Drug desensitization is a process in which a drug to which the patient is allergic is administered to the patient in small, incremental doses to induce a state of temporary tolerance to the drug. This should only be attempted if the offending drug is deemed essential and no alternatives are available. This treatment has been well established for IgE-mediated drug allergy, specifically to penicillins.

Drug desensitization for non–IgE-mediated drug allergy has also been described for various drugs. Although treatment has been shown to be effective, the underlying mechanisms for its success remain unknown.

In some situations, rapid desensitization in a few hours may be required.  In addition, desensitization over a period of days to weeks may be acceptable if the need is for prophylaxis or more chronic treatment. Desensitization via the oral route may be safer than by the IV (parenteral) route, but the process is dependent on adequate absorption and may be complicated by vomiting. A beginning dose can be selected as a fraction, possibly 1/100 or 1/1000 of the subject ’s known tolerance of the agent or by arbitrarily starting with 1:1000 to 1:10,000 dilution of the therapeutic concentration. Subsequent doses are then increased by doubling. After the therapeutic concentration (dose) is reached, the patient should continue to receive the agent.

Induction of tolerance to the offending drug is temporary and patients are still regarded as allergic to that particular drug. Should the patient require the medication 3-7 days after stopping desensitization, then the process should be reinstituted.

Desensitization protocols have been described for many drugs including penicillins, cephalosporins, Cotrimoxazole, Allopurinol, and chemotherapeutic agents.