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Cyproheptadine

Class: First Generation Antihistamines
ATC Class: R06AX02
VA Class: AH107
Chemical Name: 4-(5H-dibenzo[a,d]cyclohepten-5-ylidene)-1-methylpiperidine hydrochloride
Molecular Formula: C21H21N•HCl
CAS Number: 41354-29-4

Medically reviewed by Drugs.com on Jan 24, 2022. Written by ASHP.

Introduction

First generation antihistamine; serotonin antagonist; structurally and pharmacologically related to azatadine.

Uses for Cyproheptadine

Allergic Conditions

Treatment of cold urticaria.

Symptomatic relief of perennial (nonseasonal) and seasonal (e.g., hay fever) allergic rhinitis.

Management of nonallergic (vasomotor) rhinitis.

Management of allergic conjunctivitis caused by foods or inhaled allergens.

Management of mild, uncomplicated allergic skin manifestations of urticaria and angioedema.

Treatment of dermatographism.

Amelioration of allergic reactions to blood or plasma.

Adjunct to epinephrine and other standard measures for management of anaphylactic reactions after acute manifestations have been controlled.

Cushing’s Syndrome

Has been effective in some patients for the treatment of Cushing’s syndrome secondary to pituitary disorders; however, in most patients, other therapy (e.g., surgery, radiation therapy) is preferred.

Sexual Dysfunction

Has been effective for the management of inhibited male or female orgasm (anorgasmy) induced by tricyclic antidepressants, MAO inhibitors, fluoxetine, or antipsychotic agents. However, consider the potential for interactions between these drugs and cyproheptadine. (See Interactions.)

Anorexia Nervosa

Has been shown to stimulate appetite and weight gain in children and adults; however, few indications for clinical use. May be of some value in the treatment of anorexia nervosa; may be more effective in nonbulimic patients than in those who are bulimic.

Headache

Reportedly has been effective in some patients for the management of vascular headaches (e.g., migraine). Efficacy for prophylaxis of migraine not established in randomized controlled studies, but some experts consider the drug to be effective based on consensus and clinical experience.

Cyproheptadine Dosage and Administration

Administration

Oral Administration

Administer orally as tablets or oral solution.

Dosage

Available as cyproheptadine hydrochloride; dosage expressed in terms of the salt.

Pediatric Patients

Allergic Conditions
Oral

Children 2–6 years of age: Usual dosage is 2 mg 2 or 3 times daily; adjust as needed based on the size and response of the patient, up to maximum of 12 mg daily. (See Pediatric Use under Cautions.)

Children 7–14 years of age: Usual dosage is 4 mg 2 or 3 times daily; adjust as needed based on the size and response of the patient, up to maximum of 16 mg daily.

Adolescents ≥15 years of age: Initially, 4 mg 3 times daily; adjust based on the size and response of the patient, up to 0.5 mg/kg daily. Dosage range: 4–20 mg daily; most patients require 12–16 mg daily.

Alternatively, children ≥2 years of age may receive 0.25 mg/kg or 8 mg/m2 daily in divided doses.

Anorexia Nervosa†
Oral

Adolescents ≥13 years of age: Dosage of 2 mg 4 times daily, increased gradually over a 3-week period to up to 8 mg 4 times daily, has been used.

Adults

Allergic Conditions
Oral

Initially, 4 mg 3 times daily; adjust as needed based on the size and response of the patient, up to 0.5 mg/kg daily.

Dosage range: 4–20 mg daily; most patients require 12–16 mg daily. Some patients may require up to 32 mg daily.

Cushing’s Syndrome†
Oral

Initially, 8 mg daily in divided doses; gradually increase dosage to up to 24 mg daily in divided doses.

Anorexia Nervosa†
Oral

Dosage of 2 mg 4 times daily, increased gradually over a 3-week period to up to 8 mg 4 times daily, has been used.

Prescribing Limits

Pediatric Patients

Allergic Conditions
Oral

Children 2–6 years of age: Maximum 12 mg daily.

Children 7–14 years of age: Maximum 16 mg daily.

Adolescents ≥15 years of age: Maximum 0.5 mg/kg daily.

Anorexia Nervosa†
Oral

Adolescents ≥13 years of age: Maximum 32 mg daily.

Adults

Allergic Conditions
Oral

Maximum 0.5 mg/kg daily.

Cushing’s Syndrome†
Oral

Maximum 24 mg daily.

Anorexia Nervosa†
Oral

Maximum 32 mg daily.

Special Populations

Geriatric Patients

Select dosage with caution, starting at the lower end of the usual dosage range. (See Geriatric Use under Cautions.)

Cautions for Cyproheptadine

Contraindications

  • Neonates and premature infants.

  • Women who are breast-feeding. (See Lactation and also Pediatric Use under Cautions.)

  • Known hypersensitivity to cyproheptadine or other drugs with similar chemical structures.

  • Patients receiving MAO inhibitor therapy. (See Interactions.)

  • Known history of angle-closure glaucoma, stenosing peptic ulcer, symptomatic prostatic hypertrophy, bladder neck obstruction, or pyloroduodenal obstruction.

  • Debilitated geriatric patients.

Warnings/Precautions

Warnings

CNS Effects

Risk of marked drowsiness. Caution required when performing hazardous activities requiring mental alertness and motor coordination (e.g., driving a motor vehicle, operating machinery).

Possible excitability (especially in children). (See Pediatric Use under Cautions.)

Concurrent use of other CNS depressants may have additive CNS depressant effects. (See Interactions.)

General Precautions

Concomitant Diseases

Because of anticholinergic effects, use with caution in patients with increased intraocular pressure, active or history of respiratory disease (e.g., bronchial asthma), hyperthyroidism, or cardiovascular disease (e.g., hypertension). (See Contraindications.) Use of antihistamines generally not recommended in asthmatics who previously experienced a serious antihistamine-induced adverse bronchopulmonary effect.

Specific Populations

Pregnancy

Category B.

Lactation

Not known whether cyproheptadine is distributed into milk.

Because of potential for serious adverse effects in nursing infants, discontinue nursing or the drug. (See Pediatric Use under Cautions.)

Pediatric Use

Contraindicated in neonates and premature infants.

Safety and efficacy of cyproheptadine not established in children <2 years of age.

Cyproheptadine overdosage, particularly in infants and young children, may produce hallucinations, CNS depression, seizures, respiratory and cardiac arrest, and death.

Possible paradoxical excitement (e.g., restlessness, insomnia, tremors, euphoria, nervousness, delirium, palpitation, seizures), especially in young children. Central anticholinergic syndrome (e.g., hallucinations, agitation, confusion) has occurred.

Geriatric Use

Insufficient experience in patients ≥65 years of age to determine whether geriatric patients respond differently than younger adults; clinical experience has not revealed age-related differences. Select dosage with caution (usually starting at low end of dosage range) because of age-related decreases in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy.

Possible increased risk of dizziness, sedation, and hypotension in geriatric patients.

Contraindicated in debilitated geriatric patients.

Common Adverse Effects

Sedation, sleepiness (often transient), dizziness, disturbed coordination, restlessness, excitation.

Interactions for Cyproheptadine

Specific Drugs and Laboratory Tests

Drug

Interaction

Comments

CNS depressants (e.g., alcohol, hypnotics, sedatives, tranquilizers)

Possible additive CNS depression

Use caution to avoid overdosage; advise patient to avoid alcohol

Fluoxetine

Reversal of fluoxetine’s antidepressant effects reported in limited number of patients, possibly due to inhibition of fluoxetine’s serotonergic effects

MAO inhibitors

MAO inhibitors prolong and intensify anticholinergic effects of antihistamines

Test, antigen or histamine

Inhalation-challenge testing with histamine or antigen: Possible suppression of test response

Antigen skin testing: Possible suppression of wheal and flare reactions

Cyproheptadine Pharmacokinetics

Absorption

Bioavailability

Well absorbed following oral administration.

Distribution

Extent

Distribution into human body tissues and fluids has not been characterized.

Elimination

Metabolism

Appears to be almost completely metabolized, principally to the quaternary ammonium glucuronide conjugate.

Elimination Route

Principally in urine, as conjugates; also in feces following oral administration.

Special Populations

Elimination is reduced in renal insufficiency.

Stability

Storage

Oral

Solution

15–30°C.

Tablets

Tightly closed container at 15–30°C.

Actions

  • Has potent antihistaminic and serotonin antagonist properties; also has anticholinergic and sedative effects and reportedly has calcium-channel blocking activity.

Advice to Patients

  • Risk of drowsiness; avoid alcohol and use caution when engaging in activities requiring mental alertness and motor coordination (e.g., driving a motor vehicle, operating machinery).

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.

  • Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Cyproheptadine Hydrochloride

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Solution

2 mg/5 mL*

Cyproheptadine Hydrochloride Syrup

Tablets

4 mg*

Cyproheptadine Hydrochloride Tablets

AHFS DI Essentials™. © Copyright 2022, Selected Revisions February 1, 2016. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

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