(±)-Chlorcyclizine

300.82600

300.83

201-446-0

25246

DTXSID9048011

Oil

R - Respiratory system

2933599090

6.48000

3.55260

1.0732 (rough estimate)

<25 °C

137-145 °C @ Press: 0.1-0.15 Torr

No Data

300.8mg/L(37.5 ºC)

PKA(1)= 7.81 & PKA(2)= 2.43

ODORLESS OR ALMOST ODORLESS; ITS SOLN ARE ACID TO LITMUS; PH (1 IN 100 SOLN) BETWEEN 4.8 & 5.5 /CHLORCYCLIZINE HYDROCHLORIDE/|AQ SOLN IS ACID TO LITMUS /CHLORCYCLIZINE DIHYDROCHLORIDE/|WHITE, CRYSTALLINE POWDER /CHLORCYCLIZINE HYDROCHLORIDE/|PRISMS FROM ALCOHOL PLUS ETHER /CHLORCYCLIZINE DIHYDROCHLORIDE/|Solutions acid to litmus, pH (1 to 100 solution) 4.8-5.5 /Chlorcyclizine hydrochloride/

UN 3077 9 / PGIII

P301 + P312 + P330

H302-H400

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).

Despite widespread use, cyclizine and chlorcyclizine have rarely been linked to liver test abnormalities or to clinically apparent liver injury. In an isolated case report, cyclizine was linked to a case of clinically apparent liver injury in a child given the drug for several days to prevent motion sickness. The pattern of liver test abnormalities suggested mild viral hepatitis, but jaundice and symptoms recurred when cyclizine was restarted. There were no immunoallergic features and no evidence for autoimmunity. The reason for the general safety of cyclizine and chlorcyclizine may relate to low daily dose and limited duration of use.

SEVERAL REVIEWS BRIEFLY MENTIONED THAT ANTIHISTAMINES INTERFERE WITH ANTICOAGULANT THERAPY; HOWEVER, NO DOCUMENTATION WAS PRESENTED, NO CASE REPORTS OF ANTICOAGULATION PROBLEMS CAUSED BY ANTIHISTAMINES HAVE APPEARED. /ANTIHISTAMINES/|TERATOGENICITY OF CHLORCYCLIZINE IN MICE...IS DIMINISHED BY PRE-TREATMENT EITHER WITH SKF 525A /PROADIFEN/ OR WITH PHENOBARBITONE, & MORE THAN ONE BIOTRANSFORMATION MUST BE INVOLVED.|Plocamadine A (1 ug/ml) produced a slow onset, sustained contraction of the guinea-pig isolated ileum. This was insensitive to atropine (1 umol/l) and tetrodotoxin (1 umol/L), but was significantly reduced by H1-histamine receptor antagonists including mepyramine (10 nmol/l), chlorcyclizine (10 nmol/l) and diphenhydramine (0.1 umol/l).|A method to determine whether chlorcyclizine hydrochloride (I) antihistamine activity could be demonstrated when I was applied topically in combo with 0.5% hydrocortisone acetate (Mantadil; II) cream was described. Hydrocortisone 5%, II, and placebo cream were studied in 30 subjects. The data indicated that a wheal and flare reaction induced in the subjects was decr by the I component of the combo. /Chlorcyclizine hydrochloride/

about 85 to 90%.

Cyclizine and chlorcyclizine are first generation antihistamines that are used largely to treat or prevent motion sickness and nausea. Cyclizine has been linked to very rare instances of clinically apparent acute liver injury.

Antihistamines

Chlorcyclizine has known transformation products that include 1-[(4-Chlorophenyl)phenylmethyl]piperazine and 4-Chlorobenzophenone.

Histamine H1 Antagonists|MILDLY SEDATIVE ANTIHISTAMINIC AGENT WITH PROLONGED ACTION & LOW INCIDENCE OF TOXIC SIDE EFFECTS. CHLORCYCLIZINE HYDROCHLORIDE HAS SLIGHT ANTICHOLINERGIC & ANTISPASMODIC ACTIONS & ENHANCES ACTION OF EPINEPHRINE. IT ALSO HAS SOME LOCAL ANESTHETIC ACTION.

Although the side effects of the H1 antagonists are rarely serious and often disappear with continued therapy, they are sometimes so troublesome that the drug must be withdrawn. /H1 Antagonists/|The side effect with the highest incidence, and the one common to all H1 antagonists other than terfenadine or astemizole, is sedation. ... Concurrent ingestion of alcohol or other CNS depressants produces an additive effect that impairs motor skills. Other untoward reactions referable to central actions include dizziness, tinnitus, lassitude, incoordination, fatigue, blurred vision, diplopia, euphoria, nervousness, insomnia, and tremors. /H1 Antagonists/|... Frequent side effects involve the digestive tract and include loss of appetite, nausea, vomiting, epigastric distress, and constipation or diarrhea. ... Other side effects that are apparently caused by the antimuscarinic actions of some of the older agents include dryness of the mouth and respiratory passages, sometimes inducing cough, urinary retention or frequency, and dysuria. ... Palpitation, hypotension, headache, tightness of the chest, and tingling and weakness of the hands may also occur with the older agents. /H1 Antagonists/|Drug allergy may develop when H1 antagonists are given orally, but more commonly it results from topical application. Allergic dermatitis is not uncommon; other hypersensitivity reactions include drug fever and photosensitization. /H1 Antagonists/

4. 4= VERY TOXIC: PROBABLE ORAL LETHAL DOSE (HUMAN) 50-500 MG/KG; BETWEEN 1 TEASPOONFUL & 1 OZ FOR 70 KG PERSON (150 LB).

Readily absorbed after oral administration and widely distributed throughout the body. Metabolised by N-demethylation to form norchlorcyclizine and by N-oxidation.|Slowly excreted in the urine; measurable amounts of norchlorcyclizine have been detected in the urine for up to 3 weeks after the cessation of chronic oral administration. About 0.5% of a single dose is excreted in the urine as the N-oxide.|After a single oral dose of 2 mg/kg to 4 subjects, average peak plasma concentrations of about 0.05 mg/L and 0.03 mg/L were attained in 5 h for unchanged drug and norchlorcyclizine, respectively. After oral administration of 50 mg 3 times a day for 6 days, plasma concentrations of norchlorcyclizine of 0.05 to 0.11 mg/L were reported on the first day after the cessation of treatment and plasma concentrations of 0.02 to 0.04 mg/L were found on the 10th day after cessation of treatment [Kuntzman et al. 1973].|...RATS & MAN TREATED WITH CHLORCYCLIZINE EXCRETE CHLORCYCLIZINE N-OXIDE IN URINE. BENZHYDROLPIPERAZINES & THEIR N-DEALKYLATION PRODUCTS ARE DISTRIBUTED IN ALL TISSUES OF RATS & ARE TRANSFERRED TO FETUS.|...NORCHLORCYCLIZINE IS RETAINED IN HUMANS FOR AT LEAST 20 DAYS AFTER TERMINATION /OF CHLORCYCLIZINE/ THERAPY. .../CHLORCYCLIZINE/ GIVES VERY LOW PLASMA LEVELS SINCE.../IT IS/ MARKEDLY LOCALIZED IN TISSUES, PARTICULARLY LUNG.|STIMULATORY EFFECT OF CHRONIC CHLORCYCLIZINE ADMIN ON ITS OWN METAB IN DOGS: ON DAYS 1-7 DAILY ORAL DOSE OF 10 MG/KG RESULTED IN CHLORCYCLIZINE PLASMA LEVELS OF 4.5 PLUS OR MINUS 1.7 MG/L & ONLY TRACE AMT OF NORCHLORCYCLIZINE. /FROM TABLE/|STIMULATORY EFFECT OF CHRONIC CHLORCYCLIZINE ADMIN ON ITS OWN METAB IN DOGS: AFTER 63 DAYS ADMIN OF 15 MG/KG DAILY ORAL DOSE, PLASMA LEVELS OF CHLORCYCLIZINE WERE IN TRACE AMT & 8.3 PLUS OR MINUS 2.0 MG/L OF NORCHLORCYCLIZINE. /FROM TABLE/|For more Absorption, Distribution and Excretion (Complete) data for CHLORCYCLIZINE (6 total), please visit the HSDB record page.

High concentrations of the N-desmethyl metabolite are found in the liver, lungs, kidney, and spleen.|AFTER CHRONIC ADMIN OF...CHLORCYCLIZINE TO RATS, THE TISSUES CONTAINED DRUG METABOLITES, IN WHICH PIPERAZINE RING FISSION BY MULTIPLE OXIDATIVE N-DEALKYLATION HAD OCCURRED TO GIVE A SUBSTITUTED ETHYLENEDIAMINE. ... ACCUM OF N-(P-CHLOROBENZHYDRYL)ETHYLENEDIAMINE WAS FOUND IN RATS, TREATED WITH CHLOROCYCLIZINE.|OXIDATIVE N-DEALKYLATION IS MAIN METAB PATHWAY OF BENZHYDROLPIPERAZINES... /CHLORCYCLIZINE IS/ TRANSFORMED INTO...NORCHLORCYCLIZINE... CHLORCYCLIZINE N-OXIDE DOES NOT LIE ON METAB PATHWAY CONNECTING CHLORCYCLIZINE WITH NORCHLORCYCLIZINE, BUT RATS & MAN TREATED WITH CHLORCYCLIZINE EXCRETE CHLORCYCLIZINE N-OXIDE IN URINE.|YIELDS DEMETHYLCHLORCYCLIZINE IN RAT. /FROM TABLE/

about 12 h.

ANTIHISTAMINES ACT AS PHARMACOLOGICAL ANTAGONISTS OF HISTAMINE AT MOST OF HISTAMINE RECEPTOR SITES, ALTHOUGH NOT BY PREVENTING RELEASE OF HISTAMINE. HEPATIC MICROSOMAL ENZYME-INDUCING PROPERTIES OF CHLORCYCLIZINE...HAVE SHORTENED DURATION OF ACTION OF SOME BARBITURATES AS A RESULT OF ENZYME INDUCTION.|H1 antagonists inhibit most response of smooth muscle to histamine. Antagonism of the constrictor action of histamine on respiratory smooth muscle is easily shown or in vitro. ... Within the vascular tree, the H1 antagonists inhibit both the vasoconstrictor effects of histamine and, to a degree, the more rapid vasodilator effects that are mediated by H1 receptors on endothelial cells. Residual vasodilatation reflects the involvement of H2 receptors on smooth muscle and can be suppressed only by the concurrent administration of an H2 antagonist. Effects of the histamine antagonists on histamine induced changes in systemic blood pressure parallel these vascular effects. /H1 Antagonists/|H1 antagonists strongly block the action of histamine that results in increased capillary permeability and formation of edema and wheal. /H1 Antagonists/|All H1 antagonists ... can bind to H1 receptors in the CNS ... H1 antagonists can both stimulate and depress the CNS. /H1 Antagonists/|For more Mechanism of Action (Complete) data for CHLORCYCLIZINE (6 total), please visit the HSDB record page.

...NO EVIDENCE OF HARM TO HUMAN FETUS HAS BEEN REPORTED DESPITE WIDE USE OVER...PAST 15 YEARS.|ADULTS HAVE SURVIVED SINGLE DOSES OF 2.5-5.0 G. CHILDREN MAY BE DISPROPORTIONATELY MORE SUSCEPTIBLE; 30-60 MG/KG HAS PRODUCED SERIOUS POISONINGS & DEATH IN TODDLERS, & IN 1 FATAL CASE DOSE WAS ABOUT 10 MG/KG. /ANTIHISTAMINICS/|.../AFTER/ EXTENSIVE EPIDEMIOLOGICAL INVESTIGATIONS IN SWEDEN, CANADA & US... THERE WAS DISAGREEMENT AS TO WHETHER CHLORCYCLIZINE WAS A TERATOGEN IN HUMANS; EPIDEMIOLOGIC INVESTIGATION OF CHLORCYCLIZINE COULD NOT PROVE EXISTENCE OF HARMFUL EFFECT IN HUMANS.|In acute poisoning with H1 antagonists, their central excitatory effects constitute the greatest danger. The syndrome includes hallucinations, excitement, ataxia, incoordination, athetosis, and convulsions. Fixed, dilated pupils with a flushed face, together with sinus tachycardia, urinary retention, dry mouth, and fever, lend the syndrome a remarkable similarity to that of atropine poisoning. Terminally, there is deepening coma with cardiorespiratory collapse and death, usually within 2 to 18 hours. /H1 Antagonists/

chlorcycline

A rapid, specific and sensitive liquid chromatographic method was developed and used for the quantitation of chlorcyclizine hydrochloride and its degradation product. /Chlorcyclizine hydrochloride/

DETERMINATION OF PLASMA ANTIHISTAMINE BY NITROGEN-SPECIFIC GAS CHROMATOGRAPHY.

Pharmaceuticals|Pharmaceuticals -> Antihistamines