Promethazine
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| Routes of administration | Oral, rectal, IV, IM, topical |
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| Legal status |
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| Pharmacokinetic data | |
| Bioavailability | 88% absorbed but after first-pass metabolism reduced to 25% absolute bioavailability |
| Protein binding | 93% |
| Metabolism | Hepatic glucuronidation and sulfoxidation |
| Elimination half-life | 16-19 hours |
| Excretion | Renal and biliary |
| Identifiers | |
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| CompTox Dashboard (EPA) | |
| ECHA InfoCard | 100.000.445 |
| Chemical and physical data | |
| Formula | C17H20N2S |
| Molar mass | 284.425 g/mol g·mol−1 |
Promethazine is a first-generation H1 receptor antagonist, antihistamine and antiemetic medication. It can also have strong sedative effects although it is rarely used specifically for this. It is a prescription drug in the United States, but is available over the counter in the United Kingdom, Switzerland, and many other countries (brand names Phenergan, Promethegan, Romergan, Fargan, Farganesse, Prothiazine, Avomine, Atosil, Receptozine, Lergigan).[1]
Chemically, promethazine hydrochloride (HCl) appears as a white to faint yellow crystaline powder which is practically odorless. Slow oxidation may occur upon prolonged exposure to air causing blue discoloration. Promethazine as the hydrochloride salt is freely soluble in water and somewhat soluble in alcohol.[2]
Indications
- As a sedative.[3]
- For preoperative sedation and to counteract postnarcotic nausea.[3]
- As antiallergic medication to combat hay fever, allergic rhinitis, etc. To treat allergic reactions it can be given alone or in combination with oral decongestants like pseudoephedrine.[3]
- As an adjunct treatment for anaphylactoid conditions (IM/IV route preferred).[3]
- Together with codeine or dextromethorphan against cough.
- As a motion sickness or seasickness remedy when used with Ephedrine or Pseudoephedrine.[3]
- To combat moderate to severe morning sickness and hyperemesis gravidarum. In the UK promethazine is drug of first choice, being preferred as an older drug with which there is a greater experience of use in pregnancy (second line being metoclopramide or prochlorperazine).[4]
Contraindications
- Promethazine should not be given to children under two years of age; there is potential for fatal respiratory depression in this age group.[5]
- Hypersensitivity to phenothiazines[6]
- Closed angle glaucoma[6]
- Intoxication with alcohol or other central depressants[6]
- Severe hypotension or shock[6]
- Coma due to any reason[6]
- Severely impaired liver function[6]
- Urine hesitancy due to enlargement of the prostate gland[6]
Mechanism of action
- Promethazine is a phenothiazine derivative that competitively blocks histamine H1 receptors without blocking the secretion of histamine.[7]
- It has sedative, anti-motion-sickness, anti-emetic, and anti-cholinergic effects
Side effects
Some common side effects include:
- Blurred vision
- Confusion in the elderly
- Drowsiness, dizziness, fatigue, more rarely vertigo
- Dry mouth
- Seizures (extremely rare)
- Neuroleptic malignant syndrome (extremely rare)
- Respiratory depression in patients under age of 2 and in those with severely compromised pulmonal function
- Constipation
- Euphoria (very rare with high IV doses and/or coadministration with opioids/CNS depressants)
- Restless legs [8]
- Paresthesia
It is recommended that promethazine only be given through an existing intravenous set in a large vein and diluted to concentration no greater than 25mg per mL, not to exceed a rate of administration of 25mg a min. Serious complications including those listed above have resulted from improper parenteral administration, including those requiring surgical intervention and amputation.[9]
Laboratory examinations
All patients should have their blood pressure measured frequently. During long-term therapy, blood cell counts, liver function studies, EKG, and EEG are recommended. The intervals should be determined according to the risk profile of the patient. In high doses, promethazine can create auditory and visual hallucinations causing panic and intense fear.
Recreational use
Promethazine is sometimes used as a recreational drug in conjunction with codeine in prescription cough syrup. The syrup by itself contains 7% alcohol. The traditional mixture of Sprite and cough syrup with codeine, which is known as "purple drank", "Sizzurp", or "lean", is popularized in the rap world, especially in the Houston area.[10] It is also sometimes used to counteract nausea caused by illicit opioid use.
Politics
The U.S. Supreme Court has accepted a case involving promethazine that may influence product liability. A musician suffering from a migraine was administered Wyeth's Phenergan via IV push. The drug entered her arterial flow resulting in gangrene and subsequent amputation of her right arm below the elbow. A state jury awarded her $6 million in punitive damages. The case has been appealed to the Supreme Court on grounds of federal pre-emption and substantive due process.[11]
References
- ^ RxList: Promethazine
- ^ http://www.rxlist.com/cgi/generic/phenergan.htm RxList: Promethazine Description
- ^ a b c d e RxList Indications for Promethazine
- ^ British National Formulary (2003). "4.6 Drugs used in nausea and Vertigo - Vomiting of pregnancy". "BNF" (45 ed.).
{{cite book}}: Unknown parameter|month=ignored (help) - ^ "Letter from Wyeth Pharmaceuticals to practitioners regarding use of Phenergan in under twos" (PDF). FDA.
- ^ a b c d e f g RxList Contraindications
- ^ David J. McCann and Brett Roth, Toxicity, Antihistamine, eMedicine Toxicology, updated June 21, 2007
- ^ Cordingley Neurology
- ^ Baxter: Promethazine HCl Injection, USP Information
- ^ Peters RJ, Kelder SH, Markham CM, Yacoubian GS, Peters LA, Ellis A (2003). "Beliefs and social norms about codeine and promethazine hydrochloride cough syrup (CPHCS) onset and perceived addiction among urban Houstonian adolescents: an addiction trend in the city of lean". J Drug Educ. 33 (4): 415–25. doi:10.2190/NXJ6-U60J-XTY0-09MP. PMID 15237866.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ Liptak, Adam (2008-09-18). "Drug Label, Maimed Patient and Crucial Test for Justices". The New York Times. Retrieved 2008-10-31.
External links
- "Promethazine". U.S. National Library of Medicine and National Institutes of Health.