Doxylamine

Doxylamine
Doxylamine
Systematic (IUPAC) name
(RS)-N,N-dimethyl-2- (1-phenyl-1-pyridin-2-yl-ethoxy)- ethanamine
Clinical data
Trade names Unisom
AHFS/Drugs.com monograph
MedlinePlus a682537
Pregnancy cat.  ?
Legal status OTC
Routes Oral
Pharmacokinetic data
Bioavailability Oral: 24.7%, Intranasal: 70.8% [1]
Metabolism Hepatic
Half-life variable; 6–12 hours
Excretion Urine (primarily as metabolites)
Identifiers
CAS number 469-21-6 YesY
ATC code R06AA09
PubChem CID 3162
DrugBank APRD00937
ChemSpider 3050 YesY
UNII 95QB77JKPL YesY
KEGG D07878 YesY
ChEBI CHEBI:51380 YesY
ChEMBL CHEMBL1004 YesY
Chemical data
Formula C17H22N2O 
Mol. mass 270.369 g/mol
SMILES eMolecules & PubChem
 N(what is this?)  (verify)

Doxylamine is one of the many sedating antihistamines used by itself as a short-term sedative, and in combination with other drugs as a night-time cold and allergy relief drug. It is also used in combination with the analgesics paracetamol (acetaminophen) and codeine as an analgesic/calmative preparation, and is prescribed in combination with vitamin B6 (pyridoxine) to prevent morning sickness in pregnant women.

Contents

Indications

Doxylamine is a member of the ethanolamine class of antihistamines and has anti-allergy power superior to almost every other antihistamine on the market, with the exception of diphenhydramine (Benadryl). It is also the most effective over-the-counter sedative available in the United States [2] and is more sedating than some prescription hypnotics. One study found that doxylamine succinate was more effective than the barbiturate phenobarbital for use as a sedative.[2]

The dosage required to induce hypnosis (sleep) can be as low as 6.25 mg, but is usually effective in dosages of up to 25 mg. Higher doses are not recommended by the United States Food and Drug Administration, although single dosage recommendations of up to 50 mg are common in some countries, including Australia, where it is marketed under the names Restavit and Dozile. A recent placebo-controlled, double-blind randomized trial found the formulation of doxylamine and pyridoxine marketed as Diclectin to be effective in controlling nausea and vomiting due to pregnancy.[3]

Metabolites

The two main metabolites are desmethyldoxylamine and didesmethyldoxylamine.

Side effects

Doxylamine succinate is a potent anticholinergic and has a side-effect profile common to such drugs, including dry mouth, ataxia, urinary retention, drowsiness, memory problems, inability to concentrate, hallucinations, psychosis, and a marked increased sensitivity to external stimuli. Like many hypnotics, it should not be combined with other antihistamines, such as Zyrtec (cetirizine) or diphenhydramine, as this combination can increase the risk of serious side effects. Using doxylamine over a long period of time is not recommended and can cause dependence. However, the drug is not addictive and withdrawal effects are unlikely to be experienced with prolonged use.

Toxicity

Doxylamine succinate is generally safe for administration to healthy adults. Typical preparations that contain doxylamine range from 6.25 mg to 50 mg. The LD50 is estimated to be 50–500 mg/kg in humans.[4] Symptoms of overdose may include dry mouth, dilated pupils, insomnia, night terrors, euphoria, hallucinations, seizures, rhabdomyolysis, and death.[5] Fatalities have been reported from doxylamine overdose. These have been characterized by coma, tonic-clonic seizures and cardiorespiratory arrest. Children appear to be at a high risk for cardiorespiratory arrest. A toxic dose for children of more than 1.8 mg/kg has been reported. A 3 year old child died 18 hours after ingesting 1,000 mg doxylamine succinate.[6] Rarely, an overdose results in rhabdomyolysis and acute renal failure.[7]

Formulations

Doxylamine is primarily used as the succinic acid salt, doxylamine succinate.

  • It is the sedating ingredient of NyQuil.
  • In Commonwealth countries, such as Australia, South Africa and the United Kingdom, doxylamine is available prepared with paracetamol (acetaminophen) and codeine under the brand name Dolased, Propain Plus, Syndol, or Mersyndol, as treatment for tension headache and other types of pain.
  • Doxylamine succinate is used in general over-the-counter sleep-aids branded as Somnil, Dozile, Donormyl, Dormidina, Restavit, Unisom-2 and Sleep Aid (generic - Australia),.
  • In the United States doxylamine succinate is the active ingredient in the over-the-counter sleep-aid tablets branded as Unisom; however, the gel-cap form contains diphenhydramine hydrochloride instead.[8]
  • In Canada doxylamine succinate is the active ingredient in the over-the-counter sleep-aid tablets branded as Unisom 2; while Unisom contains diphenhydramine hydrochloride as the active ingredient.
  • It is also available in combination with vitamin B6 and folic acid under the brand name Evanorm (marketed by Ion Healthcare).
  • In Canada, doxylamine succinate and pyridoxine (vitamin B6) are the ingredients of Diclectin, which is used to prevent morning sickness.

References

  1. ^ http://www3.interscience.wiley.com/journal/98016819/abstract
  2. ^ a b http://www.drugbank.ca/drugs/DB00366
  3. ^ Am J Obstet Gynecol. 2010 Sep 13. [Epub ahead of print]
  4. ^ http://hazard.com/msds/mf/baker/baker/files/d8882.htm
  5. ^ Syed, Husnain; Sumit Som, Nazia Khan, Wael Faltas (17 March 2009). "Doxylamine toxicity: seizure, rhabdomyolysis and false positive urine drug screen for methadone". BMJ Case Reports (BMJ Group) 2003 (90): 845. doi:10.1136/bcr.09.2008.0879. http://casereports.bmj.com/cgi/content/abstract/2009/mar08_1/bcr0920080879. Retrieved 29 November 2009. 
  6. ^ http://www.medsafe.govt.nz/profs/datasheet/d/Dozilecap.pdf
  7. ^ Leybishkis B, B; Fasseas P; Ryan KF. (July 2001). "Doxylamine overdose as a potential cause of rhabdomyolysis". American journal of the medical sciences (Lippincott Williams & Wilkins) 322 (1): 48–9. doi:10.1097/00000441-200107000-00009. PMID 11465247. 
  8. ^ manufacturer's website
v · d · eAntiemetics (A04)
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M: DIG

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noco/cong/tumr, sysi/epon

proc, drug(A2A/2B/3/4/5/6/7/14/16), blte

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Look at other dictionaries:

  • Doxylamine — Général Nom IUPAC (RS) N,N diméthyl 2 (1 phényl 1 pyridin 2 yl éthoxy) éthanamine …   Wikipédia en Français

  • doxylamine — dox·yl·amine däk sil ə .mēn, mən n an antihistamine derived from pyridine and usu. administered in the form of its succinate C17H22N2O·C4H6O4 …   Medical dictionary

  • doxylamine — dox·yl·a·mine …   English syllables

  • doxylamine — däkˈsiləˌmēn, mə̇n noun Etymology: probably from d (from dimethyl) + oxy + l (from yl) + amine : an antihistamine C17H22N2O derived from pyridine and usually administered in the form of its succinate …   Useful english dictionary

  • doxylamine succinate — noun A sedating antihistamine of the ethanolamine class …   Wiktionary

  • doxylamine succinate — An antihistaminic. SYN: mereprine. * * * dox·yl·amine suc·ci·nate (dok silґə mēn) [USP] an antihistamine (H1 receptor antagonist) with sedative and anticholinergic effects; used in the treatment of allergic rhinitis, allergic… …   Medical dictionary

  • 469-21-6 — Doxylamine doxylamine Général Nom IUPAC (RS) N,N diméthyl 2 (1 phényl 1 pyridin 2 yl éthoxy) éthan …   Wikipédia en Français

  • C17H22N2O — Doxylamine doxylamine Général Nom IUPAC (RS) N,N diméthyl 2 (1 phényl 1 pyridin 2 yl éthoxy) éthan …   Wikipédia en Français

  • Donormyl — Doxylamine doxylamine Général Nom IUPAC (RS) N,N diméthyl 2 (1 phényl 1 pyridin 2 yl éthoxy) éthanam …   Wikipédia en Français

  • Lidene — Doxylamine doxylamine Général Nom IUPAC (RS) N,N diméthyl 2 (1 phényl 1 pyridin 2 yl éthoxy) éthanam …   Wikipédia en Français

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