Labeled Indications, FDA Approved:
Promethazine is a phenothiazine derivative with antidopaminergic, antihistamine, and anticholinergic properties. Other phenothiazines derivatives include prochlorperazine and chlorpromazine. Promethazine is a direct antagonist at the mesolimbic dopamine receptors and alpha-adrenergic receptor in the brain. Promethazine exhibits its antihistamine effects as an H1-receptor blocker.
Promethazine has several routes of administration, including oral, rectal, intramuscular, and intravenous. When administered orally, give with food, water, or milk to decrease gastrointestinal discomfort. The intramuscular injection must be into deep muscle tissue as the subcutaneous injection may result in tissue damage. Intravenous use should be used with caution as severe tissue damage may also occur. In selected patients, promethazine may be diluted before IV administration to prevent promethazine-induced tissues necrosis. The dosage of tablets, solutions, and suppository is generally 12.5 mg to 50 mg. There is also a syrup form of 6.25 mg/5 ml.
In pediatrics, promethazine has the same routes of administration as adults. However, dosing adjustments are necessary based on the weight of the patient and the indication. Utilizing the lowest dose of efficacy is recommended.
There are no dosage adjustments for renal or hepatic impairment.
There are several potential adverse effects of promethazine administration related to its method of action. The most common side effects include sedation, confusion, and disorientation, which may impair physical and mental abilities. However, in some cases, promethazine may paradoxically cause excitability, restlessness, or rarely seizures.
Due to promethazine’s anticholinergic properties, it may cause anticholinergic side effects, which include blurred vision, xerostomia, dry nasal passages, dilated pupils, constipation, and urinary retention. Due to these effects, promethazine has been categorized as potentially inappropriate drug in the elderly by the American Geriatrics Society.
Promethazine’s antidopaminergic properties may result in extrapyramidal symptoms, which include pseuodoparkinsonism, acute dystonia, akathisia, and tardive dyskinesia. Promethazine, therefore, may worsen symptoms in patients with Parkinson disease.
Black Box Warnings:
Less common adverse effects that prescribers should be aware of include:
Promethazine contraindications include patients with hypersensitivity to the drug, any components of the drug, or other phenothiazines. It is contraindicated in children under 2 years of age due to the risk of potentially fatal respiratory depression. Promethazine is contraindicated for subcutaneous or intra-arterial administration due to the risk of tissue damage. Contraindications also include comatose patients and patients with lower respiratory tract symptoms.
Due to promethazine’s side effect profile, any medical personnel who administers the drug should be aware of potential side effects. Healthcare providers need to monitor patients for burning or pain at the injection site, phlebitis, blistering, or swelling as this may indicate tissue damage. Extrapyramidal and anticholinergic side effects also require monitoring, and providers should be notified immediately if they appear. Promethazine is also CNS depressant, so safety measure such as side rails up and call light within reach should be in place.
The main feature of promethazine toxicity is CNS depression, tachycardia, respiratory depression, and delirium. For most overdoses, supportive care and monitoring are the treatment as there is no known antidote. Significant overdoses with profoundly depressed mental status or coma may require airway support, hemodynamic monitoring, and a higher level of care. Some studies have shown that early administration of charcoal within 2 hours may be beneficial. However, the evidence is still lacking, and further studies are necessary.
Overall, promethazine is a relatively safe medication that is very useful in several circumstances such as nausea/vomiting, allergic conditions, prevention of motion sickness, and pre/post-operative or obstetric sedation. However, any prescriber of the medication should be aware of the potential side effects and contraindications. Providers must be mindful of the two black box warning associated which include potential to cause severe tissue damage with IM/IV injection and potentially fatal respiratory depression in children under two years of age.
Therefore, close interprofessional coordination between providers (MDs, DOs, NPs, PAs), nurses, pharmacists, and other healthcare workers is necessary to improve patient outcomes and decrease adverse events when using promethazine. Pharmacists can reconcile the patient's medication profile, and report back to the nurse or prescribing clinician if any interactions exist. Nurses will often be the first to see the patient and can monitor for apparent adverse effects, either reporting to the prescriber or checking with the pharmacist regarding the adverse event profile of promethazine. Nursing is also in charge of IV administration so that they will have first-line exposure to issues such as extravasation, and can inform the clinician. The entire interprofessional healthcare team must collaborate, each discipline bringing its expertise to support positive outcomes.
|||Wallace DV,Dykewicz MS,Bernstein DI,Blessing-Moore J,Cox L,Khan DA,Lang DM,Nicklas RA,Oppenheimer J,Portnoy JM,Randolph CC,Schuller D,Spector SL,Tilles SA, The diagnosis and management of rhinitis: an updated practice parameter. The Journal of allergy and clinical immunology. 2008 Aug; [PubMed PMID: 18662584]|
|||Powell RJ,Leech SC,Till S,Huber PA,Nasser SM,Clark AT, BSACI guideline for the management of chronic urticaria and angioedema. Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology. 2015 Mar; [PubMed PMID: 25711134]|
|||Zuberbier T,Aberer W,Asero R,Bindslev-Jensen C,Brzoza Z,Canonica GW,Church MK,Ensina LF,Gim�nez-Arnau A,Godse K,Gon�alo M,Grattan C,Hebert J,Hide M,Kaplan A,Kapp A,Abdul Latiff AH,Mathelier-Fusade P,Metz M,Nast A,Saini SS,S�nchez-Borges M,Schmid-Grendelmeier P,Simons FE,Staubach P,Sussman G,Toubi E,Vena GA,Wedi B,Zhu XJ,Maurer M, The EAACI/GA(2) LEN/EDF/WAO Guideline for the definition, classification, diagnosis, and management of urticaria: the 2013 revision and update. Allergy. 2014 Jul; [PubMed PMID: 24785199]|
|||Grunberg SM,Hesketh PJ, Control of chemotherapy-induced emesis. The New England journal of medicine. 1993 Dec 9; [PubMed PMID: 8232489]|
|||Tortorice PV,O'Connell MB, Management of chemotherapy-induced nausea and vomiting. Pharmacotherapy. 1990; [PubMed PMID: 2190193]|
|||Gan TJ,Meyer TA,Apfel CC,Chung F,Davis PJ,Habib AS,Hooper VD,Kovac AL,Kranke P,Myles P,Philip BK,Samsa G,Sessler DI,Temo J,Tram�r MR,Vander Kolk C,Watcha M, Society for Ambulatory Anesthesia guidelines for the management of postoperative nausea and vomiting. Anesthesia and analgesia. 2007 Dec; [PubMed PMID: 18042859]|
|||Shupak A,Gordon CR, Motion sickness: advances in pathogenesis, prediction, prevention, and treatment. Aviation, space, and environmental medicine. 2006 Dec; [PubMed PMID: 17183916]|
|||POTTS CR,ULLERY JC, Maternal and fetal effects of obstetric analgesia. Intravenous use of promethazine and meperidine. American journal of obstetrics and gynecology. 1961 Jun; [PubMed PMID: 13737524]|
|||ACOG Practice Bulletin No. 189: Nausea And Vomiting Of Pregnancy. Obstetrics and gynecology. 2018 Jan; [PubMed PMID: 29266076]|
|||Tan PC,Khine PP,Vallikkannu N,Omar SZ, Promethazine compared with metoclopramide for hyperemesis gravidarum: a randomized controlled trial. Obstetrics and gynecology. 2010 May; [PubMed PMID: 20410771]|
|||Rumeau-Rouquette C,Goujard J,Huel G, Possible teratogenic effect of phenothiazines in human beings. Teratology. 1977 Feb; [PubMed PMID: 841482]|
|||Page CB,Duffull SB,Whyte IM,Isbister GK, Promethazine overdose: clinical effects, predicting delirium and the effect of charcoal. QJM : monthly journal of the Association of Physicians. 2009 Feb; [PubMed PMID: 19042969]|
|||Sharma A,Hamelin BA, Classic histamine H1 receptor antagonists: a critical review of their metabolic and pharmacokinetic fate from a bird's eye view. Current drug metabolism. 2003 Apr; [PubMed PMID: 12678691]|
|||Reynolds PM,MacLaren R,Mueller SW,Fish DN,Kiser TH, Management of extravasation injuries: a focused evaluation of noncytotoxic medications. Pharmacotherapy. 2014 Jun; [PubMed PMID: 24420913]|
|||Hurst S,McMillan M, Innovative solutions in critical care units: extravasation guidelines. Dimensions of critical care nursing : DCCN. 2004 May-Jun; [PubMed PMID: 15192356]|
|||American Geriatrics Society 2019 Updated AGS Beers Criteria� for Potentially Inappropriate Medication Use in Older Adults. Journal of the American Geriatrics Society. 2019 Apr; [PubMed PMID: 30693946]|
|||Starke PR,Weaver J,Chowdhury BA, Boxed warning added to promethazine labeling for pediatric use. The New England journal of medicine. 2005 Jun 23; [PubMed PMID: 15972879]|
|||Neonatal deaths associated with use of benzyl alcohol--United States. MMWR. Morbidity and mortality weekly report. 1982 Jun 11; [PubMed PMID: 6810084]|