Is Cyproheptadine (antihistamine) syrup safe for use in children?

Is Cyproheptadine Syrup Safe for Children?

Cyproheptadine syrup can be considered safe for use in children above 2 years of age, but is contraindicated in newborns and premature infants, and should be avoided in nursing mothers. 1

Age-Specific Safety Considerations

• Safety and effectiveness in children below 2 years of age have not been established, making this the critical age cutoff for use 1
• Cyproheptadine is absolutely contraindicated in newborns and premature infants due to higher risks of antihistamines in this vulnerable population 1
• The drug is contraindicated in nursing mothers because of potential serious adverse reactions in nursing infants 1
• For children 2 years and older, cyproheptadine has an established safety profile when used appropriately 1

Common Adverse Effects Profile

The most frequently reported adverse effects are generally mild and transient:

• Drowsiness/somnolence is the most common side effect, occurring in approximately 13% of pediatric patients 2, 3
• Weight gain occurs in approximately 10% of children, which may be desirable or undesirable depending on the indication 3
• Neurological symptoms including excitation, hallucinations, ataxia, and muscle twitching can occur, particularly with higher doses 4
• Most adverse effects appear rapidly after ingestion and typically resolve within 6-12 hours 4
• In a large pediatric case series, 68% of patients reported no adverse effects at all 3

Serious but Rare Complications

While uncommon, clinicians must be aware of potentially serious adverse effects:

• Hepatotoxicity is uncommon to rare, with an estimated frequency of 0.27 to 1.4 per 1,000 patients regardless of age 2
• Very rare cases of liver failure have been reported, warranting monitoring of hepatic function in long-term use 2
• One case report documented severe aggression in a 5-year-old boy that resolved after discontinuation, likely related to serotonin antagonism 5
• Special caution is needed in children with epilepsy, as convulsions have been reported as an adverse effect 6

Important Contraindications and Precautions

Beyond age restrictions, cyproheptadine should be avoided in specific clinical scenarios:

• Absolute contraindications include angle-closure glaucoma, stenosing peptic ulcer, symptomatic prostatic hypertrophy, bladder neck obstruction, and pyloroduodenal obstruction 1
• Use with caution in patients with history of bronchial asthma, increased intraocular pressure, hyperthyroidism, cardiovascular disease, or hypertension due to atropine-like effects 1
• Avoid concurrent use with MAO inhibitors, as they prolong and intensify anticholinergic effects 1
• Additive CNS depression can occur with alcohol and other CNS depressants 1

Dosing Considerations for Safety

• For general pediatric use, typical dosing is 0.25 mg/kg per day as recommended by the American Academy of Pediatrics for conditions like serotonin syndrome 6, 7
• Cyproheptadine is available as 4 mg tablets that can be divided for smaller doses or crushed and administered via nasogastric tube if needed 7
• In accidental overdoses ranging from 0.3-6.15 mg/kg, no life-threatening alterations were observed, though symptoms were frequent 4
• Lower body weight may be associated with higher odds of adverse effects, suggesting weight-based dosing is important 3

Clinical Context and Monitoring

A critical caveat is that cyproheptadine is not FDA-approved for appetite stimulation in children, despite widespread off-label use for this indication 2. The French pharmacovigilance analysis emphasizes that randomized controlled trials are needed before authorization for appetite stimulation, especially in young children 2.

Parents should be warned about activities requiring mental alertness, as antihistamines may diminish alertness or, paradoxically in young children, occasionally produce excitation 1. This dual effect makes predicting individual responses challenging in the pediatric population.