What is the proper dosage and usage of Periactin (cyproheptadine)?

Cyproheptadine (Periactin) Dosing and Usage

For adults, start with 4 mg three times daily (12 mg/day total), with most patients requiring 12-16 mg/day for adequate symptom control, though doses up to 32 mg/day may be used if needed, not exceeding 0.5 mg/kg/day. 1

Adult Dosing

• Initial dose: 4 mg (1 tablet) three times daily 1
• Typical therapeutic range: 12-16 mg/day, with the majority of patients achieving adequate relief at this dose 1
• Maximum dose: 32 mg/day for occasional patients requiring higher doses, but total daily dose should not exceed 0.5 mg/kg/day 1
• Dosing should be adjusted according to patient size and response 1

Pediatric Dosing

Ages 2-6 years:

• Calculate based on 0.25 mg/kg/day or 8 mg/m² body surface area 1
• Usual dose: 2 mg (½ tablet) two or three times daily 1
• Maximum: 12 mg/day 1

Ages 7-14 years:

• Usual dose: 4 mg (1 tablet) two or three times daily 1
• Maximum: 16 mg/day 1

For serotonin syndrome in pediatric patients: 0.25 mg/kg per day is recommended 2

Clinical Applications by Indication

Mast Cell Activation Syndrome (MCAS):

• Cyproheptadine functions as a sedating H1 antihistamine with extended anticholinergic and antiserotonergic activities 3
• Particularly helpful for gastrointestinal symptoms in MCAS patients 3
• Works better as prophylactic rather than acute treatment since it blocks histamine receptor binding before symptoms develop 3

Carcinoid Syndrome:

• Effective for managing diarrhea associated with malignant carcinoid syndrome 4
• Recommended initial dose: 0.4 mg/kg/day divided into three doses, with prompt modification to minimize side effects 4
• Therapeutic doses in studies ranged from 12-48 mg daily 4
• Relief of flushing is uncommon; primary benefit is diarrhea control, often with associated weight gain 4

Appetite Stimulation:

• 4 mg three times daily (12 mg/day total) demonstrated significant weight gain and increased calorie intake in clinical trials 5

Administration Considerations

• Tablets are 4 mg and can be divided for smaller doses 2
• Can be crushed and administered via nasogastric tube if needed 2
• Single daily dose can be given at bedtime or with the main meal to improve gastrointestinal tolerance 3, 1

Common Side Effects

Most frequent:

• Sedation and drowsiness (significant concern, particularly in elderly) 3, 4
• Dry mouth 4
• Appetite stimulation and weight gain 6, 5

Anticholinergic effects:

• Dryness of mouth and eyes 3
• Constipation 3
• Inhibition of micturition 3
• Risk of narrow-angle glaucoma provocation 3

Less common:

• Nausea and vomiting (may necessitate discontinuation in some patients) 4

Important Safety Considerations and Pitfalls

Elderly patients:

• First-generation antihistamines like cyproheptadine cause cognitive decline and sedation, particularly problematic in older adults 3
• Increased sensitivity to anticholinergic effects 3
• Higher risk with pre-existing conditions like prostatic hypertrophy, elevated intraocular pressure, or cognitive impairment 3

Performance impairment:

• Causes impairment in school and driving performance that can exist without subjective awareness of sedation 3
• Concomitant use with alcohol or other CNS-active substances further enhances impairment 3
• Effects cannot be eliminated by bedtime-only administration due to prolonged plasma half-life and active metabolites 3

Overdose risk:

• Toxic blood concentrations (0.49 mg/L) have been associated with fatalities 7
• Overdose presents with classic anticholinergic toxidrome, though miotic pupils have been reported (unusual for antihistamines) 8

Drug interactions:

• Avoid combining with other CNS depressants 3
• Be cautious with other anticholinergic medications due to additive effects 3