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 (off-label use): Oral: Initial: 2 mg 4 times per day for 1 week, then 4 mg 4 times per day (Ref).
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.
There are no dosage adjustments provided in the manufacturer's labeling. However, elimination is diminished in renal insufficiency.
There are no dosage adjustments provided in the manufacturer's labeling.
Avoid use (Ref).
(For additional information see "Cyproheptadine: Pediatric drug information")
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: 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: 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 (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: 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: 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.
There are no dosage adjustments provided in manufacturer's labeling; however, elimination is diminished in renal insufficiency.
There are no dosage adjustments provided in manufacturer's labeling
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
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.
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.
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.
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
Yes
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.
Oral: Administer liquid preparations with an accurate measuring device.
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).
Appetite, decreased secondary to chronic disease; Serotonin syndrome (serotonin toxicity)
Cyproheptadine may be confused with cyclobenzaprine
Periactin may be confused with Percodan, Persantine
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).
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]).
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]
None known.
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 decrease therapeutic effects of Agents with Clinically Relevant Anticholinergic Effects. Agents with Clinically Relevant Anticholinergic Effects may decrease therapeutic effects of Acetylcholinesterase Inhibitors. Risk C: Monitor
Aclidinium: May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk X: Avoid
Acrivastine: May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk C: Monitor
Acrivastine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Alcohol (Ethyl): CNS Depressants may increase CNS depressant effects of Alcohol (Ethyl). Risk C: Monitor
Alizapride: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Amantadine: May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk C: Monitor
Amezinium: Antihistamines may increase stimulatory effects of Amezinium. Risk C: Monitor
Amisulpride (Oral): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Articaine: May increase CNS depressant effects of CNS Depressants. Management: Consider reducing the dose of articaine if possible when used in patients who are also receiving CNS depressants. Monitor for excessive CNS depressant effects with any combined use. Risk D: Consider Therapy Modification
Azelastine (Nasal): May increase CNS depressant effects of CNS Depressants. Risk X: Avoid
Benperidol: Agents with Clinically Relevant Anticholinergic Effects may decrease therapeutic effects of Benperidol. Risk C: Monitor
Benperidol: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Benztropine: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Benztropine. Risk C: Monitor
Benzylpenicilloyl Polylysine: Coadministration of Antihistamines and Benzylpenicilloyl Polylysine may alter diagnostic results. 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 decrease therapeutic effects of Betahistine. Betahistine may decrease therapeutic effects of Antihistamines. Risk C: Monitor
Biperiden: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Biperiden. Risk C: Monitor
Blonanserin: CNS Depressants may increase CNS depressant effects 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
Bornaprine: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Bornaprine. Risk C: Monitor
Botulinum Toxin-Containing Products: May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk C: Monitor
Brexanolone: CNS Depressants may increase CNS depressant effects of Brexanolone. Risk C: Monitor
Brimonidine (Topical): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Bromopride: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Bromperidol: May increase CNS depressant effects of CNS Depressants. Risk X: Avoid
Buclizine: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Buclizine. Risk C: Monitor
Buclizine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Buprenorphine: CNS Depressants may increase CNS depressant effects 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
BusPIRone: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Cannabinoid-Containing Products: Agents with Clinically Relevant Anticholinergic Effects may increase tachycardic effects of Cannabinoid-Containing Products. Risk C: Monitor
Cannabinoid-Containing Products: CNS Depressants may increase CNS depressant effects of Cannabinoid-Containing Products. Risk C: Monitor
Certoparin: Antihistamines may increase therapeutic effects of Certoparin. Risk C: Monitor
Cetirizine (Systemic): May increase CNS depressant effects of CNS Depressants. Management: Consider avoiding this combination if possible. If required, monitor for excessive sedation or CNS depression, limit the dose and duration of combination therapy, and consider CNS depressant dose reductions. Risk D: Consider Therapy Modification
Chloral Hydrate/Chloral Betaine: CNS Depressants may increase CNS depressant effects of Chloral Hydrate/Chloral Betaine. Management: Consider alternatives to the use of chloral hydrate or chloral betaine and additional CNS depressants. If combined, consider a dose reduction of either agent and monitor closely for enhanced CNS depressive effects. Risk D: Consider Therapy Modification
Chlormethiazole: May increase CNS depressant effects 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 increase adverse/toxic effects of CNS Depressants. Risk C: Monitor
Chlorprothixene: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Chlorprothixene. Risk C: Monitor
Cimetropium: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Cimetropium. Risk X: Avoid
CloZAPine: Agents with Clinically Relevant Anticholinergic Effects may increase constipating effects 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 increase adverse/toxic effects of CNS Depressants. Risk C: Monitor
Cyclizine: May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk C: Monitor
Dantrolene: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Daridorexant: May increase CNS depressant effects 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
Darifenacin: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Darifenacin. Risk C: Monitor
DexmedeTOMIDine: CNS Depressants may increase CNS depressant effects 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
Dicyclomine: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Dicyclomine. Risk C: Monitor
Difelikefalin: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Difenoxin: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Dihydralazine: CNS Depressants may increase hypotensive effects of Dihydralazine. Risk C: Monitor
Dimethindene (Systemic): Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Dimethindene (Systemic). Risk C: Monitor
Dimethindene (Topical): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Dothiepin: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Doxylamine: CNS Depressants may increase CNS depressant effects of Doxylamine. Risk C: Monitor
DroNABinol: Agents with Clinically Relevant Anticholinergic Effects may increase tachycardic effects of DroNABinol. Risk X: Avoid
DroPERidol: May increase CNS depressant effects 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 increase constipating effects of Eluxadoline. Risk X: Avoid
Emedastine (Systemic): May increase CNS depressant effects of CNS Depressants. Management: Consider avoiding this combination if possible. If required, monitor for excessive sedation or CNS depression, limit the dose and duration of combination therapy, and consider CNS depressant dose reductions. Risk C: Monitor
Entacapone: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Esketamine (Nasal): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Fenfluramine: Cyproheptadine may decrease therapeutic effects of Fenfluramine. Fenfluramine may increase CNS depressant effects of Cyproheptadine. Risk C: Monitor
Fesoterodine: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Fesoterodine. Risk C: Monitor
Flunarizine: CNS Depressants may increase CNS depressant effects of Flunarizine. Risk X: Avoid
Flunitrazepam: CNS Depressants may increase CNS depressant effects 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
FluPHENAZine: May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk C: Monitor
Gastrointestinal Agents (Prokinetic): Agents with Clinically Relevant Anticholinergic Effects may decrease therapeutic effects of Gastrointestinal Agents (Prokinetic). Risk C: Monitor
Gepotidacin: May decrease anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk C: Monitor
Glucagon: Agents with Clinically Relevant Anticholinergic Effects may increase adverse/toxic effects of Glucagon. Specifically, the risk of gastrointestinal adverse effects may be increased. Risk C: Monitor
Glycopyrrolate (Oral Inhalation): Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Glycopyrrolate (Oral Inhalation). Risk X: Avoid
Glycopyrrolate (Systemic): Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Glycopyrrolate (Systemic). Risk C: Monitor
Glycopyrronium (Topical): May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk X: Avoid
Hyaluronidase: Antihistamines may decrease therapeutic effects of Hyaluronidase. Risk C: Monitor
HydrOXYzine: May increase CNS depressant effects 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 increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk C: Monitor
Ipratropium (Oral Inhalation): May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk X: Avoid
Itopride: Agents with Clinically Relevant Anticholinergic Effects may decrease therapeutic effects of Itopride. Risk C: Monitor
Ixabepilone: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Kava Kava: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Ketotifen (Systemic): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Kratom: May increase CNS depressant effects of CNS Depressants. Risk X: Avoid
Lemborexant: May increase CNS depressant effects 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
Levocetirizine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Levosulpiride: Agents with Clinically Relevant Anticholinergic Effects may decrease therapeutic effects of Levosulpiride. Risk X: Avoid
Lisuride: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Lofepramine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Lofexidine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Loxapine: CNS Depressants may increase CNS depressant effects of Loxapine. Management: Consider reducing the dose of CNS depressants administered concomitantly with loxapine due to an increased risk of respiratory depression, sedation, hypotension, and syncope. Risk D: Consider Therapy Modification
Magnesium Sulfate: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Maprotiline: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Maprotiline. Risk C: Monitor
Melitracen [INT]: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Melperone: May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk C: Monitor
Mequitazine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Metergoline: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Methotrimeprazine: CNS Depressants may increase CNS depressant effects of Methotrimeprazine. Methotrimeprazine may increase CNS depressant effects 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
Methoxyflurane: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Methscopolamine: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Methscopolamine. Risk C: Monitor
Metoclopramide: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
MetyraPONE: Coadministration of Cyproheptadine and MetyraPONE may alter diagnostic results. Management: Consider alternatives to the use of the metyrapone test in patients taking cyproheptadine. Risk D: Consider Therapy Modification
MetyroSINE: CNS Depressants may increase sedative effects of MetyroSINE. Risk C: Monitor
Minocycline (Systemic): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Mirabegron: Agents with Clinically Relevant Anticholinergic Effects may increase adverse/toxic effects of Mirabegron. Risk C: Monitor
Monoamine Oxidase Inhibitors: Cyproheptadine may decrease serotonergic effects of Monoamine Oxidase Inhibitors. Monoamine Oxidase Inhibitors may increase anticholinergic effects of Cyproheptadine. Risk X: Avoid
Moxonidine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Nabilone: May increase CNS depressant effects of CNS Depressants. Risk X: Avoid
Nalfurafine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Nitroglycerin: Agents with Clinically Relevant Anticholinergic Effects may decrease absorption of Nitroglycerin. Specifically, anticholinergic agents may decrease the dissolution of sublingual nitroglycerin tablets, possibly impairing or slowing nitroglycerin absorption. Risk C: Monitor
Noscapine: CNS Depressants may increase adverse/toxic effects of Noscapine. Risk X: Avoid
OLANZapine: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of OLANZapine. Risk C: Monitor
Olopatadine (Nasal): May increase CNS depressant effects of CNS Depressants. Risk X: Avoid
Opicapone: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Opioid Agonists: CNS Depressants may increase CNS depressant effects 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
Opipramol: May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk C: Monitor
Opipramol: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Orphenadrine: CNS Depressants may increase CNS depressant effects of Orphenadrine. Risk X: Avoid
Oxatomide: May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk X: Avoid
Oxomemazine: May increase CNS depressant effects of CNS Depressants. Risk X: Avoid
Oxybate Salt Products: CNS Depressants may increase CNS depressant effects 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
OxyBUTYnin: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of OxyBUTYnin. Risk C: Monitor
OxyCODONE: CNS Depressants may increase CNS depressant effects 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
Paliperidone: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Paraldehyde: CNS Depressants may increase CNS depressant effects of Paraldehyde. Risk X: Avoid
Perampanel: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Perazine: May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk C: Monitor
Periciazine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Perphenazine: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Perphenazine. Risk C: Monitor
Pipamperone: May increase adverse/toxic effects of CNS Depressants. Risk C: Monitor
Piribedil: CNS Depressants may increase CNS depressant effects of Piribedil. Risk C: Monitor
Pitolisant: Antihistamines may decrease therapeutic effects of Pitolisant. Risk X: Avoid
Pizotifen: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Potassium Chloride: Agents with Clinically Relevant Anticholinergic Effects may increase ulcerogenic effects 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
Potassium Citrate: Agents with Clinically Relevant Anticholinergic Effects may increase ulcerogenic effects 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
Pramipexole: CNS Depressants may increase sedative effects of Pramipexole. Risk C: Monitor
Pramlintide: May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. These effects are specific to the GI tract. Risk X: Avoid
Procarbazine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Promethazine: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Promethazine. Risk C: Monitor
Propantheline: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Propantheline. Risk C: Monitor
Propiverine: May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk C: Monitor
QuiNIDine: May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk C: Monitor
Ramosetron: Agents with Clinically Relevant Anticholinergic Effects may increase constipating effects of Ramosetron. Risk C: Monitor
Revefenacin: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Revefenacin. Risk X: Avoid
Rilmenidine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Rivastigmine: Agents with Clinically Relevant Anticholinergic Effects may decrease therapeutic effects of Rivastigmine. Rivastigmine may decrease therapeutic effects 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 increase adverse/toxic effects 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 increase sedative effects of ROPINIRole. Risk C: Monitor
Rotigotine: CNS Depressants may increase sedative effects of Rotigotine. Risk C: Monitor
Scopolamine: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Scopolamine. Risk C: Monitor
Secretin: Agents with Clinically Relevant Anticholinergic Effects may decrease therapeutic effects 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 Inhibitor: Cyproheptadine may decrease therapeutic effects of Selective Serotonin Reuptake Inhibitor. Risk C: Monitor
Sofpironium: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Sofpironium. Risk X: Avoid
Suvorexant: CNS Depressants may increase CNS depressant effects 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 increase CNS depressant effects of Thalidomide. Risk X: Avoid
Thiazide and Thiazide-Like Diuretics: Agents with Clinically Relevant Anticholinergic Effects may increase serum concentration of Thiazide and Thiazide-Like Diuretics. Risk C: Monitor
Thiothixene: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Thiothixene. Risk C: Monitor
Tiapride: Agents with Clinically Relevant Anticholinergic Effects may decrease therapeutic effects of Tiapride. Risk C: Monitor
Tiotropium: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Tiotropium. Risk X: Avoid
Tolterodine: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Tolterodine. Risk C: Monitor
Topiramate: Agents with Clinically Relevant Anticholinergic Effects may increase adverse/toxic effects of Topiramate. Risk C: Monitor
Tranylcypromine: May increase anticholinergic effects of Antihistamines, First Generation. Risk X: Avoid
Tricyclic Antidepressants: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Tricyclic Antidepressants. Risk C: Monitor
Trimeprazine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Trimethobenzamide: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Trimethobenzamide. Risk C: Monitor
Trospium: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Trospium. Risk C: Monitor
Umeclidinium: May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk X: Avoid
Valerian: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Zolpidem: CNS Depressants may increase CNS depressant effects 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
Zuclopenthixol: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Zuclopenthixol. Risk C: Monitor
Zuranolone: May increase CNS depressant effects 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
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]).
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.
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).
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)
Altered kidney function: Elimination is diminished in renal insufficiency.