How to Re-Challenge or Desensitize After a Drug Allergy Under Supervision

When you’ve had a serious reaction to a medication-hives, swelling, trouble breathing, or worse-it’s natural to assume you’ll never be able to take that drug again. But what if that drug is the only one that can save your life? For patients with confirmed drug allergies who need critical treatments like chemotherapy, antibiotics for cystic fibrosis, or biologics for autoimmune diseases, there’s a medically proven path forward: drug desensitization.

What Drug Desensitization Actually Does

Drug desensitization isn’t a cure for your allergy. It doesn’t change your immune system permanently. Instead, it temporarily tricks your body into tolerating a drug you’re allergic to by slowly, carefully introducing tiny amounts over hours. Think of it like slowly turning up the volume on a speaker that’s too loud-you’re giving your body time to adjust before the full blast hits.

This technique has been used since the 1980s and is now a standard of care at major hospitals like Brigham and Women’s Hospital in Boston, where Dr. Mariana C. Castells leads one of the world’s first dedicated desensitization centers. The goal? To let patients receive life-saving drugs they would otherwise have to avoid forever.

It works for IgE-mediated reactions-like anaphylaxis to penicillin or certain chemotherapy drugs-and even for non-IgE reactions, such as severe asthma triggered by aspirin or NSAIDs. The key is that the reaction must be confirmed, not assumed. If you had a rash after taking amoxicillin as a kid, that doesn’t automatically mean you’re allergic now. Skin tests and challenge tests under supervision are often needed to confirm the allergy before desensitization even begins.

When Is Desensitization Used?

Desensitization isn’t for every drug allergy. It’s reserved for situations where there are no safe, effective alternatives. That’s most common in three areas:

• Oncology: Many chemotherapy drugs, monoclonal antibodies like rituximab or cetuximab, and immune checkpoint inhibitors can trigger severe reactions. For patients with cancer, stopping treatment isn’t an option. Desensitization lets them complete their full course.
• Infectious Disease: Cystic fibrosis patients often rely on specific antibiotics like vancomycin or carbapenems. If they develop an allergy, desensitization allows them to keep fighting infections without switching to less effective drugs.
• Rheumatology and Autoimmune Conditions: Drugs like infliximab or tocilizumab are vital for rheumatoid arthritis or Crohn’s disease. When patients react, desensitization helps them stay on therapy without relapsing.

It’s also used for aspirin and NSAID hypersensitivity, especially in people with asthma or nasal polyps. In these cases, desensitization can reduce not just the risk of reactions but also the severity of their underlying condition over time.

How the Procedure Works

Desensitization is never done at home. It requires a hospital or specialized allergy clinic with emergency equipment and trained staff. Here’s how it typically unfolds:

• Start small: The first dose is usually 1/10,000th of the full therapeutic dose. For IV drugs, that might be just a few microliters diluted in saline.
• Gradual increases: Every 20 to 30 minutes, the dose is doubled. For oral drugs like aspirin, intervals are longer-usually one hour or more-because absorption is slower.
• 12 to 16 steps: Most protocols use 12 or 16 dose steps, with concentrations increasing from 1:100 to 1:10 to the full-strength solution.
• Full dose in hours: Most IV desensitizations are complete in 5 to 6 hours. Aspirin protocols can take days.

At every step, medical staff monitor you closely:

• Blood pressure every 5 minutes
• Pulse oximetry to check oxygen levels
• Heart rate and breathing sounds
• Spirometry if you have asthma
• Visual checks for hives, swelling, or flushing

If you develop symptoms-itching, wheezing, low blood pressure-the team pauses, gives you antihistamines or steroids, and may drop back to the last safe dose. They’ll then wait longer before trying again, sometimes extending the whole process by hours or even days.

What Drugs Can Be Desensitized?

Not every drug can be desensitized, but many of the most critical ones can:

• Antibiotics: Penicillins, cephalosporins, vancomycin, carbapenems
• Chemotherapy agents: Platinum drugs (cisplatin, carboplatin), taxanes (paclitaxel, docetaxel), monoclonal antibodies (rituximab, cetuximab)
• NSAIDs and aspirin: Even in patients with severe asthma or nasal polyps
• Biologics: Infliximab, tocilizumab, omalizumab
• Iron infusions: For patients with severe anemia who react to IV iron
• Local anesthetics: Lidocaine or other numbing agents, especially for patients needing repeated surgeries

The American Academy of Allergy, Asthma & Immunology (AAAAI) updated its guidelines in 2022 to include newer agents like tyrosine kinase inhibitors and immune checkpoint inhibitors, reflecting how fast this field is growing.

What Doesn’t Work for Desensitization

Some reactions are too dangerous to attempt desensitization. You should never try it if you’ve had:

• Stevens-Johnson syndrome or toxic epidermal necrolysis
• Drug reaction with eosinophilia and systemic symptoms (DRESS)
• Severe liver inflammation (hepatitis) caused by the drug
• Kidney inflammation (nephritis) linked to the medication
• Serum sickness-like reactions with joint pain, fever, and rash

These aren’t just allergic reactions-they’re immune system overreactions that damage organs. Desensitization won’t prevent that kind of damage. In fact, trying it could be life-threatening.

Temporary Tolerance-The Big Catch

This is the most important thing to understand: desensitization gives you temporary tolerance, not permanent immunity.

If you stop taking the drug for more than 24 to 48 hours, your allergy can come back. That means if you’re on a weekly chemotherapy schedule, you need to be desensitized before each dose. If you miss a dose and skip a day, you’ll need to restart the entire process.

For oral aspirin, tolerance can last longer-sometimes weeks-but even then, stopping for more than a few days often means restarting from the beginning. This makes desensitization logistically challenging but still worth it for patients who have no other options.

Who Performs This Procedure?

This isn’t something a general practitioner or ER doctor does. Desensitization requires:

• An allergist or immunologist with specific training in drug hypersensitivity
• A nurse trained in emergency response and IV administration
• Immediate access to epinephrine, steroids, antihistamines, and IV fluids
• A monitored setting-usually an inpatient unit or specialized allergy clinic

Brigham and Women’s Hospital, the Asthma Center, and other major academic medical centers have dedicated teams. In places like Durban or other regions without specialized centers, patients may need to be referred to larger hospitals in Johannesburg or Cape Town. Access is still limited, but demand is rising as more targeted therapies become standard.

Success Rates and Real Outcomes

When done correctly by experienced teams, desensitization succeeds in over 90% of cases. That means most patients who go through it complete their treatment without another reaction.

Dr. Castells’ work shows that cancer patients who undergo desensitization don’t just survive-they thrive. One study showed patients with ovarian cancer who were allergic to carboplatin but underwent desensitization had the same survival rates as those who weren’t allergic. Without desensitization, many would have been forced onto less effective, more toxic alternatives.

For cystic fibrosis patients, being able to continue on their best antibiotics means fewer hospitalizations, better lung function, and longer life expectancy. For someone with rheumatoid arthritis, staying on infliximab means staying off the wheelchair.

What Happens After?

After you’ve reached the full dose, you’ll usually stay under observation for another hour. If all’s well, you’ll be sent home with instructions to take the drug as prescribed-without skipping doses.

You’ll need to carry an emergency card listing your drug allergy and the fact that you’ve been desensitized. If you ever need emergency care, this tells providers you can’t just be given a different drug-you need the same one, and they need to know how to handle it.

Some patients are taught to self-administer maintenance doses at home under strict guidelines, but this is rare and only for oral drugs like aspirin, with direct oversight from their specialist.

Is There Any Alternative?

Sometimes. But rarely.

For antibiotics, there are often other classes-azithromycin instead of penicillin, for example. But in cancer, the drugs are often the only ones that work. For biologics, alternatives may be less effective or much more expensive. For aspirin, there’s no substitute for its anti-inflammatory and blood-thinning effects in patients with heart disease.

Desensitization isn’t the first choice. But when the first choice is the only choice, it’s the only real option.

What to Do If You Think You Need This

If you’ve had a confirmed allergic reaction to a drug you now need:

1. Ask your doctor for a referral to an allergist or immunologist who specializes in drug hypersensitivity.
2. Bring all records of your reaction-when it happened, what symptoms you had, what treatment you received.
3. Don’t assume you’re allergic forever. Many reactions are misdiagnosed.
4. If desensitization is recommended, ask about the specific protocol, success rates at that center, and what happens if you miss a dose.
5. Make sure the facility has emergency equipment on-site and staff trained in anaphylaxis management.

This isn’t a decision to rush. But it’s also not something to avoid if it’s your only path to treatment.