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Cyproheptadine: Drug information

Cyproheptadine: Drug information
2024© UpToDate, Inc. and its affiliates and/or licensors. All Rights Reserved.
For additional information see "Cyproheptadine: Patient drug information" and "Cyproheptadine: Pediatric drug information"

For abbreviations, symbols, and age group definitions show table
Pharmacologic Category
  • Histamine H1 Antagonist;
  • Histamine H1 Antagonist, First Generation;
  • Piperidine Derivative
Dosing: Adult
Allergic conditions

Allergic conditions:

Note: Second-generation H1-antihistamines are preferred for treatment of allergic rhinitis and urticaria due to less sedating and anticholinergic effects. Avoid use of cyproheptadine in patients with high-risk occupations (eg, pilots, bus drivers) or who may be more prone to anticholinergic effects (eg, older adults) (Ref).

Oral : Initial: 4 mg three times daily; maintenance: 4 to 20 mg/day in divided doses; maximum: 0.5 mg/kg/day; some patients may require up to 32 mg/day for adequate control of symptoms.

Appetite, decreased secondary to chronic disease

Appetite, decreased secondary to chronic disease (off-label use): Oral: Initial: 2 mg 4 times per day for 1 week, then 4 mg 4 times per day (Ref).

Serotonin syndrome, moderate

Serotonin syndrome (serotonin toxicity), moderate (off-label use):

Note: Reserve for patients with agitation despite discontinuation of serotonergic agent(s), adequate sedation (eg, with a benzodiazepine), and supportive care (Ref).

Oral: Initial: 12 mg once followed by 2 mg every 2 hours until clinical response. Maintenance: 4 to 8 mg every 6 hours as needed. Maximum dose: 32 mg/day (Ref).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Adult

There are no dosage adjustments provided in the manufacturer's labeling. However, elimination is diminished in renal insufficiency.

Dosing: Hepatic Impairment: Adult

There are no dosage adjustments provided in the manufacturer's labeling.

Dosing: Older Adult

Avoid use (Ref).

Dosing: Pediatric

(For additional information see "Cyproheptadine: Pediatric drug information")

Allergic conditions

Allergic conditions (nonacute):

Weight-directed or BSA-directed dosing: Children ≥2 years and Adolescents: Oral: 0.25 mg/kg/day or 8 mg/m2/day in 2 to 3 divided doses.

Fixed dosing:

2 to 6 years: Oral: 2 mg every 8 to 12 hours; maximum daily dose: 12 mg/day.

7 to 14 years: Oral: 4 mg every 8 to 12 hours; maximum daily dose: 16 mg/day.

≥15 years: Initial: Oral: 4 mg every 8 hours; titrate to effect; usual range: 12 to 16 mg/day although some patients may require up to 32 mg; maximum daily dose: 0.5 mg/kg/day.

Appetite stimulation

Appetite stimulation: Limited data available; dosing regimens variable (Ref):

Weight-directed dosing: Children ≥2 years and Adolescents: Oral: 0.25 mg/kg/day divided twice daily; age-dependent maximum daily dose: ≤6 years: 12 mg/day; 7 to 14 years: 16 mg/day; ≥15 years: 32 mg/day. Dosing based on an open-label trial of 66 pediatric cancer patients (median age: 11.7 years; range: 3 to 19 years) which reported 76% response rate (either weight gained or stabilized); mean weight gain: 2.6 kg (range: −0.1 to 10 kg); in a subset analysis, patients >9 years showed a greater response than younger patients as did patients with hematologic malignancies (Ref). In malnourished patients (n=77, ages 2 to 5 years), use was associated with significantly higher BMI compared to controls after 8 weeks of therapy (Ref). In patients with multifactorial feeding problems (eg, cleft palate, neurodevelopmental disorders), cyproheptadine improved mealtime and feeding behaviors as well as weight for age z-scores (Ref).

Fixed dosing: Children ≥5 years and Adolescents: Oral: Initial: 2 mg every 6 hours (4 times daily) for 1 week; if tolerated, increase dose to 4 mg every 6 to 8 hours; one trial did not titrate dosing and started with target maintenance dose (4 mg three times daily) (Ref). Dosing based on a short-term (12-week) double-blind, placebo-controlled trial (n=8 treatment group) and a long-term (1-year) open-label trial (n=12) in patients with cystic fibrosis (CF); results showed significant increases in weight gain (3.4 kg vs 1.1 kg in placebo); long-term results showed a generally sustained effect (eg, no further weight loss or some additional weight gain) over study duration (Ref). A placebo-controlled trial including 25 patients with CF (age ≥5 years) utilized a 12 mg/day dose (4 mg 3 times daily); after 12 weeks of therapy, use was associated with significant increase in weight compared to placebo (1.61 kg vs 0.67 kg) (Ref).

Cyclic vomiting syndrome, prophylaxis

Cyclic vomiting syndrome, prophylaxis: Limited data available:

Note: Prophylaxis is recommended for patients experiencing frequent symptoms (eg, monthly) or severe symptoms (eg, requiring hospitalization, lasting >2 days, resulting in significant school/work absences). Cyproheptadine is a first-line choice for prophylaxis in children <5 years of age; however, it is less commonly used for older children and adolescents due to adverse effects (eg, appetite stimulation, weight gain); other drugs are more likely to be effective (Ref).

Children ≥2 years and Adolescents: Oral: 0.25 to 0.5 mg/kg/day in 1 to 3 divided doses; maximum daily dose: 12 mg/day. Note: Lower starting doses followed by titration have also been reported; some experts have used a once-daily dose at bedtime to prevent daytime sedation (Ref).

Functional abdominal pain; refractory

Functional abdominal pain (dyspeptic syndrome); refractory: Limited data available: Infants ≥9 months, Children, and Adolescents ≤14 years: Oral: Reported range: 0.04 to 0.6 mg/kg/day in divided doses 2 to 3 times daily (Ref); age-dependent maximum daily doses: Infants and Children 2 to 6 years: 12 mg/day; Children and Adolescents 7 to 14 years: 16 mg/day (Ref). Dosing based on prospective and retrospective trials. In a prospective, double-blind, placebo-controlled trial including 29 patients with functional abdominal pain (age range: 2 to 14 years; n= 15 treatment group), results showed significant improvement in pain frequency and intensity with 2 weeks of cyproheptadine (0.25 to 0.5 mg/kg/day divided twice daily) compared to placebo (Ref). A retrospective, open-label trial of 80 pediatric patients (median age: 9.8 years; range: 9 months to 20 years) with dyspeptic symptoms (eg, nausea, early satiety, abdominal pain, retching after fundoplication and vomiting) which failed to respond to conventional therapy received 0.04 to 0.6 mg/kg/day of cyproheptadine (median effective dose: 0.22 mg/kg/day); the observed response rate was 55%; a higher response rate (86%) was seen with patients who experienced retching post-Nissen fundoplication (Ref).

Migraine, prevention

Migraine, prevention: Limited data available: Children ≥3 years and Adolescents: Oral: Usual range: 0.2 to 0.4 mg/kg/day divided twice daily; doses up to 1.5 mg/kg/day in divided doses 2 to 3 times daily have also been reported (Ref); age-dependent maximum daily doses: Children 3 to 6 years: 12 mg/day; Children ≥7 years and Adolescents: 16 mg/day (Ref); experience suggests younger patients more tolerant of common cyproheptadine side effects (ie, sedation, increased appetite) (Ref).

Spasticity associated with spinal cord damage

Spasticity associated with spinal cord damage: Limited data available; efficacy results variable: Oral: Children ≥12 years and Adolescents: 4 mg at bedtime; increase by a 4 mg dose every 3 to 4 days; mean daily dose: 16 mg/day in divided doses; maximum daily dose: 36 mg/day (Ref). In the most rigorous evaluation, a double-blind, placebo-controlled, crossover trial of 16 hemiplegic pediatric patients (age range: 4 to 18 years), cyproheptadine (relatively low dose: 1 to 2 mg/day) had no statistical evidence of an effect on gait nor improvement in spasticity parameters (Ref).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Pediatric

There are no dosage adjustments provided in manufacturer's labeling; however, elimination is diminished in renal insufficiency.

Dosing: Hepatic Impairment: Pediatric

There are no dosage adjustments provided in manufacturer's labeling

Adverse Reactions

The following adverse drug reactions are derived from product labeling unless otherwise specified. Reactions listed are based on reports for other agents in this same pharmacologic class (antihistamines) and may not be specifically reported for cyproheptadine.

Postmarketing:

Cardiovascular: Extrasystoles, hypotension, palpitations, tachycardia

Dermatologic: Diaphoresis, skin photosensitivity

Endocrine & metabolic: Weight gain

Gastrointestinal: Anorexia, cholestasis (Larrey 1987), constipation, diarrhea, epigastric pain, increased appetite, nausea, vomiting, xerostomia

Genitourinary: Difficulty in micturition, early menses, urinary frequency, urinary retention

Hematologic & oncologic: Agranulocytosis, hemolytic anemia, leukopenia, thrombocytopenia

Hepatic: Hepatic failure (Chertoff 2014), hepatic impairment, hepatitis (Larrey 1987), jaundice (Henry 1978)

Hypersensitivity: Anaphylactic shock, hypersensitivity reaction

Nervous system: Ataxia, chills, confusion, dizziness, drowsiness, euphoria, excitement, fatigue, hallucination, headache, hysteria, insomnia, irritability, nervousness, neuritis, paresthesia, restlessness, sedated state, seizure, tightness in chest or throat, tremor, vertigo

Ophthalmic: Blurred vision, diplopia

Otic: Labyrinthitis (acute), tinnitus

Respiratory: Dry nose, dry throat, nasal congestion, thickening of bronchial secretions, wheezing

Contraindications

Use in newborn or premature infants or breastfeeding mothers; hypersensitivity to cyproheptadine or any component of the formulation; monoamine oxidase inhibitor therapy; angle-closure glaucoma; stenosing peptic ulcer; symptomatic prostatic hypertrophy; bladder neck obstruction; pyloroduodenal obstruction; elderly, debilitated patients.

Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Warnings/Precautions

Concerns related to adverse effects:

• CNS depression: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving).

Disease-related concerns:

• Cardiovascular disease: Use with caution in patients with cardiovascular disease (including hypertension and ischemic heart disease).

• Increased intraocular pressure: Use with caution in patients with increased intraocular pressure.

• Respiratory disease: Use with caution in patients with asthma or other chronic breathing disorders.

• Thyroid dysfunction: Use with caution in patients with thyroid dysfunction.

Special populations:

• Older adults: Antihistamines are more likely to cause dizziness, sedation, and hypotension and other anticholinergic effects in older adults; avoid use (Beers Criteria [AGS 2019]; manufacturer's labeling).

• Pediatric: Antihistamines may cause excitation in young children.

Warnings: Additional Pediatric Considerations

Excessive dosages of antihistamine in infants and young children may cause hallucinations, CNS depression, seizures, and death. Use with caution and use the lowest effective dose in children ≥2 years of age and avoid concomitant use with other medications having respiratory depressant effects.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Syrup, Oral, as hydrochloride:

Generic: 2 mg/5 mL (473 mL, 946 mL)

Tablet, Oral, as hydrochloride:

Generic: 4 mg

Generic Equivalent Available: US

Yes

Pricing: US

Syrup (Cyproheptadine HCl Oral)

2 mg/5 mL (per mL): $0.14 - $0.76

Tablets (Cyproheptadine HCl Oral)

4 mg (per each): $0.15 - $1.61

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Administration: Pediatric

Oral: Administer liquid preparations with an accurate measuring device.

Use: Labeled Indications

Allergic conditions: Perennial and seasonal allergic rhinitis; vasomotor rhinitis; allergic conjunctivitis caused by inhalant allergens and foods; mild, uncomplicated allergic skin manifestations of urticaria and angioedema; amelioration of allergic reactions to blood or plasma; cold urticaria; dermatographism; adjunctive anaphylactic therapy (following epinephrine and other standard measures).

Use: Off-Label: Adult

Appetite, decreased secondary to chronic disease; Serotonin syndrome (serotonin toxicity)

Medication Safety Issues
Sound-alike/look-alike issues:

Cyproheptadine may be confused with cyclobenzaprine

Periactin may be confused with Percodan, Persantine

High alert medication:

The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drugs (pediatric liquid medications requiring measurement) which have a heightened risk of causing significant patient harm when used in error (High-Alert Medications in Community/Ambulatory Care Settings).

Older Adult: High-Risk Medication:

Beers Criteria: Cyproheptadine, a first-generation antihistamine, is identified in the Beers Criteria as a potentially inappropriate medication to be avoided in patients 65 years and older (independent of diagnosis or condition) due to its potent anticholinergic properties resulting in increased risk of confusion, dry mouth, constipation, and other anticholinergic effects or toxicity; use should also be avoided due to reduced clearance with advanced age and tolerance associated with use as a hypnotic. Exposure to concurrent anticholinergic drugs also increases risk of falls, delirium, and dementia; consider total anticholinergic burden when conducting medication reviews (Beers Criteria [AGS 2023]).

International issues:

Periactin brand name for cyproheptadine [US, multiple international markets] may be confused with Perative brand name for an enteral nutrition preparation [multiple international markets] and brand name for ketoconazole [Argentina]

Metabolism/Transport Effects

None known.

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.

Acetylcholinesterase Inhibitors: May diminish the therapeutic effect of Agents with Clinically Relevant Anticholinergic Effects. Agents with Clinically Relevant Anticholinergic Effects may diminish the therapeutic effect of Acetylcholinesterase Inhibitors. Risk C: Monitor therapy

Aclidinium: May enhance the anticholinergic effect of Agents with Clinically Relevant Anticholinergic Effects. Risk X: Avoid combination

Agents with Clinically Relevant Anticholinergic Effects: May enhance the adverse/toxic effect of other Agents with Clinically Relevant Anticholinergic Effects. Risk C: Monitor therapy

Alcohol (Ethyl): CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl). Risk C: Monitor therapy

Alizapride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Amantadine: May enhance the anticholinergic effect of Agents with Clinically Relevant Anticholinergic Effects. Risk C: Monitor therapy

Amezinium: Antihistamines may enhance the stimulatory effect of Amezinium. Risk C: Monitor therapy

Azelastine (Nasal): May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination

Benperidol: Agents with Clinically Relevant Anticholinergic Effects may diminish the therapeutic effect of Benperidol. Risk C: Monitor therapy

Benzylpenicilloyl Polylysine: Antihistamines may diminish the diagnostic effect of Benzylpenicilloyl Polylysine. Management: Suspend systemic H1 antagonists for benzylpenicilloyl-polylysine skin testing and delay testing until systemic antihistaminic effects have dissipated. A histamine skin test may be used to assess persistent antihistaminic effects. Risk D: Consider therapy modification

Betahistine: Antihistamines may diminish the therapeutic effect of Betahistine. Betahistine may diminish the therapeutic effect of Antihistamines. Risk C: Monitor therapy

Blonanserin: CNS Depressants may enhance the CNS depressant effect of Blonanserin. Management: Use caution if coadministering blonanserin and CNS depressants; dose reduction of the other CNS depressant may be required. Strong CNS depressants should not be coadministered with blonanserin. Risk D: Consider therapy modification

Botulinum Toxin-Containing Products: May enhance the anticholinergic effect of Agents with Clinically Relevant Anticholinergic Effects. Risk C: Monitor therapy

Brexanolone: CNS Depressants may enhance the CNS depressant effect of Brexanolone. Risk C: Monitor therapy

Brimonidine (Topical): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Bromopride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Bromperidol: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination

Buprenorphine: CNS Depressants may enhance the CNS depressant effect of Buprenorphine. Management: Consider reduced doses of other CNS depressants, and avoiding such drugs in patients at high risk of buprenorphine overuse/self-injection. Initiate buprenorphine at lower doses in patients already receiving CNS depressants. Risk D: Consider therapy modification

Cannabinoid-Containing Products: Agents with Clinically Relevant Anticholinergic Effects may enhance the tachycardic effect of Cannabinoid-Containing Products. Risk C: Monitor therapy

Cannabinoid-Containing Products: CNS Depressants may enhance the CNS depressant effect of Cannabinoid-Containing Products. Risk C: Monitor therapy

Chloral Betaine: May enhance the adverse/toxic effect of Agents with Clinically Relevant Anticholinergic Effects. Risk C: Monitor therapy

Chlormethiazole: May enhance the CNS depressant effect of CNS Depressants. Management: Monitor closely for evidence of excessive CNS depression. The chlormethiazole labeling states that an appropriately reduced dose should be used if such a combination must be used. Risk D: Consider therapy modification

Chlorphenesin Carbamate: May enhance the adverse/toxic effect of CNS Depressants. Risk C: Monitor therapy

Chlorprothixene: Agents with Clinically Relevant Anticholinergic Effects may enhance the anticholinergic effect of Chlorprothixene. Risk C: Monitor therapy

Cimetropium: Agents with Clinically Relevant Anticholinergic Effects may enhance the anticholinergic effect of Cimetropium. Risk X: Avoid combination

CloZAPine: Agents with Clinically Relevant Anticholinergic Effects may enhance the constipating effect of CloZAPine. Management: Consider alternatives to this combination whenever possible. If combined, monitor closely for signs and symptoms of gastrointestinal hypomotility and consider prophylactic laxative treatment. Risk D: Consider therapy modification

CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Risk C: Monitor therapy

Daridorexant: May enhance the CNS depressant effect of CNS Depressants. Management: Dose reduction of daridorexant and/or any other CNS depressant may be necessary. Use of daridorexant with alcohol is not recommended, and the use of daridorexant with any other drug to treat insomnia is not recommended. Risk D: Consider therapy modification

DexmedeTOMIDine: CNS Depressants may enhance the CNS depressant effect of DexmedeTOMIDine. Management: Monitor for increased CNS depression during coadministration of dexmedetomidine and CNS depressants, and consider dose reductions of either agent to avoid excessive CNS depression. Risk D: Consider therapy modification

Difelikefalin: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Dimethindene (Systemic): Agents with Clinically Relevant Anticholinergic Effects may enhance the anticholinergic effect of Dimethindene (Systemic). Risk C: Monitor therapy

Dimethindene (Topical): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Doxylamine: CNS Depressants may enhance the CNS depressant effect of Doxylamine. Risk C: Monitor therapy

DroPERidol: May enhance the CNS depressant effect of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (eg, opioids, barbiturates) with concomitant use. Risk D: Consider therapy modification

Eluxadoline: Agents with Clinically Relevant Anticholinergic Effects may enhance the constipating effect of Eluxadoline. Risk X: Avoid combination

Esketamine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Fenfluramine: May enhance the CNS depressant effect of Cyproheptadine. Cyproheptadine may diminish the therapeutic effect of Fenfluramine. Risk C: Monitor therapy

Flunarizine: CNS Depressants may enhance the CNS depressant effect of Flunarizine. Risk X: Avoid combination

Flunitrazepam: CNS Depressants may enhance the CNS depressant effect of Flunitrazepam. Management: Reduce the dose of CNS depressants when combined with flunitrazepam and monitor patients for evidence of CNS depression (eg, sedation, respiratory depression). Use non-CNS depressant alternatives when available. Risk D: Consider therapy modification

Gastrointestinal Agents (Prokinetic): Agents with Clinically Relevant Anticholinergic Effects may diminish the therapeutic effect of Gastrointestinal Agents (Prokinetic). Risk C: Monitor therapy

Glucagon: Agents with Clinically Relevant Anticholinergic Effects may enhance the adverse/toxic effect of Glucagon. Specifically, the risk of gastrointestinal adverse effects may be increased. Risk C: Monitor therapy

Glycopyrrolate (Oral Inhalation): Agents with Clinically Relevant Anticholinergic Effects may enhance the anticholinergic effect of Glycopyrrolate (Oral Inhalation). Risk X: Avoid combination

Glycopyrronium (Topical): May enhance the anticholinergic effect of Agents with Clinically Relevant Anticholinergic Effects. Risk X: Avoid combination

Hyaluronidase: Antihistamines may diminish the therapeutic effect of Hyaluronidase. Risk C: Monitor therapy

HydrOXYzine: May enhance the CNS depressant effect of CNS Depressants. Management: Consider a decrease in the CNS depressant dose, as appropriate, when used together with hydroxyzine. Increase monitoring of signs/symptoms of CNS depression in any patient receiving hydroxyzine together with another CNS depressant. Risk D: Consider therapy modification

Ipratropium (Nasal): May enhance the anticholinergic effect of Agents with Clinically Relevant Anticholinergic Effects. Risk C: Monitor therapy

Ipratropium (Oral Inhalation): May enhance the anticholinergic effect of Agents with Clinically Relevant Anticholinergic Effects. Risk X: Avoid combination

Itopride: Agents with Clinically Relevant Anticholinergic Effects may diminish the therapeutic effect of Itopride. Risk C: Monitor therapy

Ixabepilone: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Kava Kava: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Kratom: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination

Lemborexant: May enhance the CNS depressant effect of CNS Depressants. Management: Dosage adjustments of lemborexant and of concomitant CNS depressants may be necessary when administered together because of potentially additive CNS depressant effects. Close monitoring for CNS depressant effects is necessary. Risk D: Consider therapy modification

Levosulpiride: Agents with Clinically Relevant Anticholinergic Effects may diminish the therapeutic effect of Levosulpiride. Risk X: Avoid combination

Lisuride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Lofexidine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Loxapine: CNS Depressants may enhance the CNS depressant effect of Loxapine. Risk D: Consider therapy modification

Magnesium Sulfate: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Methotrimeprazine: CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Methotrimeprazine may enhance the CNS depressant effect of CNS Depressants. Management: Reduce the usual dose of CNS depressants by 50% if starting methotrimeprazine until the dose of methotrimeprazine is stable. Monitor patient closely for evidence of CNS depression. Risk D: Consider therapy modification

Metoclopramide: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

MetyraPONE: Cyproheptadine may diminish the diagnostic effect of MetyraPONE. Management: Consider alternatives to the use of the metyrapone test in patients taking cyproheptadine. Risk D: Consider therapy modification

MetyroSINE: CNS Depressants may enhance the sedative effect of MetyroSINE. Risk C: Monitor therapy

Mianserin: May enhance the anticholinergic effect of Agents with Clinically Relevant Anticholinergic Effects. Risk C: Monitor therapy

Minocycline (Systemic): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Mirabegron: Agents with Clinically Relevant Anticholinergic Effects may enhance the adverse/toxic effect of Mirabegron. Risk C: Monitor therapy

Monoamine Oxidase Inhibitors: May enhance the anticholinergic effect of Cyproheptadine. Cyproheptadine may diminish the serotonergic effect of Monoamine Oxidase Inhibitors. Risk X: Avoid combination

Nabilone: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination

Nitroglycerin: Agents with Clinically Relevant Anticholinergic Effects may decrease the absorption of Nitroglycerin. Specifically, anticholinergic agents may decrease the dissolution of sublingual nitroglycerin tablets, possibly impairing or slowing nitroglycerin absorption. Risk C: Monitor therapy

Olopatadine (Nasal): May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination

Opioid Agonists: CNS Depressants may enhance the CNS depressant effect of Opioid Agonists. Management: Avoid concomitant use of opioid agonists and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Risk D: Consider therapy modification

Orphenadrine: CNS Depressants may enhance the CNS depressant effect of Orphenadrine. Risk X: Avoid combination

Oxatomide: May enhance the anticholinergic effect of Agents with Clinically Relevant Anticholinergic Effects. Risk X: Avoid combination

Oxomemazine: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination

Oxybate Salt Products: CNS Depressants may enhance the CNS depressant effect of Oxybate Salt Products. Management: Consider alternatives to this combination when possible. If combined, dose reduction or discontinuation of one or more CNS depressants (including the oxybate salt product) should be considered. Interrupt oxybate salt treatment during short-term opioid use Risk D: Consider therapy modification

OxyCODONE: CNS Depressants may enhance the CNS depressant effect of OxyCODONE. Management: Avoid concomitant use of oxycodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Risk D: Consider therapy modification

Paraldehyde: CNS Depressants may enhance the CNS depressant effect of Paraldehyde. Risk X: Avoid combination

Perampanel: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Piribedil: CNS Depressants may enhance the CNS depressant effect of Piribedil. Risk C: Monitor therapy

Pitolisant: Antihistamines may diminish the therapeutic effect of Pitolisant. Risk X: Avoid combination

Potassium Chloride: Agents with Clinically Relevant Anticholinergic Effects may enhance the ulcerogenic effect of Potassium Chloride. Management: Patients on drugs with substantial anticholinergic effects should avoid using any solid oral dosage form of potassium chloride. Risk X: Avoid combination

Potassium Citrate: Agents with Clinically Relevant Anticholinergic Effects may enhance the ulcerogenic effect of Potassium Citrate. Management: Patients on drugs with substantial anticholinergic effects should avoid using any solid oral dosage form of potassium citrate. Risk X: Avoid combination

Pramipexole: CNS Depressants may enhance the sedative effect of Pramipexole. Risk C: Monitor therapy

Pramlintide: May enhance the anticholinergic effect of Agents with Clinically Relevant Anticholinergic Effects. These effects are specific to the GI tract. Risk X: Avoid combination

Procarbazine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

QuiNIDine: May enhance the anticholinergic effect of Agents with Clinically Relevant Anticholinergic Effects. Risk C: Monitor therapy

Ramosetron: Agents with Clinically Relevant Anticholinergic Effects may enhance the constipating effect of Ramosetron. Risk C: Monitor therapy

Revefenacin: Agents with Clinically Relevant Anticholinergic Effects may enhance the anticholinergic effect of Revefenacin. Risk X: Avoid combination

Rivastigmine: Agents with Clinically Relevant Anticholinergic Effects may diminish the therapeutic effect of Rivastigmine. Rivastigmine may diminish the therapeutic effect of Agents with Clinically Relevant Anticholinergic Effects. Management: Use of rivastigmine with an anticholinergic agent is not recommended unless clinically necessary. If the combination is necessary, monitor for reduced anticholinergic effects. Risk D: Consider therapy modification

Ropeginterferon Alfa-2b: CNS Depressants may enhance the adverse/toxic effect of Ropeginterferon Alfa-2b. Specifically, the risk of neuropsychiatric adverse effects may be increased. Management: Avoid coadministration of ropeginterferon alfa-2b and other CNS depressants. If this combination cannot be avoided, monitor patients for neuropsychiatric adverse effects (eg, depression, suicidal ideation, aggression, mania). Risk D: Consider therapy modification

ROPINIRole: CNS Depressants may enhance the sedative effect of ROPINIRole. Risk C: Monitor therapy

Rotigotine: CNS Depressants may enhance the sedative effect of Rotigotine. Risk C: Monitor therapy

Rufinamide: May enhance the adverse/toxic effect of CNS Depressants. Specifically, sleepiness and dizziness may be enhanced. Risk C: Monitor therapy

Secretin: Agents with Clinically Relevant Anticholinergic Effects may diminish the therapeutic effect of Secretin. Management: Avoid concomitant use of anticholinergic agents and secretin. Discontinue anticholinergic agents at least 5 half-lives prior to administration of secretin. Risk D: Consider therapy modification

Selective Serotonin Reuptake Inhibitors: Cyproheptadine may diminish the therapeutic effect of Selective Serotonin Reuptake Inhibitors. Risk C: Monitor therapy

Suvorexant: CNS Depressants may enhance the CNS depressant effect of Suvorexant. Management: Dose reduction of suvorexant and/or any other CNS depressant may be necessary. Use of suvorexant with alcohol is not recommended, and the use of suvorexant with any other drug to treat insomnia is not recommended. Risk D: Consider therapy modification

Thalidomide: CNS Depressants may enhance the CNS depressant effect of Thalidomide. Risk X: Avoid combination

Thiazide and Thiazide-Like Diuretics: Agents with Clinically Relevant Anticholinergic Effects may increase the serum concentration of Thiazide and Thiazide-Like Diuretics. Risk C: Monitor therapy

Tiotropium: Agents with Clinically Relevant Anticholinergic Effects may enhance the anticholinergic effect of Tiotropium. Risk X: Avoid combination

Topiramate: Agents with Clinically Relevant Anticholinergic Effects may enhance the adverse/toxic effect of Topiramate. Risk C: Monitor therapy

Tranylcypromine: May enhance the anticholinergic effect of Antihistamines, First Generation. Risk X: Avoid combination

Trimeprazine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Umeclidinium: May enhance the anticholinergic effect of Agents with Clinically Relevant Anticholinergic Effects. Risk X: Avoid combination

Valerian: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Zolpidem: CNS Depressants may enhance the CNS depressant effect of Zolpidem. Management: Reduce the Intermezzo brand sublingual zolpidem adult dose to 1.75 mg for men who are also receiving other CNS depressants. No such dose change is recommended for women. Avoid use with other CNS depressants at bedtime; avoid use with alcohol. Risk D: Consider therapy modification

Zuranolone: May enhance the CNS depressant effect of CNS Depressants. Management: Consider alternatives to the use of zuranolone with other CNS depressants or alcohol. If combined, consider a zuranolone dose reduction and monitor patients closely for increased CNS depressant effects. Risk D: Consider therapy modification

Pregnancy Considerations

Outcome data following maternal use of cyproheptadine during pregnancy are limited (Heinonen 1977; Kasperlik-Załuska 1980; Khir 1982; Sadovsky 1972). Per the product labeling, based on two studies, an increased risk of congenital abnormalities was not observed following maternal use of cyproheptadine during the first, second, or third trimesters in two studies of pregnant patients; however, the possibility of harm cannot be ruled out.

Algorithms are available for the treatment of acute rhinitis and urticaria. First-generation oral antihistamines are generally not recommended for use in pregnant patients due to side effects (AAAAI/ACAAI [Dykewicz 2020]; EAACI [Zuberbier 2022]).

Breastfeeding Considerations

It is not known if cyproheptadine is present in breast milk.

Drowsiness and irritability have been reported in breastfed infants exposed to antihistamines (Ito 1993).

Antihistamines may decrease maternal serum prolactin concentrations when administered prior to the establishment of nursing (Messinis 1985).

Use of a second-generation antihistamine is preferred when an oral antihistamine is needed in lactating patients (Butler 2014). Cyproheptadine is contraindicated in patients who are breastfeeding.

Mechanism of Action

A potent antihistamine and serotonin antagonist with anticholinergic effects; competes with histamine for H1-receptor sites on effector cells in the gastrointestinal tract, blood vessels, and respiratory tract (Paton 1985).

Pharmacokinetics (Adult Data Unless Noted)

Absorption: Well absorbed (Graudins 1998)

Metabolism: Primarily by hepatic glucuronidation to metabolites (Hintze 1975)

Half-life elimination: Metabolites: ~16 hours (Paton 1985)

Time to peak, plasma: Metabolites: 6 to 9 hours (Paton 1985)

Excretion: Urine (~40% primarily as metabolites); feces (2% to 20%, <6% as unchanged drug)

Pharmacokinetics: Additional Considerations (Adult Data Unless Noted)

Altered kidney function: Elimination is diminished in renal insufficiency.

Brand Names: International
International Brand Names by Country
For country code abbreviations (show table)

  • (AE) United Arab Emirates: Periactin;
  • (AR) Argentina: Azulina;
  • (AT) Austria: Periactin;
  • (AU) Australia: Periactin;
  • (BD) Bangladesh: Arictin;
  • (BE) Belgium: Periactin;
  • (BF) Burkina Faso: Nurabol;
  • (BG) Bulgaria: Cyprotol | Peritol;
  • (BR) Brazil: Periatin | Preptin;
  • (CH) Switzerland: Periactin;
  • (CI) Côte d'Ivoire: Nurabol;
  • (CL) Chile: Ciproactin | Viternum;
  • (CN) China: Cyproheptadine;
  • (CO) Colombia: Ciproheptadina | Periactin | Viternum;
  • (CZ) Czech Republic: Peritol;
  • (DE) Germany: Peritol;
  • (DO) Dominican Republic: Prolyn;
  • (EC) Ecuador: Ciproheptadina | Complamin | Periactin;
  • (EE) Estonia: Periactin | Peritol;
  • (EG) Egypt: Cyptadine | Triactin;
  • (ES) Spain: Periactin;
  • (FI) Finland: Anarexol;
  • (FR) France: Periactine;
  • (GB) United Kingdom: Periactin;
  • (GR) Greece: Adekin | Periactin;
  • (HK) Hong Kong: Appetin | C.h. | Ciprodin | Cyprodin | Cyprogin | Cyproheptadine | Periact | Periactin | Qualiactin | U eatin | Uni-Heptadine | Uni-heptadine;
  • (HU) Hungary: Peritol;
  • (ID) Indonesia: Alphahist | Apeton | Arsigran | Cylat | Ennamax | Erphacyp | Esprocy | Glocyp | Graperide | Heptasan | Kensip | Lexahist | Nebor | New cypromin | Omesip | Poncohist | Procydin | Profut | Prohessen | Pronam | Pronicy | Pronimax;
  • (IE) Ireland: Periactin;
  • (IN) India: Abitol | Add app | Afdigrow | Anabol | Anorexin | Apeat | Apectin | Apenorm | Apetamin | Apetone | Apetox | Apitol | App Up | Appetin pl | Appodin g | Appri | Aptivin | Bal Riactin | Cadictin | Cadlactin | Ciplactin | Cipron | Cym | Cyphoden | Cyprollion | Cyprotol | Cyptan | Cyptol | Eptocol | Hepdine | Heptadine | Heptidin | Hungree | Ibiapt | Ioplex | Lupactin | Lycip | Normatone | Osactin | Pepon | Peritol | Practin | Rarritol | Sp lysin | Toractin;
  • (IQ) Iraq: Afractin | Cibtaden | Citadine | Cyproctin | Cyprodad | Cyprodine | Cyprosaf | Periahist;
  • (IT) Italy: Periactin;
  • (JO) Jordan: Periactin;
  • (JP) Japan: Cyproatin | Cyproatin taiyo | Cyproatin towa | Cypromin | Cyptazin | Ifrasarl | Ifrasarl showa | Periactin;
  • (KE) Kenya: Ciplactin | Plactinic | Uniactin;
  • (KR) Korea, Republic of: Cyprodin | Periactin | Pratin | Prohethin;
  • (KW) Kuwait: Periactin | Triactin;
  • (LB) Lebanon: Periactin;
  • (LT) Lithuania: Ciplactin | Peritol;
  • (LU) Luxembourg: Periactin;
  • (LV) Latvia: Ciplactin | Peritol;
  • (MA) Morocco: Antinorex | Apetine | Aractine | Nurabol | Periactine | Pernabol;
  • (MX) Mexico: Viternum;
  • (MY) Malaysia: Cyproheptadine | Cyproheptadine HCL;
  • (NG) Nigeria: Curegold | Cyprigold | Cyproheptadine | Cypropek | Garylong | Rich apetie syrup | Vema tone;
  • (NL) Netherlands: Periactin;
  • (NO) Norway: Cyproheptadine HCL | Peritol;
  • (NZ) New Zealand: Periactin;
  • (PK) Pakistan: Cyprodin | Periactin | Stanzar;
  • (PL) Poland: Peritol | Protadina;
  • (PR) Puerto Rico: Cyproheptadine HCL | Periactin;
  • (PT) Portugal: Ciproral | Periactin | Supersan | Viternum;
  • (QA) Qatar: Periactin | Triactin;
  • (RO) Romania: Biohept | Ciproheptadina arena;
  • (RU) Russian Federation: Peritol;
  • (SA) Saudi Arabia: Periactin;
  • (SE) Sweden: Periactin;
  • (SG) Singapore: Cyproheptadine | Cyprotin | Periactin | Pilian;
  • (SK) Slovakia: Peritol;
  • (TH) Thailand: Anpro | Appedine | Baby | Bozo | Cycodine | Cyheptine | Cypro | Cyprodine | Cyprogin | Cyproheptadin | Cyproheptadine | Cypromed p | Cypromide | Cyprono | Cypropicco | Cyprosian | Cyprotec | Cyprotin | Kentidine | Mano | Periactin | Perry | Polytab | Pondnaheptin | Proretin | Star;
  • (TN) Tunisia: Cipractine | Ciptadine;
  • (TR) Turkey: Prakten | Sipraktin;
  • (TW) Taiwan: Antimin | Antisemin | Appitamine | Ceriatin | Chilieanzin | Cyhepdin | Cyllermin | Cypro | Cyprodin | Cyprodine | Cyproh | Cyprohepatadine | Cyproheptadine | Cyproheptadine HCL | Cypromin | Cypromine | Cytadine | Dariactin | Dechimin | Earmin | Feri | Fulimin | Huavine | Komian | Nekmin | Outallergin | Pelion | Periactin | Perian | Pilian | Piminton | Prozine | Serodine | Showmin | Synmin;
  • (UA) Ukraine: Peritol | Peritonil;
  • (UG) Uganda: Cypolive | Procip | Toractin;
  • (UY) Uruguay: Ciprogal;
  • (VE) Venezuela, Bolivarian Republic of: Cyprodin | Periactin;
  • (ZA) South Africa: Cipla-actin | Periactin;
  • (ZM) Zambia: Apectine | Ciplactin | Cyproheptadine | Power apetite | Prodin | Super apeti
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