Cyproheptadine

287.406

287.40

204-928-9

2YHB6175DO

DTXSID8022872

CRYSTALS FROM DIL ETHANOL

R - Respiratory system

29143900

3.2

4.7

Solid

0.9917 (rough estimate)

112.3-113.3 °C

419.7°C (rough estimate)

194.5ºC

1.8240 (estimate)

H2O: soluble

Store below 40 deg C (104 deg F), preferably between 15 and 30 deg C (59 and 86 deg F), unless otherwise specified by manufacturer. Store in a well-closed container.

6.03E-08mmHg at 25°C

LD50 orl-rat: 295 mg/kg 27ZQAG -,69,72

CRYSTALS FROM ABSOLUTE ETHANOL + ETHER. UV MAX (0.1 N H2SO4): 224,285 NM (E AT 1 CM AND 1%= 1,656,355) /HCL/

I; II; III

RELATIVELY STABLE IN LIGHT, STABLE @ ROOM TEMP. /HCL/

SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.

Manufacturers, packers, and distributors of drug and drug products for human use are responsible for complying with the labeling, certification, and usage requirements as prescribed by the Federal Food, Drug, and Cosmetic Act, as amended (secs 201-902, 52 Stat. 1040 et seq., as amended; 21 U.S.C. 321-392).

Kaliner MA; am Fam Physician 45 (3): 1337-42 (1992). Nonsedating antihistamines: pharmacology, clinical efficacy and adverse effects.

Unlike most first generation antihistamines, cyproheptadine has been associated with several instances of clinically apparent liver injury. The few cases that have been described had a time to onset of 1 to 6 weeks and a cholestatic or mixed pattern of liver enzyme elevations. Immunoallergic and autoimmune features were not present and most patients recovered rapidly without residual. Acute liver failure due to cyproheptadine has not been described.

Concurrent use may potentiate the CNS depressant effects of either these medications /alcohol or other CNS depression-producing medications/ or antihistamines; also, concurrent use of maprotiline or tricyclic antidepressants may potentiate the anticholinergic effects of either antihistamines or these medications. /Antihistamines/|Anticholinergic effects may be potentiated when these medications /anticholinergics or other medications with anticholinergic activity/ are used concurrently with antihistamines; patients should be advised to report occurrence of gastrointestinal problems promptly since paralytic ileus may occur with concurrent therapy. /Antihistamines/|Concurrent use of monoamine oxidase (MAO) inhibitors with antihistamines may prolong the intensify the anticholinergic and CNS depressant effects of antihistamines; concurrent use is not recommended. /Antihistamines/|Concurrent use /of ototoxic medications/ with antihistamines may mask the symptoms of ototoxicity such as tinnitus, dizziness, or vertigo. /Antihistamines/|For more Interactions (Complete) data for CYPROHEPTADINE (12 total), please visit the HSDB record page.

96 to 99%

For treatment of 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, and as therapy for anaphylactic reactions adjunctive to epinephrine.

Cyproheptadine is a first generation antihistamine used in the treatment of allergic rhinitis and urticaria and as an appetite stimulant. Cyproheptadine has been linked to rare instances of clinically apparent liver injury.

Antihistamines

Anti-Allergic Agents; Antipruritics; Gastrointestinal Agents; Histamine H1 Antagonists; Serotonin Antagonists|IT IS EFFECTIVE FOR...PREVENTION OF REACTIONS TO BLOOD OR PLASMA IN PT WITH KNOWN HISTORY OF SUCH REACTIONS, DERMOGRAPHISM, & AS THERAPY FOR ANAPHYLACTIC REACTIONS ADJUNCTIVE TO EPINEPHRINE & OTHER STANDARD MEASURES AFTER ACUTE MANIFESTATIONS HAVE BEEN CONTROLLED. /HCL/|IT IS PROBABLY EFFECTIVE IN MILD, LOCAL REACTIONS TO INSECT BITES, PHYSICAL ALLERGY, & MINOR DRUG & SERUM REACTIONS CHARACTERIZED BY PRURITUS. IT IS POSSIBLY EFFECTIVE IN PRURITUS OF...CONTACT DERMATITIS & PRURITUS OF CHICKEN POX. /HCL/|CYPROHEPTADINE...HAS BEEN REPORTED TO BE EFFECTIVE IN SOME PATIENTS /IN THE PROPHYLAXIS OF MIGRAINE/, BUT RESULTS OF CONTROLLED STUDIES HAVE DEMONSTRATED THAT IT IS ONLY SLIGHTLY BETTER THAN A PLACEBO.|For more Therapeutic Uses (Complete) data for CYPROHEPTADINE (16 total), please visit the HSDB record page.

PERSONS TAKING ANTIHISTAMINES SHOULD BE ALERTED TO THEIR SEDATIVE EFFECTS & SHOULD BE CAUTIONED NOT TO DRIVE AN AUTOMOBILE, FLY AN AIRPLANE, OR OPERATE HAZARDOUS MACHINERY WHILE ON SUCH MEDICATION. /ANTIHISTAMINES/|Potential Adverse Effects On Fetus: No problems in animal studies. Controlled studies not done in humans. Potential Side Effects On Breast-Fed Infant: Not known if secreted. FDA Category: B (B = Studies in laboratory animals have not demonstrated a fetal risk, but there are no controlled studies in pregnant women; or animal studies have shown an adverse effect (other than a decrease in fertility), but controlled studies in pregnant women have not demonstrated a risk to the fetus in the first trimester and there is no evidence of a risk in later trimesters.) /from Table II/|Side effects of cyproheptadine include those common to other H1 antagonist, such as drowsiness. Weight gain and increased growth in children have been observed and been attributed to an interference with regulation of the secretion growth hormone.|Small amounts of antihistamines are distributed into breast milk; use is not recommended in nursing mothers because of the risk of adverse effects, such as unusual excitement or irritability, in infants. /Antihistamines/|For more Drug Warnings (Complete) data for CYPROHEPTADINE (8 total), please visit the HSDB record page.

Cyproheptadine is a piperidine antihistamine. Unlike other antihistamines, this drug also antagonizes serotonin receptors. This action makes Cyproheptadine useful in conditions such as vascular headache and anorexia. Cyproheptadine does not prevent the release of histamine but rather competes with free histamine for binding at HA-receptor sites. Cyproheptadine competitively antagonizes the effects of histamine on HA-receptors in the GI tract, uterus, large blood vessels, and bronchial smooth muscle. Most antihistamines possess significant anticholinergic properties, but Cyproheptadine exerts only weak anticholinergic actions. Blockade of central muscarinic receptors appears to account for Cyproheptadine's antiemetic effects, although the exact mechanism is unknown. Cyproheptadine also competes with serotonin at receptor sites in smooth muscle in the intestines and other locations. Antagonism of serotonin on the appetite center of the hypothalamus may account for Cyproheptadine's ability to stimulate appetite. Cyproheptadine also has been used to counter vascular headaches, which many believe are caused by changes in serotonin activity, however it is unclear how Cyproheptadine exerts a beneficial effect on this condition.

Agents, usually topical, that relieve itching (pruritus). (See all compounds classified as Antipruritics.)|Drugs that bind to but do not activate serotonin receptors, thereby blocking the actions of serotonin or SEROTONIN RECEPTOR AGONISTS. (See all compounds classified as Serotonin Antagonists.)|Agents that are used to treat allergic reactions. Most of these drugs act by preventing the release of inflammatory mediators or inhibiting the actions of released mediators on their target cells. (From AMA Drug Evaluations Annual, 1994, p475) (See all compounds classified as Anti-Allergic Agents.)|Drugs used for their effects on the gastrointestinal system, as to control gastric acidity, regulate gastrointestinal motility and water flow, and improve digestion. (See all compounds classified as Gastrointestinal Agents.)|Drugs that selectively bind to but do not activate histamine H1 receptors, thereby blocking the actions of endogenous histamine. Included here are the classical antihistaminics that antagonize or prevent the action of histamine mainly in immediate hypersensitivity. They act in the bronchi, capillaries, and some other smooth muscles, and are used to prevent or allay motion sickness, seasonal rhinitis, and allergic dermatitis and to induce somnolence. The effects of blocking central nervous system H1 receptors are not as well understood. (See all compounds classified as Histamine H1 Antagonists.)

Well absorbed after oral administration.|After a single 4 mg oral dose of14C-labelled cyproheptadine HCl in normal subjects, given as tablets 2% to 20% of the radioactivity was excreted in the stools. At least 40% of the administered radioactivity was excreted in the urine.|H1 antagonists are eliminated more rapidly by children than by adults and more slowly in those with severe liver disease. /H1 Receptor Antagonists/|The H1 antagonists are well absorbed from the gastrointestinal tract. Following oral administration, peak plasma concentrations are achieved in 2 to 3 hours ... . /H1 Receptor Antagonists/|To investigate the pharmacokinetics of cyproheptadine (CPH) and its metabolites, the plasma concn and urinary excretion of CPH and its detectable metabolites were determined after iv admin of parent or synthesized metabolites to rats. The plasma CPH concn time course was subjected to biexponential calculation following the iv admin of CPH, producing the temporal and low plasma concn of desmethylcyproheptadine (DMCPH) and the sustained plasma concn of desmethylcyproheptadine epoxide (DMCPHepo). DMCPH was also eliminated according to the biexponential equation, after iv admin of performed DMCPH, forming DMCPHepo in plasma. On the other hand, no detectable DMCPHepo was found in plasma after the iv admin of cyproheptadine epoxide (CPHepo). All cmpd administered had large distribution volumes and were most entirely excreted as DMCPHepo in urine; this excretion continued for a long time. However, the urinary excretion pattern of DMCPHepo after CPHepo was different from those after CPH and MCPH. The mean residence times of the epoxidized metabolites estimated from the urinary data were much longer than those from the plasma concn data, suggesting either a gradual reflux of the metabolites from a tissue depot into systemic circulation under those plasma concn close of detection limit, or one interaction which delays excretion into the urine. This study suggests that both metabolic pathways of CPH, through DMCPH nd CPHepo, to DMCPHepo are possible, but that the demethylation largely occurs prior to epoxidation; also that the extensive and persistent distribution of DMCPHepo to tissues may relate to the toxicity of CPH reported in rats.|Twelve diphenhydramine and cyproheptadine derivatives were synthesized and screened for Hl-receptor antagonist activity at the isolated guinea pig ileum and for H2-receptor antagonist activity at the isolated guinea pig right atrium. The cmpd showed high Hl- and H2-receptor antagonist activity. The incorporation of the diphenhydramine and cyproheptadine components provided high affinity to Hl-receptors. All compounds elicited a dual mode of competitive and noncompetitive antagonism. The nitroethenediamines with 4-fluoro-4-methyl-substituted diphenhydramine as the Hl-receptor antagonist moiety displayed the most potent Hl- and H2-receptor antagonist effects.|The blood brain barrier transport system for Hl-antagonists was studied using primary cultured bovine brain capillary endothelial cells to study the effects of five H1-antagonists (azelastine, ketotifen, cyproheptadine, emedastine, and cetirizine) on the uptake of radiolabeled mepyramine (pyrilamine). The uptake of mepyramine was inhibited by various H1-antagonists. Ketotifen competitively inhibited mepyramine uptake, and lipophilic basic drugs significantly inhibited mepyramine uptake. The results indicated that H1-antagonists are transported across the blood brain barrier via a carrier mediated transport system common to lipophilic basic drugs.

Hepatic (cytochrome P-450 system) and some renal.|In humans, the metabolism of a number of tertiary amine containing pharmacological agents to quaternary ammonium linked glucuronides, catalyzed by UDP-glucuronosyltransferase (UGT), represents a unique and important metabolic pathway for these compounds. A full length cDNA encoding human UGTl.4 (the so-called minor human bilirubin UGT) was inserted into the expression vector pREP9 and transfected into human embryonic kidney 293 cells, and stable transfectants were obtained after geneticin selection. As expected, the expressed protein had low catalytic activity toward bilirubin. However, expressed human UGTl.4 protein exhibited glucuronidation activity toward tertiary amine substrates, such as imipramine, cyproheptadine, tripelennamine, and chlorpromazine, which form quaternary ammonium linked glucuronides. Carcinogenic primary amines (beta-naphthylamine, benzidine, and 4-aminobiphenyl) also reacted with the expressed UGTl.4 protein at rates approximately 10-fold higher than the rates for quaternary ammonium glucuronide formation. Although a number of other UGT gene products are capable of catalyzing the glucuronidation of primary amine substrates, expressed human UGTl.4 protein is the only UGT isoform that has been shown to conjugate tertiary amine substrates, forming quaternary ammonium linked glucuronides.|Cyproheptadine has known human metabolites that include Cyproheptadine N-glucuronide.

Cyproheptadine competes with free histamine for binding at HA-receptor sites. This antagonizes the effects of histamine on HA-receptors, leading to a reduction of the negative symptoms brought on by histamine HA-receptor binding. Cyproheptadine also competes with serotonin at receptor sites in smooth muscle in the intestines and other locations. Antagonism of serotonin on the appetite center of the hypothalamus may account for Cyproheptadine's ability to stimulate appetite.|CYPROHEPTADINE...IS A SEROTONIN & HISTAMINE ANTAGONIST...|... It is an effective H1 blocker. Cyproheptadine also has prominent 5-H blocking activity on smooth muscle by virtue of its binding to 5-HT2A receptors. ... It has weak anticholinergic activity and possess mild central depressant properties.

For treatment of overdose: Since there is no specific antidote for overdose with antihistamines, treatment is symptomatic and supportive with possible utilization of the following: Induction of emesis (syrup of ipecac recommended); however, precaution against aspiration is necessary, especially in infants and children. Gastric lavage (isotonic or 0.45% sodium chloride solution) if patient is unable to vomit within 3 hours of ingestion. Saline cathartics (milk of magnesia) are sometimes used. Vasopressors to treat hypotension; however, epinephrine should not be used since it may further lower blood pressure. Oxygen and intravenous fluids. Precaution against use of stimulants (analeptic agents) because they may cause seizures. /Antihistamines/

This compound is thought to inhibit the contractile effect of serotinin on smooth muscles by competing with serotonin for its receptor. 41 Pregnancies were treated with 4 to 16 mg and no teratogenic effects were observed.

Antergan

Available commercially as the free base and as the hydrochloride sesquihydrate salt.

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