Doxylamin

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)

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.

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.

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.

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.

Because doxylamine is available over the counter, the risk of overdose is a concern. Adverse effects due to hypersensitivity to the drug include hypotension, urticaria, and decreased oxygen saturation. Common adverse effects include impaired vigilance, atropine-like effects, impaired coordination, and drowsiness during the day—all of which could pose problems for high-risk fall patients and those operating heavy machinery or who drive a vehicle.

Toxicity associated with antihistamine use is due to overdose following oral ingestion, either unintentional or intentional suicide attempt—most commonly in young and elderly populations. Toxicity from intravenous, intramuscular, or topical routes of administration rarely occurs in the household setting. Toxicity presents as antimuscarinic and hallucinogenic effects. The mnemonic 'dry as a bone, hot as a hare, red as a beet, blind as a bat, full as a flask, and mad as a hatter' has been used to remember the presentation of acute anticholinergic toxicity. This mnemonic represents the findings of anhidrosis, hyperthermia, reddening of the skin, mydriasis, hallucinations, urinary retention, and delirium, respectively.

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

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.

Drug-Induced Liver Injury Severity and Toxicity (DILIst)

doxylamine

DILI Negative

Oral

DOI:10.1016/j.drudis.2019.09.022

THERAPEUTIC DOSES MAY PRODUCE CNS DEPRESSION & INCOORDINATION, WHILE OVERDOSAGE IS MORE APT TO PRODUCE EXCITEMENT, ATAXIA, & CONVULSIONS. /SUCCINATE/

Most reproduction studies in various animal species using doxylamine and pyridoxine alone or in fixed combination have not revealed evidence of harm to the fetus. Studies in rats and mice using doxylamine succinate dosages up to 125 times the maximum human dosage did not reveal evidence of observable congenital abnormalities, but wavy ribs and diaphragmatic hernias occurred in rats at dosages 125-375 times the maximum human dosage; an overall increase in fetal wastage, varying from zero to threefold, occurred in most rodents receiving dosages 125 or more times greater than the maximum human dosage. In a small study in monkeys receiving a fixed combination of doxylamine succinate and pyridoxine hydrochloride throughout fetal organogenesis at dosages 10-20 times the maximum human dosage, intraventricular septal defects were present in 4 of 7 fetuses delivered on day 100 of gestation (full-term gestation is about 160 days), while 2 fetuses aborted on the 46th and 56th day of gestation appeared to be developing normally and 3 other fetuses allowed to develop to term were normal. The importance of septal defects in these monkeys is not known, since an opening in the septum is usually present early during fetal development in monkeys. In other studies in monkeys receiving the fixed combination for shorter periods of time, there was no evidence of fetal toxicity.

The objective of this study was to provide a qualitative description of the histological and ultrastructural alterations induced by three chondrogenesis inhibitors: retinoic acid and 6-aminonicotinamide, two teratogens, and doxylamine succinate, a nonteratogen cmpd. In addition, in order to have a basis for the interpretation of the morphological alterations induced by the test cmpd, the histological and ultrastructural changes which occur during the time course of chondrogenesis in control cultures were described and compared with those in rat embryo limb buds. ... Doxylamine succinate at 50 ug/ml affected both differentiation and proliferation; pigment deposits were observed in chondrocytes, suggesting phospholipid metabolism disorders. /Doxylamine succinate/

We assessed the effectiveness of five in vitro assays in predicting in vivo tumor growth stimulation by the H1-antihistamines loratadine, astemizole, cetirizine, bydroxyzine, and doxylamine. ... Potency of each agent was ranked 1-5 in each of the following in vitro assays: 1) inhibition of (3H)histamine binding to microsomal HIC, 2) inhibition of histamine binding to microsomal P450, 3) inhibition of the P450-catalyzed demethylation of aminopyrine, 4) inhibition of lymphocyte mitogenesis, and 5) stimulation of tumor colony formation. An overall rank score was assigned to each drug and correlated with tumor growth stimulation in vivo. Two laboratories conducted in vivo studies in a blinded fashion. Female C57Bl and C3H mice were given a sc injection on day 1 of syngeneic B16F10 melanoma cells (5), respectively. Mice were randomly assigned to treatment groups, then received a single, daily ip injection of an estimated human-equivalent dose (or range of doses) of antihistamine or vehicle control for 18-21 days before being killed. Tumors were surgically removed and wet weights compared statistically among groups. ... The cumulative potency of each drug in affecting tumor growth or growth mechanisms in the five in vitro assays ranked as follows: Loratidine and astemizole ranked highest and were equally potent, followed in decreasing order by hydroxyzine, doxylamine, and cetirizine. A significant correlation (r = 0.97; p < 0.02) was observed between the rank order of potency of the antihistamines in all five in vitro assays and the rank order to enhance tumor growth in vivo:Loratidine and astemizole significantly (p < 0.001) promoted the growth of both melanoma and fibrosarcoma, hydroxyzine significantly (p < 0.001) promoted the growth of melanoma, while doxylamine and cetirizine did not promote the growth of either tumor.

Evaluation: There is inadequate evidence in humans for the carcinogenicity of doxylamine succinate. There is limited evidence in experimental animals for the carcinogenicity of doxylamine succinate. Overall evaluation: Doxylamine succinate is not classifiable as to its carcinogenicity in humans (Group 3). /Doxylamine succinate/

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).

MEDICATION

Use (kg; approx.) in Germany (2009): >1000

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.

(1977) No Data

(1979) No Data

(1977) 5X10+4 G-PRINCPL CUSTMS DISTS-SUCCINATE

(1979) 4X10+5 G-PRINCPL CUSTMS DISTS-SUCCINATE

(1977) PROBABLY MORE THAN 9.1X10+5 G-SUCCINATE

(1979) PROBABLY MORE THAN 9.1X10+5 G-SUCCINATE

PREPD FROM PHENYL-2-PYRIDYLMETHYLCARBINOL & BETA-N,N-DIMETHYLAMINOETHYL CHLORIDE IN PRESENCE OF SODAMIDE IN XYLENE... SPERBER ET AL., J AM CHEM SOC 71,887 (1949)

2-Acetylpyridine + phenylmagnesium bromide + 2-dimethylaminoethyl chloride hydrochloride (Grignard reaction/ether formation)

Pyridine + acetophenone + 2-diethylaminoethyl chloride hydrochloride (Grignard reagent formation/Grignard reaction/ether formation)

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.