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
Uses for Cyproheptadine Hydrochloride
Has been effective in some patients for the treatment of Cushing’s syndrome† secondary to pituitary disorders;14 15 16 17 18 19 20 21 48 52 53 63 however, in most patients, other therapy (e.g., surgery, radiation therapy) is preferred.21 39 48
Has been effective for the management of inhibited male or female orgasm† (anorgasmy) induced by tricyclic antidepressants,55 57 58 66 MAO inhibitors,54 56 fluoxetine,68 or antipsychotic agents.56 However, consider the potential for interactions between these drugs and cyproheptadine.5 66 (See Interactions.)
Has been shown to stimulate appetite and weight gain in children32 33 and adults;34 35 36 however, few indications for clinical use.40 May be of some value in the treatment of anorexia nervosa†;37 38 41 46 47 59 60 may be more effective in nonbulimic patients than in those who are bulimic.59
Reportedly has been effective in some patients for the management of vascular headaches† (e.g., migraine).30 31 43 44 71 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.71
Cyproheptadine Hydrochloride Dosage and Administration
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.5 74 75 (See Pediatric Use under Cautions.)
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.74 75 Dosage range: 4–20 mg daily; most patients require 12–16 mg daily.74 75
Cautions for Cyproheptadine Hydrochloride
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).74 75 c (See Contraindications.) Use of antihistamines generally not recommended in asthmatics who previously experienced a serious antihistamine-induced adverse bronchopulmonary effect.
Risk of overdosage and toxicity (including death) in children <2 years of age receiving OTC preparations containing antihistamines, cough suppressants, expectorants, and nasal decongestants alone or in combination for relief of symptoms of upper respiratory tract infection.72 73 Limited evidence of efficacy for these preparations in this age group; appropriate dosages not established.72 Therefore, FDA recommended not to use such preparations in children <2 years of age; safety and efficacy in older children currently under evaluation. Because children 2–3 years of age also are at increased risk of overdosage and toxicity, some manufacturers of oral nonprescription cough and cold preparations recently agreed to voluntarily revise the product labeling to state that such preparations should not be used in children <4 years of age. During the transition period, some preparations on pharmacy shelves will have the new recommendation (“do not use in children <4 years of age”), while others will have the previous recommendation (“do not use in children <2 years of age”). FDA recommends that parents and caregivers adhere to dosage instructions and warnings on the product labeling that accompanies the preparation and consult a clinician about any concerns. Clinicians should ask caregivers about use of OTC cough/cold preparations to avoid overdosage.
Possible paradoxical excitement (e.g., restlessness, insomnia, tremors, euphoria, nervousness, delirium, palpitation, seizures), especially in young children.74 75 c Central anticholinergic syndrome (e.g., hallucinations, agitation, confusion) has occurred.
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.5 74 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.5 74
Common Adverse Effects
Interactions for Cyproheptadine Hydrochloride
Specific Drugs and Laboratory Tests
CNS depressants (e.g., alcohol, hypnotics, sedatives, tranquilizers)
Use caution to avoid overdosage;c advise patient to avoid alcohol
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 Hydrochloride Pharmacokinetics
Distribution into human body tissues and fluids has not been characterized.7
Tightly closed container at 15–30°C.74
Advice to Patients
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Many prescription cough, cold, and allergy preparations commercially available in the US have not been approved by FDA.500 Because of the potentially serious health risks associated with unapproved preparations, FDA announced on March 3, 2011, that it would take enforcement action (e.g., seizure, injunction, other judicial or administrative proceeding) against any currently marketed and listed unapproved cough, cold, and allergy preparation manufactured on or after June 1, 2011 or shipped on or after August 30, 2011.500 For additional information and for a complete list of unapproved cough, cold, and allergy preparations affected by this FDA notice, see FDA website ().
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
2 mg/5 mL*
Cyproheptadine Hydrochloride Syrup
Cyproheptadine Hydrochloride Tablets
This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 02/2013. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.
Cyproheptadine HCl 2MG/5ML Syrup (ACTAVIS MID ATLANTIC): 120/$24.38 or 360/$50.02
Cyproheptadine HCl 4MG Tablets (CYPRESS PHARMACEUTICAL): 30/$13.99 or 60/$19.98
This report on medications is for your information only, and is not considered individual patient advice. Because of the changing nature of drug information, please consult your physician or pharmacist about specific clinical use.
The American Society of Health-System Pharmacists, Inc. and Drugs.com represent that the information provided hereunder was formulated with a reasonable standard of care, and in conformity with professional standards in the field. The American Society of Health-System Pharmacists, Inc. and Drugs.com make no representations or warranties, express or implied, including, but not limited to, any implied warranty of merchantability and/or fitness for a particular purpose, with respect to such information and specifically disclaims all such warranties. Users are advised that decisions regarding drug therapy are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and the information is provided for informational purposes only. The entire monograph for a drug should be reviewed for a thorough understanding of the drug's actions, uses and side effects. The American Society of Health-System Pharmacists, Inc. and Drugs.com do not endorse or recommend the use of any drug. The information is not a substitute for medical care.
AHFS Drug Information. © Copyright, 1959-2013, Selected Revisions January 11, 2012. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.
1. Schering. Optimine prescribing information. In: Huff BB, ed. Physicians’ desk reference. 38th ed. Oradell, NJ: Medical Economics Company Inc; 1984:1795-7.
2. The United States pharmacopeia, 21st rev, and The national formulary, 16th ed. Rockville, MD: The United States Pharmacopeial Convention, Inc; 1984:267, 1450, 1484.
3. Hoffman JP (Merck, Sharp and Dohme): Personal communication; 1978 May 15.
4. United States Pharmacopeia Dispensing Information (USP DI). Vol I. Drug information for the health care provider. Rockville, MD: The United States Pharmacopeial Convention, Inc; 1983:142.
5. Merck & Co. Periactin (cyproheptadine) tablets and syrup prescribing information. West Point, PA; 1999 Sept.
6. Stone CA, Wenger HC, Ludden CT et al. Antiserotonin-antihistaminic properties of cyproheptadine. J Pharmacol Exp Ther. 1961; 131:73-84.
7. Hintze KL, Wold JS, Fischer LJ. Disposition of cyproheptadine in rats, mice, and humans and identification of a stable epoxide metabolite. Drug Metab Dispos. 1975; 3:1-9. [IDIS 50715] [PubMed 234828]
8. Porter CC, Arison BH, Gruber VF et al. Human metabolism of cyproheptadine. Drug Metab Dispos. 1975; 3:189-97. [IDIS 52901] [PubMed 238818]
9. Kennedy KA, Halmi KA, Fischer LJ. Urinary excretion of a quaternary ammonium glucuronide metabolite of cyproheptadine in humans undergoing chronic drug therapy. Life Sci. 1977; 21:1813-20. [PubMed 604709]
10. Fischer LJ, Thies RL, Charkowski D et al. Formation and urinary excretion of cyproheptadine glucuronide in monkeys, chimpanzees, and humans. Drug Metab Dispos. 1980; 8:422-4. [IDIS 128861] [PubMed 6109610]
11. Wanderer AA, St. Pierre JP, Ellis EF. Primary acquired cold urticaria: double-blind comparative study of treatment with cyproheptadine, chlorpheniramine, and placebo. Arch Dermatol. 1977; 113:1375-7. [IDIS 89712] [PubMed 334082]
12. Sigler RW, Evans R III, Horakova Z et al. The role of cyproheptadine in the treatment of cold urticaria. J Allergy Clin Immunol. 1980; 65:309-12. [IDIS 112895] [PubMed 6102102]
13. Buckley RH, Mathews KP. Common “allergic” skin diseases. JAMA. 1982; 248:2611-22. [IDIS 160684] [PubMed 7143623]
14. Krieger DT, Amorosa L, Linick F. Cyproheptadine-induced remission of Cushing’s disease. N Engl J Med. 1975; 293:893-6. [IDIS 55425] [PubMed 1177986]
15. Krieger DT. Cyproheptadine for pituitary disorders. N Engl J Med. 1976; 295:394-5. [PubMed 934231]
16. Grant DB, Atherden SM. Cushing’s disease presenting with growth failure: clinical remission during cyproheptadine therapy. Arch Dis Child. 1979; 54:466-8. [IDIS 99588] [PubMed 475431]
17. Hsu TH, Gann DS, Tsan KW et al. Cyproheptadine in the control of Cushing’s disease. Johns Hopkins Med J. 1981; 149:77-83. [IDIS 137249] [PubMed 6265685]
18. Jimenez-Alonso J, Munoz-Avila J, Jaimez L et al. Cyproheptadine-induced remission of Cushing’s disease due to pituitary basophil adenoma. Drug Intell Clin Pharm. 1982; 16:962-5. [IDIS 161163] [PubMed 6295736]
19. Griffith DN, Rose EJ. Pregnancy after cyproheptadine treatment for Cushing’s disease. N Engl J Med. 1981; 305:893-4. [IDIS 137895] [PubMed 7278892]
20. Kasperlik-Zaluska A, Migdalska B, Hartwig W et al. Two pregnancies in a woman with Cushing’s syndrome treated with cyproheptadine: case report. Br J Obstet Gynaecol. 1980; 87:1171-3. [PubMed 7437385]
21. Gold EM. The Cushing syndromes: changing views of diagnosis and treatment. Ann Intern Med. 1979; 90:829-44. [IDIS 95709] [PubMed 219743]
22. Hartwig W, Kasperlik-Zaluska A, Wilczynska J et al. Cyproheptadine for pituitary disorders. N Engl J Med. 1976; 295:394. [PubMed 934231]
23. Krieger DT, Condon EM. Cyproheptadine treatment of Nelson’s syndrome: restoration of plasma ACTH circadian periodicity and reversal of response to TRF. J Clin Endocrinol Metab. 1978; 46:349-52. [IDIS 101716] [PubMed 220278]
24. Aronin N, Krieger DT. Sustained remission of Nelson’s syndrome after stopping cyproheptadine treatment. N Engl J Med. 1980; 302:453-5. [IDIS 110686] [PubMed 6243392]
25. Hsu TH. Management of virilizing congenital adrenal hyperplasia with cyproheptadine. Ann Intern Med. 1980; 92:628-30. [IDIS 113155] [PubMed 7387003]
26. Wortsman J, Soler NG, Hirschowitz J. Cyproheptadine in the management of the galactorrhea-amenorrhea syndrome. Ann Intern Med. 1979; 90:923-5. [IDIS 96572] [PubMed 571691]
27. Vroom FQ, Brown RE, Dempsey H et al. Studies on several possible antiserotonin compounds in a patient with the functioning carcinoid syndrome. Ann Intern Med. 1962; 56:941-5. [PubMed 13926919]
28. Berry EM, Maunder C, Wilson M. Carcinoid myopathy and treatment with cyproheptadine (Periactin). Gut. 1974; 15:34-8. [IDIS 45837] [PubMed 4274414]
29. Harris AL, Smith IE. Regression of carcinoid tumour with cyproheptadine. BMJ. 1982; 285:475. [IDIS 155028] [PubMed 6809131]
30. Curran DA, Lance JW. Clinical trial of methysergide and other preparations in the management of migraine. J Neurol Neurosurg Psychiatry. 1964; 27:463-9. [PubMed 14213477]
31. Lance JW, Curran DA, Anthony M. Investigations into the mechanism and treatment of chronic headache. Med J Aust. 1965; 2:909-14. [PubMed 5322372]
32. Lavenstein AF, Decaney EP, Lasagna L et al. Effect of cyproheptadine on asthmatic children. JAMA. 1962; 180:912-6. [PubMed 14462919]
33. Bergen SS. Appetite stimulating properties of cyproheptadine. Am J Dis Child. 1964; 108:270-3. [PubMed 14168064]
34. Noble RE. Effect of cyproheptadine on appetite and weight gain in adults. JAMA. 1969; 209:2054-5. [PubMed 4897366]
35. Silverstone T, Schuyler D. The effect of cyproheptadine on hunger, calorie intake, and body weight in man. Psychopharmacologia. 1975; 40:335-40. [PubMed 1096217]
36. Pawlowski GJ. Cyproheptadine: weight-gain and appetite stimulation in essential anorexic adults. Curr Ther Res Clin Exp. 1975; 18:673-8. [PubMed 812645]
37. Goldberg SC, Halmi KA, Eckert ED. Cyproheptadine in anorexia nervosa. Br J Psychiatry. 1979; 134:67-70. [PubMed 367480]
38. Halmi KA, Eckert E, Falk JR. Cyproheptadine for anorexia nerovsa. Lancet. 1982; 1:1357-8. [IDIS 151434] [PubMed 6123657]
39. Vaughan GM, Taylor TJ. Cushing’s syndrome. In: Conn HF, ed. Current therapy: latest approved methods of treatment for the practicing physician, 1983. Philadelphia: WB Saunders Company; 1983:472-7.
40. Anon. Cyproheptadine. Lancet. 1978; 1:367-8.
41. Goldberg SC, Eckert ED, Halmi KA et al. Effects of cyproheptadine on symptoms and attitudes in anorexia nervosa. Arch Gen Psychiatry. 1980; 37:1083. [IDIS 123856] [PubMed 7416909]
42. Peroutka SJ, Allen GS. The calcium antagonist properties of cyproheptadine: implications for antimigraine action. Neurology. 1984; 34:304-9. [PubMed 6538269]
43. Lance JW, Anthony M, Somerville B. Comparative trial of serotonin antagonists in the management of migraine. Br Med J. 1970; 1:327-30. [PubMed 4906701]
44. Bille B, Ludvigsson J, Sanner G. Prophylaxis of migraine in children. Headache. 1977; 17:61-3. [PubMed 324951]
45. Greenberger P, Patterson R. Safety of therapy for allergic symptoms during pregnancy. Ann Intern Med. 1978; 89:234-7. [PubMed 28058]
46. Falk JR, Halmi KA, Tyron WW. Activity measures in anorexia nervosa. Arch Gen Psychiatry. 1985; 42:811-4. [PubMed 4015326]
47. Herzog DB, Copeland PM. Eating disorders. N Engl J Med. 1985; 313:295-303. [IDIS 202663] [PubMed 2861566]
48. Burch WM. Cushing’s disease: a review. Arch Intern Med. 1985; 145:1106-11. [IDIS 200607] [PubMed 3923962]
49. Kaplowitz PB, Jennings S. Enhancement of linear growth and weight gain by cyproheptadine in children with hypopituitarism receiving growth hormone therapy. J Pediatr. 1987; 110:140-3. [IDIS 225707] [PubMed 3794875]
50. Douglas WW. Histamine and 5-hydroxytryptamine (serotonin) and their antagonists. In: Gilman AG, Goodman LS, Rall TW et al, eds. Goodman and Gilman’s the pharmacological basis of therapeutics. 7th ed. New York: Macmillan Publishing Company; 1985:605-38.
51. Anthony M. Serotonin antagonists. Aust N Z J Med. 1984; 6:888-95.
52. Wiesen M, Ross F, Kreiger DT. Prolonged remission of a case of Cushing’s disease following cessation of cyproheptadine therapy. Acta Endocrinol (Copenh). 1983; 102:436-8. [PubMed 6829265]
53. Couch RM, Smail PJ, Dean HJ et al. Prolonged remission of Cushing disease after treatment with cyproheptadine. J Pediatr. 1984; 104:906-8. [IDIS 186484] [PubMed 6327962]
54. DeCastro RM. Reversal of MAOI-induced anorgasmia with cyproheptadine. Am J Psychiatry. 1985; 142:783. [IDIS 200783] [PubMed 4039897]
55. Riley AJ, Riley EJ. Cyproheptadine and antidepressant-induced anorgasmia. Br J Psychiatry. 1986; 148:217-8. [PubMed 3697592]
56. Jeffries JJ. Cyproheptadine and drug-induced anorgasmia. Can J Psychiatry. 1987; 32:79. [PubMed 2880654]
57. Sovner R. Treatment of tricyclic antidepressant-induced orgasmic inhibition with cyproheptadine. J Clin Psychopharmacol. 1984; 4:169. [PubMed 6736278]
58. Steele TE, Howell EF. Cyproheptadine for imipramine-induced anorgasmia. J Clin Psychopharmacol. 1986; 6:326-7. [IDIS 221973] [PubMed 3771824]
59. Halmi KA, Eckert E, LaDu TJ et al. Anorexia nervosa: treatment efficacy of cyproheptadine and amitriptyline. Arch Gen Psychiatry. 1986; 43:177-81. [IDIS 212256] [PubMed 3511877]
60. Johnson C, Stuckey M, Mitchell J. Psychopharmacological treatment of anorexia nervosa and bulimia: review and synthesis. J Nerv Ment Dis. 1983; 171:524-34. [PubMed 6310046]
61. Mylan Pharmaceuticals Inc. Cyproheptadine hydrochloride tablets, USP prescribing information. Morgantown, WV; 1985 Feb.
62. Merck Sharp & Dohme. Periactin prescribing information. In: Huff BB, ed. Physicians’ desk reference. 41st ed. Oradell, NJ: Medical Economics Company Inc; 1987 (Suppl A):A43.
63. Khir ASM, How J, Bewsher PD. Successful pregnancy after cyproheptadine treatment for Cushing’s disease. Eur J Obstet Gynecol Reprod Biol. 1982; 13:343-7. [PubMed 7128894]
64. Padfield NL. Carcinoid syndrome: comparison of pretreatment regimes in the same patient. Ann R Coll Surg Engl. 1987; 69:16-7. [PubMed 2952043]
65. Kvols LK. Metastatic carcinoid tumors and the carcinoid syndrome: a selective review of chemotherapy and hormonal therapy. Am J Med. 1986; 81(Suppl 6B):49-55. [IDIS 224868] [PubMed 2432781]
66. Pontius EB. Case report of an anticholinergic crisis associated with cyproheptadine treatment of desipramine-induced anorgasmia. J Clin Psychopharmacol. 1988; 8:230-1. [IDIS 242985] [PubMed 3379154]
67. Merck Sharp & Dohme. Periactin tablets and syrup prescribing information. In: Physician’s desk reference. 52nd ed. Montvale, NJ: Medical Economics Company Inc; 1998:1720-1.
68. McCormick S, Olin J, Brotman AW. Reversal of fluoxetine-induced anorgasmia by cyproheptadine in two patients. J Clin Psychiatry. 1990; 51:383-4. [IDIS 272903] [PubMed 2211550]
69. Feder R. Reversal of antidepressant activity of fluoxetine by cyproheptadine in three patients. J Clin Psychiatry. 1991; 52:163-4. [IDIS 281251] [PubMed 2016249]
70. Fluoxetine/cyproheptadine. In: Tatro DS, Olin BR, Hebel SK eds. Drug interaction facts. St. Louis: JB Lippincott Co; 1992(Jan):344c.
71. Ramadan NM, Silberstein SD, Freitag F et al. Evidence-based guidelines for migraine headache in the primary care setting: pharmacological management for prevention of migraine. St. Paul, MN; 2001. From the American Academy of Neurology web site.
72. Srinivasan A, Budnitz D, Shehab N et al. Infant deaths associated with cough and cold medications—two states, 2005. MMWR Morb Mortal Wkly Rep. 2007; 56:1-4. [PubMed 17218934]
73. Food and Drug Administration. Cough and cold medications in children less than two years of age. Rockville, MD; 2007 Jan 12. From FDA website.
74. Corepharma LLC. Cyproheptadine hydrochloride (Cyproheptadine Hydrochloride) tablet prescribing information. Middlesex, NJ; 2006 Jun.
75. Alpharma USPD. Cyproheptadine hydrochloride oral solution prescribing information. Baltimore, MD; 2005 Jun.
500. +Food and Drug Administration. Drugs for human use; unapproved and misbranded oral drugs labeled for prescription use and offered for relief of symptoms of cold, cough, or allergy, enforcement action dates. Notice. [Docket No. FDA-2011-N-0100] Fed Regist. 2011; 76:11794-8.
c. AHFS drug information 2007. McEvoy GK, ed. Antihistamines general statement. Bethesda, MD: American Society of Health-System Pharmacists; 2007:1-8.