What to Do If Your Allergy Medications Stop Working

One of the most common complaints heard from allergy sufferers is that certain allergy drugs will stop working for them over time. This may occur after months or years of use and is most common among people who have chronic allergy symptoms.

Some people will insist that they've developed an "immunity" to the medications or have become "drug-resistant" in the same that they can become resistant to antibiotics.

What actually happens is that the body no longer reacts to the drug in the same way. A worsening of your condition could also be to blame.

Man blowing nose at home on the couch
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How Allergy Drugs Work

Much of the confusion regarding the loss of a drug effect stems from the misuse of the terms "immunity" and "resistance."

Immunity is the body's defense against a harmful substance. Resistance describes the process wherein a bacteria, virus, or other disease-causing agent changes (mutates) and is able to overcome the effects of the drug. Neither of these processes applies to changes in how certain allergy medications work.

With an allergy, the immune system overreacts to an otherwise harmless substance and floods the body with a chemical known as histamine. The main function of histamine is to trigger inflammation, the body's natural response to injury. It does so by dilating blood vessels so that immune cells can get closer to the site of an injury or infection.

In the absence of injury or infection, histamine can trigger an array of adverse symptoms, including itching, rash, sneezing, runny nose, stomach ache, nausea, and vomiting. Allergy medications are used to counter these effects because they are able to block (inhibit) the inflammatory process.

Among them:

  • Antihistamines work by preventing histamine from attaching to cells of the skin, gastrointestinal tract, and respiratory tract.
  • Corticosteroids work by tempering the immune response and reducing inflammation, either locally with topical ointments or sprays, or systemically with oral or injected medications.
  • Beta-agonists commonly used in asthma inhalers relax constricted airways in the lungs.
  • Anticholinergics, also used in inhalers, work by blocking a neurotransmitter called acetylcholine, thereby reducing bronchial spasms and constriction.

In none of these instances does a substance mutate or the immune system alters its natural response. What happens instead is that the body develops a tolerance to the drug, particularly if overused.

Understanding Drug Tolerance

In pharmacology, when certain drugs are overused, they can stop working as the body becomes progressively desensitized to their effects. This is referred to as drug tolerance. While increasing the dosage may restore the drug action, the benefits tend to be short-lived.

There are two major reasons why this might occur:

  • Dynamic tolerance describes the process where a cell becomes less responsive to a drug the longer it is exposed to it. In some ways, it is no different from the way that the taste receptors on our tongues adapt to extra-spicy foods if exposed to them repeatedly.
  • Kinetic tolerance occurs when the body responds to the ongoing presence of a drug and begins to break it down and excrete it more actively, lowering the drug concentration.

With certain drugs, particularly psychoactive drugs, drug tolerance may be associated with drug dependence or addiction. This is not so much the case with allergy medications since the developing tolerance reduces the efficacy of a drug rather than our need for it.

Bronchodilators and Corticosteroids

Some classes of allergy medication are prone to tolerance, while others are not.

The risk can be high with beta-agonists. For this class of inhaled medication, the tolerance is primarily dynamic and linked to prolonged use or overuse of long-acting beta-agonists (LABAs) like Serevent (salmeterol), particularly when used on their own. When this happens, it can have a knock-on effect, inducing tolerance to short-acting beta-agonists (SABAs) used in rescue inhalers.

The same doesn't appear to be the case with anticholinergic inhalants like Spiriva Respimat (tiotropium bromide) or glycopyrronium bromide, for which there is little risk of tolerance.

Dynamic tolerance can also occur with certain corticosteroid formulations, particularly topical ointments, and nasal sprays. Their unimpeded use can rapidly desensitize the skin and mucosal tissues to the vasoconstrictive (vessel-shrinking) effects of the drugs.

Paradoxically, inhaled corticosteroids can significantly reduce the risk of tolerance to beta-agonists when used in combination therapy.


The causes for the diminished effect of antihistamine drugs are far less clear. The bulk of evidence will tell you that drug tolerance does not occur no matter how long or aggressively the drugs are used. If anything, their prolonged use will reduce a person's tolerance to their side effects, particularly drowsiness.

This doesn't undermine the plethora of claims that the effects of antihistamines can wane over time. More often than not, the waning effects are related more to the natural course of the allergy than to the drugs themselves.

In many allergy sufferers, a mild hypersensitive reaction can become progressively worse over time, particularly with certain food allergies or cross-reactive responses that become vulnerable to multiple allergy triggers (allergens).

A study conducted in 2012 suggested that as many as one in seven users reported that antihistamines stopped working for them after several months or years. This was especially true for people with seasonal allergic rhinitis (hay fever).

So, while you may believe the drugs are useless, it may be that your symptoms have gotten worse or your sensitivity to an allergen has increased significantly.

What to Do

If a genuine drug tolerance has occurred, it is often reversible by taking a "drug holiday" and removing the substance from your body for a period of time. You can then re-challenge yourself to the drug, altering its use so that the problem does not recur.

If faced with recurrent or severe asthma attacks, your healthcare provider will typically prescribe a combination inhalant like Advair or Symbicort, which combines a LABA with a corticosteroid drug. The combination can reduce the risk of drug tolerance and failure.

If you believe that a drug is failing, consider your symptoms when you first started treatment versus those you have now. In some cases, the antihistamine you may have initially used for sneezing will not work if you are suddenly dealing with nasal congestion. As your allergy symptoms change, so, too, will the drugs you need to treat them.

It also helps to stage treatment so that you use one type of drug to manage your daily symptoms and another to treat an acute event. Your allergist can help you select the drugs. Some people prefer this approach over the common approach of increasing dosages in tandem with the severity of your symptoms.

A Word From Verywell

It can be frustrating to finally find an allergy management regimen that works only to have it stop working. Communicating changes in your symptoms to your healthcare provider, instead of trying to tough things out, can go a long way in helping you zero in on a new course of action that can bring you symptom relief again. Aside from the possibilities of drug tolerance and a worsening condition, remember that changes in exposures (such as moving to a new area) could also be affecting you.

5 Sources
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
  1. Peper A. Aspects of the relationship between drug dose and drug effect. Dose Response. 2009;7(2):172-92. doi:10.2203/dose-response.08-019.Peper

  2. Tamm M, Richards D, Beghe B, et al. Inhaled corticosteroid and long-acting β2-agonist pharmacological profiles: effective asthma therapy in practice. Respir Med. 2012;106(1):S9-19. doi:10.1016/S0954-6111(12)70005-7

  3. Nardini S, Camiciottoli G, Locicero S, et al. COPD: maximization of bronchodilationMultidiscip Respir Med. 2014;9:50. doi:10.1186/2049-6958-9-50

  4. Beasley R, Martinez FD, Hackshaw A, Rabe KF, Sterk PJ, Djukanovic R. Safety of long-acting beta-agonists: urgent need to clear the air remains. Eur Respir J. 2009;33(1):3-5. doi:10.1183/09031936.00163408

  5. Meltzer EO, Blaiss MS, Naclerio RM, et al. Burden of allergic rhinitis: allergies in America, Latin America, and Asia-Pacific adult surveys. Allergy Ashtma Proceed. 2012;33(Suppl 1):S113-41. doi:10.2500/aap.2012.33.3603

By Daniel More, MD
Daniel More, MD, is a board-certified allergist and clinical immunologist. He is an assistant clinical professor at the University of California, San Francisco School of Medicine and currently practices at Central Coast Allergy and Asthma in Salinas, California.