Sulfa Desensitization

Background

Trimethoprim-sulfamethoxazole (TMP-SMX), also known as Septra, Bactrim, and cotrimoxazole, is a key antibiotic for prophylaxis and treatment of several HIV-related illnesses. It is the most effective prophylaxis and the first-line treatment for Pneumocystis jiroveci pneumonia (PCP). In addition, it is effective in preventing toxoplasmosis encephalitis in severely immunocompromised patients who have evidence of previous exposure (see chapter Opportunistic Infection Prophylaxis), and it is effective against certain bacterial infections. TMP-SMX is quite inexpensive, which is a rarity in the field of HIV treatment. Because of its effectiveness and availability, it is used widely throughout the world. However, adverse reactions to TMP-SMX and other sulfa drugs occur in a high proportion of HIV-infected patients (roughly 25%), and such reactions may limit treatment options.

Desensitization to TMP-SMX should be considered when there are no reasonable or available alternatives and the patient has not experienced severe reactions (e.g., Stevens-Johnson syndrome or toxic epidermal necrolysis) to sulfa drugs. Several methods of desensitizing patients with previous reactions to TMP-SMX have been tried. These methods vary in starting dosage and length of dosage escalation, but success rates are around 80% in most cases and may be higher in patients with CD4 counts of <200 cells/µL.

S: Subjective

The patient reports a previous adverse reaction to sulfa drugs, such as erythema, pruritus, or rash. The patient has no history of anaphylaxis, Stevens-Johnson syndrome, or toxic epidermal necrolysis, and no reaction involving vesiculation, desquamation, ulceration, exfoliative dermatitis, etc.

O: Objective

CD4 count <200 cells/µL, or other important indication for TMP-SMX.

A: Assessment

Reaction to sulfa, possibly reversible with desensitization protocol.

P: Plan

Begin 9- to 13-day desensitization protocol, starting with pediatric oral suspension, which contains 40 mg of TMP and 200 mg of SMX per 5 mL (1 teaspoon). Gradually increase the dosage according to the protocol.

If there is any concern about the severity of a previous reaction, have the patient take the initial morning dose in the clinic so that the patient may be monitored for 3-4 hours before going home. (This assumes that emergency treatment, including IV access materials, IV fluids, epinephrine, antihistamines, and steroids, are readily available.)

Many experts recommend treatment with an antihistamine medication starting 1 day before initiation of the desensitization regimen and continuing daily until the dosage escalation is completed.

More rapid desensitization protocols are available (see "References," below) for patients urgently needing treatment with TMP-SMX.

Desensitization Regimen

Use commercially available pediatric suspension (containing TMP 8 mg and SMX 40 mg per mL [40 mg/200 mg per 5 mL]), followed by double-strength tablets, as follows:

Table 1. Sulfa Desensitization Regimen
DaysDosage (TMP/SMX)Volume or Tablet

Note: These day ranges are approximate; patients can be advanced more quickly or more slowly, depending on their reactions to the dosages.

In the event of mild reaction: If the patient experiences a mild reaction or itching (i.e., mild morbilliform rash without fever, systemic symptoms, or mucosal involvement), the dosage can be reduced to the last tolerated step or continued at the same dosage for an additional day, while simultaneously treating the rash or reaction. Antihistamines or antipyretics may be used to treat symptoms of mild reactions. If the reaction diminishes, the patient may advance to the next dosage (consider more gradual increase of dosages); if the reaction worsens or if systemic symptoms develop, TMP-SMX should be discontinued.

In the event of severe reaction: The desensitization regimen should be discontinued and the patient should be treated appropriately for the reaction.

1-38 mg/40 mg1 mL
4-616 mg/80 mg2 mL
7-940 mg/200 mg5 mL (or 1/2 single-strength tablet)
9-1280 mg/400 mg1/2 double-strength tablet (or 1 single-strength tablet)
13 and thereafter160 mg/800 mg1 double-strength tablet

Patient Education

For home desensitization regimen

  • Explain the benefits of using TMP-SMX. Be sure the patient understands and is able to follow these instructions:
    • The patient should measure the dose carefully and take it each morning, followed by a glass (6-8 oz) of water. (The patient should do a demonstration, if possible, using an oral syringe that will be used for the actual measuring at home.)
  • TMP-SMX can cause severe illness unless close attention is paid to any problems that may occur. It is extremely important for the patient to check his/her body temperature each afternoon. If the temperature is more than 100.5°F by mouth, the patient should stop taking the drug and contact the clinic. Note: If shaking chills occur, the body temperature should be checked as soon as the shaking stops, and the patient should contact the clinic.
  • If the patient develops a rash, blisters on the skin or in the mouth, or vomiting, he or she should stop taking TMP-SMX and go the clinic or emergency room immediately. The skin should be checked each evening, and any time itching occurs.
  • If mild itching or a faint rash occurs, diphenhydramine (Benadryl) 25-50 mg PO can be taken Q4H as needed. If itching or rash persists, continue with the same dosage for an additional day; the patient should contact the clinic if there are questions or concerns.
  • The patient should contact the clinic for alternative dosage instructions in the event of persistent itching without rash.
  • Other adverse events should be reported immediately.

For all desensitized patients

  • Desensitization may be effective only as long as the allergic individual is continuously exposed to the drug. After desensitization is complete, continue with the daily dosage. If the drug is stopped (even for a few days), the entire regimen may have to be repeated, as patients may have a recurrence of the adverse reaction.

References

  • Carr A, Penny R, Cooper DA. Efficacy and safety of rechallenge with low-dose trimethoprim-sulfamethoxazole in previously hypersensitive HIV-infected patients. AIDS. 1993 Jan;7(1):65-71.
  • Conant M, Dybul M. Trimethoprim-sulfamethoxazole hypersensitivity and desensitization in HIV disease. In: Program and abstracts of the VIII International Conference on AIDS/III STD World Congress; July 19-24, 1992; Amsterdam. Abstract PO-B-3291.
  • Leoung GS, Stanford JF, Giordano MF, et al. Trimethoprim-sulfamethoxazole (TMP-SMZ) dose escalation versus direct rechallenge for Pneumocystis carinii pneumonia prophylaxis in human immunodeficiency virus-infected patients with previous adverse reaction to TMP-SMZ. J Infect Dis. 2001 Oct 15;184(8):992-7.
  • Nguyen MT, Weiss PJ, Wallace MR. Two-day oral desensitization to trimethoprim-sulfamethoxazole in HIV-infected patients. AIDS. 1995 Jun;9(6):573-5.
  • Piketty C, Gilquin J, Kazatchkine MD. Efficacy and safety of desensitization to trimethoprim-sulfamethoxazole in human immunodeficiency virus-infected patients. J Infect Dis. 1995 Aug;172(2):611.
  • Rich, JD, Sullivan, T, Greineder, D, Kazanjian, PH. Trimethoprim/sulfamethoxazole incremental dose regimen in human immunodeficiency virus-infected persons. Ann Allergy Asthma Immunol 1997; 79:409.
  • Torgovnick J, Arsura E. Desensitization to sulfonamides in patients with HIV infection. Am J Med. 1990 May;88(5):548-9.
  • White MV, Haddad ZH, Brunner E, et al. Desensitization to trimethoprim sulfamethoxazole in patients with acquired immune deficiency syndrome and Pneumocystis carinii pneumonia. Ann Allergy. 1989 Mar;62(3):177-9.

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Abbreviations for Dosing Terminology

BID
twice daily
BIW
twice weekly
IM
intramuscular (injection), intramuscularly
IV
intravenous (injection), intravenously
PO
oral, orally
Q2H, Q4H, etc.
every 2 hours, every 4 hours, etc.
QAM
every morning
QD
once daily
QH
every hour
QHS
every night at bedtime
QID
four times daily
QOD
every other day
QPM
every evening
TID
three times daily
TIW
three times weekly