(±)-Doxylamine

270.37

270.37

207-414-2

DTXSID1022970

LIQ

R - Respiratory system

25.4

2.151

Doxylamine is a clear colorless liquid. (NTP, 1992)

1.043 g/cm3

<25 °C

137-141 °C @ Press: 0.5 Torr

174.5ºC

1.5486 (estimate)

soluble in acids.

Store below 40 deg C (104 deg F), preferably between 15 and 39 deg C (59 and 86 deg F), unless otherwise specified by manufacturer. Store in a well-closed container. Protect from light.

Slightly volatile

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

WHITE OR CREAMY WHITE POWDER; CHARACTERISTIC ODOR /SUCCINATE/|Darkens on exposure to light.

No rapid reaction with air. No rapid reaction with water.

Amines, Phosphines, and Pyridines

DOXYLAMINE is an amine. Amines are chemical bases. They neutralize acids to form salts plus water. These acid-base reactions are exothermic. The amount of heat that is evolved per mole of amine in a neutralization is largely independent of the strength of the amine as a base. Amines may be incompatible with isocyanates, halogenated organics, peroxides, phenols (acidic), epoxides, anhydrides, and acid halides. Flammable gaseous hydrogen is generated by amines in combination with strong reducing agents, such as hydrides

P264, P270, P301+P312, P330, P501

H302

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).

This compound is not very flammable but any fire involving this compound may produce dangerous vapors. You should evacuate the area. All firefighters should wear full-body protective clothing and use self-contained breathing apparatuses. You should extinguish any fires involving this chemical with a dry chemical, carbon dioxide, foam, or halon extinguisher. (NTP, 1992)

SMALL SPILLS AND LEAKAGE: If you should spill this chemical, use absorbent paper to pick up all liquid spill material. Seal the absorbent paper, as well as any of your clothing which may be contaminated, in a vapor-tight plastic bag for eventual disposal. Wash any surfaces you may have contaminated with a strong 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. STORAGE PRECAUTIONS: You should keep this material in a tightly-closed container under an inert atmosphere, and store it in a freezer. (NTP, 1992)

MINIMUM PROTECTIVE CLOTHING: When working with this chemical, you should wear impervious coveralls, shoe covers and gloves. 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. (NTP, 1992)

Signs of overdose include wheezing, tightness in the chest, fever, itching, bad cough, blue skin color, fits, swelling of face, lips, tongue, or throat.

Despite widespread use over many decades, doxylamine has not been linked to liver test abnormalities or to clinically apparent liver injury. The reason for its safety may relate its short half-life and limited duration of use.

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 DOXYLAMINE (7 total), please visit the HSDB record page.

Used alone as a short-term sleep aid, in combination with other drugs as a night-time cold and allergy relief drug. Also used in combination with Vitamin B6 (pyridoxine) to prevent morning sickness in pregnant women.

Doxylamine is a first generation antihistamine that is used for symptoms of allergic rhinitis and the common cold and as a short acting sedative. Doxylamine has not been linked to instances of clinically apparent acute liver injury.

Antihistamines

Anti-Allergic Agents; Antiemetics; Antitussive Agents; Histamine H1 Antagonists; Sedatives, Nonbarbiturate|ANTIHISTAMINIC AGENT PROBABLY EFFECTIVE FOR SYMPTOMATIC TREATMENT OF... ALLERGIC RHINITIS, VASOMOTOR RHINITIS, ALLERGIC CONJUNCTIVITIS DUE TO INHALANT ALLERGENS & FOODS, MILD, UNCOMPLICATED ALLERGIC SKIN MANIFESTATIONS OF URTICARIA & ANGIOEDEMA, AMELIORATION & PREVENTION OF...REACTIONS TO BLOOD OR PLASMA... /SUCCINATE/|VET USE: AS ARE OTHER ANTIHISTAMINES IN STOMATITIS, LAMINITIS, URTICARIA, RESPIRATORY DISORDERS, BLOAT, & INDIGESTION IN CATTLE; IN URTICARIA & LAMINITIS IN HORSES; IN DERMATITIS, URTICARIA, MOTION SICKNESS, & IN PREVENTION OF DEPIGMENTATION IN BLUE NOSED DOGS. /SUCCINATE/|Antihistamines are indicated in the prophylactic and symptomatic treatment of perennial and seasonal allergic rhinitis, vasomotor rhinitis, and allergic conjunctivitis due to inhalant allergens and foods. /Antihistamines; Included in US product labeling/|For more Therapeutic Uses (Complete) data for DOXYLAMINE (9 total), please visit the HSDB record page.

PERSONS TAKING ANTIHISTAMINES SHOULD BE ALERTED TO THEIR SEDATIVE EFFECTS & SHOULD BE CAUTIONED NOT TO DRIVE AUTOMOBILE, FLY AIRPLANE, OR OPERATE HAZARDOUS MACHINERY... /ANTIHISTAMINES/|VET: USE OF ANTIHISTAMINES IN STOMATITIS, GANGRENOUS MASTITIS, METRITIS, & TOXIC ENGORGEMENTS HAVE BEEN QUESTIONED. /SUCCINATE/|Like other antihistamines, doxylamine should not be used in premature or full-term neonates. Safety and efficacy of doxylamine as a nighttime sleep aid in children younger than 12 years of age have not been established. In addition, children may be more prone than adults to paradoxically experience CNS stimulation rather than sedation when antihistamines are used as nighttime sleep aids. Because doxylamine may cause marked drowsiness that may be potentiated by other CNS depressants (e.g., sedatives, tranquilizers), the antihistamine should be used in children receiving one of these drugs only under the direction of a physician. As an antihistamine, doxylamine should be used in children 2 to younger than 6 years of age only under the direction of a physician; use of the drug in children younger than 2 years of age is not recommended.|Because of the potential for serious adverse reactions to antihistamines in nursing infants, a decision should be made whether to discontinue nursing or doxylamine, taking into account the importance of the drug to the woman.|For more Drug Warnings (Complete) data for DOXYLAMINE (11 total), please visit the HSDB record page.

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

Doxylamine is an antihistamine commonly used as a sleep aid. This drug is also used to relieve symptoms of hay fever (allergic rhinitis), hives (rash or itching), and other allergic reactions. Doxylamine is a member of the ethanolamine class of antihistamines and has anti-allergy power far superior to virtually every other antihistamine on the market, with the exception of diphenhydramine (Benadryl). It is also the most powerful over-the-counter sedative available in the United States, and more sedating than many prescription hypnotics. In a study, it was found to be superior to even the barbiturate, phenobarbital for use as a sedative. Doxylamine is also a potent anticholinergic.

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

Readily absorbed via the gastrointestinal tract.|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/|Elimination and metabolic profiles of the glucuronide products of doxylamine and its N-demethylated metabolites were determined after the oral admin of (14)C-doxylamine succinate (13.3 and 133 mg/kg doses) to male and female Fischer 344 rats. The cumulative urinary and fecal eliminations of these conjugated doxylamine metaboites at the 13.3 mg/kg dose were 44.4 + or - 4.2% and 47.3 + or - 8.1% of the total recoverd dose for male and female rats, respectively. The cumulative urinary and fecal eliminations of conjugated doxylamine metabolites at the 133 mg/kg dose were 55.2 + or - 2.6% and 47.9 + or - 2.5% of the total recovered dose for male and female rats, respectively. The conjugated doxylamine metabolites that were isolated, quantitiated, and identified are doxylamine O-glucuronide, N-desmethyl-doxylamine O-glucuronide, and N,N-didesmethyldoxylamine O-glucuronide.|The elimination of doxylamine and metabolites was determined after iv admin of (14)C-doxylamine succinate at 0.7 and 13.3 mg/kg to the adult female rhesus monkey. Although the total recovery of radioactivity was the same for the low- and high-dose studies (90.2%), the rate of plasma elimination of doxylamine and its demethylated metabolite (desmethyldoxylamine) was slower for the high dose group. The 24 hr urinary excretion of doxylamine metabolites, desmethyl- and didesmethyldoxylamine, was significantly incr and the polar doxylamine metabolites were significantly decr as the iv doxylamine succinate dose was incr. The plasma elimination of GC-detected doxylamine was determined after po admin of Bendectin (doxylamine succinate and pyridoxine hydrochloride) /also contains dicyclomine hydrochloride/ at 7, 13.3, and 27 mg/kg to adult female rhesus monkeys. As the dose incr, the clearance of doxylamine decr. A statistically evaluated fit of the po data to a single-compartment, parallel first-order elimination model and a single-compartment, parallel first- and second-order (Michaelis-Menten) elimination model indicated that the more complex model containing the second-order process was most consistent with the observed elimination data. /Doxylamine succinate/

Hepatic.|The conjugated doxylamine metabolites that were isolated, quantitiated, and identified are doxylamine O-glucuronide, N-desmethyl-doxylamine O-glucuronide, and N,N-didesmethyldoxylamine O-glucuronide.|Analysis of doxylamine N-oxide and pyrilamine N-oxide as synthetic standards and biologically derived metabolites by thermospray mass spectrometry (TSP/MS) provided (M + H) + ions for each metabolite. ... In addition, TSP/MS and TSP/MS/MS analysis of ring-hydroxylated N-desmethyldoxylamine ... is also reported.

10 hours|The drug has an elimination half-life of about 10 hours in healthy adults.

Like other antihistamines, doxylamine acts by competitively inhibiting histamine at H1 receptors. It also has substantial sedative and anticholinergic effects.

SYMPTOMS: Symptoms of exposure to this compound include, drowsiness, vertigo, nervousness, epigastric pain, headache, palpitation, diarrhea, disorientation and irritability. ACUTE/CHRONIC HAZARDS: Toxic. (NTP, 1992)

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. IMMEDIATELY transport the victim after flushing eyes to a hospital even if no symptoms (such as redness or irritation) develop. SKIN: IMMEDIATELY flood affected skin with water while removing and isolating all contaminated clothing. Gently wash all affected skin areas thoroughly with soap and water. If symptoms such as redness or irritation develop, IMMEDIATELY call a physician and be prepared to transport the victim to a hospital for treatment. INHALATION: IMMEDIATELY leave the contaminated area; take deep breaths of fresh air. If symptoms (such as wheezing, coughing, shortness of breath, or burning in the mouth, throat, or chest) develop, call a physician and be prepared to transport the victim to a hospital. Provide proper respiratory protection to rescuers entering an unknown atmosphere. Whenever possible, Self-Contained Breathing Apparatus (SCBA) should be used; if not available, use a level of protection greater than or equal to that advised under Protective Clothing. INGESTION: DO NOT INDUCE VOMITING. If the victim is conscious and not convulsing, give 1 or 2 glasses of water to dilute the chemical and IMMEDIATELY call a hospital or poison control center. Be prepared to transport the victim to a hospital if advised by a physician. If the victim is convulsing or unconscious, do not give anything by mouth, ensure that the victim's airway is open and lay the victim on his/her side with the head lower than the body. DO NOT INDUCE VOMITING. IMMEDIATELY transport the victim to a hospital. (NTP, 1992)

NO EVIDENCE OF TERATOGENIC EFFECTS FOUND IN INFANTS OF 2298 WOMEN WHO TOOK BENDECTIN DURING PREGNANCY.|ASSOC WAS FOUND FOR AMNIOTIC BANDS CASES--A SUBGROUP OF LIMB REDUCTIONS. ASSOC ALSO FOUND WHEN DATA STRATIFIED TO REFLECT 1976 CHANGE IN FORMULATION. THESE STATISTICAL ASSOC DO NOT ESTABLISH CAUSAL RELATIONSHIP BETWEEN BENDECTIN & BIRTH DEFECTS. /BENDECTIN/|IN LARGE, PROSPECTIVE, OBSERVATIONAL STUDY OF PREGNANCY & CHILD DEVELOPMENT, THE ANTINAUSEANT DRUGS PRESCRIBED TO GRAVIDAS FOR NAUSEA & VOMITING IN 1ST 84 DAYS OF PREGNANCY WERE EVALUATED. THERE WAS NO INDICATION THAT BENDECTIN WAS ASSOC WITH TERATOGENIC EFFECTS. /BENDECTIN/|There is considerable controversy regarding the teratogenic potential, if any, of doxylamine; however, after evaluating extensive data and information concerning the possible teratogenicity of the drug, the US Food and Drug Administration (FDA) concluded that it is unlikely that doxylamine is teratogenic. FDA recognizes, however, that despite the large number of pregnancies evaluated to date the possibility that doxylamine may be weakly teratogenic cannot be excluded. Doxylamine was commercially available in the US for the treatment of nausea and vomiting associated with pregnancy in combination with dicyclomine and pyridoxine until 1976, and then in combination with only pyridoxine until 1983 when the manufacturer voluntarily discontinued manufacturing and distributing the combination. Most epidemiologic studies (case-control and cohort) in which fixed combinations of doxylamine and pyridoxine with or without dicyclomine were used during pregnancy indicate that an association between use of these combinations and adverse fetal effects does not appear to exist, but the possibility that the drug is weakly teratogenic cannot be excluded. In a few studies, a weak association between use of the fixed combinations during pregnancy and specific fetal abnormalities (e.g., pyloric stenosis, cardiac defects, oral clefts) was reported, but a causal relationship with the drugs was not established and these findings have not been confirmed by many other studies. Women considering self-medication with doxylamine during pregnancy should consult a health professional for advice regarding the relative risks and benefits of such therapy.|For more Human Toxicity Excerpts (Complete) data for DOXYLAMINE (12 total), please visit the HSDB record page.

Doxylamine

SYRUP NF: 6.25 MG/5 ML; TABLETS NF: 12.5 & 25 MG. /SUCCINATE/|PDR(34TH ED) 1205 (1980). EACH SPECIALLY COATED BENDECTIN TABLET CONTAINS: DECAPRYN (DOXYLAMINE SUCCINATE)--ANTIHISTAMINE 10 MG; PYRIDOXINE HYDROCHLORIDE 10 MG.|Available commercially as the hydrogen succinate.|Mereprine, Alsadorm, Decapryn succinate, Gittalun, Hoggar N, Sedaplus, Unisom /Succinate/|A combination with pyridoxine hydrochloride /which/ has been marketed as Bendectin for nausea of pregnancy.

A COMBINATION WITH METHYLETHYLAMINOPHENOLPROPANOL HCL (NETHAMINE) & THEOPHYLLINE AMINOISOBUTANOL IS MARKETED AS NETHAPRIN.

THIN-LAYER CHROMATOGRAPHY.|Analysis of doxylamine N-oxide and pyrilamine N-oxide as synthetic standards and biologically derived metabolites by thermospray mass spectrometry (TSP/MS) provided (M + H) + ions for each metabolite. TSP/tandem mass spectrometry (TSP/MS/MS) of the (M + H) + ions provided fragment ions characteristic of these metabolites. In addition, TSP/MS and TSP/MS/MS analysis of ring-hydroxylated N-desmethyldoxylamine, N-desmethylpyrilamine and O-dealkylated pyrilamine is also reported. A fragmentation pathway for analysis by MS/MS of pyrilamine and its metabolites is also proposed. The results demonstrate the utility of TSP/MS for biologically derived metabolites of pyrilamine and doxylamine.|... GC methods using a rubidium-sensitized nitrogen detector were developed for analysis of doxylamine succinate in animal feed, human urine, and wastewater at levels as low as 1 ppm, 100 ppb, and 100 ppb, respectively. Sample extracts were cleaned up by liquid-liquid partitioning, followed by additional cleanup on a column of silica gel. Data are presented concerning the stability of the drug in animal feed, extraction efficiencies, and the use of the silica gel cleanup column to separate the caffeine interference from doxylamine in extracts of human urine. Partition values and ancillary data concerning analysis of the drug in feed, by HPLC at levels as low as 10 ppm are also reported.

Plasma doxylamine concn were measured by a newly developed GC method in 16 healthy male volunteers (aged 19-28 yr) who received a single oral dose of 25 mg doxylamine. Pharmacokinetics of doxylamine were determined from multiple plasma doxylamine concn measured during the 24 hr postdose. Mean kinetic variables were peak plasma level (99 ng/ml), time of peak (2.4 hr postdose), elimination half-life (10.1 hr) and apparent oral clearance (217 ml/min). It was suggested that analogous analytic methodology can be used to study the pharmacokinetics of other drugs of the same class as doxylamine.

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