Meclizine

390.95

390.95

209-323-3

169189

DTXSID0023242

R06AE05|R - Respiratory system

2933599090

6.5

5.8

Solid

1.159 g/cm3

217-224

230 °C @ Press: 2 Torr

253.3ºC

H2O: 0.1gm/100ml

Meclizine hydrochloride preparations should be stored at a temp less than 40 deg C, preferably between 15-30 deg C; the conventional tablets should be stored in well-closed containers. /Meclizine hydrochloride/

208.2 Ų [M+H]+ [CCS Type: TW, Method: Major Mix IMS/Tof Calibration Kit (Waters)]

HAS SLIGHT ODOR; TASTELESS; MELTS BETWEEN 217 & 224 °C /MECLIZINE HYDROCHLORIDE/|WHITE OR SLIGHTLY YELLOWISH, CRYSTALLINE POWDER /MECLIZINE HYDROCHLORIDE/

R22;R36/37/38

S26-S37/39

Xn

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).

The oral and intraperitoneal LD50 in mouse are 1600 mg/kg and 625 mg/kg, respectively. The lowest published toxic dose (TDLo) in rats via the oral route is 800 mg/kg.[MSDS] Symptoms of overdose mainly involve CNS depression with drowsiness, coma, and convulsions. Hypotension may also occur, particularly in the elderly. In children, anticholinergic effects and CNS stimulation, characterized by hallucinations, seizures, trouble sleeping, are more likely to occur. In case of overdose, symptomatic and supportive treatment is recommended. In case of recent ingestion, induction of emesis or gastric lavage should be initiated to limit further drug absorption. Although there is no known antidote to meclizine, physostigmine may be useful to counteract the CNS anticholinergic effects of meclizine.

Despite widespread use, meclizine has not been linked to liver test abnormalities or to clinically apparent liver injury. The reason for its safety may relate to low daily dose and limited duration of use.

There is limited data on the protein binding profile of meclizine.

Indicated for the symptomatic treatment of nausea, vomiting, and dizziness associated with motion sickness, and management of vertigo due to various causes, including radiation sickness, Meniere’s syndrome, labyrinthitis and other vestibular disturbances.

Meclizine is a first generation antihistamine that is used largely to treat vertigo and motion sickness. Meclizine has not been linked to instances of clinically apparent acute liver injury.

Antihistamines

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

Anti-Allergic Agents; Antiemetics; Histamine H1 Antagonists|A LONG-ACTING ANTIHISTAMINIC AGENT WHICH IS EFFECTIVE IN PREVENTION OR TREATMENT OF NAUSEA, VOMITING & DIZZINESS ASSOC WITH MOTION SICKNESS. ... ACTION OF SINGLE DOSE PERSISTS FOR 9-24 HR. /MECLIZINE HYDROCHLORIDE/|... H1 antagonists, notably dimenhydrinate and meclizine, are often of benefit in vestibular disturbances, such as Meniere's disease, and in other types of true vertigo.|...LARGE DRUG SURVEILLANCE PROGRAMS HAVE NOT DEMONSTRATED BIRTH DEFECTS CLINICALLY IN DOSAGE RANGES EMPLOYED.|For more Therapeutic Uses (Complete) data for MECLIZINE (10 total), please visit the HSDB record page.

CHILDREN DOSAGE HAS NOT BEEN ESTABLISHED.|WOMAN WITH CIRRHOSIS HAD EXTRAPYRAMIDAL DISORDERS PRIOR TO DEATH IN COMA, FOLLOWING 1 TABLET/DAY FOR 4 DAYS OF ANCOLOXIN (MECLIZINE 25 MG & PYRIDOXINE 50 MG). EXTREME CAUTION IS EMPHASIZED IN PRESCRIBING DRUGS METAB IN LIVER TO PT WITH CHRONIC LIVER DISEASE.|... Meclizine may impair their ability to perform hazardous activities requiring mental alertness or physical coordination (e.g., operating machinery or driving ... ). In addition, additive CNS depression may occur when antihistamines, such as meclizine, are admin concomitantly with other CNS depressants including barbiturates, tranquilizers, and alcohol. If meclizine is used concomitantly with other depressant drugs, caution should be used to avoid overdosage. The anticholinergic effects of the drug should be considered when admin meclizine to patients with angle-closure glaucoma or prostatic hypertrophy. Meclizine is contraindicated in patients who are hypersensitive to it.|Safety and efficacy of meclizine in children younger than 12 yr of age have not been established; therefore ... use ... is not recommended.|Meclizine is teratogenic in animals. Although retrospective studies in humans suggest that the use of meclizine during pregnancy is probably not assoc with teratogenic effects, the manufacturers state that the drug is contraindicated in women who are or may become pregnant.

Meclizine works on the higher centres of the brain to reduce nausea, vomiting, or vertigo. It is effective against nausea and vomiting arising from many causes, including motion sickness and disorders affecting the vestibular system. The onset of action of meclizine is about 1 hour, with effects lasting between 8 to 24 hours. Meclizine is reported to cause drowsiness due to its anticholinergic actions.

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 to prevent NAUSEA or VOMITING. (See all compounds classified as Antiemetics.)|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.)

Most histamine H1 antagonists are reported to be readily absorbed following oral administration. Upon oral administration, the time to reach peak plasma concentrations (Cmax) of meclizine is about 3 hours post-dose, with the value ranging from 1.5 to 6 hours.|Meclizine is excreted in the urine as metabolites and in the feces as unchanged drug.|The volume of distribution of meclizine in humans has not been fully studied. It is proposed that meclizine may be excreted into breast milk.|There is limited data on the clearance of meclizine.|BENZHYDROLPIPERAZINES & THEIR N-DEALKYLATION PRODUCTS ARE DISTRIBUTED IN ALL TISSUES OF RATS & TRANSFERRED TO FETUS.|The drug is excreted in feces unchanged and in urine as norchlorcyclizine. /Meclizine hydrochloride/

There is limited human data on meclizine metabolism. According to the findings of _in vitro_ studies, meclizine may undergo aromatic hydroxylation or benzylic oxidation mediated by the hepatic CYP2D6 enzyme.|OXIDATIVE N-DEALKYLATION IS MAIN METAB PATHWAY OF BENZHYDROLPIPERAZINES... NORCHLORCYCLIZINE IS...MAJOR METABOLITE OF MECLIZINE.|The metabolic fate of meclizine in humans in unknown. In rats, meclizine is metabolized (probably in the liver) to norchlorcyclizine. This metabolite is distributed throughout most body tissues and crosses the placenta.

Meclizine has a plasma elimination half-life of about 5-6 hours in humans.|The drug has a plasma half-life of 6 hr. /Meclizine hydrochloride/

Vomiting is a centrally regulated reflex mechanism that initiates from the vomiting center and the chemoreceptor trigger zone (CTZ) located in the medulla. Motion sickness is also regulated by CTZ. The blood-brain barrier near the CTZ is relatively permeable to circulating mediators and CTZ can transmit impulses to vomiting center located in the brainstem. Different receptors responding to different factors, including histamine, 5-HT, enkephalins, substance P, and dopamine, are expressed along the brainstem to activate respective pathways and contribute to the control of vomiting. Histamine H1 receptors are expressed on the vestibular nuclei and nucleus of the solitary tract (NTS) that are activated by motion sickness and stimuli from the pharynx and stomach. When activated, H1 receptor signaling from these nuclei is transmitted to the CTZ and vomiting centre. Through its antagonistic action on the H1 receptors, meclizine primarily works by inhibiting signaling pathway transduction through histaminergic neurotransmission from the vestibular nuclei and NTS to the CTZ and medullary vomiting center. Meclizine may also decrease the labyrinth excitability and vestibular stimulation.|HI-RECEPTOR BLOCKERS HAVE ESTABLISHED & VALUED PLACE IN SYMPTOMATIC TREATMENT OF...ALLERGIC DISEASES, IN WHICH THEIR USEFULNESS...ATTRIBUTABLE TO THEIR ANTAGONISM OF HISTAMINE. ...CENTRAL PROPERTIES OF SOME...ARE OF...THERAPEUTIC VALUE...IN SUPPRESSING MOTION SICKNESS. /H1-RECEPTOR BLOCKERS/|Meclizine has CNS depressant, anticholinergic, antiemetic, antispasmodic, and local anesthetic effects in addition to antihistaminic activity. The drug depresses labyrinth excitability and conduction in vestibular-cerebellar pathways. The antiemetic and antimotion-sickness actions of meclizine result, at least in part, from its central anticholinergic and CNS depressant properties.

Central excitaton is also a striking feature of poisoning, which not uncommonly results in convulsions, particularly in infants. /H1 Antagonists/|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 12 to 18 hours. /H1 Antagonists/|SIDE EFFECT WITH HIGHEST INCIDENCE, &...COMMON TO ALL DRUGS IN THIS GROUP, IS SEDATION. ... OTHER UNTOWARD REACTIONS REFERABLE TO CENTRAL ACTIONS INCL DIZZINESS, TINNITUS, LASSITUDE, INCOORDINATION, FATIGUE, BLURRED VISION, DIPLOPIA, EUPHORIA, NERVOUSNESS, INSOMNIA & TREMORS. /H1 ANTAGONISTS/|...FREQUENT SIDE EFFECTS INVOLVE DIGESTIVE TRACT & INCL LOSS OF APPETITE, NAUSEA, VOMITING, EPIGASTRIC DISTRESS & CONSTIPATION OR DIARRHEA. /H1 ANTAGONISTS/|For more Human Toxicity Excerpts (Complete) data for MECLIZINE (10 total), please visit the HSDB record page.

Agyrax

UCB 5062, ANCOLAN, BONAMINE, BONINE, CALMONAL, DIADRIL, HISTAMETIZINE, NAVICALM, NEO-ISTAFENE, PEREMESIN, POSTAFEN SUPP, SABARI, SEA-LEGS & VERITAB. /DIHYDROCHLORIDE/

Piperazine, 1-[(4-chlorophenyl)phenylmethyl]-4-[(3-methylphenyl)methyl]-: INACTIVE

MECLIZINE TABLETS ANALYZED BY GAS LIQUID CHROMATOGRAPHY.|COLORIMETRIC METHOD FOR QUANTITATIVE DETERMINATION OF MECLIZINE HCL IN DOSAGE FORMS, BASED ON ION PAIR EXTRACTION WITH METHYL ORANGE, IS PRESENTED. TABLETS (25 MG BONINE CHEWABLE) & CAPSULES WERE ASSAYED.|FLUORESCENCE & PHOSPHORESCENCE OF ANTIHISTAMINES HAVING THE DIPHENYLMETHANE CHROMOPHORE. EFFECT OF HALIDE IONS ON LUMINESCENCE.

Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients|Pharmaceuticals|Pharmaceuticals -> Antihistamines