To see all protocols that comply with the WHO Essential Medicine List 

This document is an evidence-based summary to complement treatment protocols and includes background and rationale for specific point of care actions. It is not intended to be a comprehensive literature review of all available evidence.

The most common hypersensitivity reaction to sulfonamides is a delayed reaction characterised by erythema, maculopapular or morbilliform rash, urticaria and pruritus. In most cases the immunological mechanism involved is unknown, but it is not thought to be IgE-mediated.r

Desensitisation is contraindicated in patients with a history of drug rash with eosinophilia and systemic symptoms (DRESS) or Stevens–Johnson syndrome / toxic epidermal necrolysis (SJS/TEN).

Desensitisation protocols should only be initiated under medical supervision.

Pneumocystis jirovecii (carinii) pneumonia is the most common infection for which sulfonamide therapy is required despite a history of sulfonamide hypersensitivity. Premedication with an antihistamine and corticosteroids reduces the incidence of early reactions.

Desensitisation is effective as long as the patient is receiving the drug but the patient's sensitivity returns soon after the drug is ceased. Do not restart sulfonamides without re-desensitising.

After desensitisation, daily dosing is required for tolerance to develop, therefore intermittent dosing is not appropriate.r

Rapid oral trimethoprim+sulfamethoxazole desensitisation protocol for adultsr

Step (at 1-hour intervals)

Trimethoprim+sulfamethoxazole preparation

Amount

Sulfamethoxazole dose (mg)

Cumulative sulfamethoxazole dose (mg)

1 (at 0 hours)

suspension* diluted 1:2000 (0.004+0.02 mg/mL)

1 mL

0.02

0.02

2 (at 1 hour)

suspension* diluted 1:200 (0.04+0.2 mg/mL)

1 mL

0.2

0.22

3 (at 2 hours)

suspension* diluted 1:20 (0.4+2 mg/mL)

1 mL

2

2.22

4 (at 3 hours)

suspension* diluted 1:2 (4+20 mg/mL)

1 mL

20

22.22

5 (at 4 hours)

undiluted suspension (8+40 mg/mL)

5 mL

200

222.22

6 (at 5 hours)**

tablet (160+800 mg)

1 tablet

800

1022.22

7 (at 6 hours)***

tablet (160+800 mg)

2 tablets

1600

2622.22

* Use trimethoprim+sulfamethoxazole 40+200 mg per 5 mL suspension.

** If the therapeutic dose will be 1 tablet (160+800 mg strength), stop at step 6. Two hours later, administer 1 tablet and then continue therapy at the usual dosing interval. For prophylaxis of Pneumocystis jirovecii pneumonia or Toxoplasma gondii encephalitis in immunocompromised patients, use one of the daily treatment regimens rather than the 3 times weekly regimen 

*** If the therapeutic dose will be 2 tablets (160+800 mg strength), stop at step 7. Two hours later, administer 2 tablets and then continue therapy at the usual dosing interval.

Published April 2019. © Therapeutic Guidelines Ltd (eTG March 2021 edition).

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This document reflects what is currently regarded as safe practice. While every effort has been made to ensure the accuracy of the content at the time of publication, the Cancer Institute NSW does not accept any liability, with respect to loss, damage, injury or expense arising from any such errors or omission in the contents of this work. Any reference throughout the document to specific pharmaceuticals and/or medical products as examples does not imply endorsement of any of these products. While eviQ endeavours to link to reliable sources that provide accurate information, eviQ and the Cancer Institute NSW do not endorse or accept responsibility for the accuracy, currency, reliability or correctness of the content of linked external information source. Use is subject to eviQ’s disclaimer available at www.eviQ.org.au

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22 Feb 2024