indication

For the treatment of allergic disorders, and nausea/vomiting.

pharmacology

Promethazine, a phenothiazine, is an H1-antagonist with anticholinergic, sedative, and antiemetic effects and some local anesthetic properties. Promethazine is used as an antiemetic or to prevent motion sickness.

mechanism of action

Like other H1-antagonists, promethazine competes with free histamine for binding at H1-receptor sites in the GI tract, uterus, large blood vessels, and bronchial muscle. The relief of nausea appears to be related to central anticholinergic actions and may implicate activity on the medullary chemoreceptor trigger zone.

toxicity

Symptoms of overdose include mild depression of the central nervous system and cardiovascular system to profound hypotension, respiratory depression, unconsciousness, and sudden death. Other reported reactions include hyperreflexia, hypertonia, ataxia, athetosis, and extensor-plantar reflexes (Babinski reflex). LD₅₀=55mg/kg (I.V. in mice)

biotransformation

Hepatic

absorption

On average, 88% of a promethazine dose is absorbed after oral administration; however, the absolute bioavailability is only 25% because of first-pass clearance.

half life

16-19 hours

route of elimination

Promethazine hydrochloride is metabolized in the liver, with the sulfoxides of promethazine and N-desmethylpromethazine being the predominant metabolites appearing in the urine.

drug interactions

Amphetamine: Decreased anorexic effect, may increase pyschotic symptoms

Benzphetamine: Antipsychotics may diminish the stimulatory effect of Amphetamines. Monitor effectiveness of amphetamine therapy when altering concurrent antipsychotic therapy as antipsychotic agents may impair the stimulatory effect of amphetamines.

Bromocriptine: The phenothiazine decreases the effect of bromocriptine

Cisapride: Increased risk of cardiotoxicity and arrhythmias

Desvenlafaxine: Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.

Dexfenfluramine: Decreased anorexic effect, may increase pyschotic symptoms.

Dextroamphetamine: Decreased anorexic effect, may increase pyschotic symptoms

Diethylpropion: Decreased anorexic effect, may increase psychotic symptoms.

Donepezil: Possible antagonism of action

Fenfluramine: Decreased anorexic effect, may increase psychotic symptoms.

Galantamine: Possible antagonism of action

Gatifloxacin: Increased risk of cardiotoxicity and arrhythmias

Grepafloxacin: Increased risk of cardiotoxicity and arrhythmias

Guanethidine: Promethazine may decrease the effect of guanethidine.

Levofloxacin: Increased risk of cardiotoxicity and arrhythmias

Mazindol: Decreased anorexic effect, may increase psychotic symptoms.

Methamphetamine: Decreased anorexic effect, may increase pyschotic symptoms

Metrizamide: Increased risk of convulsions

Phendimetrazine: Decreased anorexic effect, may increase pyschotic symptoms

Phenmetrazine: Decreased anorexic effect, may increase pyschotic symptoms

Phentermine: Decreased anorexic effect, may increase psychotic symptoms.

Phenylpropanolamine: Decreased anorexic effect, may increase psychotic symptoms.

Rivastigmine: Possible antagonism of action

Sparfloxacin: Increased risk of cardiotoxicity and arrhythmias

Tacrine: The therapeutic effects of the central acetylcholinesterase inhibitor, Tacrine, and/or the anticholinergic, Promethazine, may be reduced due to antagonism. The interaction may be beneficial when the anticholinergic action is a side effect. Monitor for decreased efficacy of both agents.

Terbinafine: Terbinafine may reduce the metabolism and clearance of Promethazine. Consider alternate therapy or monitor for therapeutic/adverse effects of Promethazine if Terbinafine is initiated, discontinued or dose changed.

Terfenadine: Increased risk of cardiotoxicity and arrhythmias

Thiotepa: Thiotepa, a strong CYP2B6 inhibitor, may decrease the metabolism and clearance of Promethazine, a CYP2B6 substrate. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of Promethazine if Thiotepa is initiated, discontinued or dose changed.

Tramadol: Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.

Tranylcypromine: Increased risk of serotonin syndrome. Use caution during concomitant therapy and monitor for symptoms of serotonin syndrome.

Trazodone: Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.

Trimethobenzamide: Trimethobenzamide and Promethazine, two anticholinergics, may cause additive anticholinergic effects and enhance their adverse/toxic effects. Monitor for enhanced anticholinergic effects.

Trimipramine: Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.

Triprolidine: Triprolidine and Promethazine, two anticholinergics, may cause additive anticholinergic effects and enhance their adverse/toxic effects. Monitor for enhanced anticholinergic effects.

Trospium: Trospium and Promethazine, two anticholinergics, may cause additive anticholinergic effects and enhanced adverse/toxic effects. Monitor for enhanced anticholinergic effects.

Venlafaxine: Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.

Zolmitriptan: Use of two serotonin modulators, such as zolmitriptan and promethazine, increases the risk of serotonin syndrome. Consider alternate therapy or monitor for serotonin syndrome during concomitant therapy.