DESCRIPTION

Cyproheptadine HCl is an antihistaminic and antiserotonergic agent.

Cyproheptadine hydrochloride is a white to slightly yellowish, crystalline solid, 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 and structural formula of the anhydrous salt is:

Cyproheptadine HCl is available in tablets for oral administration containing 4 mg of cyproheptadine hydrochloride. Each tablet also contains the following inactive ingredients: dibasic calcium phosphate dihydrate, magnesium stearate, microcrystalline cellulose, polyoxyl (40) stearate, purified water, sodium starch glycolate, and stearic acid.

CLINICAL PHARMACOLOGY

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.

Pharmacokinetics and Metabolism

After a single 4 mg oral dose of 14C-labelled cyproheptadine HCl in normal subjects, given as tablets 2% to 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 principal metabolite found in human urine has been identified as a quaternary ammonium glucuronide conjugate of cyproheptadine. Elimination is diminished in renal insufficiency.

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.

CONTRAINDICATIONS

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 PRECAUTIONS; Drug Interactions)

Angle-closure glaucoma

Stenosing peptic ulcer

Symptomatic prostatic hypertrophy

Bladder neck obstruction

Pyloroduodenal obstruction

Elderly, debilitated patients

WARNINGS

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).

GENERAL PRECAUTIONS

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

ADVERSE REACTIONS

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, hallucination, 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, heptatic 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.

OVERDOSAGE

Antihistamine overdosage reactions may vary from central nervous system depression to stimulation especially in pediatric patients. Also, atropine-like signs and symptoms (dry mouth; fixed, dilated pupils; flushing, etc.) as well as gastrointestinal symptoms may occur.

If vomiting has not occurred spontaneously the patient should be induced to vomit with syrup of ipecac.

If the patient is unable to vomit, perform gastric lavage followed by activated charcoal. Isotonic or ½ isotonic saline is the lavage of choice. Precautions against aspiration must be taken especially in infants and children.

When life threatening CNS signs and symptoms are present, intravenous physostigmine salicylate may be considered. Dosage and frequency of administration are dependent on age, clinical response, and recurrence after response. (See package circulars for physostigmine products.)

Saline cathartics, as milk of magnesia, by osmosis draw water into the bowel and, therefore, are valuable for their action in rapid dilution of bowel content.

Stimulants should not be used.

Vasopressors may be used to treat hypotension.

The oral LD50of cyproheptadine is 123 mg/kg, and 295 mg/kg in the mouse and rat, respectively.

DOSAGE AND ADMINISTRATION

DOSAGE SHOULD BE INDIVIDUALIZED ACCORDING TO THE NEEDS AND THE RESPONSE OF THE PATIENT.

Each Cyproheptadine HCl Tablet contains 4 mg of cyproheptadine hydrochloride.

Pediatric Patients

Age 2 to 6 years

The total daily dosage for pediatric patients may be calculated on the basis of body weight or body area using approximately 0.25 mg/kg/day or 8 mg per square meter of body surface (8 mg/m2).

The usual dose is 2 mg (1/2 tablet) two or three times a day, adjusted as necessry to the size and response of the patient. The dose is not to exceed 12 mg a day.

Age 7 to 14 years

The usual dose is 4 mg (1 tablet) two or three times a day, adjusted as necessary to the size and response of the patient. The dose is not to exceed 16 mg a day.

Adults

The total daily dose for adults should not exceed 0.5 mg/kg/day.

The therapeutic range is 4 mg to 20 mg a day, with the majority of patients requiring 12 mg to 16 mg a day. An occasional patient may require as much as 32 mg a day for adequate relief. It is suggested that dosage be initiated with 4 mg (1 tablet) three times a day and adjusted according to the size and response of the patient.

HOW SUPPLIED

Cyproheptadine Hydrochloride Tablets 4 mg are white, round, scored, compressed tablets, debossed "Par 043" on one side. They are available in bottles of 100 (NDC 49884-043-01) and 1000 (NDC 49884-043-10).

Store at controlled room temperature,15° to 30°C (59° to 86°F), in a well-closed container.

Manufactured by:

PAR PHARMACEUTICAL, INC.

Spring Valley, NY 10977

R04/2008

PRINCIPAL DISLAY PANEL - 4MG 100'S