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 (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: 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 (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: 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: 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.
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
(For additional information see "Cyproheptadine: Drug information")
Allergic conditions: Oral: Initial: 4 mg 3 times daily; maintenance: 4 to 20 mg daily in divided doses; maximum: 0.5 mg/kg/day; some patients may require up to 32 mg/day for adequate control of symptoms
Decreased appetite secondary to chronic disease (off-label use): Oral: Initial: 2 mg 4 times per day for one week, then 4 mg 4 times per day (Homnick 2004; Homnick 2005)
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).
Spasticity associated with spinal cord damage (off-label use): Oral: Initial: 2 to 4 mg every 8 hours; maximum: 8 mg every 8 hours (Barbeau 1982; Wainberg 1990)
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
No dosage adjustment provided in manufacturer's labeling. However, elimination is diminished in renal insufficiency.
No dosage adjustment provided in manufacturer's labeling.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Syrup, Oral, as hydrochloride:
Generic: 2 mg/5 mL (10 mL [DSC], 473 mL)
Tablet, Oral, as hydrochloride:
Generic: 4 mg
Yes
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.
Oral syrup: Store at 20°C to 25°C (68°F to 77°F); protect from light.
Oral tablets: Store at 20°C to 25°C (68°F to 77°F).
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 (FDA approved in ages ≥2 years and adults); has also been used to promote weight gain by appetite stimulation in various disease states (eg, cystic fibrosis, cancer-related cachexia), migraine prophylaxis, prevention of episodes of cyclic vomiting, management of refractory dyspeptic symptoms, and treatment of spasticity associated with spinal cord damage.
Note: Although FDA approved as adjunctive therapy for anaphylaxis, H1 and H2 antihistamine agents are generally considered second or third line (not for initial or sole treatment of anaphylaxis); preferred H1 antihistamine agents include diphenhydramine or nonsedating cetirizine; cyproheptadine is not considered a therapeutic option (AAAAI/ACAAI/JCAAI [Lieberman 2015]; WAO [Simons 2015]).
Cyproheptadine may be confused with cyclobenzaprine
Periactin may be confused with Percodan, Persantine
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).
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]
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
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.
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:
• Elderly: Antihistamines are more likely to cause dizziness, sedation and hypotension in elderly patients.
• 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.
None known.
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
Amphetamines: May diminish the sedative effect of Antihistamines. 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: 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
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
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. Risk C: Monitor therapy
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
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
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
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 women; 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 women (BSACI [Scadding 2017]; Murase 2014; Zuberbier 2018).
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)
Renal function impairment: Elimination is diminished in renal insufficiency.
Syrup (Cyproheptadine HCl Oral)
2 mg/5 mL (per mL): $0.13 - $0.14
Tablets (Cyproheptadine HCl Oral)
4 mg (per each): $0.15 - $1.61
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