Promethazine hydrochloride is an odorless white to faint yellow crystalline powder. Bitter taste. A 10% solution in water has a pH of 3.5-5.0. (NTP, 1992)
Solubilitygreater than or equal to 100 mg/mL at 72 °F (NTP, 1992)
Human Drugs · 3 items
Breast Feeding; Lactation; Milk, Human; Antiemetics; Antipruritics; Phenothiazines
FDA approved drugs -> Active ingredient
FDA approved drugs -> Active ingredient
Melting Point446 to 450 °F (decomposes) (NTP, 1992)
Physical DescriptionPromethazine hydrochloride is an odorless white to faint yellow crystalline powder. Bitter taste. A 10% solution in water has a pH of 3.5-5.0. (NTP, 1992)
Collision Cross Section162.7 Ų [M+H]+ [CCS Type: TW; Method: calibrated with polyalanine and drug standards]
Physicochemical properties
Melting point
230 · 230-232°C
Flash point
9 ℃ · 9℃
storage temp.
2 · 2-8°C
solubility
Very soluble in water, freely soluble in ethanol (96 per cent) and in methylene chloride.
Safety & regulation
Safety information is for reference only and does not replace the supplier’s Safety Data Sheet (SDS), applicable regulations, or professional assessment.
GHS classification
GHS Classification · 5 items
This chemical does not meet GHS hazard criteria for 0.7% (1 of 142) of reports.
Danger
H302 (92.3%): Harmful if swallowed [Warning Acute toxicity, oral]
P261, P264, P264+P265, P270, P271, P272, P273, P280, P301+P317, P302+P352, P304+P340, P305+P351+P338, P305+P354+P338, P317, P319, P321, P330, P332+P317, P333+P317, P337+P317, P362+P364, P391, P403+P233, P405, and P501 (click each P-code to see the statement)
Aggregated GHS information provided per 142 reports by companies from 19 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.
Hazard information
Regulatory Information10H-Phenothiazine-10-ethanamine, N,N,.alpha.-trimethyl-, monohydrochloride: Does not have an individual approval but may be used under an appropriate group standard
Other Safety InformationIMAP assessments - 10H-Phenothiazine-10-ethanamine, N,N,.alpha.-trimethyl-, monohydrochloride: Environment tier I assessment
Fire HazardsFlash point data for this chemical are not available; however, it is probably combustible. (NTP, 1992)
Health Hazards · 1 item
SYMPTOMS: Symptoms of exposure to this compound include excitement, sleepiness, convulsions and rigidity. Other symptoms include leukopenia, agranulocytosis, drowsiness, confusion and stupor. Acute transitory myopia may occur. Central nervous system effects may also occur. It may cause an increase in blood pressure, mild hypotension, jaundice, extra-pyramidal reactions and photosensitivity. It may also cause dizziness, central nervous system depression, vomiting, local anesthesia, abdominal pain, diarrhea and dryness of the mouth, throat and nose. Symptoms of exposure to this type of compound include muscular weakness, tachycardia, nausea, sedation, tinnitus, lassitude, incoordination, fatigue, blurred vision, diplopia, euphoria, nervousness, insomnia, tremors, loss of appetite, epigastric distress, constipation, cough, urinary retention or frequency, dysuria, palpitation, headache, tightness of the chest, tingling, heaviness and weakness of the hands, allergic dermatitis, fever, hemolytic anemia (rare), fixed and dilated pupils, and flushing. In children, exposure can cause hallucinations, excitement, ataxia, incoordination, athetosis and convulsions.
Chemistry & industry
Pharmacology
Metabolism/MetabolitesHepatic
Route of Elimination: Promethazine hydrochloride is metabolized in the liver, with the sulfoxides of promethazine and N-desmethylpromethazine being the predominant metabolites appearing in the urine.
Half Life: 16-19 hours
FDA Pharmacological Classification · 6 items
PROMETHAZINE HCI
Phenothiazine [EPC]; Phenothiazines [CS]
PROMETHAZINE HCL
Phenothiazines [CS]; Phenothiazine [EPC]
PROMETHAZINE HYDROCHLORIDE
Phenothiazines [CS]; Phenothiazine [EPC]
MeSH Pharmacological Classification · 3 items
Agents, usually topical, that relieve itching (pruritus).
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.
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)
Uses & manufacturing
UsesFor the treatment of allergic disorders, and nausea/vomiting.
General Manufacturing Information10H-Phenothiazine-10-ethanamine, N,N,.alpha.-trimethyl-, hydrochloride (1:1): INACTIVE
PROMETHAZINE HYDROCHLORIDE is sensitive to light. In aqueous solution, it is degraded by heat and light (more rapidly in air or oxygen). Incompatible with alkalis and alkaline solutions such as those of aminophylline, soluble barbiturates and phenytoin sodium. Iron(III) and copper(III) accelerate the degradation (NTP, 1992).
Air and Water ReactionsSlowly oxidizes in air, acquiring a blue color. Also turns blue on exposure to moisture. Water soluble.
Hazard Classes and CategoriesAcute Tox. 4 (92.3%)
Safety & protection
Fire FightingFires involving this material can be controlled with a dry chemical, carbon dioxide or Halon extinguisher. (NTP, 1992)
First Aid · 1 item
EYES: First check the victim for contact lenses and remove if present. Flush victim's eyes with water or normal saline solution for 20 to 30 minutes while simultaneously calling a hospital or poison control center. Do not put any ointments, oils, or medication in the victim's eyes without specific instructions from a physician. If symptoms (such as redness or irritation) develop, immediately transport the victim to a hospital.
Nonfire Spill Response · 1 item
SMALL SPILLS AND LEAKAGE: If you spill this chemical, you should dampen the solid spill material with water, then transfer the dampened material to a suitable container. Use absorbent paper dampened with water to pick up any remaining material. Seal your contaminated clothing and the absorbent paper in a vapor-tight plastic bag for eventual disposal. Wash all contaminated surfaces with a soap and water solution. Do not reenter the contaminated area until the Safety Officer (or other responsible person) has verified that the area has been properly cleaned.
Personal Protective Equipment (PPE) · 1 item
RECOMMENDED RESPIRATOR: Where the neat test chemical is weighed and diluted, wear a NIOSH-approved half face respirator equipped with an organic vapor/acid gas cartridge (specific for organic vapors, HCl, acid gas and SO2) with a dust/mist filter.
Toxicology
Exposure RoutesOn average, 88% of a promethazine dose is absorbed after oral administration; however, the absolute bioavailability is only 25% because of first-pass clearance.
Toxicity Summary · 1 item
Like other H1-antagonists, promethazine competes with free histamine for binding at H1-receptor sites in the GI tract, uterus, large blood vessels, and bronchial muscle. The relief of nausea appears to be related to central anticholinergic actions and may implicate activity on the medullary chemoreceptor trigger zone.
Signs and Symptoms · 1 item
Symptoms of overdose include mild depression of the central nervous system and cardiovascular system to profound hypotension, respiratory depression, unconsciousness, and sudden death. Other reported reactions include hyperreflexia, hypertonia, ataxia, athetosis, and extensor-plantar reflexes (Babinski reflex).
Carcinogen Classification · 6 items
Promethazine Hydrochloride
TR-425: Toxicology and Carcinogenesis Studies of Promethazine Hydrochloride (CASRN 58-33-3) in F344/N Rats and B6C3F1 Mice (Gavage Studies) (1993 )
12/01/92
No Evidence
No Evidence
No Evidence
Drug Induced Liver Injury · 6 items
Drug Induced Liver Injury Rank (DILIrank 2.0)
Promethazine hydrochloride
vLess-DILI-concern
5
Adverse reactions
DOI:10.1016/j.drudis.2016.02.015
Effects During Pregnancy and Lactation◉ Summary of Use during Lactation
UsesFor the treatment of allergic disorders, and nausea/vomiting.
UsesPromethazine is a first generation histamine H1 receptor antagonist (Ki = 2.6 nM) whose antihistamine activity has been reported in guinea pigs and mice at ED50 values of 0.43 and 5.9 mg/kg, respectively. Promethazine can penetrate the CNS, depressing central H1 receptor activity, which may relate to its sedative properties, and can also inhibit muscarinic acetylcholine receptors (Ki = 22 nM). Furthermore, 32 mg/kg promethazine demonstrates antiemetic effects in ferret models of motion sickness or chemotherapy-induced nausea.
UsesPromethazine hydrochloride is used as antihistamine; antiemetic; central nervous system depressant; sedative; anticholinergic; antiserotoninergic; local anesthetic; in the treatment of motion sickness, cough linctuses, nausea, and allergic conditions; used to control Parkinsonian symptoms and as central nervous system depressant; in pills, syrup, injections and suppositories.
General DescriptionOdorless white to faint yellow crystalline powder. Bitter taste. A 10% solution in water has a pH of 3.5-5.0.
General DescriptionPromethazine hydrochloride,(±)10-[2-(dimethylamino)-propyl]phenothiazinemonohydrochloride (Phenergan), occurs as a white tofaint yellow crystalline powder that is very soluble in water,in hot absolute alcohol, and in chloroform. Its aqueous solutionsare slightly acid to litmus.
