<!-- Definition and medical uses -->
Promethazine, sold under the brand name Phenergan among others, is a first-generation antihistamine, sedative, and antiemetic used to treat allergies, nausea, and vomiting. It may also help with some symptoms associated with the common cold 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). Promethazine is taken by mouth (oral), as a rectal suppository, or by injection into a muscle (IM). Use of promethazine is not recommended in those less than two years old, due to potentially negative effects on breathing.
<!-- History and culture -->
Promethazine was made in the 1940s by a team of scientists from Rhône-Poulenc laboratories. It was approved for medical use in the United States in 1951. In 2023, it was the 230th most commonly prescribed medication in the United States, with more than 1million prescriptions; and the combination with dextromethorphan was the 252nd most commonly prescribed medication in the United States, with more than 1million prescriptions.
Medical uses
thumb|right|upright|Phenergan (promethazine) [[blister pack 25mg tablets]]
Promethazine has a variety of medical uses, including:
- Sedation
- For nausea and vomiting associated with anesthesia or chemotherapy. It is commonly used postoperatively as an antiemetic. The antiemetic activity increases with increased dosing; however, side effects also increase, which often limits maximal dosing.
- For allergies such as hay fever and together with other medications in anaphylaxis
- Hemolytic disease of the newborn
- Dry mouth
- Respiratory depression in patients under the age of two and those with severely compromised pulmonary function
- Blurred vision, xerostomia, dry nasal passages, dilated pupils, constipation, and urinary retention. (due to its anticholinergic effects)
Less frequent:
- Cardiovascular side effects to include arrhythmias and hypotension 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.
Promethazine is listed as one of the drugs with the highest anticholinergic activity in a study of anticholinergic burden, including long-term cognitive impairment.
Overdose
Promethazine in overdose can produce signs and symptoms including CNS depression, hypotension, respiratory depression, unconsciousness, and sudden death. Other reactions may include hyperreflexia, hypertonia, ataxia, athetosis, and extensor-plantar reflexes. Despite structural differences, promethazine exhibits a strikingly similar binding profile to promazine, another phenothiazine compound. Both promethazine and promazine exhibit comparable neuroleptic potency, with a neuroleptic potency of 0.5. However, dosages used therapeutically, such as for sedation, have no antipsychotic effect. It acts primarily as a strong antagonist of the H<sub>1</sub> receptor (antihistamine, K<sub>i</sub> = 1.4 nM) and a moderate mACh receptor antagonist (anticholinergic), 5-HT<sub>2C</sub>, and α<sub>1</sub>-adrenergic receptors, where it acts as an antagonist at all sites, as well. New studies have shown that promethazine acts as a strong non-competitive selective NMDA receptor antagonist, with an EC50 of 20 μM;
Another notable use of promethazine is as a local anesthetic, by blockage of sodium channels.
|-
| α1B-adrenoceptor (Rat)
| 21
|
|-
| Calmodulin (Bovine)
| 50000
|
|
History
Promethazine was first synthesized by a group at Rhone-Poulenc (which later became part of Sanofi) led by Paul Charpentier in the 1940s. The team was seeking to improve on diphenhydramine; the same line of medical chemistry led to the creation of chlorpromazine.
Society and culture
As of July 2017, it is marketed under many brand names worldwide: Allersoothe, Antiallersin, Anvomin, Atosil, Avomine, Closin N, Codopalm, Diphergan, Farganesse, Fenazil, Fenergan, Fenezal, Frinova, Hiberna, Histabil, Histaloc, Histantil, Histazin, Histazine, Histerzin, Lenazine, Lergigan, Nufapreg, Otosil, Pamergan, Pharmaniaga, Phenadoz, Phenerex, Phenergan, Phénergan, Pipolphen, Polfergan, Proazamine, Progene, Prohist, Promet, Prometal, Prometazin, Prometazina, Promethazin, Prométhazine, Promethazinum, Promethegan, Promezin, Proneurin, Prothazin, Prothiazine, Prozin, Pyrethia, Quitazine, Reactifargan, Receptozine, Romergan, Sominex, Sylomet, Vertigon, Xepagan, Zinmet, and Zoralix.
Product liability lawsuit
In 2009, the US Supreme Court ruled on a product liability case involving promethazine. Diana Levine, a woman with a migraine, was administered Wyeth's Phenergan via IV push. The drug was injected improperly, resulting in gangrene and subsequent amputation of her right forearm below the elbow. A state jury awarded her $6 million in punitive damages.
The case was appealed to the Supreme Court on grounds of federal preemption and substantive due process. The Supreme Court upheld the lower courts' rulings, stating that "Wyeth could have unilaterally added a stronger warning about IV-push administration" without acting in opposition to federal law. In effect, this means drug manufacturers can be held liable for injuries if warnings of potential adverse effects, approved by the US Food and Drug Administration (FDA), are deemed insufficient by state courts.
In September 2009, the FDA required a boxed warning be put on promethazine for injection, stating the contraindication for subcutaneous administration. The preferred administrative route is intramuscular, which reduces the risk of surrounding muscle and tissue damage.