Schedule H

Oral

• Tablets: 4 mg

• Syrup: 2 mg/5 mL

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

1. Allergic Rhinitis, Urticaria, Allergic Dermatoses

Parameter Recommendation

Starting dose 4 mg once daily (preferably at bedtime)

Titration Increase by 4 mg every 2–3 days based on response and tolerability

Usual maintenance dose 4 mg three times daily (12 mg/day)

Maximum dose 32 mg/day in divided doses

Clinical notes Administer preferably at bedtime due to sedation; short-term use preferred; consider second-generation antihistamines for long-term management

1. Appetite Stimulation

Parameter Recommendation

Starting dose 2 mg twice daily

Titration Increase gradually based on response and tolerance

Usual maintenance dose 4 mg twice to three times daily (8–12 mg/day)

Maximum dose 16 mg/day

Clinical notes Not first-line for undernutrition; address underlying cause first; use short-term only; avoid in obesity

Secondary Indications – Adults Only (Off-label, if any)

Indication Dose Titration Duration Notes Evidence Basis

Migraine prophylaxis — OFF-LABEL Starting: 4 mg at bedtime May increase to 4 mg twice daily Trial for 4–6 weeks Specialist supervision recommended Small RCTs; accepted in Indian neurology practice

Serotonin syndrome (adjunctive) — OFF-LABEL 4–8 mg initially, then 4 mg every 6 hours As per clinical response Until symptoms resolve Specialist/critical care setting only Case series; mechanism-based use

PAEDIATRIC DOSING (Specialist Only)

Primary Indications (Approved / Standard in India)

1. Allergic Conditions (Rhinitis, Urticaria, Allergic Dermatoses)

2–6 years 0.25 mg/kg/day 0.25 mg/kg/day in 2–3 divided doses 12 mg/day 2–3 times daily

7–14 years 4 mg once daily 4 mg 2–3 times daily 16 mg/day 2–3 times daily

14 years Adult dosing Adult dosing 32 mg/day As per adult schedule

Safety Monitoring:

• Monitor for excessive sedation, paradoxical excitation, feeding difficulty

• Assess weight gain at each visit

1. Appetite Stimulation

2–6 years 2 mg once daily 0.25 mg/kg/day in divided doses 8 mg/day Short-term only (2–4 weeks)

7–14 years 2 mg twice daily 4 mg twice daily 12 mg/day Short-term only (2–4 weeks)

Clinical Notes:

• Address underlying nutritional deficiencies first

• Not for routine use in "picky eaters"

• Specialist supervision recommended

Secondary Indications – Paediatric Doses (Off-label, if any)

Indication Age Dose Maximum Duration Notes Evidence Basis

Migraine prophylaxis — OFF-LABEL ≥2 years 0.2–0.4 mg/kg/day in 2 divided doses 12 mg/day 4–8 weeks trial Paediatric neurology supervision mandatory Small case series; off-label practice in India

Cyclic vomiting syndrome — OFF-LABEL ≥2 years 0.25–0.5 mg/kg/day in 2–3 divided doses 12 mg/day Long-term under specialist care Paediatric gastroenterology supervision Limited evidence; specialist practice

Clear Statement:

Cyproheptadine is contraindicated in children below 2 years of age due to risk of respiratory depression and CNS toxicity. Use in children 2–6 years requires careful dose calculation and close monitoring.

Mild to moderate impairment No specific dose adjustment required; use with caution

Severe impairment Limited data; use lowest effective dose with enhanced monitoring for sedation and anticholinergic effects

Haemodialysis No specific data; not expected to be significantly dialysed due to high protein binding

Peritoneal dialysis No data available

• Known hypersensitivity to cyproheptadine or structurally related antihistamines

• Narrow-angle glaucoma (untreated)

• Symptomatic bladder neck obstruction or urinary retention

• Acute asthma attack (may thicken bronchial secretions)

• Concurrent use with monoamine oxidase inhibitors (MAOIs) or within 14 days of MAOI discontinuation

• Newborns, premature infants, and children below 2 years of age

• Stenosing peptic ulcer

• Pyloroduodenal obstruction

• Elderly patients — increased sensitivity to anticholinergic and sedative effects

• Children aged 2–6 years — increased risk of paradoxical CNS stimulation

• Epilepsy or history of seizures — may lower seizure threshold

• Prostatic hypertrophy without obstruction

• Hepatic impairment — metabolism may be reduced

• Cardiovascular disease — anticholinergic effects may be problematic

• Hyperthyroidism

• Raised intraocular pressure

• Concurrent CNS depressants — additive sedation

• Driving or operating machinery — significant impairment of alertness

• Prolonged use for appetite stimulation — risk of excessive weight gain

Parameter Details

Overall Safety Not formally classified in India; generally avoided unless essential

Human Data Limited; no clear evidence of teratogenicity but insufficient safety data

Preferred Alternatives Second-generation antihistamines (loratadine, cetirizine) preferred for allergic conditions

When May Be Used Only if benefit clearly outweighs risk; short-term use only; specialist input recommended

Third Trimester Concern Potential for neonatal sedation and feeding difficulty if used near delivery

Monitoring Fetal growth; neonatal sedation and withdrawal symptoms if used late in pregnancy

Parameter Details

Compatibility Likely compatible in low doses; use with caution

Drug Levels in Milk Low (limited data available)

Preferred Alternatives Loratadine, cetirizine (non-sedating, lower milk transfer)

Potential Infant Effects May reduce milk production (anti-prolactin effect); infant sedation, irritability, feeding difficulty

Infant Monitoring Drowsiness, poor feeding, irritability, weight gain

Recommendation Avoid if possible; if essential, use lowest effective dose and monitor infant closely

Parameter Recommendation

Starting dose 2–4 mg once daily (preferably at bedtime)

Titration Slow; increase by 2 mg every 3–5 days based on tolerability

Maximum dose Lowest effective dose; avoid exceeding 12 mg/day

Special Risks Excessive sedation, confusion, delirium, constipation, urinary retention, orthostatic hypotension, increased fall risk

Recommendation Consider second-generation antihistamines as first-line; use cyproheptadine only if non-sedating options inadequate

Interacting Drug Effect / Mechanism Management

MAO inhibitors (phenelzine, tranylcypromine, selegiline) Profound enhancement of anticholinergic effects; hypertensive crisis risk Contraindicated — do not use concurrently or within 14 days of MAOI

CNS depressants (opioids, benzodiazepines, barbiturates, alcohol) Additive CNS depression; excessive sedation; respiratory depression risk Avoid combination if possible; if essential, use reduced doses and monitor closely

Anticholinergic agents (tricyclic antidepressants, atropine, oxybutynin) Enhanced anticholinergic toxicity — confusion, hyperthermia, tachycardia, urinary retention Avoid combination in elderly; monitor for anticholinergic syndrome

Ototoxic drugs (aminoglycosides) May mask early symptoms of ototoxicity (tinnitus, dizziness) Use with caution; enhanced audiometric monitoring

Interacting Drug Effect / Mechanism Management

SSRIs (fluoxetine, sertraline) Theoretical risk of serotonin syndrome; may also antagonise serotonin effects Monitor for serotonin symptoms; note: cyproheptadine used therapeutically for serotonin syndrome

Tricyclic antidepressants Additive sedation and anticholinergic effects Use with caution; monitor for confusion, dry mouth, constipation

CYP3A4 inhibitors (erythromycin, ketoconazole, itraconazole) May increase cyproheptadine plasma levels Monitor for enhanced sedation

Antihypertensives Additive hypotensive effect; increased orthostatic hypotension risk Monitor blood pressure, especially in elderly

Antiepileptics May lower seizure threshold Monitor seizure control; adjust antiepileptic dose if needed

Betahistine Cyproheptadine may antagonise therapeutic effect of betahistine Avoid concurrent use

• Sedation, drowsiness (most common)

• Dry mouth

• Increased appetite and weight gain

• Dizziness, lightheadedness

• Constipation

• Blurred vision

• Fatigue

• Thickening of bronchial secretions

• Nausea

Adverse Effect Notes

Seizures Rare; especially at high doses or in predisposed patients

Acute angle-closure glaucoma In patients with narrow angles; presents with eye pain, visual disturbance

Severe anticholinergic syndrome Delirium, hyperthermia, tachycardia, urinary retention — discontinue and treat supportively

Paradoxical CNS stimulation More common in children — agitation, hyperexcitability, hallucinations

Hepatotoxicity Rare idiosyncratic hepatitis; discontinue if jaundice or LFT elevation occurs

Agranulocytosis Very rare; presents with fever, sore throat, infection

Respiratory depression Risk in infants and overdose situations — immediate medical attention required

After initiation (1–2 weeks) Sedation level; appetite and weight change; feeding pattern and behaviour in children

Long-term (if >4–6 weeks) Weight monitoring (avoid excessive gain); liver function tests; behaviour changes in children; reassess need for continued therapy

Single-ingredient formulations:

• Ciplactin (Cipla)

• Periactin (Organon)

• Cypractin (Unichem)

• Apetito (Synmedic)

• Practin (Alkem)

• Cypon (Geno)

Common Fixed-Dose Combinations (FDCs):

Note: FDCs for appetite stimulation are widely marketed but should be used judiciously; prefer single-ingredient formulation when possible.

• NLEM Status: Not included in NLEM 2022

• Government supply: Limited availability

1. Age restriction is critical: Absolutely contraindicated in children below 2 years due to risk of respiratory depression and fatal CNS toxicity — this is a common prescribing error.

1. Sedation limits daytime utility: Preferably administer at bedtime; if daytime dosing required, warn about driving and machinery operation impairment.

1. Short-term appetite stimulation only: Not a substitute for addressing underlying causes of poor appetite/weight loss; limit use to 2–4 weeks and reassess.

1. Second-generation antihistamines preferred for allergies: Reserve cyproheptadine for cases where sedation is acceptable or specifically desired (e.g., nocturnal pruritus).

1. Paradoxical excitation in children: Monitor young children for agitation, insomnia, or hyperexcitability — may require discontinuation.

1. Weight gain is predictable: Counsel patients that increased appetite and weight gain are expected effects, not just side effects — this can be beneficial or problematic depending on context.

cyproheptadine; antihistamine; first-generation; sedating; appetite-stimulant; urticaria; allergic-rhinitis; migraine-prophylaxis; paediatric-caution; elderly-caution; Schedule-H

RxIndia v1.0 — 10 Jan 2025

• CDSCO approved product information

• Indian Pharmacopoeia

• IAP Guidelines for Paediatric Drug Use

• API Textbook of Medicine

• AIIMS Drug Formulary

• Goodman & Gilman's The Pharmacological Basis of Therapeutics

• Indian paediatric neurology and dermatology specialist practice consensus