Doxylamine

Doxylamine

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Systematic (IUPAC) name
(RS)-N,N-dimethyl-2- (1-phenyl-1-pyridin-2-yl-ethoxy)- ethanamine
Clinical data
Pregnancy category	US: A (No risk in human studies)
Routes of administration	Oral
Legal status
Legal status	OTC
Pharmacokinetic data
Bioavailability	Oral: 24.7%, Intranasal: 70.8%
Metabolism	Hepatic
Biological half-life	variable; 6–12 hours
Excretion	Urine (primarily as metabolites)
Identifiers
CAS Number	469-21-6
ATC code	R06AA09 (WHO)
PubChem	CID 3162
DrugBank	APRD00937
ChemSpider	3050
Chemical data
Formula	C17H22N2O
Molar mass	270.369 g/mol[[]]
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Doxylamine succinate 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.

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, and is more sedating than some prescription hypnotics. One study found that doxylamine succinate is possibly more effective than the barbiturate phenobarbital for use as a sedative^{Citation Needed}. 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.

Metabolites

The two main metabolites are desmethyldoxylamine and didesmethyldoxylamine.

Formulations

• It is the sedating ingredient of NyQuil and Syndol
• In Commonwealth countries, such as Australia, Canada, South Africa and the United Kingdom, doxylamine is available prepared with paracetamol (acetaminophen) and codeine under the brand name Dolased, 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 and Unisom-2.
• In the United States doxylamine succinate is the active ingredient in the over-the-counter sleep-aid tablets branded as Unisom; however, according to the manufacturer's website, the gel-cap form contains diphenhydramine hydrochloride instead.
• 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.

Side effects

Doxylamine succinate is a potent anticholinergic and has a side-effect profile common to such drugs, including dry mouth, ataxia, urinary retention, and drowsiness.

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. Symptoms of overdose may include dry mouth, dilated pupils, insomnia, euphoria, hallucinations, seizures, rhabdomyolysis, and death. Fatalities have been reported from doxylamine overdose. These have been characterized by coma, grand mal 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. Rarely, an overdose results in rhabdomyolysis and acute renal failure.

References

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