Cyproheptadine

Cyproheptadine is available in the following forms:

• Oral Solution
• Oral Tablet

Adverse reactions which have been reported with the use of antihistamines are as follows:

Central Nervous System

Sedation and sleepiness (often transient), dizziness, disturbed coordination, confusion, restlessness, excitation, nervousness, tremor, irritability, insomnia, paresthesias, neuritis, convulsions, euphoria, hallucinations, hysteria, faintness.

Integumentary

Allergic manifestation of rash and edema, excessive perspiration, urticaria, photosensitivity.

Special Senses

Acute labyrinthitis, blurred vision, diplopia, vertigo, tinnitus.

Cardiovascular

Hypotension, palpitation, tachycardia, extrasystoles, anaphylactic shock.

Hematologic

Hemolytic anemia, leukopenia, agranulocytosis, thrombocytopenia.

Digestive System

Cholestasis, hepatic failure, hepatitis, hepatic function abnormality, dryness of mouth, epigastric distress, anorexia, nausea, vomiting, diarrhea, constipation, jaundice.

Genitourinary

Urinary frequency, difficult urination, urinary retention, early menses.

Respiratory

Dryness of nose and throat, thickening of bronchial secretions, tightness of chest and wheezing, nasal stuffiness.

Miscellaneous

Fatigue, chills, headache, increased appetite/weight gain.

Read the entire FDA prescribing information for Cyproheptadine (Cyproheptadine Hydrochloride)

Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Stop using cyproheptadine and call your doctor at once if you have:

• a light-headed feeling, like you might pass out;

• tremor, seizure (convulsions);

• confusion, hallucinations;

• little or no urination;

• fast or pounding heartbeats;

• easy bruising or bleeding;

• ringing in your ears; or

• pale or yellowed skin, dark colored urine, fever, weakness.

Common side effects may include:

• drowsiness, dizziness;

• dry mouth, nose, or throat;

• constipation;

• blurred vision; or

• feeling restless or excited (especially in children).

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Cyproheptadine HCl, USP is an antihistaminic and antiserotonergic agent. Cyproheptadine hydrochloride, USP is a white to slightly yellowish crystalline solid, with a molecular weight of 350.89, which is soluble in water, freely soluble in methanol, sparingly soluble in ethanol, soluble in chloroform, and practically insoluble in ether. It is the sesquihydrate of 4-(5H-dibenzo[a,d] cyclohepten-5-ylidene)-1-methylpiperidine hydrochloride. The molecular formula of the anhydrous salt is C21H21N•HCl and the structural formula of the anhydrous salt is:

C21H21N•HCl M.W. 350.89

Cyproheptadine hydrochloride, USP is available for oral administration in 4 mg tablets. Inactive ingredients include: lactose monohydrate, magnesium stearate, microcrystalline cellulose, and pregelatinized starch.

Newborn or Premature Infants

This drug should not be used in newborn or premature infants.

Nursing Mothers

Because of the higher risk of antihistamines for infants generally and for newborns and prematures in particular, antihistamine therapy is contraindicated in nursing mothers.

Other Conditions

Hypersensitivity to Cyproheptadine and other drugs of similar chemical structure.

Monoamine oxidase inhibitor therapy (See DRUG INTERACTIONS.)

Angle-closure glaucoma

Stenosing peptic ulcer

Symptomatic prostatic hypertrophy

Bladder neck obstruction

Pyloroduodenal obstruction

Elderly, debilitated patients

Pediatric Patients

Overdosage of antihistamines, particularly in infants and young children, may produce hallucinations, central nervous system depression, convulsions, respiratory and cardiac arrest, and death.

Antihistamines may diminish mental alertness; conversely, particularly, in the young child, they may occasionally produce excitation.

CNS Depressants

Antihistamines may have additive effects with alcohol and other CNS depressants, e.g., hypnotics, sedatives, tranquilizers, antianxiety agents.

Activities Requiring Mental Alertness

Patients should be warned about engaging in activities requiring mental alertness and motor coordination, such as driving a car or operating machinery.

Antihistamines are more likely to cause dizziness, sedation, and hypotension in elderly patients (see PRECAUTIONS, Geriatric Use).

Adverse reactions which have been reported with the use of antihistamines are as follows:

Central Nervous System

Sedation and sleepiness (often transient), dizziness, disturbed coordination, confusion, restlessness, excitation, nervousness, tremor, irritability, insomnia, paresthesias, neuritis, convulsions, euphoria, hallucinations, hysteria, faintness.

Integumentary

Allergic manifestation of rash and edema, excessive perspiration, urticaria, photosensitivity.

Special Senses

Acute labyrinthitis, blurred vision, diplopia, vertigo, tinnitus.

Cardiovascular

Hypotension, palpitation, tachycardia, extrasystoles, anaphylactic shock.

Hematologic

Hemolytic anemia, leukopenia, agranulocytosis, thrombocytopenia.

Digestive System

Cholestasis, hepatic failure, hepatitis, hepatic function abnormality, dryness of mouth, epigastric distress, anorexia, nausea, vomiting, diarrhea, constipation, jaundice.

Genitourinary

Urinary frequency, difficult urination, urinary retention, early menses.

Respiratory

Dryness of nose and throat, thickening of bronchial secretions, tightness of chest and wheezing, nasal stuffiness.

Miscellaneous

Fatigue, chills, headache, increased appetite/weight gain.

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

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)

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 (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)

Initial dose: 4 mg orally three times a day
Maintenance dose: 12 to 16 mg/day, occasionally up to 32 mg/day but not to exceed 0.5 mg/kg/day

4 to 8 mg orally three times a day

Summary of Use during Lactation

Unless it is intentionally being used to lower maternal serum prolactin levels, cyproheptadine should be avoided during lactation because it may interfere with lactation, particularly in combination with a sympathomimetic such as pseudoephedrine or before lactation is well established. The nonsedating antihistamines are preferred alternatives.

Drug Levels

Maternal Levels. Relevant published information was not found as of the revision date.

Infant Levels. Relevant published information was not found as of the revision date.

Effects in Breastfed Infants

Relevant published information on cyproheptadine was not found as of the revision date. In one telephone follow-up study, mothers reported irritability and colicky symptoms in 10% of infants exposed to various antihistamines and drowsiness was reported in 1.6% of infants. None of the reactions required medical attention and none of the infants were exposed to cyproheptadine.[1]

Effects on Lactation and Breastmilk

Cyproheptadine 16 to 24 mg daily lowers serum prolactin in the treatment of amenorrhea-galactorrhea syndrome because of its antiserotonin activity.[2] Additionally, antihistamines in relatively high doses given by injection can decrease basal serum prolactin in nonlactating women and in early postpartum women.[3][4] However, suckling-induced prolactin secretion is not affected by antihistamine pretreatment of postpartum mothers.[3] Whether lower oral doses of cyproheptadine have the same effect on serum prolactin or whether the effects on prolactin have any consequences on breastfeeding success have not been studied. It is possible that these effects would interfere with initiation of lactation, but the prolactin level in a mother with established lactation may not affect her ability to breastfeed.

Alternate Drugs to Consider

Desloratadine, Fexofenadine, Loratadine

References

1. Ito S, Blajchman A, Stephenson M et al. Prospective follow-up of adverse reactions in breast-fed infants exposed to maternal medication. Am J Obstet Gynecol. 1993;168:1393-9. PMID: 8498418

2. Wortsman J, Soler NG, Hirschowitz J. Cyproheptadine in the management of the galactorrhea-amenorrhea syndrome. Ann Intern Med. 1979;90:923-5. PMID: 571691

3. Messinis IE, Souvatzoglou A, Fais N et al. Histamine H1 receptor participation in the control of prolactin secretion in postpartum. J Endocrinol Invest. 1985;8:143-6. PMID: 3928731

4. Pontiroli AE, De Castro e Silva E, Mazzoleni F et al. The effect of histamine and H1 and H2 receptors on prolactin and luteinizing hormone release in humans: sex differences and the role of stress. J Clin Endocrinol Metab. 1981;52:924-8. PMID: 7228996

Substance Name

Cyproheptadine

CAS Registry Number

129-03-3

Drug Class

Antihistamines