Meclizine

5.8

4.22

0.1g/100mL

FREELY SOL IN CHLOROFORM, PYRIDINE; SLIGHLY SOL IN DIL ACIDS, ALCOHOL; PRACTICALLY INSOL IN WATER, ETHER /MECLIZINE DIHYDROCHLORIDE/

FREELY SOL IN METHYLACETAMIDE, PYRIDINE, CHLOROFORM, ACID-ALCOHOL-WATER MIXT /MECLIZINE HYDOCHLORIDE/

1.03e-03 g/L

Breast Feeding; Lactation; Milk, Human; Antiemetics; Antihistamines; Anti-Allergic Agents

Pharmaceuticals

Positive

4.57

2.7

Agilent XCT

Electrospray ionization

formic acid (5.3nM)

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

182.41 Ų [M+H-H2O]+ [CCS Type: TW; Method: calibrated with polyalanine and drug standards]

HAS SLIGHT ODOR; TASTELESS; MELTS BETWEEN 217 & 224 °C /MECLIZINE HYDROCHLORIDE/

WHITE OR SLIGHTLY YELLOWISH, CRYSTALLINE POWDER /MECLIZINE HYDROCHLORIDE/

Warning

H319 (100%): Causes serious eye irritation [Warning Serious eye damage/eye irritation]

P264+P265, P280, P305+P351+P338, and P337+P317 (click each P-code to see the statement)

The GHS information provided by 1 company from 1 notification to the ECHA C&L Inventory.

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).

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.

Common adverse effects of patients taking meclizine include drowsiness, urinary retention, dry mouth, headache, fatigue, and vomiting. On rare occasions, there have been reports of blurred vision and anaphylactic reactions when taking meclizine.

There are no specific antidotes available for meclizine overdose. Treatment is primarily supportive and focused on symptoms. Symptoms of an overdose may include signs of CNS depression such as drowsiness, seizures, and coma. Hypotension can occur, but it is more likely to be seen in older people. The anticholinergic effects and CNS stimulation of an overdose in children can present with hallucinations, seizures, and insomnia. With recent ingestion, induce emesis or perform gastric lavage to prevent further drug absorption. Activated charcoal is also an option. There is no known antidote for meclizine, but physostigmine can help to counter the systemic anticholinergic effects of meclizine.

Along with its actions as an antagonist at H₁-receptors, meclizine also possesses anticholinergic, central nervous system depressant, and local anesthetic effects. Meclizine depresses labyrinth excitability and vestibular stimulation and may affect the medullary chemoreceptor trigger zone.

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.

Benchmark Dataset for the Liver Toxicity Knowledge Base (LTKB)

meclizine

Antivert®

Antihistamines

Not Applicable

no-DILI-concern

.../IN 1963 WAS 1ST REPORT OF/ PRODUCTION OF CLEFT PALATE BY HIGH DOSAGE OF MECLIZINE IN RATS... /IT WAS SUGGESTED/ THAT NORCHLORCYCLIZINE, WHICH IS A METABOLITE.../OF MECLIZINE/ IS PROBABLE ACTIVE FORM OF TERATOGEN.

TERATOGENICITY HAS BEEN REPORTED IN SWINE, MICE, RABBITS, RATS & DOGS.

◉ Summary of Use during Lactation

◈ What is meclizine?

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).

R06AE05

R - Respiratory system

QR - Respiratory system

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.

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.

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/

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.

Hepatic Half Life: 6 hours

3L5TQ84570

MECLIZINE

Established Pharmacologic Class [EPC] - Antiemetic

Physiologic Effects [PE] - Emesis Suppression

Meclizine is an Antiemetic. The physiologic effect of meclizine is by means of Emesis Suppression.

MECLIZINE

Drugs used to prevent NAUSEA or VOMITING.

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.

Drugs that bind to but do not activate CHOLINERGIC RECEPTORS, thereby blocking the actions of ACETYLCHOLINE or cholinergic agonists.

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)

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/

MEDICATION (VET)

MEDICATION

Use (kg) in Switzerland (2009): >25

For the prevention and treatment of nausea, vomiting, or dizziness associated with motion sickness.

Pharmaceuticals -> Antihistamines

Pharmaceuticals