Understanding sulfonamide allergy 

Sulfonamide allergy is defined as a hypersensitivity reaction to medicines containing a sulfonamide chemical group in their molecular structure.

It is not an allergy to medicines that contain sulfur in their formulation or as a salt, such as sulfites. You cannot tell from the name of a medicine whether it contains a sulfonamide chemical group. For example, gliclazide, furosemide and acetazolamide all contain a sulfonamide group.

There is no test for sulfonamide allergy status.

Sulfonamide allergy is sometimes called ‘sulfa allergy’. The term ‘sulfa allergy’ is misleading, restrictive, and should ideally be avoided. Instead you should document:

• The exact medicine that caused the reaction
• The nature of the reaction

In people who have had an allergy to a medicine, document if the medicine contains a sulfonamide group.

People with a history of sulfonamide allergy may be at increased risk of allergic reactions in general.

Signs of sulfonamide allergy

Sulfonamide allergy reactions can include:

• Hives
• Angioedema
• Anaphylaxis
• Serum sickness-like symptoms (e.g. rash, urticarial, fever)
• Immune-induced thrombocytopenia
• Drug Rash with Eosinophilia and Systemic Symptoms (DRESS)
• Stevens-Johnson syndrome and Toxic Epidermal Necrolysis (TEN)
• Immunologic hepatitis
• Immunologic nephropathy

Types of sulfonamides

Sulfonamides can be split into two groups: sulfonamide antibiotics and non-antibiotic sulfonamides.

Sulfonamide antibiotics have a different chemical structure to non-antibiotic sulfonamides. Evidence of cross-sensitivity between the two groups is lacking.

Sulfonamide antibiotics, such as sulfadiazine and sulfamethoxazole (found in co-trimoxazole), are the second most reported cause of antibiotic allergy after penicillin allergy.

Compared to sulfonamide antibiotics, non-antibiotic sulfonamides have a lower risk of severe hypersensitivity reactions such as anaphylaxis and Stevens-Johnson syndrome.

Documenting sulfonamide allergy

Clear documentation of past allergies is important when choosing medicines for people with sulfonamide allergy.

Allergy history

You should always:

• Take a full medical history to identify any previous allergic reactions.
• Identify the suspected medicine and the reaction type.
• Check what medicines the person has tolerated previously. They may have taken other sulfonamides without showing signs of an allergic reaction. This should be considered as part of the risk-benefit assessment of choosing a medicine.
• Clearly document any allergies in the person’s notes and communications.

Some resources suggest that cross-sensitivity is more likely to occur in people with a pre-disposition to allergic reactions.

Choosing medicines

Conduct a careful risk versus benefit assessment before using medicines in people with suspected sulfonamide allergy. Adopt the following approach when choosing medicines.

Manufacturers’ advice

Check the Summary of Product Characteristics (SmPCs) for information about sulfonamide allergy, sulphonamide allergy, or ‘sulfa allergy’. This may be found in sections 4.3 Contraindications and 4.4 Specialist warnings and precautions for use.

SmPCs can be found on the Electronic Medicines Compendium or the MHRA website.

When reviewing SmPCs, note that advice from manufacturers can vary, even for the same medicine.

Presence of a sulfonamide group

As advice from manufacturers can vary, check the chemical structure of the medicine to confirm the presence or absence of the sulfonamide chemical group.

Below is the basic chemical structure of sulfonamides.

The chemical structure of medicines can be found in resources such as DrugBank.

Sulfonamide antibiotics

Manufacturers of sulfonamide antibiotics contraindicate their use in people with a history of sulfonamide allergy. Sulfadiazine, silver sulfadiazine, sulfamethoxazole and sulfadoxine are examples of sulfonamide antibiotics.

People who are allergic to one sulfonamide antibiotic (e.g. sulfamethoxazole) are likely to be allergic to another.

Non-antibiotic sulfonamides

Some non-antibiotic sulfonamides are contraindicated and others are cautioned for use in people with previous sulfonamide allergy. Advice from manufacturers can vary, even for the same medicine.

There can also be differences in the chemical structures between medicines in the same class, meaning one medicine is suitable to use while others may not be.

Choosing or prescribing non-antibiotic sulfonamides is determined on a case by case basis.

Some common non-antibiotic sulfonamides are discussed below. The list is not exhaustive and the manufacturers advice should always be consulted.

Aminosalicylates

There is little evidence of cross-sensitivity between sulfonamide antibiotics and non-antibiotic sulfonamides, with the exception of sulfasalazine.

Sulfasalazine is contraindicated in people with sulfonamide allergy because it is metabolised to sulfapyridine (a sulfonamide antibiotic).

Alternative aminosalicylates suitable for people with sulfonamide allergy include basalazide and mesalazine.

Triptans

Sumatriptan, almotriptan and naratriptan contain a sulfonamide chemical group so a risk versus benefit analysis should be conducted before prescribing.

Eletriptan, frovatriptan, rizatriptan and zolmitriptan do not contain the sulfonamide chemical group so can be used.

Alpha-blockers

Tamsulosin contains a sulfonamide chemical group so a risk versus benefit analysis should be conducted before prescribing.

Doxazosin, prazosin and alfuzosin do not contain the sulfonamide group so can be used.

Complex scenarios and further advice

In people who have an allergy to sulfonamide antibiotics and require treatment with a sulfonamide antibiotic:

• Consider alternative antibiotics based on sensitivity tests or seek advice from microbiology.
• Seek advice from an allergy specialist if there are no appropriate alternative options.

Seek further advice from the SPS Medicines Advice Service when:

• the clinical scenario is complex
• you have doubts and require a second opinion