Source: Medicines and Medical Devices Safety Authority (NZ) Revision Year: 2018 Publisher: Pharmaco (NZ) Ltd, 4 Fisher Crescent, Mt Wellington, Auckland 1060, Telephone: 09 377 3336
Pharmacotherapeutic group: Antihistamines for systemic use
ATC code: R06AA02
Diphenhydramine is an ethanolamine antihistamine with anticholinergic and sedative effects.
The primary action of diphenhydramine is the antagonism of certain effect of histamine such as broncho-constriction and capillary dilation.
The most frequently encountered secondary effects of diphenhydramine are related to central nervous system depression. The effects vary from slight drowsiness to deep sleep and have been reported to include the inability to concentrate, lassitude, dizziness, muscular weakness and incoordination. However, the sedative action of diphenhydramine has been found to be of some value for occasional use in the relief of nighttime sleeplessness. The sedative action may last up to 6 hours but often diminishes after a few days as tolerance to this effect develops.
Other actions of diphenhydramine include an antiemetic effect and some anticholinergic activity which can produce blurred vision, dry mouth, and gastroinstestinal disturbances (e.g. nausea, vomiting, epigastric pain, diarrhoea).
Diphenhydramine is well absorbed following oral administration with the drug appearing in plasma within 15 minutes. High first-pass metabolism in the liver appears to affect systemic availability with only 40-60% of oral dose reaching the systemic circulation as unchanged diphenhydramine. Peak plasma concentrations are achieved within 1-4 hours. The sedative effect appears to be maximal within 1-3 hours after administration of a single dose of diphenhydramine and appears to be positively correlated with plasma drug concentration, with marked drowsiness and/or sleep occurring at plasma concentrations of 70 ng/ml or greater.
Diphenhydramine is widely distributed throughout the body including the CNS. The drug crosses the placenta and has been detected in human milk although the extent has not been quantitated. Diphenhydramine is approximately 80-85% protein bound in-vitro. Less extensive protein binding has been reported in healthy oriental adults and in adults with liver cirrhosis.
The terminal elimination half-life of diphenhydramine appears to range from 2.4-9.3 hours in healthy adults. It may be prolonged in adults with liver cirrhosis.
Diphenhydramine is rapidly and almost completely metabolised. Following oral administration of a single 100 mg dose in healthy adults, about 50-75% of the dose is excreted in urine within 4 days almost completely as metabolites. Most urinary excretion occurs within the first 24-48 hours and only about 1% of a single dose is excreted unchanged in the urine.
Long-term animal studies to determine the mutagenic and carcinogenic potential of diphenhydramine have not been performed to date.
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