Promethazine


Article Author:
Brittin Southard


Article Editor:
Yasir Al Khalili


Editors In Chief:
Stephen Leslie
Karim Hamawy


Managing Editors:
Avais Raja
Orawan Chaigasame
Carrie Smith
Abdul Waheed
Khalid Alsayouri
Trevor Nezwek
Radia Jamil
Patrick Le
Anoosh Zafar Gondal
Saad Nazir
William Gossman
Hassam Zulfiqar
Steve Bhimji
John Shell
Matthew Varacallo
Heba Mahdy
Ahmad Malik
Sarosh Vaqar
Mark Pellegrini
James Hughes
Beata Beatty
Nazia Sadiq
Hajira Basit
Phillip Hynes
Tehmina Warsi


Updated:
7/7/2019 1:09:54 PM

Indications

Labeled Indications, FDA Approved:

  • Allergic Conditions: Promethazine is a first-generation antihistamine, and thus it is indicated for a variety of allergic conditions including seasonal allergic rhinitis, allergic conjunctivitis, uncomplicated skin manifestations of urticaria and angioedema, and adjunctive therapy to epinephrine for anaphylactic reactions.[1][2][3]
  • Nausea and Vomiting: Phenothiazines such as promethazine have substantial antiemetic activity. Promethazine is used to control nausea and vomiting in association with anesthesia or chemotherapy. It is commonly used post-operatively as an antiemetic. The antiemetic activity increases with increased dosing, however, side effects also increase, which often limits maximal dosing. [4][5][6]
  • Motion Sickness: Promethazine can serve as prophylactic therapy for motion sickness. It is most effective when given 30 minutes to 1 hour before undergoing the triggering event.[7]
  • Sedation: Promethazine can be used as adjunctive therapy with other analgesics to provide preoperative, postoperative, or obstetric sedation.[8]

Off-Label Usage:

  • Nausea and vomiting associated with pregnancy: According to the American College of Obstetrics promethazine is useful in nausea and vomiting during pregnancy when preferred agents do not provide symptomatic relief. A double-blinded randomized controlled trial of intravenous promethazine versus metoclopramide in women with hyperemesis gravidarum found similar efficacy between to the two drugs in controlling nausea and vomiting at 24 hours but found increased side effects in the promethazine group such as dry mouth, drowsiness, dizziness, and dystonia. Research has also identified phenothiazines as a potential cause of congenital malformations in one study, but other studies attest to their safety. Promethazine is classified as category C by the FDA. Alternative therapies may be indicated before promethazine considering the risks to the fetus and adverse effects to the mother.[9][10][11]

Mechanism of Action

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.[12][13]

Administration

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 prior to 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.[14][15]

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.

Adverse Effects

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.[16]

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.[16]

Black Box Warnings:

  1. In children less than 2 years old, reports exist of respiratory depression resulting in fatalities. For this reason, there is US Black Box Warning on the use of promethazine in children less than 2 years of age.[17][18]
  2. Promethazine may cause serious tissue injury on injection, including gangrene regardless of the route of administration. This effect may occur as a result of extravasation, unintentional intra-arterial administration, and intraneuronal or perineuronal infiltration, which may manifest as burning, pain, erythema, edema, severe spasms, phlebitis, thrombophlebitis, venous thrombosis, sensory loss, paralysis, and palsies.[14][15]

Less common adverse effects that prescribers should be aware of include:

  • The neuroleptic malignant syndrome may have associations with promethazine usage as well, which manifests as increased body temperature, confusion or altered mental status, sweating, autonomic instability, and “lead pipe” rigidity.
  • Cardiovascular side effects to include arrhythmias and hypotension.
  • Liver damage and cholestatic jaundice have also been reported with its use.
  • Bone marrow suppression resulting in agranulocytosis, thrombocytopenia, and leukopenia.
  • Depression of the thermoregulatory mechanism resulting in hypothermia/hyperthermia.

Contraindications

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.[17][14]

Monitoring

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.

Toxicity

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.[12]

Enhancing Healthcare Team Outcomes

Overall, promethazine is a relatively safe medication that is very useful in a number of 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. It is especially crucial that providers are aware 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 own expertise to support positive outcomes.


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Promethazine - Questions

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Which is true regarding IV promethazine administration recommendations?



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What is the generic drug for Phenergan?



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Promethazine is in which medication class?



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Which of the following treatments is contraindicated in children less than 2 years old due to the risk of fatal respiratory depression?



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A patient enters the pharmacy with a prescription for promethazine suppository 25 mg. What would the correct signa include for the route?



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A 65-year-old female with a history of diabetes types 2, hypertension, and asthma is in the post-anesthesia care unit (PACU) following an uncomplicated right arthroscopy. The patient is complaining of pain and burning in her right cephalic vein. There is erythema and swelling at the IV site. Extravasation of the IV is suspected. The patient was recently complaining of nausea and vomiting, and so was given an IV drug to help with the patient's symptoms. Which of the following drugs has a black box warning for severe tissue damage during extravasation?



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A 12-month-old female is experiencing postoperative nausea and vomiting (PONV) after uncomplicated strabismus surgery. The patient was given dexamethasone and ondansetron during the case. In the postanesthesia care unit (PACU), the patient is administered a drug for symptomatic relief of PONV. The patient stops vomiting, but then the PACU nurse notices that the patient has become extremely drowsy. Vital signs show a heart rate of 90/min, blood pressure 90/60 mmHg, respiratory rate 8/min, temperature 37 C, and SpO2 of 90% on room air. What medication was most likely given to this patient?



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A 24-year-old G1P0 female at 15 weeks presents to labor and delivery triage due to uncontrolled vomiting. She has vomited 5-6 times in the last 4 hours. She has tried home remedies which did not improve her symptoms. A physical exam is significant for dry mucous membranes and normal skin turgor. All other aspects of the physical exam have normal findings. Vitals signs include a blood pressure of 115/70 mmHg, pulse 85/min, respiratory rate 12/min, and SpO2 99% on room air. A complete metabolic panel is drawn and shows all values within normal limits. The patient is given 1L IV fluids and 4 mg of ondansetron. On revaluation in 30 minutes, she continues to complain of nausea. A second-line antiemetic is given, which causes the patient to become drowsy and mildly disoriented. What property of the second antiemetic most likely caused these side effects?



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A 44-year-old female with a past medical history significant for hypertension is brought to the emergency department by ambulance for altered mental status and diaphoresis. The patient had a right knee arthroscopy under general anesthesia five days ago, which was complicated by postoperative nausea and vomiting. Family members state that she was treated with multiple medications to stop her vomiting. She was discharged the same day of surgery and had been making an uneventful recovery at home. She takes hydrochlorothiazide for hypertension, which is well controlled. She has been taking acetaminophen for pain at home as prescribed by her surgeon. Vital signs are taken and show a blood pressure of 150/90 mmHg, pulse 110/min, respiratory rate 18/min, temperature 101.4 F, and SpO2 97% on room air. A physical exam is significant for tachycardia, diaphoresis, muscle rigidity, and mild confusion (able to state her name, location, but not date). Labs are drawn and show a leukocytosis, elevated CPK, and mild transaminitis. The patient is diagnosed with neuroleptic malignant syndrome (NMS) is admitted to the wards for further monitoring and treatment. What is the likely etiology of NMS in this patient?



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Promethazine - References

References

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]
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]
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]
Grunberg SM,Hesketh PJ, Control of chemotherapy-induced emesis. The New England journal of medicine. 1993 Dec 9;     [PubMed]
Tortorice PV,O'Connell MB, Management of chemotherapy-induced nausea and vomiting. Pharmacotherapy. 1990;     [PubMed]
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]
Shupak A,Gordon CR, Motion sickness: advances in pathogenesis, prediction, prevention, and treatment. Aviation, space, and environmental medicine. 2006 Dec;     [PubMed]
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]
ACOG Practice Bulletin No. 189: Nausea And Vomiting Of Pregnancy. Obstetrics and gynecology. 2018 Jan;     [PubMed]
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]
Rumeau-Rouquette C,Goujard J,Huel G, Possible teratogenic effect of phenothiazines in human beings. Teratology. 1977 Feb;     [PubMed]
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]
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]
Reynolds PM,MacLaren R,Mueller SW,Fish DN,Kiser TH, Management of extravasation injuries: a focused evaluation of noncytotoxic medications. Pharmacotherapy. 2014 Jun;     [PubMed]
Hurst S,McMillan M, Innovative solutions in critical care units: extravasation guidelines. Dimensions of critical care nursing : DCCN. 2004 May-Jun;     [PubMed]
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]
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]
Neonatal deaths associated with use of benzyl alcohol--United States. MMWR. Morbidity and mortality weekly report. 1982 Jun 11;     [PubMed]

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