![CYPROHEPTADINE SYRUP [PHARMACEUTICAL ASSOCIATES, INC.]](https://medic.hrt.org//dailymed/images/e3b94a78-0d41-4618-aca5-b1770f945559/cyproheptadine-01.jpg)
![CYPROHEPTADINE SYRUP [PHARMACEUTICAL ASSOCIATES, INC.]](https://medic.hrt.org//dailymed/images/e3b94a78-0d41-4618-aca5-b1770f945559/cyproheptadine-02.jpg)
![CYPROHEPTADINE SYRUP [PHARMACEUTICAL ASSOCIATES, INC.]](https://medic.hrt.org//dailymed/images/e3b94a78-0d41-4618-aca5-b1770f945559/cyproheptadine-03.jpg)
| NDC | 0121-0788-16, 0121-4788-05, 0121-4788-10 |
| Set ID | e3b94a78-0d41-4618-aca5-b1770f945559 |
| Category | HUMAN PRESCRIPTION DRUG LABEL |
| Packager | Pharmaceutical Associates, Inc. |
| Generic Name | |
| Product Class | |
| Product Number | |
| Application Number | ANDA091295 |
- SPL UNCLASSIFIED SECTION
-
DESCRIPTION
Each 5 mL (one teaspoonful) contains: Cyproheptadine hydrochloride 2 mg. Alcohol 5%.
Inactive ingredients: citric acid, D&C Yellow No.10, peppermint flavor, purified water, sodium benzoate, sodium citrate and sucrose.
Cyproheptadine hydrochloride is an antihistaminic and antiserotonergic agent. Cyproheptadine hydrochloride is a white to slightly yellowish, crystalline solid, with a molecular weight of 350.88, which is slightly 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:
-
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-labeled cyproheptadine HCl in normal subjects, given as tablets or oral solution, 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 of cyproheptadine oral solution. 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
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
-
WARNINGS
Children
Overdosage of antihistamines, particularly in infants and children, may produce hallucinations, central nervous system depression, convulsions and death.
Antihistamines may diminish mental alertness; conversely, particularly in the young child, they may occasionally produce excitation.
-
PRECAUTIONS
General
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
Information for Patients
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.
Drug Interactions
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, anti-anxiety agents.
Carcinogenesis, Mutagenesis, Impairment of Fertility
Long-term carcinogenic studies have not been done with cyproheptadine.
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.
Pregnancy
Pregnancy Category B
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.
Nursing Mothers
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 CONTRAINDICATIONS).
Pediatric Use
Safety and effectiveness in pediatric patients below the age of two years have not been established. (see CONTRAINDICATIONS, Newborn or Premature Infants, and WARNINGS, Children).
-
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, 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: 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 children. 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 1/2 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 LD50 of 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.
Although intended primarily for administration to children, the oral solution is also used for administration to adults who cannot swallow tablets.
Children
The total daily dosage for children may be calculated on the basis of body weight or body area using approximately 0.25 mg/kg/day (0.11 mg/lb/day) or 8 mg per square meter of body surface (8 mg/m2).
Adults
The total daily dose for adults should not exceed 0.5 mg/kg/day (0.23 mg/lb/day). The therapeutic range is 4 to 20 mg a day, with the majority of patients requiring 12 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 (two teaspoonfuls) three times a day and adjusted according to the size and response of the patient.
-
HOW SUPPLIED
Cyproheptadine Hydrochloride Syrup (Cyproheptadine Hydrochloride Oral Solution, USP) (2 mg/5 mL), a pale yellow, peppermint flavored liquid, is available in the following oral dosage forms:
NDC 0121-0788-16 – Bottles of 16 fl oz (473 mL)
NDC 0121-4788-05 – 5 mL Unit Dose Cups, 10 cups per tray
NDC 0121-4788-10 – 10 mL Unit Dose Cups, 10 cups per tray
- SPL UNCLASSIFIED SECTION
- PRINCIPAL DISPLAY PANEL - 473 mL Bottle Label
-
PRINCIPAL DISPLAY PANEL - 5 mL Cup Label
Delivers 5 mL
NDC 0121-4788-05CYPROHEPTADINE HYDROCHLORIDE
SYRUP
(Cyproheptadine Hydrochloride Oral Solution,USP)2 mg/5 mL
CONTAINS ALCOHOL 5%
FOR INSTITUTIONAL USE ONLYUsual Dosage: See Package Insert for
Complete Dosage Recommendations.Rx ONLY
PHARMACEUTICAL ASSOCIATES, INC.
GREENVILLE, SC 29605A47880500
-
INGREDIENTS AND APPEARANCE
CYPROHEPTADINE
cyproheptadine syrupProduct Information Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:0121-0788 Route of Administration ORAL Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength CYPROHEPTADINE (UNII: 2YHB6175DO) (CYPROHEPTADINE - UNII:2YHB6175DO) CYPROHEPTADINE 2 mg in 5 mL Inactive Ingredients Ingredient Name Strength ALCOHOL (UNII: 3K9958V90M) CITRIC ACID MONOHYDRATE (UNII: 2968PHW8QP) D&C YELLOW NO. 10 (UNII: 35SW5USQ3G) WATER (UNII: 059QF0KO0R) SODIUM BENZOATE (UNII: OJ245FE5EU) SODIUM CITRATE (UNII: 1Q73Q2JULR) SUCROSE (UNII: C151H8M554) Product Characteristics Color YELLOW (PALE) Score Shape Size Flavor PEPPERMINT Imprint Code Contains Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:0121-0788-16 473 mL in 1 BOTTLE Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANDA ANDA091295 07/29/2013 CYPROHEPTADINE
cyproheptadine syrupProduct Information Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:0121-4788 Route of Administration ORAL Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength CYPROHEPTADINE (UNII: 2YHB6175DO) (CYPROHEPTADINE - UNII:2YHB6175DO) CYPROHEPTADINE 2 mg in 5 mL Inactive Ingredients Ingredient Name Strength ALCOHOL (UNII: 3K9958V90M) CITRIC ACID MONOHYDRATE (UNII: 2968PHW8QP) D&C YELLOW NO. 10 (UNII: 35SW5USQ3G) WATER (UNII: 059QF0KO0R) SODIUM BENZOATE (UNII: OJ245FE5EU) SODIUM CITRATE (UNII: 1Q73Q2JULR) SUCROSE (UNII: C151H8M554) Product Characteristics Color YELLOW (PALE) Score Shape Size Flavor PEPPERMINT Imprint Code Contains Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:0121-4788-05 4 in 1 CASE 1 10 in 1 TRAY 1 5 mL in 1 CUP, UNIT-DOSE 2 NDC:0121-4788-10 4 in 1 CASE 2 10 in 1 TRAY 2 10 mL in 1 CUP, UNIT-DOSE Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANDA ANDA091295 07/29/2013 Labeler - Pharmaceutical Associates, Inc. (044940096) Establishment Name Address ID/FEI Business Operations Pharmaceutical Associates, Inc. 097630693 MANUFACTURE(0121-0788, 0121-4788)
