Clinical Manual for Management of the HIV-Infected Adult
2006 Edition

Section 10: Resources

Sulfa Desensitization

July 2006

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 infection, and it is effective against certain bacterial infections. TMP-SMX also is quite inexpensive, which is a rarity in the world 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.

Desensitization to TMP-SMX should be considered when there are no reasonable or available alternatives and the patient has not experienced severe reactions (eg, Stevens-Johnson syndrome) 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 those patients with <200 CD4 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 question 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 and IV fluids, antihistamines, and steroids, are readily available.)

Treat with an antihistamine medication 1 day before starting the desensitization regimen and continue daily until the dose 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), followed by double-strength tablets, as follows:

Table 1. Sulfa Desensitization Regimen

Days Dosage (TMP/SMX) Volume or Tablet 1-3 8 mg/40 mg 1 mL 3-6 16 mg/80 mg 2 mL 5-9 40 mg/200 mg 5 mL 7-12 80 mg/400 mg 1/2 double-strength tablet (or 1 single-strength tablet) 9-10 and thereafter 160 mg/800 mg 1 double-strength tablet

In the event of mild reaction: If the patient experiences a mild reaction or itching, the same dosage should be given for an additional day. If the reaction diminishes, the patient may advance to the next dosage; if the reaction worsens, the TMP-SMX should be discontinued. Antihistamines or antipyretics may be used to treat symptoms of mild reactions.

In case of severe reaction: the desensitization regimen should be discontinued.

Patient Education

For home desensitization regimen

Explain the benefits of using TMP-SMX. Be sure the patient understands and is able to follow instructions.

• Measure your 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 the syringe that will be used for the actual measuring at home.)
• TMP-SMX can make you very ill unless you pay attention to any problems you have. It is extremely important that you check your temperature each afternoon. If your temperature is more than 100.5° F by mouth, stop taking the drug and contact your clinician. Note: If you have shaking chills, check your temperature as soon as the shaking stops, and contact the clinic. If you continue the medication despite a red rash and/or fever, serious illness or a life-threatening reaction may occur. Report any adverse event immediately.
• Stop the regimen and return to the clinic or emergency room immediately if you develop a red rash, blisters on your skin or in your mouth, or vomiting. Check your skin each evening, and any time you notice itching.

If you have mild itching or a faint rash, you can take diphenhydramine (Benadryl) 25-50 mg. every 4 hours as needed. If this persists, stay with the same dosage for an additional day; and call or go to the clinic if you have questions or concerns.

• Call or go to the clinic for alternate dosage instructions in the event of persistent itching without rash.

For all desensitized patients

• After desensitization is complete, continue to take the daily dosage. If the drug is stopped, the entire regimen may have to be repeated.

References

• Bartlett JG, Cheever L. A Guide to Primary Care of People with HIV/AIDS, 2004 Edition. Rockville, MD: Department of Health and Human Services, HIV/AIDS Bureau. 2004. Available online at hab.hrsa.gov/tools/primarycareguide/.
• Carr A, Penny R, Cooper DA. Efficacy and safety of rechallenge with low-dose trimethoprim-sulphamethoxazole in previously hypersensitive HIV-infected patients. AIDS. 1993 Jan;7(1):65-71.
• Conant M, Dybul M. Trimethoprim-sulfphamethoxazole 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.
• 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.