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Cyproheptadine: Drug information

Cyproheptadine: Drug information
(For additional information see "Cyproheptadine: Patient drug information" and see "Cyproheptadine: Pediatric drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
Pharmacologic Category
  • Histamine H1 Antagonist;
  • Histamine H1 Antagonist, First Generation;
  • Piperidine Derivative
Dosing: Adult
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 (Homnick 2004; Homnick 2005).

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 (Boyer 2005; Sun-Edelstein 2008).

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 (Boyer 2005; Sun-Edelstein 2008).

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

No dosage adjustment provided in manufacturer's labeling. However, elimination is diminished in renal insufficiency.

Dosing: Hepatic Impairment: Adult

No dosage adjustment provided in manufacturer's labeling.

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 (Harrison 2019):

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 (Couluris 2008). 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 (Najib 2014). 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. (Sant'Anna 2014).

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) (Epifanio 2012; Homnick 2004; Homnick 2005). 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 (Homnick 2004; Homnick 2005). 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) (Epifanio 2012).

Cyclic vomiting syndrome; prevention

Cyclic vomiting syndrome; prevention: Limited data available: Children 2 to <5 years: Oral: 0.25 to 0.5 mg/kg/day in divided doses once or twice daily (Li 2018); some patients may require doses divided 3 times daily (Andersen 1997); maximum daily dose: 12 mg/day; some clinicians have used once-daily dose at bedtime to prevent daytime sedation (Li 2018).

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 (Madani 2016; Rodriguez 2013; Sadeghian 2008); 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 (Madani 2016; Sadeghian 2008; manufacturer's labeling). 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 (Sadeghian 2008). 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 (Rodriguez 2013).

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 (Brenner 2008; Kacperski 2016; Kliegman 2020; Lewis 2006); age-dependent maximum daily doses: Children 3 to 6 years: 12 mg/day; Children ≥7 years and Adolescents: 16 mg/day (Lewis 2006; manufacturer's labeling); experience suggests younger patients more tolerant of common cyproheptadine side effects (ie, sedation, increased appetite) (Lewis 2004; Lewis 2004a).

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 (Gracies 1997). 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 (Khodadadeh 1998).

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

Dosing: Older Adult

Avoid use (Beers Criteria [AGS 2019]).

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

Administration: Pediatric

Oral: Usually administered in 2 to 4 divided doses (eg, every 6 to 12 hours); for some uses (eg, cyclic vomiting syndrome), once-daily administration at bedtime has been used for some indications to improve tolerability of sedative effects.

Use: Labeled Indications

See "Use: Unsupported"

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

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 (Beers Criteria [AGS 2019]).

Pharmacy Quality Alliance (PQA): Cyproheptadine is identified as a high-risk medication in patients 65 years and older on the PQA’s, Use of High-Risk Medications in the Elderly (HRM) performance measure, a safety measure used by the Centers for Medicare and Medicaid Services (CMS) for Medicare plans (PQA 2017).

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]

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.

Frequency not defined.

Cardiovascular: Extrasystoles, hypotension, palpitations, tachycardia

Central nervous system: Ataxia, chills, confusion, dizziness, drowsiness, euphoria, excitement, fatigue, hallucination, headache, hysteria, insomnia, irritability, nervousness, neuritis, paresthesia, restlessness, sedation, seizure, vertigo

Dermatologic: Diaphoresis, skin photosensitivity, skin rash, urticaria

Gastrointestinal: Abdominal pain, anorexia, cholestasis, constipation, diarrhea, increased appetite, nausea, vomiting, xerostomia

Genitourinary: Difficulty in micturition, urinary frequency, urinary retention

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

Hepatic: Hepatic failure, hepatitis, jaundice

Hypersensitivity: Anaphylactic shock, angioedema, hypersensitivity reaction

Neuromuscular & skeletal: Tremor

Ophthalmic: Blurred vision, diplopia

Otic: Labyrinthitis (acute), tinnitus

Respiratory: Nasal congestion, pharyngitis, thickening of bronchial secretions

Contraindications

Use in newborn or premature infants or breast-feeding 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.

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.

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 Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.

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

Aclidinium: May enhance the anticholinergic effect of Anticholinergic Agents. Risk X: Avoid combination

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 Anticholinergic Agents. Risk C: Monitor therapy

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

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

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

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: May diminish the therapeutic effect of Antihistamines. Antihistamines may diminish the therapeutic effect of Betahistine. 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 Anticholinergic Agents. 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: Anticholinergic Agents 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 Anticholinergic Agents. 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

Cimetropium: Anticholinergic Agents may enhance the anticholinergic effect of Cimetropium. Risk X: Avoid combination

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

Doxylamine: May enhance the CNS depressant effect of CNS Depressants. Management: The manufacturer of Diclegis (doxylamine/pyridoxine), intended for use in pregnancy, specifically states that use with other CNS depressants is not recommended. 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: Anticholinergic Agents 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): Anticholinergic Agents may diminish the therapeutic effect of Gastrointestinal Agents (Prokinetic). Risk C: Monitor therapy

Glucagon: Anticholinergic Agents 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): Anticholinergic Agents may enhance the anticholinergic effect of Glycopyrrolate (Oral Inhalation). Risk X: Avoid combination

Glycopyrronium (Topical): May enhance the anticholinergic effect of Anticholinergic Agents. 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 (Oral Inhalation): May enhance the anticholinergic effect of Anticholinergic Agents. Risk X: Avoid combination

Itopride: Anticholinergic Agents may diminish the therapeutic effect of Itopride. 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: Anticholinergic Agents 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

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 Anticholinergic Agents. Risk C: Monitor therapy

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

Mirabegron: Anticholinergic Agents 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

Nitroglycerin: Anticholinergic Agents 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 Anticholinergic Agents. 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: Anticholinergic Agents 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: Anticholinergic Agents may enhance the ulcerogenic effect 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 Anticholinergic Agents. 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

Ramosetron: Anticholinergic Agents may enhance the constipating effect of Ramosetron. Risk C: Monitor therapy

Revefenacin: Anticholinergic Agents may enhance the anticholinergic effect of Revefenacin. Risk X: Avoid combination

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

Tiotropium: Anticholinergic Agents may enhance the anticholinergic effect of Tiotropium. Risk X: Avoid combination

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

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

Umeclidinium: May enhance the anticholinergic effect of Anticholinergic Agents. 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

Pregnancy Considerations

Per the product labeling, 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.

Although cyproheptadine is approved for the treatment of allergic conditions, such as rhinitis, pruritus, and urticaria, other agents are preferred for use in pregnant patients (BSACI [Scadding 2017]; Murase 2014; EAACI [Zuberbier 2018]).

Breastfeeding Considerations

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

Use while breastfeeding is contraindicated by the manufacturer. In general, if a nursing infant is exposed to a first generation antihistamine via breast milk, they should be monitored for irritability or drowsiness. When treatment is needed in breastfeeding women, second generation antihistamines are preferred (Butler 2014). Antihistamines may decrease maternal serum prolactin concentrations when administered prior to the establishment of nursing (Messinis 1985).

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

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

Altered kidney function: Elimination is diminished in renal insufficiency.

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.

Brand Names: International
  • Adekin (GR);
  • Antisemin (TW);
  • Apetamin-P (LK);
  • Apeton 4 (ID);
  • Cipla-Actin (ZA);
  • Ciplactin (IN, VN);
  • Ciprogal (UY);
  • Ciprovit-A (PE);
  • Ciptadine (JO);
  • Cyheptine (TH);
  • Cypon Plain (LK);
  • Cyprodin (TW);
  • Cyprogin (TH);
  • Cypromin (JP, TW);
  • Cyprono (TH);
  • Cyprosian (TH);
  • Cyprotin (SG);
  • Cyprotol (BG);
  • Cyptadine (EG);
  • Cytadine (TW);
  • Ennamax (ID);
  • Glocyp (ID);
  • Gubamine (AR);
  • Heptin (LK);
  • Istam-Far (GR);
  • Klarivitina (ES);
  • Kulinet (GR);
  • Pangavit Pediátrico (MX);
  • Periactin (AE, AT, AU, BF, BH, BJ, CH, CI, CO, CY, DK, EC, EE, ES, ET, FI, GB, GH, GM, GN, IL, IQ, IR, IT, JO, KE, KW, LB, LR, LU, LY, MA, ML, MR, MT, MU, MW, MY, NE, NG, NL, OM, PK, PL, PT, QA, RU, SA, SC, SD, SE, SK, SL, SN, SY, TH, TN, TR, TZ, UG, VE, YE, ZM, ZW);
  • Periactine (FR);
  • Peritol (BB, BM, BS, BZ, CZ, GY, HN, HU, IN, JM, LK, PL, PR, RO, RU, SK, SR, TT, UA);
  • Petina (MY);
  • Pilian (MY, TW);
  • Prakten (TR);
  • Prevet (EG);
  • Prohessen (ID);
  • Pronicy (ID);
  • Showmin (TW);
  • Triactin (QA);
  • Trimetabol (CO);
  • Viturnum (CL)


For country code abbreviations (show table)
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