What is the difference between promethazine (Phenergan) and hydroxyzine?

From the Guidelines

Promethazine and hydroxyzine are both antihistamines with sedative properties, but they differ in their pharmacological properties, uses, and side effects. The main difference between promethazine and hydroxyzine lies in their chemical structure and receptor affinity. Promethazine is a phenothiazine antihistamine that strongly blocks H1 receptors and has significant anticholinergic effects, making it more effective for nausea and vomiting, while hydroxyzine is a piperazine antihistamine with a lower affinity for H1 receptors and fewer anticholinergic effects, making it more suitable for anxiety and itching 1. Some key points to consider when choosing between promethazine and hydroxyzine include:

• Promethazine has stronger antiemetic properties and is more effective for nausea and vomiting, but it carries a higher risk of extrapyramidal symptoms (movement disorders) due to its dopamine-blocking effects 1.
• Hydroxyzine is often preferred for anxiety and itching, and it has fewer anticholinergic side effects compared to promethazine 1.
• Dosing varies by indication: promethazine is typically given as 12.5-25mg every 4-6 hours for nausea or allergies, while hydroxyzine is usually prescribed as 25-100mg 3-4 times daily for anxiety or itching 1.
• Both medications should be used cautiously in elderly patients and those with certain medical conditions due to their sedative and anticholinergic properties 1. It's essential to weigh the benefits and risks of each medication and consider individual patient factors, such as medical history and current medications, when deciding between promethazine and hydroxyzine.

From the FDA Drug Label

Promethazine is a phenothiazine derivative which differs structurally from the antipsychotic phenothiazines by the presence of a branched side chain and no ring substitution. Hydroxyzine hydrochloride is unrelated chemically to the phenothiazines, reserpine, meprobamate or the benzodiazepines.

The main differences between promethazine and hydroxyzine are:

• Chemical structure: Promethazine is a phenothiazine derivative, while hydroxyzine is unrelated to phenothiazines.
• Mechanism of action: Promethazine is an H1 receptor blocking agent with sedative and antiemetic effects, while hydroxyzine's action may be due to a suppression of activity in certain key regions of the subcortical area of the central nervous system.
• Pharmacological effects: Both drugs have antihistaminic and antiemetic effects, but hydroxyzine also has bronchodilator activity, analgesic effects, and mild antisecretory activity 2 3.

From the Research

Differences between Promethazine and Hydroxyzine

• Promethazine and hydroxyzine are both antihistamines, but they have different therapeutic uses and side effect profiles 4, 5.
• Promethazine is used for the treatment of nausea and vomiting, and has antihistaminic, sedative, anti-kinetotic, antiemetic, and antimuscarinic effects 4.
• Hydroxyzine is used for the treatment of generalized anxiety disorder (GAD) and has anxiolytic effects 5.
• Both promethazine and hydroxyzine can cause sedation, but hydroxyzine has been shown to have a more pronounced inhibitory effect on cutaneous responses and less sedative effect than some other antihistamines 6.
• Promethazine has been associated with rare but serious limb-threatening adverse effects after extravasation or inadvertent intra-arterial injection, and its use should be cautious 4.
• Hydroxyzine has been shown to be effective in treating GAD, but its use is limited by the high risk of bias in the included studies and the small number of studies 5.

Comparison of Efficacy and Safety

• Hydroxyzine has been compared to other anxiolytic agents, such as benzodiazepines and buspirone, and has been shown to be equivalent in terms of efficacy, acceptability, and tolerability 5.
• Promethazine has been compared to other antiemetic agents, and its use is recommended with caution due to the risk of serious patient harm 4.
• The choice of antiemetic drug depends on the cause of nausea and vomiting, and promethazine is a first-line option for nausea and vomiting in some cases 7.

Mechanism of Action

• Both promethazine and hydroxyzine are histamine H1 receptor competitive antagonists, but they have different mechanisms of action and effects on the body 8, 6.
• Promethazine has antihistaminic, sedative, anti-kinetotic, antiemetic, and antimuscarinic effects, while hydroxyzine has anxiolytic effects 4, 5.
• The next generation of antihistamines has been developed to have fewer sedative effects and more specific mechanisms of action 8.