CYPROHEPTADINE HYDROCHLORIDE — cyproheptadine hydrochloride tablet
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Cyproheptadine HCl, is an antihistaminic and antiserotonergic agent. Cyproheptadine hydrochloride 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:
Cyproheptadine hydrochloride is available for oral administration in 4 mg tablets. Inactive ingredients include: lactose monohydrate, magnesium stearate, microcrystalline cellulose, and sodium starch glycolate.
Cyproheptadine is a serotonin and histamine antagonist with anticholinergic and sedative effects. Antiserotonin and antihistamine drugs appear to compete with serotonin and histamine, respectively, for receptor sites.
After a single 4 mg oral dose of 14C-labelled Cyproheptadine HCl in normal subjects, given as tablets, 2-20% of the radioactivity was excreted in the stools. Only about 34% of the stool radioactivity was unchanged drug, corresponding to less than 5.7% of the dose. At least 40% of the administered radioactivity was excreted in the urine. No detectable amounts of unchanged drug were present in the urine of patients on chronic 12-20 mg daily doses. The principle metabolite found in human urine has been identified as a quaternary ammonium glucuronide conjugate of cyproheptadine. Elimination is diminished in renal insufficiency.
Pharmacokinetics and Metabolism:
CYPROHEPTADINE HYDROCHLORIDE Indications and Usage
Perennial and seasonal allergic rhinitis Vasomotor rhinitis Allergic conjunctivitis due to inhalant allergens and foods Mild, uncomplicated allergic skin manifestations of urticaria and angioedema Amelioration of allergic reactions to blood or plasma Cold urticaria Dermatographism
As therapy for anaphylactic reactions adjunctive to epinephrine and other standard measures after the acute manifestations have been controlled.
This drug should not be used in newborn or premature infants.
Newborn or Premature Infants:
Because of the higher risk of antihistamines for infants generally and for newborns and prematures in particular, antihistamine therapy is contraindicated in nursing mothers.
Hypersensitivity to cyproheptadine and other drugs of similar chemical structure. Monoamine oxidase inhibitor therapy (see .) Angle-closure glaucoma Stenosing peptic ulcer Symptomatic prostatic hypertrophy Bladder neck obstruction Pyloroduodenal obstruction Elderly, debilitated patients
Overdosage of antihistamines, particularly in infants and young children, may producehallucinations, 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.
Antihistamines may have additive effects with alcohol and other CNS depressants, e.g., hypnotics, sedatives, tranquilizers, antianxiety agents.
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 ). Activities Requiring Mental Alertness: PRECAUTIONS, Geriatric Use
Cyproheptadine has an atropine-like action and, therefore, should be used with caution in patients with: History of bronchial asthma Increased intraocular pressure Hyperthyroidism Cardiovascular disease Hypertension
Antihistamines may diminish mental alertness; conversely, particularly, in the young child, they may occasionally produce excitation. Patients should be warned about engaging in activities requiring mental alertness and motor coordination, such as driving a car or operating machinery.
Information for Patients:
MAO inhibitors prolong and intensify the anticholinergic effects of antihistamines. Antihistamines may have additive effects with alcohol and other CNS depressants, e.g., hypnotics, sedatives, tranquilizers, antianxiety agents.
Long-term carcinogenic studies have not been done with cyproheptadine.
Carcinogenesis, Mutagenesis, Impairment of Fertility:
Cyproheptadine had no effect on fertility in a two-litter study in rats or a two generation study in mice at about 10 times the human dose.
Cyproheptadine did not produce chromosome damage in human lymphocytes or fibroblasts in vitro; high doses (10-4M) were cytotoxic. Cyproheptadine did not have any mutagenic effect in the Ames microbial mutagen test; concentrations of above 500 mcg/plate inhibited bacterial growth.
Reproduction studies have been performed in rabbits, mice, and rats at oral or subcutaneous doses up to 32 times the maximum recommended human oral dose and have revealed no evidence of impaired fertility or harm to the fetus due to cyproheptadine. Cyproheptadine has been shown to be fetotoxic in rats when given by intraperitoneal injection in doses four times the maximum recommended human oral dose. Two studies in pregnant women, however, have not shown that cyproheptadine increases the risk of abnormalities when administered during the first, second and third trimesters of pregnancy. No teratogenic effects were observed in any of the newborns. Nevertheless, because the studies in humans cannot rule out the possibility of harm, cyproheptadine should be used during pregnancy only if clearly needed.
Pregnancy Category B:
It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, and because of the potential for serious adverse reactions in nursing infants from cyproheptadine, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother (see ).
Nursing Mothers: CONTRAINDICATIONS
Safety and effectiveness in pediatric patients below the age of two have not been established. (see , and ).
Pediatric Use: CONTRAINDICATIONS, Newborn or Premature Infants WARNINGS, Pediatric Patients
Clinical studies of Cyproheptadine HCl tablets did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy (see ).
Geriatric Use: WARNINGS, Activities Requiring Mental Alertness
Adverse reactions which have been reported with the use of antihistamines are as follows:
Sedation and sleepiness (often transient), dizziness, disturbed coordination, confusion, restlessness, excitation, nervousness, tremor, irritability, insomnia, paresthesias, neuritis, convulsions, euphoria, hallucinations, hysteria, faintness.
Central Nervous System:
Allergic manifestation of rash and edema, excessive perspiration, urticaria, photosensitivity.
Acute labyrinthitis, blurred vision, diplopia, vertigo, tinnitus.
Hypotension, palpitation, tachycardia, extrasystoles, anaphylactic shock.
Hemolytic anemia, leukopenia, agranulocytosis, thrombocytopenia.
Cholestasis, hepatic failure, hepatitis, hepatic function abnormality, dryness of mouth, epigastric distress, anorexia, nausea, vomiting, diarrhea, constipation, jaundice.
Urinary frequency, difficult urination, urinary retention, early menses.
Dryness of nose and throat, thickening of bronchial secretions, tightness of chest and wheezing, nasal stuffiness.
Fatigue, chills, headache, increased appetite/weight gain. Miscellaneous:
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