Clinical Guide > Resources and References > Sulfa Desensitization

Sulfa Desensitization

January 2011

Chapter Contents


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 dose 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

For all desensitized patients