Katana VentraIP

Promethazine

Promethazine, sold under the brand name Phenergan among others, is a first-generation antihistamine, antipsychotic, sedative, and antiemetic used to treat allergies, insomnia, and nausea. It may also help with some symptoms associated with the common cold[4] and may also be used for sedating people who are agitated or anxious, an effect that has led to some recreational use (especially with codeine).[5][6][7] Promethazine is taken by mouth (oral), as a rectal suppository, or by injection into a muscle (IM).[4]

Clinical data

Phenergan, many others[1]

Monograph

a682284

  • AU: C

By mouth, rectal, intravenous, intramuscular, topical

88% absorbed but after first-pass metabolism reduced to 25% absolute bioavailability[2]

93%

Liver glucuronidation and sulfoxidation

10–19 hours[2][3]

Kidney and Bile duct

100.000.445

C17H20N2S

284.42 g·mol−1

Racemic mixture

Common side effects of promethazine include confusion and sleepiness;[4] consumption of alcohol or other sedatives can make these symptoms worse.[4] It is unclear if use of promethazine during pregnancy or breastfeeding is safe for the fetus.[4][6] Use of promethazine is not recommended in those less than two years old, due to potentially negative effects on breathing.[4] Use of promethazine by injection into a vein is not recommended, due to potential skin damage.[4] Promethazine is in the phenothiazine family of medications.[4] It is also a moderate anticholinergic, which produces its sedative effects. This also means high or toxic doses can act as a deliriant.[8]


Promethazine was made in the 1940s by a team of scientists from Rhône-Poulenc laboratories.[9] It was approved for medical use in the United States in 1951.[4] It is a generic medication and is available under many brand names globally.[1] In 2021, it was the 188th most commonly prescribed medication in the United States, with more than 2 million prescriptions.[10][11] In 2021, the combination with dextromethorphan was the 289th most commonly prescribed medication in the United States, with more than 600,000 prescriptions.[10][12]

Sedation

[13]

In Germany, it is approved for the treatment of agitation and agitation associated with underlying psychiatric disorders with a maximum daily dose of 200 mg.

[14]

For nausea and vomiting associated with anesthesia or chemotherapy. It is commonly used postoperatively as an . The antiemetic activity increases with increased dosing; however, side effects also increase, which often limits maximal dosing.[13]

antiemetic

For moderate to severe and hyperemesis gravidarum: In the UK, Promethazine is the drug of first choice. Promethazine is preferred during pregnancy because it is an older drug and there is more data regarding the use of it during pregnancy. Second choice medications, which are used if Promethazine isn't tolerated or the patient cannot take it, are metoclopramide or prochlorperazine.[15][13]

morning sickness

For allergies such as and together with other medications in anaphylaxis[4]

hay fever

To aid with symptoms of the [4]

common cold

,[4] including space sickness[16]

Motion sickness

[4]

Hemolytic disease of the newborn

before surgery[4]

Anxiety

Short-term [17]

insomnia

Promethazine has a variety of medical uses, including:

pseudoparkinsonism, acute dystonia (effects due to dopamine D2 receptor antagonism)[13]

Tardive dyskinesia

Confusion in the elderly

[13]

Drowsiness, dizziness, fatigue, more rarely

vertigo

Known to have effects on and dopamine receptors.[18]

serotonin

Dry mouth

[13]

Nausea

[19]

in patients under age of two and in those with severely compromised pulmonary function[20]

Respiratory depression

Blurred vision, xerostomia, dry nasal passages, dilated pupils, constipation, and urinary retention. (due to its anti-cholinergic effects)

[13]

Chest discomfort/pressure (In children less than 2 years old)

[13]

[21]

Akathisia

Some documented side effects include:


Less frequent:


Rare side effects include:


Because of potential for more severe side effects, this drug is on the list to avoid in the elderly.[22] In many countries (including the US and UK), promethazine is contraindicated in children less than two years of age, and strongly cautioned against in children between two and six, due to problems with respiratory depression and sleep apnea.[23]


Promethazine is listed as one of the drugs of highest anticholinergic activity in a study of anticholinergenic burden, including long-term cognitive impairment.[24]

Overdose[edit]

Promethazine in overdose can produce signs and symptoms including CNS depression, hypotension, respiratory depression, unconsciousness, and sudden death.[25] Other reactions may include hyperreflexia, hypertonia, ataxia, athetosis, and extensor-plantar reflexes.[25] Atypically and/or rarely, stimulation, convulsions, hyperexcitability, and nightmares may occur.[25] Anticholinergic effects like dry mouth, dilated pupils, flushing, gastrointestinal symptoms, and delirium may occur as well.[25] Treatment of overdose is supportive and based on symptoms.[25]

Chemistry[edit]

Solid promethazine hydrochloride is a white to faint-yellow, practically odorless, crystalline powder. Slow oxidation may occur upon prolonged exposure to air, usually causing blue discoloration. Its hydrochloride salt is freely soluble in water and somewhat soluble in alcohol. Promethazine is a chiral compound, occurring as a mixture of enantiomers.[42]

History[edit]

Promethazine was first synthesized by a group at Rhone-Poulenc (which later became part of Sanofi) led by Paul Charpentier in the 1940s.[43] The team was seeking to improve on diphenhydramine; the same line on medical chemistry led to the creation of chlorpromazine.[44]

with as Actithiol Antihistaminico, Mucoease, Mucoprom, Mucotal Prometazine, and Rhinathiol;

carbocisteine

with (acetaminophen) as Algotropyl, Calmkid, Fevril, Phen Plus, and Velpro-P;

paracetamol

with and dextromethorphan as Choligrip na noc, Coldrex Nočná Liečba, Fedril Night Cold and Flu, Night Nurse, and Tachinotte;

paracetamol

with , phenylephrine, and salicylamide as Flukit;

paracetamol

with as Axcel Dextrozine and Hosedyl DM;

dextromethorphan

with and ephedrine as Methorsedyl;

dextromethorphan

with and pseudoephedrine as Sedilix-DM;

dextromethorphan

with and phenylephedrine as Sedilix-RX;

dextromethorphan

with as Codo-Q Junior and Tixylix;

pholcodine

with and ephedrine as Phensedyl Dry Cough Linctus;

pholcodine

with and phenylephedrine as Russedyl Compound Linctus;

pholcodine

with and phenylpropanolamine as Triple 'P';

pholcodine

with as Kefei and Procodin;

codeine

with and ephedrine as Dhasedyl, Fendyl, and P.E.C.;

codeine

with and dextromethorphan as Dhasedyl DM;

ephedrine

with as Psico-Soma, and Psicosoma;

glutamic acid

with as Tussisedal; and

noscapine

with and phenobarbital as Vegetamin.[1]

chlorpromazine