What is the use of Cyproheptadine (Periactin)?

From the Guidelines

Cyproheptadine is a sedating H1 antihistamine with extended anticholinergic and antiserotonergic activities and may be used to help gastrointestinal symptoms in patients with Mast Cell Activation Syndrome (MCAS) or other conditions, as noted in the 2019 study by the aaaai mast cell disorders committee work group 1.

Key Points

• Cyproheptadine is a first-generation antihistamine medication that blocks H1 histamine receptors and also has antiserotonergic, anticholinergic, and appetite-stimulating properties.
• It is commonly prescribed at doses of 4-8 mg taken 2-4 times daily for adults, with a maximum daily dose of 32 mg, as seen in various clinical contexts.
• For children, dosing is typically weight-based, starting at 0.25 mg/kg/day divided into 2-3 doses, as indicated for different conditions including appetite stimulation in cystic fibrosis patients 2.
• Cyproheptadine is used off-label for migraine prevention, appetite stimulation in underweight patients, and management of serotonin syndrome, with specific dosing recommendations such as 12 to 24 mg over 24 hours for serotonin syndrome 3.
• Common side effects include drowsiness, dry mouth, increased appetite, and weight gain, which patients should be aware of, especially when starting treatment, and should avoid alcohol and other CNS depressants while taking this medication.

Clinical Use

• The medication works by antagonizing histamine receptors to reduce allergic symptoms, while its effect on serotonin receptors accounts for its use in serotonin syndrome and migraine prevention.
• The appetite-stimulating effect occurs through its action on the hypothalamus, making it useful for conditions where increased appetite is beneficial, such as in cystic fibrosis patients 2.
• Given the potential for cognitive decline associated with anticholinergic effects, particularly in the elderly, caution should be exercised when prescribing cyproheptadine to this population, as highlighted in the 2019 study 1.

From the FDA Drug Label

CLINICAL PHARMACOLOGY Cyproheptadine is a serotonin and histamine antagonist with anticholinergic and sedative effects. Pharmacokinetics and Metabolism After a single 4 mg oral dose of 14C-labelled cyproheptadine hydrochloride in normal subjects, given as tablets, 2% to 20% of the radioactivity was excreted in the stools. Only about 34% of the stool radioactivity was unchanged drug, corresponding to less than 5. 7% of the dose. At least 40% of the administered radioactivity was excreted in the urine. No detectable amounts of unchanged drug were present in the urine of patients on chronic 12 mg to 20 mg daily doses. The principle metabolite found in human urine has been identified as a quaternary ammonium glucuronide conjugate of cyproheptadine. Elimination is diminished in renal insufficiency.

Key Points:

• Cyproheptadine is a serotonin and histamine antagonist with anticholinergic and sedative effects.
• The drug is eliminated through both urine and stools, with a significant portion of the dose excreted as a metabolite in the urine.
• Renal insufficiency can diminish elimination of the drug. The information provided in the drug label does not directly answer a specific question about Cyproheptadine, as no question was posed regarding its pharmacology, pharmacokinetics, or metabolism 4.

From the Research

Cyproheptadine Overview

• Cyproheptadine is an antihistamine that has been used in the treatment of various allergic conditions, including atopic dermatitis and pruritus 5.
• The evidence for its use in atopic dermatitis is inconclusive, and more clinical trials are needed to determine its efficacy 5.

Mechanism of Action and Efficacy

• Cyproheptadine has been shown to suppress histamine-induced pruritus in normal subjects, with a fivefold increase in the histamine dose required to produce pruritus 6.
• However, its efficacy compared to other antihistamines, such as diphenhydramine and hydroxyzine, varies, with hydroxyzine being more effective in suppressing histamine-induced pruritus 6.

Side Effects and Hypersensitivity

• Common side effects of cyproheptadine include drowsiness, which occurs with all three drugs 6.
• Hypersensitivity reactions to antihistamines, including cyproheptadine, have been reported, with manifestations ranging from urticaria and anaphylaxis to contact dermatitis and fixed drug eruption 7.

Comparison with Other Treatments

• The efficacy of cyproheptadine in treating seasonal allergic rhinitis has not been directly compared to other treatments, such as nasal steroid sprays, in the provided studies.
• However, other antihistamines, such as loratadine, have been compared to nasal steroid sprays, with varying results depending on the symptoms being treated 8.