CYPROHEPTADINE HYDROCHLORIDE
Clinical safety rating: safe
Animal studies have demonstrated safety
Cyproheptadine is a potent antihistamine (H1 receptor antagonist) and antiserotonergic agent (5-HT2 receptor antagonist). It also exhibits weak anticholinergic and sedative properties. It blocks histamine-mediated vasodilation, increased capillary permeability, and pruritus, as well as serotonin-mediated effects on appetite and mood.
| Metabolism | Hepatic metabolism primarily via hydroxylation and glucuronidation; CYP450 enzymes involved (CYP3A4, CYP2C9, CYP2D6). |
| Excretion | Primarily renal (appreciable unchanged drug and metabolites); biliary/fecal elimination minor (<5%). |
| Half-life | Terminal half-life approximately 8–16 hours in adults; may be prolonged in elderly or hepatic impairment. |
| Protein binding | ~96–99% bound, primarily to albumin. |
| Volume of Distribution | Approximately 8–12 L/kg (large, indicating extensive tissue distribution, including CNS). |
| Bioavailability | Oral bioavailability is not well quantified due to extensive first-pass metabolism; estimated ~50–80%. |
| Onset of Action | Oral: 30–60 minutes; topical (not standard): unknown; antihistaminic effect begins ~1 hour. |
| Duration of Action | 4–6 hours for antihistaminic effect; appetite stimulant effect may persist longer; single dose typically effective for 6–8 hours. |
4 mg orally three times daily; range 4-20 mg/day, not to exceed 0.5 mg/kg/day
| Dosage form | TABLET |
| Renal impairment | No specific guidelines; use caution in moderate to severe renal impairment (CrCl <30 mL/min) due to potential accumulation |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: reduce dose by 50%; Child-Pugh C: avoid use |
| Pediatric use | 2-6 years: 2 mg orally every 8-12 hours (max 12 mg/day); 7-14 years: 4 mg orally every 8-12 hours (max 16 mg/day) |
| Geriatric use | Initiate at 2 mg twice daily; increase slowly; monitor for anticholinergic effects, falls, and cognitive decline |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
CNS depressants may enhance sedative effects May cause drowsiness and impair mental and physical abilities.
| Breastfeeding | Excreted in human milk; M/P ratio not established. Due to potential for adverse effects (e.g., sedation, anticholinergic effects) in nursing infants, caution is advised. Consider risk-benefit; use lowest effective dose or alternative. |
| Teratogenic Risk | FDA Pregnancy Category B. Animal studies have not demonstrated fetal risk, but no adequate human studies in pregnant women. Cyproheptadine crosses the placenta. Use only if clearly needed. First trimester: limited data, theoretical risk of anticholinergic effects. Second and third trimesters: may cause fetal tachycardia or transient neonatal withdrawal symptoms if used near term. |
■ FDA Black Box Warning
None
| Common Effects | appetite stimulation |
| Serious Effects |
["Hypersensitivity to cyproheptadine or any component of the formulation","Concurrent use with monoamine oxidase inhibitors (MAOIs)","Angle-closure glaucoma","Symptomatic prostatic hypertrophy","Bladder neck obstruction","Stenosing peptic ulcer","Pyloroduodenal obstruction","Elderly or debilitated patients (relative contraindication)"]
| Precautions | ["Caution in patients with glaucoma, urinary retention, pyloric/duodenal obstruction, prostatic hypertrophy, or bladder neck obstruction due to anticholinergic effects.","May cause sedation, impaired alertness, and dizziness; avoid driving or operating heavy machinery.","Use with caution in elderly patients (increased risk of anticholinergic effects), children, and patients with asthma or COPD.","Concurrent use with MAOIs increases risk of severe anticholinergic effects and hypertension.","May mask early signs of ototoxicity (e.g., tinnitus, dizziness) in patients receiving aminoglycosides."] |
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| Fetal Monitoring | Monitor maternal vital signs and for signs of anticholinergic toxicity (dry mouth, blurred vision, urinary retention). Fetal heart rate monitoring if used near term. Observe neonate for transient withdrawal symptoms if maternal use in third trimester. |
| Fertility Effects | No specific studies on human fertility. Animal studies indicate no impairment of fertility at therapeutic doses. Possible suppression of lactation due to anticholinergic properties may affect postpartum fertility indirectly. |