What is a Medication Challenge? Answers from an Expert

Are you confused about whether or not you need a drug challenge test?  Or has your allergist mentioned that you need a medication challenge and you’re unsure what exactly that means?

Or did you read my article on penicillin allergy testing and got confused when I mentioned you might need a drug challenge?

Let me clarify this for you real fast.

woman taking a medication challenge

A medication challenge is one of the most common procedures that we, as allergists, do to help our patients.

It is also a procedure filled with all the drama, uncertainty, political infighting and ‘he said she said’ type of arguments you would normally expect to find on an episode of Maury (seriously, it’s kinda crazy.)

I’ll do my best to explain the essentials of a medication challenge so that you can have the correct answers.

And, for fun, I’ll share some of the drama too (because, seriously, who doesn’t love a little medical drama?!)

Who should read this article?

I’ve targeted a specific group with this article:  people who have drug allergy and want to know the details about medication challenge testing.  It’s not many of you…

But if you want to know about drug challenges, you won’t find a better resource.

As a result, you should read this article:

  • If you are intrigued at the prospect of penicillin allergy testing and want to know what I meant by a medication challenge
  • If you have a medication allergy and want to know why you need a drug challenge test
  • If your allergist said you need a medication challenge and you want to know what a normal drug challenge protocol entails

What is a medication challenge?

No drama yet.  The concept of a medication challenge is easy:

We give you a medication and see what happens.

Now, this isn’t some Dr. Frankenstein’s Monster (yes, I know the difference!) type of experiement with your health.  And it’s not done without safeguards and planning.  But the only way to truly know whether you have a medication allergy or not is to take the medicine and see what happens.

If you have a drug allergy, there is no way to know whether or not you have a true drug allergy vs a drug adverse reaction without giving you the medication.

Quite simply:  we give you the medicine and see what happens.

But we try to do this as safely as possible.

But we don’t just give you a dose of medicine, close the door and yell “best of luck.”

Ideally, a good allergist should take a thorough history and add allergy testing to establish a pre-test probability and then divide the medication into small increments and have you slowly take each dose in the safety of the clinic while being monitored.


What about allergy testing for drug allergies?

Drug challenges still need to be done despite skin testing
Skin testing is not as reliable with medication allergy as with other allergies

Whenever we talk about allergy testing, we mention skin testing and not medication challenges.  So what about skin testing for medication allergies?

An allergy test is great for detecting seasonal, pet, and year round allergies.  It is also pretty good in detecting food allergies in a properly chosen patient.

But a skin test for medications is not as reliable.

  • A positive skin test:
    • Could mean you have an allergy
    • Or it could mean the medicine irritated your skin.
  • A negative skin test:
    • Could mean you don’t have an allergy
    • Or the test wasn’t able to capture your reaction.

As a result, the skin test for medication allergies is not an absolute but should be used as a guide to determing pre-test probability before a drug challenge.

Controversy #1:

Maury image for portray drama about drug challenge protocols
Allergist drama? Yup. It happens.

Allergist A:  will happily do a skin test for you and then tell you that skin test means everything in a dogmatic belief of the test.  And then send you off with the plan that if you do have an allergic reaction, just come on back and we’ll know for sure (oh, and I hope it’s not life threatening).

Allergist B:  will tell you that since the skin test isn’t accurate, every patient could possibly have a life threatening reaction.  Since they can’t know for sure… why do any testing and just avoid the medication for life (because it’s no big deal to avoid medications, right?!)

Allergist C (for Chris Webber):  will tell you that the allergy test is not perfect but adds the information to your very well taken history and together, it serves a role in giving a bigger picture of your potential for a future reaction.

 There is one exception to this:  penicillin testing.

Thankfully, penicillin testing (the most common medication allergy) has VERY good skin testing.  We test to the major components of penicillin in a standardized and manufactured test called PrePen.

This test is so good that a negative test in a properly selected patient can approach 100% in clearing you of a penicillin allergy!  At a minimum, it can make it so that the medication challenge is done only when there is a low risk of reaction… and so it is easy to test you for penicillin!

What is a normal medication challenge?

Medication challenge protocol
A lemon-head challenge is much like a medication challenge. I would guess.

So now you can see why a drug challenge is the only way to know for sure whether or not you have a medication allergy (in non-penicillin drugs).

But again, “take the pill and see what happens” is a great way to frame one of Keanu Reeve’s best movies ever (#1 – Matrix.  #2 – Point Break.  #3 – the Replacements.  #4 – John Wick.  Unless you think there is a better order, then let me know).  But this is a pretty crappy way to check for allergies.

Instead, we divide medications into smaller doses, or steps, and slowly progress through the medication while monitoring you in the clinic.

An example drug challenge protocol might be:

  1. Take 1/8th of a full strength dose and get monitored for 30 minutes.
  2. If no reaction happens, take another 1/8th of a dose and, again, get monitored for 30 mintues.
  3. If you’re still good, increase to 1/4th of a dose and… you guessed it… 30 minutes.
  4. If all that is good, finish with 1/2 of a dose and wait for 30-60 minutes.

By the end, you had a full dose but it was done slowly and safely.

The benefit of this approach:

  • If you have a reaction, it will be to a lower dose and should be more minor and easier to treat
  • If not, you are lowering your pretest probability making the test safer as time goes on

Easy, right?

Controversy #2

drug challenge protocols and allergy
Ask 5 allergists for a drug challenge protocol and you’ll get 3 different answers from 1 allergist while the other 4 allergists go in circles about computer records and medical billing)

Allergist A:  will tell you that the procedure will last all day.  Their first dose is a diluted slurry mixed down to 1/1000th of a dose and you’re given that.  You will progress slowly until, at the end of 6 hours, you are at 1/10 of a dose and sent home from the clinic (this is actually a real example.  It starts conservatively and never gets you to the full dose so technically you don’t know if you are safe.  Why do this?  This particular allergist charged by the hour… so they got 6 hours of money and assumed no risk.  But didn’t help you at all.  A true story.  Sad smile)

Allergist B:  will tell you that by doing a challenge, you might re-activate your immune system and remind it you had an allergy.  Thus, a normal allergy challenge could be setting you up for a problem so just keep avoiding the medication forever (I explain why allergist B keeps saying this stuff at the end).

Allergist C (again, perhaps for Chris Webber?):  will use the skin test and history to make a pretest probability.  And then create a drug challenge protocol that will get you to a full dose as safely AND QUICKLY as possible.  The goal is to get you answers and not waste your time but always prioritizing safety. (man, this guy seems like a great allergist! #nobias)

General guidelines for drug challenge protocols

There will probably never be an absolute protocol for medication challenges.  My specialty’s best attempt through the Drug Allergy National Guidelines, reads more like a government document that tries to give cursory appeasement to sides while simultaneously accomplishing nothing definitive.

There are a few absolutes that should be followed on every drug challenge test:

  1. The final dose should be the full strength medication – so that you can know you’ve tested what the patient will be given in the future.
  2. The pacing should be done in the safest manner possible
  3. A consideration should be made to continue the medication for 5 days afterwards to rule out any delayed reaction or medication adverse reaction
  4. Every allergist should be able to argue why their way is the best while also arging why the exact same way done by another provider could be the worst (yeah, we have issues).

To help, I have included a few of my “general drug challenge protocols” at the end that you can read if you want more specific information want more specific information.

What to look for in an allergist BEFORE getting a medication challenge?

I’m sure everyone would like to see Allergist C.  And we’re out there… but so are Allergist’s A and B.

There is no guaranteed way to pick the best allergist, but I think a simple phone call could give you a pretty good chance at picking correctly if you ask these questions to the front desk:

  1. Do you do oral medication challenges?
    • If the answer is yes, then you’ve passed the first hurdle.
    • If it’s no… clearly a bad choice.
  2. How long do medication challenges take?
    • I think it is reasonable to estimate a drug challenge test at 1/2 a day.
    • If they say an entire day or mulitple days… I’d be suspicious.
    • If they say an hour then I’d worry they are looking to not do a challenge instead of finding a way to do one.
  3. Does the challenge go to a full dose of medication.
    • The answer needs to be yes.
    • Anything else is an improper drug challenge.

And I think that’s about all you can do.  But if this makes you nervous (or if you’re like me and you think your phone is an amazing texting device that has a bug where people can call you) just email me and I’ll look up some allergists in your area and try to do this for you.


If you have a drug allergy, the alternative medications might cost more, have more side effects or be less effective.  Checking whether or not you are truly allergic is a great way to possibly clear your allergy.

For medications, skin testing is not a precise tool in giving you an absolute answer (except maybe with penicillin, which I talk about in my penicillin allergy article).  Instead, most allergists will need to do some type of medication challenge.

A normal drug challenge should be set up where you take a small amount of the medication while being monitored by an allergist and then slowly and safely increase the dose until you take a full dose of the medication.  An oral medicaiotn challenge gives you very clear results:

  • If you go through a medication challenge without a problem, you are not allergic
  • If you have a reaction during the drug challenge, you might be allergic

But finding an allergist who does a proper drug challenge test is surprisingly difficult.  Our specialty is filled with controversy and drama on the subject.

To help with this, I included some questions which you can ask the allergist’s office to see if they will be a good fit.


Next Steps

The next steps you need to take have nothing to do with this blog.  Decide whether or not you want to check your medication allergy and, if you do, call an allergist near you (or email me and I’ll find a good choice for you).

And if you have any experiences (good or bad) with medication challenges, leave them in the comments below.  Toss in a little allergist drama if you want.  We’ll all enjoy reading it.



  1. Allergy Diagnostic Testing Practice Parameters
  2. Drug allergy: an updated practice parameter (2010)

Additional Reading

Not everyone cares about WHY allergists have drama.  And probably even fewer care about specific drug challenge test protocols.  But if you do, I included this at the end to be thorough.

Why the Controversy?

I’m going to call this straight and not pull any punches.

Drug challenges are resource intensive and do not get reimbursed very well from insurance companies.  If everything goes as planned (meaning no reaction) a medication challenge can take one staff (nurse or MA) and a room for up to half a day and reimburses about the same as a single new patient.  Using that room to see new patients, a clinic could make 6 times as much money as a drug challenge.

In addition, a drug challenge does come at a risk of a potentially life threatening anaphylaxis.  While a good allergist mitigates your risk, it can never be zero.  So some allergists see medication challenges as a waste of resources that also incurs a risk of a severe, life-threatening allergic reaction.

From a business perspective, drug challenges are not the best move.

As a result, some allergists accept the lower reimbursement but add on time-based codes which reimburses better… but takes your time for no medical reason.

Luckily, many allergists (like Allergist C) believe that an allergist’s job is to treat their patient the correct way and advocate medication challenges when appropriate.  The way I do this in my clinic is to schedule them on days where I have additional staff and where I have additional rooms available.  Easy enough.

I just wish more allergists felt this way.

Sample Drug Challenge Protocols

There is no one way to create a drug challeng test.  Instead, I thought it would be valueable to show you how I approach them (in general) and give you a frame of reference for a way to look at medication challenges.

Drug Challenge Protocol #1 – High Risk Medication Challenge

If your history was very concerning for a true allergic reaction, you would have a high risk of reaction.  I’d probably do a skin test and if it were positive it might push me to call it a full allergy and not risk a drug challenge test.  If it were negative, you’d be at a lower-high risk or a high-medium risk and I might do a medication challenge.

A typical high risk drug challenge protocol could look like this:

Dose amount Total given
Step 1 1/16th dose 1/16th dose
Step 2 1/16th dose 1/8th dose
Step 3 1/8th dose 1/4th dose
Step 4 1/4th dose 1/2 dose
Step 5 1/2 dose 1 dose


Drug Challenge Protocol #2 – Moderate Risk Medication Challenge

If your history was one where you could equally have an allergic reaction or an adverse reaction, you’d be a moderate risk.  In this case, a positive skin test would push you to a high-moderate or low-high risk.  If it were normal, you’d be reduced to a low-moderate or high-low risk.

A typical moderate risk drug challenge protocol could look like this:

Dose amount Total given
Step 1 1/8th dose 1/8th dose
Step 2 1/8th dose 1/4th dose
Step 3 1/4th dose 1/2 dose
Step 4 1/2 dose 1 dose


Drug Challenge Protocol #3 – Low Risk Medication Challenge

If your history was suspicious for a medication adverse reaction and not a drug allergy, you’d be a low risk.  I’d still do skin testing to get a little more information.  If skin testing were high, you’d be at a high-low risk.  If it were negative, you’d be at a low-low risk and possibly have an even more aggressive challenge.

For low risk drug challenges, these are possible drug challenge protocols.:

Low Risk Drug Challenge Protocol #1

Dose amount Total given
Step 1 1/4th dose 1/4th dose
Step 2 1/4th dose 1/2 dose
Step 3 1/2 dose 1 dose

Low Risk Drug Challenge Protocol #2

Dose amount Total given
Step 1 1/4th dose 1/4th dose
Step 2 3/4th dose 1 dose

Low Risk Drug Challenge Protocol #3 (sometimes used with vaccines)

Dose amount Total given
Step 1 1/10th dose 1/10th dose
Step 2 9/10th dose 1 dose

These are not all inclusive and merely show you one reasonable way to approach drug challenge tests.  If you have any questions, please feel free to contact me and I’ll be happy to help

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