MCAD: Medications and Treatments

Please note: This post contains affiliate links from which I may make a commission, with no additional cost to the purchaser. This post was updated 5/20/20.

Mast Cell Activation Disorders can be quite complex to treat. Able to attack any system in the body, there’s a wide range of symptoms one must account for when treating these disorders. In my previous posts, we discussed how eating a low histamine diet can help you avoid flares, along with other ways to avoid triggers and prevent flares. The final components to achieving the best health possible with MCAS are therapeutic and rescue medications. Given the complexity of the disease, the list of medications used to treat the disease is not a short one.

Suffering from allergies or a mast cell disorder and not sure where to turn next? This list provides a number of options from a variety of medication classes to help you get the relief and stability of health you need!

I will be covering a wide range of drugs, available by prescription and OTC. Try as one might, a MCAD usually requires the assistance of a physician to treat, given the complexity of these disorders and the need for specific medications at doses that are usually not available without a prescription (and shouldn’t be taken at higher doses without a physician’s supervision). Dr. Afrin and his peers state in a 2016 article for the NIH that “Recent mutational studies revealed that each patient has an individual pattern of genetic and epigenetic alterations which may affect the intracellular signal transduction pathways and receptive sites involved in sensory perception. As a consequence, mediator formation and release as well as inhibition of apoptosis and/or increase in proliferation are determined by individual genetic and epigenetic conditions and represent potential targets for therapy. Hence, there is need of highly personalized therapy for the disease.”

Self-Injectable Epinephrine

Two doses should be carried by all patients with a mast cell disorder at all times, even if previous anaphylaxis has not occurred (though frankly my immunologist disagrees with this statement, so don’t be surprised if yours does, too). Both the patient and family members/caregivers should be trained on administering epinephrine!

To see a video on how to inject the EpiPen®, click here.


There are a wide variety of antihistamines available. Unsurprisingly, many people with MCAD find that there are one or two in which they react, so it’s good to have options! Sometimes what you’re reacting to are the additives, such as dyes or preservatives. Try additive-free options to see if the problem clears up. These options can be a little more expensive, but worth a few more pennies if you find one histamine works better for you over another without the fillers.

H1 antihistamines: Benadryl (diphenhydramine), Atarax (hydroxyzine), Tavist (Clemastine), Allergra* (Fexofenadine), Claritin* (Loratidine), Xyzal* (levocetirizine), Zaditor (Ketotifen) and Zyrtec* (cetirizine). In technical terms, H1’s block mutual activation of mast cells via H1-histamine receptors. They antagonize H1-histamine receptor-mediated symptoms (Afrin, et al.). In laymen’s terms, they help alleviate allergic symptoms such as itching, abdominal pain, flushing, headaches and brain fog. Unfortunately, long term use of antihistamines is also associated with cognitive impairment (TMS), something people with MCAD already struggle with, so the use of an antioxidant to help counteract these problems is really helpful.

While generation 2 antihistamines (denoted by an asterisk*) are less likely to cause drowsiness and usually are longer acting, first generation antihistamines are faster acting and better in emergency situations. However, the preference is to treat MCAD with second and third generation antihistamines (Afrin, et al.) and use first generation antihistamines as rescue, or “as-needed” medications when second and third generation antihistamines aren’t enough.

For some patients facing serious and constant anaphylactoid reactions and dysautonomic states, sometimes continuous diphenhydramine infusion is used. “In a small series of ten MCAS patients suffering almost continuous anaphylactoid/dysautonomic flares, continuous diphenhydramine infusion at 10–14.5 mg/h appeared effective in most patients at dramatically reducing flare rates and appeared safely sustainable at stable dosing for at least 21 months (Afrin 2015). Stabilization has enabled successful trials of other helpful medications, but no patient has yet successfully stopped continuous diphenhydramine infusion. (Afrin, et al.)”

Ketotifen also has mast cell stabilizing properties. Mast cell stabilizers prevent the release of mediators. The oral formulation is not available in the US, and has to be obtained from overseas or compounded, if possible. Dosing is usually started at 1mg twice daily and increased in increments of 1mg twice daily until desired effects are noted and balanced with an acceptable side effect profile. As described by Afrin, single dosing is usually 6mg or less, and can be taken up to four times a day, according to Mast Attack. Ketotifen eye drops are available in the U.S. and can help with ocular symptoms such as dry, itchy, watery, swollen, irritated eyes. My eyes were so degraded by histamine; they would no longer focus properly, getting stuck frequently on one focal point and causing blurred vision. So long as I remember to apply my ketotifen drops twice a day, they operate normally and I can even wear contacts again.

H2 antihistamines: Work much the same way as H1’s and are used to treat gastrointestinal symptoms such as reflux, stomach pain, diarrhea, itching, flushing, headaches and brain fog. They include Zantac (Ranitidine), Axid (Nizatidine), Pepsid (Fomotidine), and Tagament (Cimetidine), (TMS).

If H2 antihistamines aren’t enough to combat GERD (heart burn that occurs 2 or more times per week), a proton-pump inhibitor like Nexium can be added, though I’d use caution with this if you have a stomach condition that causes low motility such as gastroparesis. Proton-pump inhibitors can slow motility further, as can anti-histamines, which usually aren’t a negotiable medication for masties. Instead, try addressing the problem with diet, which will be covered in part 3 of this series, or other natural remedies which aren’t harmful to motility, covered in Natural Treatments for Gastroparesis Part Two.

Stinging Nettle Tea: Despite the reputation of its scratchy leaves, stinging nettle has surprising antihistamine properties and makes a nice, mild tea. Drunk daily, it helps to mediate allergic respiratory and gastric symptoms and can even alleviate the symptoms interstitial cystitis, a common condition for masties.

Mast Cell Stabilizers

Mast cell stabilizers help to regulate the release of chemicals from mast cells, reducing symptoms overall. Unlike antihistamines, stabilizers take time to work, often needing weeks or even months before seeing significant improvement of symptoms. The first significant improvements I noted when taking the naturally occurring mast cell stabilizer quercetin was in my energy levels and brain fog. It took time before seeing other symptoms begin to change (see my full account here). My understanding is that this is common with all mast cell stabilizers. It can take 4 months or more before knowing how well they may help.

Cromolyn: The most well known mast cell stabilizer is noted to block mast cell receptor 35, which is increased when IgE is present. Cromolyn has extremely poor absorption, with 98% of oral doses being excreted unchanged. When inhaled, absorption increases to around 5%. Oral dosing is from 100-200mg 2-4 times daily. When nebulized, dosing is usually 20mg 2-4 times daily. Of note, patients usually experience a resurgence of symptoms when first starting the medication that may last 3-4 days (MA).

Quercetin: A natural bioflavinoid, quercetin can effectively inhibit secretion of histamine, leukotrienes and prostaglandins and is actually more effective than cromolyn (the only prescribed mast cell stabilizer) in inhibiting IL-8 and TNF release from LAD2 mast cells stimulated by SP. Moreover, Quercetin reduces IL-6 release from hCBMCs in a dose-dependent manner. Quercetin inhibits cytosolic calcium level increase and NF-kappa B activation. Interestingly, Quercetin is effective prophylactically, while cromolyn must be added together with the trigger or it rapidly loses its effect. In two pilot, open-label, clinical trials, Quercetin significantly decreased contact dermatitis and photosensitivity, skin conditions that do not respond to conventional treatment (Quercetin and MCADs). It also proved very effective in treating my symptoms of interstitial cystitis, firming up my skin and lessening the frequency of my subluxations.

Vitamin C: This vitamin works in two ways to help MCAD patients. It causes increased degradation of histamine while also decreasing histamine formation by inhibition of histidine decarboxylase (Afrin, et al.).

Pentosan: This medication is commonly used in interstitial cystitis, a mast cell disorder that affects the genitourinary tract. Though Pentosan seems to be most effective in the GU tract, some patients report decrease in other symptoms while on this medication (MA).

Leukotriene inhibitors: help with respiratory symptoms and overall mast cell stability. Singulair (Montelukast) is the most common Leutotriene (MA).

Third and Fourth Line Medications

Third and Fourth Line Medications come with a variety of risks to patients and are so named because they are only utilized when outcomes are poor when utilizing first and second line medications traditionally used to treat a condition.

Aspirin therapy (under direct supervision of a physician): A useful tool if prostaglandins are elevated. Helps with flushing, brain fog and bone pain, if aspirin is tolerated. In MCAS patients for whom aspirin is inappropriate (such as those with low platelets or decreased kidney function), COX2 inhibitors like Celebrex are sometimes used (MA).

Acute and chronic immunosuppressive therapies: Are considered second and third line medications sometimes used when autoimmune symptoms are present or no other medications have been effective. These therapies include Glucocorticoids, azathioprine, methotrexate, ciclosporine, hydroxyurea, and tamoxifen. The effectiveness of these therapies can be moderate to having no effect at all (Afrin, et al.).

Omaluzimab (Xolair): An anti-IgE monoclonal antibody, it is not entirely clear why this medication works for some and requires more study. It has an acceptable risk-benefit profile and should be used for 3-4 months before determining effectiveness (Afrin, et al.).

Tyrosine Kinase Inhibitors: Traditionally chemotherapy drugs, imatinib and dasatinib have been used as a last resort in MCAS patients. Patients on these medications require careful monitoring for pulmonary and renal issues. All chemo patients are at increased risk of infection (MA).

Pain Relievers

I recently received this information from a researcher on twitter and wanted to include it here. Normally, I’d include the information and not the full graphic, but I’ve decided that all the information on here is really quite useful. I do want to point out a couple of things. First, not under the cannabinoid receptor agonists that it isn’t just CBD that’s essential to treating mast cell activation, but several components found in the marijuana plant. I point this out, because a lot of people use CBD oil and miss all the other great benefits of marijuana. You may be doing yourself a major disservice if you’re using a CBD oil versus an MMJ oil or smoking or vaping the whole bud and you have an MCAD.

I also find it extremely interesting that the reason that tricyclic antidepressants work is because they reduce mast cell activity. They’re used heavily in ME/CFS and fibromyalgia, which are not considered to be MCAD, but should they?

There are many more drugs which can be taken to treat specific symptoms and of course many for comorbid conditions, but these are the most important drugs to know about when attempting to address the overall symptoms and mechanisms behind these disorders. Treat the problem of misbehaving mast cells and you will need to treat fewer symptoms overall. The most important medications in the arsenal against misbehaving mast cells are mast cell mediators and H1 and H2 antihistamines. Other medications are symptom specific and should be used when appropriate to achieve the best results. Be sure to work with a qualified specialist to help you decide which are best for you and at what dose.

Mast Cell Activation Syndrome, Allergies , Asthma and other mast cell issues can spell big trouble for many. Find out what's currently available for treatment both by prescription and over the counter to get your symptoms under control fast!

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