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 receptors 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 tissue 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 categorizes as a 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 two 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. [Level 5]
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