PERIACTIN
Clinical safety rating: caution
Comprehensive clinical and safety monograph for PERIACTIN (PERIACTIN).
Cyproheptadine is a first-generation antihistamine with anticholinergic and antiserotonergic properties. It acts as a competitive antagonist at histamine H1 receptors and serotonin 5-HT2 receptors, thereby inhibiting histamine-mediated allergic symptoms and serotonin-mediated effects such as increased gastrointestinal motility and vascular permeability.
| Metabolism | Hepatic metabolism primarily via hydroxylation and glucuronidation; cytochrome P450 enzymes (CYP3A4, CYP2D6) are involved; elimination half-life approximately 16 hours. |
| Excretion | Renal (40-50% as metabolites, <5% unchanged); biliary/fecal (minor, ~10-20%) |
| Half-life | 10-12 hours terminal elimination half-life; steady-state reached in 2-3 days |
| Protein binding | 90-95% bound to plasma proteins (albumin) |
| Volume of Distribution | 10-20 L/kg (large, indicating extensive tissue distribution) |
| Bioavailability | Oral: 50-60% due to first-pass metabolism |
| Onset of Action | Oral: 30-60 minutes; parenteral not available in US |
| Duration of Action | 4-6 hours for antihistamine effect; sedative effects may persist 6-8 hours |
| Molecular Weight | 310.43 |
4 mg orally three times daily; adjust as needed. Maximum: 32 mg/day.
| Dosage form | SYRUP |
| Renal impairment | For GFR < 15 mL/min: use with caution and consider reducing dose. No specific guidelines available. |
| Liver impairment | Child-Pugh Class C: contraindicated. Class A or B: use with caution, reduce dose by 50%. |
| Pediatric use | 2-6 years: 2 mg orally 2-3 times daily; 7-14 years: 4 mg orally 2-3 times daily. Maximum daily dose: 0.5 mg/kg. |
| Geriatric use | Start at 2 mg orally twice daily; increase gradually. Monitor for sedation, confusion, and anticholinergic effects. |
| 1st trimester | Limited human data; animal studies show teratogenicity at high doses. Use only if benefit outweighs risk. |
| 2nd trimester | Avoid due to anticholinergic effects and potential for uterine hypertonicity. |
| 3rd trimester | Contraindicated near term due to risk of prolonged labor, neonatal respiratory depression, and withdrawal symptoms. |
Clinical note
Comprehensive clinical and safety monograph for PERIACTIN (PERIACTIN).
| Placental transfer | Crosses placenta; detected in fetal tissues. |
| Breastfeeding | Excreted into breast milk; may cause irritability, drowsiness, or respiratory depression in the infant. Not recommended for nursing mothers. |
| Lactation Rating |
■ FDA Black Box Warning
None
| Serious Effects |
Hypersensitivity to cyproheptadine or any componentAngle-closure glaucomaUrinary retentionAsthma attackConcurrent MAOI therapyLower respiratory tract symptomsPremature or full-term neonatesBreastfeedingProlonged QT interval
| Precautions | Use with caution in patients with glaucoma, history of bronchial asthma, hyperthyroidism, cardiovascular disease, hypertension, or prostatic hypertrophy; may impair mental alertness and cause drowsiness; anticholinergic effects may exacerbate symptoms of narrow-angle glaucoma, pyloroduodenal obstruction, or bladder neck obstruction; elderly patients are more sensitive to anticholinergic effects; use in neonates and premature infants is contraindicated due to increased risk of sudden infant death syndrome. |
| Food/Dietary | Avoid alcohol and grapefruit juice; alcohol increases sedation, and grapefruit juice may alter drug metabolism. No specific food restrictions. |
Loading safety data…
| L4 (Possibly Hazardous) |
| Teratogenic Risk | Cyproheptadine is a pregnancy category B drug. Animal studies have not demonstrated fetal risk, but adequate human studies in pregnant women are lacking. First trimester: No known teratogenic effects. Second and third trimesters: Limited data; potential for anticholinergic effects (e.g., tachycardia, constipation) in fetus if used near term. Avoid use during pregnancy unless clearly needed. |
| Fetal Monitoring | Monitor maternal blood pressure, heart rate, and signs of anticholinergic toxicity (e.g., urinary retention, blurred vision). For fetus, monitor heart rate and growth if used chronically. No specific fetal monitoring required with short-term use. |
| Fertility Effects | Cyproheptadine may suppress prolactin secretion, theoretically impairing ovulation and lactation. Animal studies have shown no significant fertility impairment, but human fertility data are lacking. |
| Clinical Pearls | Periaktin (cyproheptadine) is a first-generation antihistamine with potent antiserotonergic and appetite-stimulating properties, making it useful for serotonin syndrome, carcinoid syndrome, and underweight patients. It can cause significant sedation and anticholinergic effects; avoid in elderly, glaucoma, and urinary retention. Monitor for weight gain and hypoglycemia in diabetics. |
| Patient Advice | Take exactly as prescribed; do not exceed recommended dose. · May cause drowsiness; avoid driving or operating machinery until you know how it affects you. · Avoid alcohol and other central nervous system depressants. · Report any vision changes, difficulty urinating, or rapid heartbeat. · You may experience increased appetite and weight gain. · Do not take with other antihistamines or medications containing antihistamines. |