Why are Pepcid (famotidine), diphenhydramine, and Decadron (dexamethasone) given for allergic reactions?

From the Guidelines

Pepcid (famotidine), diphenhydramine, and Decadron (dexamethasone) are given together to treat allergic reactions because they target different aspects of the allergic response, with epinephrine remaining the first-line treatment for anaphylaxis. The combination of these medications is often referred to as "triple therapy" and is particularly effective because it blocks multiple pathways of the allergic response simultaneously. According to the most recent study 1, anaphylaxis is an acute, life-threatening systemic allergic reaction that may have a wide range of clinical manifestations, and epinephrine administered intramuscularly is the first-line treatment. Diphenhydramine is an H1 antihistamine that blocks the primary histamine receptors responsible for allergic symptoms like itching, hives, and swelling, while famotidine is an H2 antihistamine that blocks histamine receptors in the stomach but also helps reduce hives and skin symptoms when combined with traditional antihistamines. Dexamethasone is a corticosteroid that reduces inflammation by suppressing the immune response more broadly. For severe allergic reactions, typical dosing might include diphenhydramine 25-50mg, famotidine 20mg, and dexamethasone 4-10mg, all given intravenously for rapid effect. However, as stated in 1, antihistamines and glucocorticoids should not be administered prior to, or in place of, epinephrine, and their use is associated with reduced length of hospital stay but have not shown any benefit of preventing return visits to the ED following discharge. It's also important to note that, as mentioned in 1, the first-line treatment for anaphylaxis is epinephrine, and adjunctive treatment may include H1 antihistamine, H2 antihistamine, and corticosteroid. In addition, 1 and 1 provide information on the use of diphenhydramine and other medications in the treatment of allergic reactions, but the most recent and highest quality study 1 should be prioritized. Therefore, the combination of Pepcid, diphenhydramine, and Decadron is a useful adjunctive therapy for allergic reactions, but epinephrine should always be the first-line treatment.

Some key points to consider when administering these medications include:

• Epinephrine is the first-line treatment for anaphylaxis
• Diphenhydramine and famotidine can be used as adjunctive therapy to prevent symptom recurrence and manage ongoing inflammation
• Dexamethasone can be used to reduce inflammation by suppressing the immune response more broadly
• The combination of these medications should be used with caution and under the guidance of a healthcare professional.

It's also important to note that, as stated in 1, the clinical criteria proposed in 2006 by National Institute of Allergy and Infectious Diseases (NIAID) continue to provide a helpful framework in approaching patients with acute allergic symptoms, and diagnosis and management of anaphylaxis must occur rapidly. In addition, the use of antihistamines and glucocorticoids in anaphylaxis management is not supported by clear evidence, but they continue to be routinely used. Therefore, it's essential to prioritize the use of epinephrine as the first-line treatment for anaphylaxis, and to use adjunctive therapy with caution and under the guidance of a healthcare professional.

In terms of dosing, typical dosing might include diphenhydramine 25-50mg, famotidine 20mg, and dexamethasone 4-10mg, all given intravenously for rapid effect, but this should be tailored to the individual patient's needs and medical history. It's also important to note that, as mentioned in 1, the timing of onset for antihistamines is considered too slow and could lead to incomplete or ineffective treatment, and epinephrine should always be administered first. Therefore, the combination of Pepcid, diphenhydramine, and Decadron is a useful adjunctive therapy for allergic reactions, but epinephrine should always be the first-line treatment, and the use of antihistamines and glucocorticoids should be tailored to the individual patient's needs and medical history.

From the FDA Drug Label

WARNINGS Because rare instances of anaphylactoid reactions have occurred in patients receiving parenteral corticosteroid therapy, appropriate precautionary measures should be taken prior to administration, especially when the patient has a history of allergy to any drug. CLINICAL PHARMACOLOGY ...Their synthetic analogs, including dexamethasone, are primarily used for their potent anti-inflammatory effects in disorders of many organ systems.

The combination of Pepcid (famotidine), diphenhydramine, and Decadron (dexamethasone) is given for allergic reactions because:

• Dexamethasone is used for its potent anti-inflammatory effects to reduce swelling and inflammation associated with allergic reactions 2 3.
• Diphenhydramine is an antihistamine that helps to relieve symptoms of allergic reactions, such as itching, redness, and hives.
• Pepcid (famotidine) is an H2 blocker that reduces stomach acid production, which can help to alleviate gastrointestinal symptoms associated with allergic reactions, such as heartburn and stomach upset. Key points to consider:
• Corticosteroids, like dexamethasone, can mask some signs of infection and may affect the results of certain tests, such as the nitroblue-tetrazolium test for bacterial infection 2.
• Dexamethasone should be used with caution in patients with a history of allergy to any drug, as it can cause anaphylactoid reactions 2.

From the Research

Medications for Allergic Reactions

• Pepcid (famotidine), diphenhydramine, and Decadron (dexamethasone) are commonly given for allergic reactions.
• The combination of these medications is used to alleviate symptoms of acute allergic reactions, including pruritus and urticaria 4.
• Diphenhydramine is an H1-receptor antagonist, while famotidine is an H2-receptor antagonist, and dexamethasone is a glucocorticoid.

Rationale for Combination Therapy

• The use of diphenhydramine and famotidine in combination has been shown to be effective in treating acute urticaria, with the combination being more effective than diphenhydramine alone 4.
• The addition of dexamethasone to the combination of diphenhydramine and famotidine has been used as a prophylactic regimen for paclitaxel-associated hypersensitivity reactions, with a comparable incidence of hypersensitivity reactions to the standard regimen 5.

Comparison of Antihistamines

• Diphenhydramine is a first-generation antihistamine that can have adverse effects on the central nervous system, while newer antihistamines such as loratadine and desloratadine are nonsedating but less efficacious than cetirizine or fexofenadine 6.
• The choice of antihistamine may depend on the specific clinical scenario and the need to minimize sedation.

Use of Glucocorticoids

• The use of glucocorticoids such as dexamethasone in the treatment of allergic reactions is common, but the evidence for its effectiveness is limited 7.
• In some cases, the use of glucocorticoids may not provide additional benefit beyond the use of antihistamines alone.

Rare but Serious Reactions

• Anaphylactic reactions to medications such as famotidine and ranitidine can occur, although they are rare 8.
• Cross-reactivity to other H2 receptor antagonists may not be demonstrated, and a safe alternative drug can be found for patients who experience anaphylactic reactions.