually 100-250 ml)

Background Info / References

1] Castells MC, Solensky R. Rapid drug desensitization for immediate hypersensitivity reactions. UpToDate®. 2014;07. https://www.uptodate.com. Accessed: 8/7/2014.

Desensitization key points:

Requirements before proceeding: [1] Patient should have a proven history of an immediate-type drug allergy AND [2] There are NO acceptable alternate drugs.
Immediate reactions - Occur within one hour of exposure. [Reactions include: flushing ,pruritus, urticaria, shortness of breath, chest tightness, angioedema, N&V, hypotension, etc. Delayed-reactions occur > 1 hour after exposure.
Contraindications to desensitization: Never attempt desensitization in patients with extreme allergic responses such as Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiform or similar reactions that include a desquamation or skin blistering component. Also avoid desensitization in patients with a history of the following types of reactions: hepatitis, nephritis, serum sickness reactions.
Ideally only highly trained specialists with experience with desensitization procedures should perform the technique.
Patient's with a history of more severe reactions other than those mentioned above may require a lengthy desensitization procedure that is initiated with a much lower concentration that is used by this program. [Sixteen-step procedure exists].
It is possible that late-occurring reactions may occur after desensitization with prolonged therapy with the offending agent such as serum sickness, hemolytic anemia, and nephritis.
REMEMBER that a desensitization procedure brings about a TEMPORARY tolerance. Interruptions in therapy or after discontinuation of therapy, the patient's hypersensitivity may return QUICKLY.
Most routes can be used for a desensitization procedure including IV, oral, and subcutaneous. The final route of administration can deviate from the initial route used for desensitization. Example: IV desensitization procedure --> oral therapy thereafter.
The desensitization procedure may have to be aborted for severe reactions including intractable hypotension or laryngeal edema that does not immediately respond to therapy with epinephrine. As mentioned earlier experience with the desensitization process is imperative.

A 12-step algorithm has been used successfully at several institutions for a variety of drugs in patients with immediate hypersensitivity. This protocol uses three solutions (100-250ml each). Solution 3: standard therapeutic solution of the drug that is usually given IV. Solution 2 is a 10-fold dilution of 3 and solution 1 is a 100-fold dilution of 2.

Desensitization has been performed with this protocol to treat patients with an immediate hypersensitivity to the following drugs: Penicillins and other beta-lactams, including ertapenem, imipenem, and meropenem. Cephalosporins. Fluoroquinolones. Vancomycin.

Procedure length (average): 6 hours.

Sample copy of the algorithm using a final dose of 1000mg and volume of 100ml. Note: the first eleven steps are infused over 15 minutes at various infusion rates (dose escalation).

For specialized instructions regarding management of symptoms during this process as well as other important considerations, please refer to the original source above.

2] Sancho MC, Breslow R, Sloane D, Castells M. Desensitization for Hypersensitivity Reactions to Medications. French LE (ed): Adverse Cutaneous Drug Eruptions. Chem Immunol Allergy. Basel, Karger, 2012, vol 97, pp 217-233.

Rapid drug desensitization (RDD):

Technique that induces temporary tolerance to a drug.
Patients with IgE and non- IgE hypersensitivity reactions (HSRs) can generally safely receive the offending drug while inhibiting the targeted adverse reactions.
Successful desensitization using the 12 step protocol has been achieved with the following drugs: nafcillin, penicillin, cefazolin, and ceftriaxone. Other agents were listed including ceftazidime.

"Patients with negative skin testing should not require desensitization."

3] Castells M. Rapid desensitization for hypersensitivity reactions to medications. Immunol Allergy Clin North Am 2009; 29:585.

Rapid Desensitization to B-Lactam antibiotics Including Penicillin and Cephalosporins
Antibiotic and Number of Desensitization's performed (2005-2006) - Brigham and Women’s Hospital - using the 12-step protocol:
-------------------------------------
Ancef    1
Ceftaxidime   7
Ceftriaxone 4
Cefazolin   1
Ciprofloxacin 1
Ertapenem 1
Imipenem   9
Meropenem 1
Nafcillin   3
Penicillin   7
Piperacillin   3
Trimethoprim 1
Zosyn 3
-----------------------------------
TOTAL 42

Sample of the program's output:

Solution:	Total Volume	Concentration	Dose
Solution 1	100 mL	0.100 mg/mL	10 mg
Solution 2	100 mL	1.00 mg/mL	100 mg
Solution 3	100 mL	10.00 mg/mL	1000 mg

Step	Solution#	Rate (mL/hr)	Time (minutes)	Volume infused per step (mL)	Dose administered with this step (mg)	Cumulative Dose (mg)
1	1	2	15	0.5	0.050	0.050
2	1	5	15	1.25	0.125	0.175
3	1	10	15	2.5	0.25	0.425
4	1	20	15	5	0.5	0.925
5	2	5	15	1.25	1.25	2.175
6	2	10	15	2.5	2.5	4.675
7	2	20	15	5	5	9.675
8	2	40	15	10	10	19.675
9	3	10	15	2.5	25	44.675
10	3	20	15	5	50	94.675
11	3	40	15	10	100	194.675
12	3	80	60.40	80.53	805.325	1000

References

Castells MC, Solensky R. Rapid drug desensitization for immediate hypersensitivity reactions. UpToDate®. 2014;07. https://www.uptodate.com. Accessed: 8/7/2014.
Castells M. Rapid desensitization for hypersensitivity reactions to medications. Immunol Allergy Clin North Am 2009; 29:585.
Sancho MC, Breslow R, Sloane D, Castells M. Desensitization for Hypersensitivity Reactions to Medications. French LE (ed): Adverse Cutaneous Drug Eruptions. Chem Immunol Allergy. Basel, Karger, 2012, vol 97, pp 217-233.