Cyproheptadine hydrochloride

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# Overview
Cyproheptadine hydrochloride is an antihistamine that is FDA approved for the treatment of allergic conjunctivitis, perennial and seasonal allergic rhinitis, dermatographic urticaria, hypersensitivity reaction, to blood or plasma; or mild allergic skin manifestations, urticaria due to cold and vasomotor rhinitis..   Common adverse reactions include weight gain, xerostomia, central nervous system depression and somnolence.

# Adult Indications and Dosage

## FDA-Labeled Indications and Dosage (Adult)

### Indications
- 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

### Dosage
- The total daily dose for adults should not exceed 0.5 mg/kg/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 (1 tablet) three times a day and adjusted according to the size and response of the patient.

## Off-Label Use and Dosage (Adult)

### Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Cyproheptadine hydrochloride in adult patients.

### NonGuideline-Supported Use
- Loss of appetite
- Migraine
- Pruritus
- Schizophrenia
- Spasticity - Spinal cord injury

# Pediatric Indications and Dosage

## FDA-Labeled Indications and Dosage (Pediatric)

### 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 necessary 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.

## Off-Label Use and Dosage (Pediatric)

### Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Cyproheptadine hydrochloride in pediatric patients.

### NonGuideline-Supported Use
There is limited information regarding Off-Label NonGuideline-Supported Use of Cyproheptadine hydrochloride in pediatric patients.

# 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
- 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.

# Adverse Reactions

## Clinical Trials Experience
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

## Postmarketing Experience
There is limited information regarding Cyproheptadine hydrochloride Postmarketing Experience in the drug label.

# 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, antianxiety agents.

# Use in Specific Populations

### Pregnancy
Pregnancy Category (FDA): 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.
Pregnancy Category (AUS): A
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Cyproheptadine hydrochloride in women who are pregnant.

### Labor and Delivery
There is no FDA guidance on use of Cyproheptadine hydrochloride during labor and delivery.

### 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

### Pediatric Use
Safety and effectiveness in pediatric patients below the age of two have not been established.

### Geriatic Use
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.

### Gender
There is no FDA guidance on the use of Cyproheptadine hydrochloride with respect to specific gender populations.

### Race
There is no FDA guidance on the use of Cyproheptadine hydrochloride with respect to specific racial populations.

### Renal Impairment
There is no FDA guidance on the use of Cyproheptadine hydrochloride in patients with renal impairment.

### Hepatic Impairment
There is no FDA guidance on the use of Cyproheptadine hydrochloride in patients with hepatic impairment.

### Females of Reproductive Potential and Males
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.

### Immunocompromised Patients
There is no FDA guidance one the use of Cyproheptadine hydrochloride in patients who are immunocompromised.

# Administration and Monitoring

### Administration
Oral

### Monitoring
There is limited information regarding Cyproheptadine hydrochloride Monitoring in the drug label.

# IV Compatibility
There is limited information regarding the compatibility of Cyproheptadine hydrochloride and IV administrations.

# 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, mydriasis; 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 patient is unable to vomit, perform gastric lavage followed by activated charcoal. Isotonic or 12 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.
- 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.

# Pharmacology

## Mechanism of Action
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.

## Structure
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-dibenzocyclohepten-5-ylidene)-1-methylpiperidine hydrochloride. The molecular formula of the anhydrous salt is C21H21NHCl and the structural formula of the anhydrous salt is:

## Pharmacodynamics
There is limited information regarding Cyproheptadine hydrochloride Pharmacodynamics in the drug label.

## Pharmacokinetics
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.

## Nonclinical Toxicology
Long-term carcinogenic studies have not been done with cyproheptadine.
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.

# Clinical Studies
There is limited information regarding Cyproheptadine hydrochloride Clinical Studies in the drug label.

# How Supplied
- 4 mg of Cyproheptadine HCl packaged in bottles of 100 tablets
- NDC 51991-838-01
- 4 mg of Cyproheptadine HCl packaged in bottles of 1000 tablets
- NDC 51991-838-10.

## Storage
Store at 20 - 25C (68 - 77F)

# Images

## Drug Images

## Package and Label Display Panel

# Patient Counseling Information
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

# Precautions with Alcohol
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.

# Brand Names
- Periactin 

# Look-Alike Drug Names
There is limited information regarding Cyproheptadine hydrochloride Look-Alike Drug Names in the drug label.

# Drug Shortage Status

# Price