But even if antihistamines are working at first, they may stop working for hives. That’s when you’ll likely need to try a different option.
“Although over-the-counter antihistamines can usually be enough to provide relief, the activity of hives can wax and wane, which means antihistamines may be more or less effective at different times,” says Dr. Weiler. “When it becomes less effective, there are other choices in stepping up treatment.”
Here are four options your doctor might recommend if your antihistamines stop working for you.
1. H2 Blockers
When over-the-counter medications — such as cetirizine (Zyrtec Allergy), fexofenadine (Allegra Hives), levocetirizine (Xyzal Allergy 24HR), and loratadine (Claritin) — don’t work well for you, your doctor may prescribe a medication known as an H2 blocker, or H2 antihistamine. Commonly prescribed for certain gastrointestinal issues, these drugs work by targeting histamine receptors in the stomach and blood vessels. That can bring down swelling and redness. Options include:
- cimetidine
- famotidine
- nizatidine
2. Corticosteroids
Oral corticosteroids (also called steroids or glucocorticoids) such as montelukast and prednisone could be the next step if antihistamines aren’t working, Dr. Camp says.
These prescription medications work by reducing inflammation throughout your body. They’re similar to cortisol, a hormone that your body makes naturally. They can also relieve pain and temporarily suppress the immune system so it stops releasing histamines.
But steroids aren’t a long-term treatment. They’ll only be used to relieve a hives-related rash when it’s acute (short-term) rather than chronic (long-term). That’s because the chances of getting side effects — such as mood changes, muscle weakness, weight gain, and stomach irritation — increase the longer you take them.
3. Biologics
A next step in treatment is to consider biologic medications, particularly when hives become frequent or intense, and don’t respond to antihistamines or corticosteroids, says Amiirah Aujnarain, MD, an allergist, immunologist, and pediatrician at Kindercare Pediatrics in East York, Ontario, Canada.
“These medications target an antibody called immunoglobulin E (IgE), which [is] released by the immune system, usually when an allergen is detected,” she says. “This approach must be done under a specialist’s care.”
About 30 percent of chronic hives are linked with IgE. Biologics work by binding to this antibody and reducing its effects — a process that decreases the release of histamine as well.
One example of a biologic that targets IgE is called omalizumab (Xolair), which alters the immune response to reduce symptoms.
In April 2025, the U.S. Food and Drug Administration (FDA) approved dupilumab (Dupixent) for the treatment of chronic hives (also called chronic spontaneous urticaria) in people who still have symptoms despite treatment with H1 antihistamines. Dupixent targets inflammatory proteins in the body called interleukin (IL)-4 and IL-13, which also targets the eventual production of IgE.
4. Lifestyle Changes
Certain lifestyle changes can help address hives, and they may also play a role in preventing flare-ups of hives in the future.Those include:
- With the help of your doctor, identify and avoid any food triggers that may prompt symptoms.
- Reduce exposure to airborne allergens, like pet dander or pollen.
- Use detergents and soaps without scents or dyes, which could irritate your skin.
- Avoid extreme temperature changes, which can prompt hives or worsen symptoms for some people.
- Do your best to manage stress, which doesn’t directly cause hives but can make them worse.
- Wear loose-fitting, lightweight clothing to avoid skin irritation.
These lifestyle changes can be helpful for reducing the frequency, duration, and intensity of hives. But they’re often used as an addition to medications, not as a replacement.
The Takeaway
- Over-the-counter (H1) antihistamines are nearly always the first line of treatment for a hives rash, since these meds can block histamine, a chemical in the body that prompts hives symptoms.
- Prescription antihistamines, corticosteroids, and biologic medications are the next steps when over-the-counter options aren’t working for you.
- Some lifestyle changes may help ease hives. But they’re often used along with medication rather than in place of it.
- If you’re getting more-frequent hives, and especially if they’re becoming worse and you’re not getting relief from over-the-counter antihistamines, talk with your doctor about other options that can help.
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