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  1. Pharmacology. Cyproheptadine is a first-generation histamine 1 (H1) blocker with nonspecific serotonin (5-HT) antagonism. The administration of cyproheptadine to patients with serotonin syndrome appears to antagonize excessive stimulation of 5-HT1A and 5-HT2 receptors, resulting in improvements in clinical symptoms (based on anecdotal case reports).

  2. Indications. Cyproheptadine may be beneficial in alleviating mild to moderate symptoms in cases of suspected serotonin syndrome.

  3. Contraindications

    1. Known hypersensitivity to cyproheptadine.

    2. Angle-closure glaucoma.

    3. Stenosing peptic ulcer.

    4. Symptomatic prostatic hypertrophy.

    5. Bladder neck obstruction.

    6. Pyloroduodenal obstruction.

  4. Adverse effects

    1. Transient mydriasis and urinary retention may result from anticholinergic properties.

    2. Use in pregnancy. FDA Category B (Introduction). Unlikely to cause harm with short-term therapy.

  5. Drug or laboratory interactions. Additive anticholinergic effects when given with other antimuscarinic drugs.

  6. Dosage and method of administration (adults and children): The initial dose is 4–12 mg orally, followed by 4 mg every 1–4 hours as needed until symptoms resolve or a maximum daily dose of 32 mg is reached (children: 0.25 mg/kg/d divided every 6 hours with a maximum of 12 mg/d).

  7. Formulations

    1. Oral. Cyproheptadine hydrochloride (Periactin, others), 4-mg tablets, 2-mg/5 mL syrup.

    2. Suggested minimum stocking levels to treat a 100-kg adult for the first 8 hours and 24 hours: cyproheptadine hydrochloride, first 8 hours: 32 mg or eight tablets (4 mg each); first 24 hours: 32 mg or eight tablets (4 mg each).

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