Skip to Content
Be ready for a severe allergy emergency. Read more >>

Cyproheptadine

Pronunciation

Pronunciation

(si proe HEP ta deen)

Index Terms

  • Cyproheptadine HCl
  • Cyproheptadine Hydrochloride
  • Periactin

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Syrup, Oral, as hydrochloride:

Generic: 2 mg/5 mL (10 mL, 473 mL)

Tablet, Oral, as hydrochloride:

Generic: 4 mg

Pharmacologic Category

  • Histamine H1 Antagonist
  • Histamine H1 Antagonist, First Generation
  • Piperidine Derivative

Pharmacology

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 (Hintze 1975)

Excretion

Urine (~40% primarily as metabolites); feces (2% to 20%, <6% as unchanged drug)

Time to Peak

Plasma: 6 to 9 hours (Paton 1985)

Half-Life Elimination

Metabolites: ~16 hours (Paton 1985)

Special Populations: Renal Function Impairment

Elimination is diminished in renal insufficiency.

Use: Labeled Indications

Allergic conditions: Perennial and seasonal allergic rhinitis; vasomotor rhinitis; allergic conjunctivitis caused by inhalant allergens and foods; mild, uncomplicated allergic skin manifestations of urticaria and angioedema; amelioration of allergic reactions to blood or plasma; cold urticaria; dermatographism; adjunctive anaphylactic therapy.

Use: Unlabeled

Migraine headache prophylaxis, pruritus, serotonin syndrome, spasticity associated with spinal cord damage

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.

Dosing: Adult

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)

Migraine headache prophylaxis (off-label use): Oral: 2 mg every 12 hours (with or without propranolol) (Holland 2012; Rao 2000)

Serotonin syndrome (off-label use): Oral: Initial: 12 mg followed by 2 mg every 2 hours or 4 to 8 mg every 6 hours as needed for symptom control (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)

Dosing: Geriatric

Refer to adult dosing. Initiate therapy at the lower end of the dosage range.

Dosing: Pediatric

Allergic conditions:

Children 2 to 6 years: Oral: Usual dose: 0.25 mg/kg/day or 8 mg/m2/day in 2 to 3 divided doses or 2 mg 2 or 3 times daily; maximum: 12 mg/day

Children ≥7 years and Adolescents ≤14 years: Oral: Usual dose: 4 mg 2 or 3 times daily; maximum: 16 mg/day

Adolescents >14 years: Oral: Refer to adult dosing

Episodic migraine preventions (off-label use): Children ≥3 years and Adolescents: Oral: Usual dose: 0.2 to 0.4 mg/kg/day divided twice daily; maximum: 0.5 mg/kg/day (Lewis 2004a; Lewis 2004b)

Dosing: Renal Impairment

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

Dosing: Hepatic Impairment

No dosage adjustment provided in manufacturer’s labeling.

Storage

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).

Drug Interactions

AbobotulinumtoxinA: Anticholinergic Agents may enhance the anticholinergic effect of AbobotulinumtoxinA. Monitor therapy

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

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

Alcohol (Ethyl): CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl). Monitor therapy

Amphetamines: May diminish the sedative effect of Antihistamines. Monitor therapy

Analgesics (Opioid): Anticholinergic Agents may enhance the adverse/toxic effect of Analgesics (Opioid). Specifically, the risk for constipation and urinary retention may be increased with this combination. Monitor therapy

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

Azelastine (Nasal): CNS Depressants may enhance the CNS depressant effect of Azelastine (Nasal). 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. Consider therapy modification

Betahistine: Antihistamines may diminish the therapeutic effect of Betahistine. Monitor therapy

Blonanserin: CNS Depressants may enhance the CNS depressant effect of Blonanserin. Consider therapy modification

Brimonidine (Topical): May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

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 patches (Butrans brand) at 5 mcg/hr in adults when used with other CNS depressants. Consider therapy modification

Cannabis: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

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

CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Monitor therapy

Dimethindene: May enhance the CNS depressant effect of CNS Depressants. 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. Monitor therapy

Dronabinol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Droperidol: May enhance the CNS depressant effect of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (e.g., opioids, barbiturates) with concomitant use. Consider therapy modification

Eluxadoline: Anticholinergic Agents may enhance the constipating effect of Eluxadoline. Avoid combination

Flunitrazepam: CNS Depressants may enhance the CNS depressant effect of Flunitrazepam. Consider therapy modification

Gastrointestinal Agents (Prokinetic): Anticholinergic Agents may diminish the therapeutic effect of Gastrointestinal Agents (Prokinetic). Monitor therapy

Glucagon: Anticholinergic Agents may enhance the adverse/toxic effect of Glucagon. Specifically, the risk of gastrointestinal adverse effects may be increased. Avoid combination

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

Hyaluronidase: Antihistamines may diminish the therapeutic effect of Hyaluronidase. Management: Patients receiving antihistamines (particularly at larger doses) may not experience the desired clinical response to standard doses of hyaluronidase. Larger doses of hyaluronidase may be required. Consider therapy modification

HYDROcodone: CNS Depressants may enhance the CNS depressant effect of HYDROcodone. Management: Consider starting with a 20% to 30% lower hydrocodone dose when using together with any other CNS depressant. Dose reductions in the other CNS depressant may also be warranted. Consider therapy modification

HydrOXYzine: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Ipratropium (Oral Inhalation): May enhance the anticholinergic effect of Anticholinergic Agents. Avoid combination

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

Kava Kava: May enhance the adverse/toxic effect of CNS Depressants. Monitor therapy

Levosulpiride: Anticholinergic Agents may diminish the therapeutic effect of Levosulpiride. Avoid combination

Magnesium Sulfate: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

MAO Inhibitors: May enhance the anticholinergic effect of Cyproheptadine. Cyproheptadine may diminish the serotonergic effect of MAO Inhibitors. Avoid combination

Methotrimeprazine: CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Methotrimeprazine may enhance the CNS depressant effect of CNS Depressants. Management: Reduce adult dose of CNS depressant agents by 50% with initiation of concomitant methotrimeprazine therapy. Further CNS depressant dosage adjustments should be initiated only after clinically effective methotrimeprazine dose is established. Consider therapy modification

MetyroSINE: CNS Depressants may enhance the sedative effect of MetyroSINE. Monitor therapy

Mianserin: May enhance the anticholinergic effect of Anticholinergic Agents. Monitor therapy

Minocycline: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Mirabegron: Anticholinergic Agents may enhance the adverse/toxic effect of Mirabegron. Monitor therapy

Mirtazapine: CNS Depressants may enhance the CNS depressant effect of Mirtazapine. Monitor therapy

Nabilone: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

OnabotulinumtoxinA: Anticholinergic Agents may enhance the anticholinergic effect of OnabotulinumtoxinA. Monitor therapy

Orphenadrine: CNS Depressants may enhance the CNS depressant effect of Orphenadrine. Avoid combination

Oxatomide: May enhance the anticholinergic effect of Anticholinergic Agents. Avoid combination

OxyCODONE: CNS Depressants may enhance the CNS depressant effect of OxyCODONE. Management: When oxycodone is combined with another CNS depressant, a dose reduction of one or both agents should be considered. The extended release oxycodone starting dose should be reduced 50% to 67% when initiated in patients already receiving CNS depressants. Consider therapy modification

Paraldehyde: CNS Depressants may enhance the CNS depressant effect of Paraldehyde. Avoid combination

Perampanel: May enhance the CNS depressant effect of CNS Depressants. Management: Patients taking perampanel with any other drug that has CNS depressant activities should avoid complex and high-risk activities, particularly those such as driving that require alertness and coordination, until they have experience using the combination. Consider therapy modification

Piribedil [INT]: CNS Depressants may enhance the CNS depressant effect of Piribedil [INT]. Monitor therapy

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. Avoid combination

Pramipexole: CNS Depressants may enhance the sedative effect of Pramipexole. Monitor therapy

Pramlintide: May enhance the anticholinergic effect of Anticholinergic Agents. These effects are specific to the GI tract. Consider therapy modification

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

RimabotulinumtoxinB: Anticholinergic Agents may enhance the anticholinergic effect of RimabotulinumtoxinB. Monitor therapy

ROPINIRole: CNS Depressants may enhance the sedative effect of ROPINIRole. Monitor therapy

Rotigotine: CNS Depressants may enhance the sedative effect of Rotigotine. Monitor therapy

Rufinamide: May enhance the adverse/toxic effect of CNS Depressants. Specifically, sleepiness and dizziness may be enhanced. Monitor therapy

Secretin: Anticholinergic Agents may diminish the therapeutic effect of Secretin. Management: Avoid using drugs with substantial anticholinergic effects in patients receiving secretin whenever possible. If such agents must be used in combination, monitor closely for a diminished response to secretin. Consider therapy modification

Selective Serotonin Reuptake Inhibitors: Cyproheptadine may diminish the therapeutic effect of Selective Serotonin Reuptake Inhibitors. Monitor therapy

Sodium Oxybate: May enhance the CNS depressant effect of CNS Depressants. Management: Consider alternatives to combined use. When combined use is needed, consider minimizing doses of one or more drugs. Use of sodium oxybate with alcohol or sedative hypnotics is contraindicated. Consider therapy modification

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. Consider therapy modification

Tapentadol: May enhance the CNS depressant effect of CNS Depressants. Management: Start tapentadol at a dose of one-third to one-half of the normal dose if being initiated in a patient who is taking another drug with CNS depressant effects. Monitor closely for evidence of excessive CNS depression. Consider therapy modification

Tetrahydrocannabinol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Thalidomide: CNS Depressants may enhance the CNS depressant effect of Thalidomide. Avoid combination

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

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

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

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

Umeclidinium: May enhance the anticholinergic effect of Anticholinergic Agents. Avoid combination

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. Consider therapy modification

Test Interactions

Diagnostic antigen skin test results may be suppressed; false positive serum TCA screen (Wians 1993)

Adverse Reactions

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

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.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Special populations:

• Elderly: Antihistamines are more likely to cause dizziness, sedation and hypotension in elderly patients.

• Pediatric: Antihistamines may cause excitation in young children.

Pregnancy Risk Factor

B

Pregnancy Considerations

Adverse events have been observed in some animal reproduction studies. Maternal antihistamine use has generally not resulted in an increased risk of birth defects; however, information specific to cyproheptadine is limited. Antihistamines are recommended for the treatment of rhinitis, urticaria, and pruritus with rash in pregnant women (although second generation antihistamines may be preferred). Antihistamines are not recommended for treatment of pruritus associated with intrahepatic cholestasis in pregnancy.

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience fatigue, headache, blurred vision, constipation, dry mouth, anxiety, nausea, or agitation. Have patient report immediately to prescriber signs of liver problems (dark urine, feeling tired, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or yellow skin or eyes), severe dizziness, passing out, tachycardia, arrhythmia, urinary retention, severe loss of strength and energy, confusion, hallucinations, mood changes, seizures, chills, pharyngitis, insomnia, bruising, or bleeding (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.

Hide