Cyproheptadine
Cyproheptadine Hydrochloride
Also known as: Ciplactin · Cyheptine · Cyprogin · Cyprono · Cyprosian · Klarivitina · Nuran · Periactine · Periactinol · Periatin · Peritol · Polytab · Practin · Preptin · Supersan · Trimetabol · Cyproheptadini hydrochloridum · Cyproheptadine hydrochloride
Reviewed by the VetSheet Veterinary TeamUpdated Apr 5, 2026Evidence-based veterinary reference
Doses are a clinical reference for licensed veterinary professionals. Always confirm against the current label and the individual patient.
Dosing by species
🌎 NA — North America🌍 EU — Europe
Dogs
| Indication | Dose | Route | Frequency | Duration | Region |
|---|---|---|---|---|---|
| As an antihistamine | 0.3-2 mg/kg | PO | twice daily | — | 🌎 NA |
| As an appetite stimulant | 0.2 mg/kg | PO | q12h | — | 🌎 NA |
| For adjunctive treatment of serotonin syndrome | 1.1 mg/kg | PO | q4-6h | until signs have resolved | 🌎 NA |
| Management of allergic disease / Appetite stimulation | 0.1-0.5 mg/kg | PO | q8-12h | — | 🌍 EU |
- As an appetite stimulant: May be dosed less frequently if inappetence is mild.
- For adjunctive treatment of serotonin syndrome: In cases where PO dosing not possible (severe vomiting), may crush tablets and mix with saline and give rectally.
Cats
| Indication | Dose | Route | Frequency | Duration | Region |
|---|---|---|---|---|---|
| As an appetite stimulant | 2-4 mg per cat | PO | once or twice daily | — | 🌎 NA |
| As an appetite stimulant | 1-4 mg/cat, or 0.35-1 mg/kg | PO | once or twice a day | — | 🌎 NA |
| As an appetite stimulant | 2 mg per cat | PO | q12h | — | 🌎 NA |
| As an appetite stimulant | 0.35-1 mg/kg | PO | q12h | — | 🌎 NA |
| As an appetite stimulant in cats with renal insufficiency | 1 mg per cat | PO | q12h | — | 🌎 NA |
| As an antihistamine/antipruritic | 2 mg per cat | PO | q12h | — | 🌎 NA |
| As an antihistamine/antipruritic | 2 mg per cat or 1.1 mg/kg | PO | q12h | — | 🌎 NA |
| For feline asthma | 2 mg | PO | q12h | — | 🌎 NA |
| For adjunctive treatment of serotonin syndrome | 2-4 mg (total dose) | PO | q4-6h | until signs have resolved | 🌎 NA |
| Management of allergic disease / Appetite stimulation / Aortic thromboembolism | 0.1-0.5 mg/kg | PO | q8-12h | — | 🌍 EU |
- As an appetite stimulant: May be dosed less frequently if inappetence is mild.
- For feline asthma: Particularly when cats are maxed out on dosages of corticosteroids and terbutaline. Therapeutic response may not be seen for 4-7 days, but CNS depression can occur in 24 hours.
- For adjunctive treatment of serotonin syndrome: In cases where PO dosing not possible (severe vomiting), may crush tablets and mix with saline and give rectally.
Horses
| Indication | Dose | Route | Frequency | Duration | Region |
|---|---|---|---|---|---|
| For photic head shaking | 0.3-0.6 mg/kg | PO | q12h | — | 🌎 NA |
| For photic head shaking | 0.3 mg/kg | PO | twice daily | — | 🌎 NA |
| For treatment of equine Cushing's | 0.25 mg/kg | PO | once a day | 4-8 weeks | 🌎 NA |
| For treatment of equine Cushing's | 65-125 mg (total dose) | PO | once daily | — | 🌎 NA |
| For treatment of equine Cushing's (adjunctive) | 0.5 mg/kg | PO | q12h | — | 🌎 NA |
- For photic head shaking: ARCI UCGFS Class 4 Drug
- For photic head shaking: ARCI UCGFS Class 4 Drug
- For treatment of equine Cushing's: If no response (clinical signs and plasma ACTH), increase dosage frequency to twice daily. Approximately 1/3 of horses may benefit, non-responders should be switched to pergolide.
- For treatment of equine Cushing's: Pergolide is the drug of choice as it is much more effective then cyproheptadine.
- For treatment of equine Cushing's (adjunctive): Add if only a limited response to a pergolide dose of 0.006 mg/kg and endocrinologic tests remain abnormal. Continue to monitor blood glucose and endocrinologic tests.
Doses are a clinical reference for licensed veterinary professionals. Always confirm against the current label and the individual patient.
Overview
Cyproheptadine is a first-generation antihistamine with potent antiserotonin properties. In veterinary medicine, it is most notably utilized for its off-target effects rather than its antihistamine capabilities.
Key Veterinary Uses:
- Appetite Stimulant: Historically a first-line appetite stimulant for cats, though it has been largely superseded by mirtazapine or capromorelin in modern practice. It is still a viable alternative when other options are unavailable or contraindicated.
- Serotonin Syndrome Antidote: It is the gold standard adjunctive treatment for serotonin toxicity (e.g., accidental ingestion of human SSRIs/SNRIs or 5-HTP supplements) in dogs and cats.
- Equine Medicine: Used in horses for the management of photic head shaking and as a second-line or adjunctive therapy for Pituitary Pars Intermedia Dysfunction (PPID / Equine Cushing's Disease), though pergolide is vastly superior for PPID.
- Feline Asthma & Pruritus: Occasionally used for eosinophilic airway inflammation or allergic skin disease, though clinical efficacy is often marginal.
Clinical Pearl: Cyproheptadine requires hepatic metabolism and renal excretion; dose adjustments are recommended in feline chronic kidney disease (CKD).
Mechanism of action
Cyproheptadine exhibits a multi-receptor antagonism profile:
- Serotonin (5-HT) Antagonism: Competitively binds to 5-HT2A receptors in the hypothalamus → blocks serotonin-induced satiety → stimulates appetite. In serotonin syndrome, blocking these receptors reverses life-threatening neuromuscular and autonomic hyperactivity.
- Histamine (H1) Antagonism: Competes with histamine for H1-receptors on effector cells → prevents histamine-mediated capillary permeability, smooth muscle spasm, and pruritus. It does not prevent histamine release.
- Anticholinergic Activity: Weakly antagonizes muscarinic receptors → leads to common side effects like dry mouth and urinary retention.
- Calcium Channel Blockade: Exhibits mild calcium channel blocking properties, which may contribute to its efficacy in equine photic head shaking.
Safety & warnings
Contraindications
- Hypersensitivity to cyproheptadine
- Prostatic hypertrophy
- Bladder neck obstruction
- Severe cardiac failure
- Pyeloduodenal obstruction
- Urinary retention (relative)
- Angle-closure glaucoma (relative)
- Pyloroduodenal obstruction (relative)
Adverse effects
- Sedation / CNS depression
- Paradoxical hyperexcitability or agitation (especially in cats)
- Anticholinergic effects (dry mucous membranes, urinary retention, tachycardia)
- Hemolytic anemia in cats (rare)
- Polyphagia (in dogs at higher doses)
- Mild depression, anorexia, or lethargy (in horses)
- Mild sedation
- Weight gain
- Reduced seizure threshold
Precautions
Use with caution in patients with conditions exacerbated by anticholinergic effects (e.g., glaucoma, urinary retention, GI stasis).
Laboratory Considerations:
- Allergy Testing: Antihistamines decrease the wheal and flare response. Discontinue 3-7 days prior to intradermal skin testing.
- Endocrine Testing: May increase amylase and prolactin serum levels when administered with thyrotropin-releasing hormone (TRH).
Drug interactions
Additive CNS depression
Cyproheptadine may decrease the efficacy of the SSRI due to its serotonin antagonist properties
Monitoring
- Clinical efficacy (e.g., body weight if used for anorexia, resolution of neurologic signs if used for serotonin syndrome)
- Adverse effects (sedation, anticholinergic signs)
- Serum BUN/Creatinine in cats with long-term use
- Appetite and weight gain
- Resolution of allergic signs
- Neurological status (seizure activity)
Pharmacokinetics
Half-life
Absorption
Well absorbed after oral administration.
Distribution
Distribution characteristics are not well described. It is not known if cyproheptadine is distributed into milk.
Metabolism
Nearly completely metabolized in the liver.
Elimination
Metabolites are excreted in the urine; elimination is reduced in renal failure.
Overdose
There are no specific antidotes available for cyproheptadine overdose.
Clinical Signs of Toxicity:
- Extensions of pharmacological effects: profound CNS depression (though paradoxical CNS stimulation/seizures may occur).
- Severe anticholinergic effects: extreme drying of mucous membranes, tachycardia, urinary retention, hyperthermia.
- Hypotension.
Management:
- Decontamination: Standard gut emptying protocols (emesis/activated charcoal) if caught early and patient is stable.
- Supportive Care: IV fluids for hypotension, temperature regulation.
- Specific Interventions: Physostigmine may be considered for life-threatening central anticholinergic effects. Diazepam should be employed to treat seizures if they occur.
Note: Horses receiving 2x the recommended dose apparently showed no untoward effects.
Available products
Formulations
- Oral Tablets
- Oral Syrup
- 4 mg oral tablet
Veterinary
- None (No veterinary-labeled products available)
Human-labeled
- Cyproheptadine HCl Oral Tablets: 4 mg
- Cyproheptadine HCl Oral Syrup: 2 mg/5 mL
- Periactin 4 mg tablets
Regulatory status
POM
POM
No regulatory data for: 🇺🇸 US · 🇭🇰 HK · 🇹🇼 TW · 🇯🇵 JP · 🇰🇷 KR · 🇦🇺 AU
Storage & stability
Store tablets and oral solution at room temperature in tight, light-resistant containers. Avoid freezing.
Client information
Cyproheptadine is a medication often used to stimulate appetite in cats, or to treat specific allergic or neurologic conditions in pets.
What to Expect:
- Sedation: Your pet may become sleepy or lethargic. This is the most common side effect.
- Dry Mouth: You may notice your pet smacking their lips or drinking more water due to dry mucous membranes.
Important Warnings:
- The "Zoomies" (Paradoxical Agitation): Some cats react oppositely to this medication and become highly agitated, vocal, or hyperactive. Contact your veterinarian if this occurs, as the dose may need to be lowered or stopped.
- Seek Immediate Care If: Your cat becomes profoundly weak, unresponsive, or develops pale gums.
- Horses: May show mild depression, loss of appetite, or lethargy.
- Missed Doses: If you miss a dose, give it when you remember, but never give two doses at once to catch up.
VetSheet drug reference is intended for licensed veterinary professionals as a clinical decision-support aid, not a substitute for professional judgement or the manufacturer’s current label.