What is the recommended adult dosing range and maximum daily dose of promethazine?

Promethazine Dosing and Maximum Dose in Adults

For nausea and vomiting in adults, administer promethazine 12.5–25 mg every 4–6 hours as needed, with a maximum frequency of every 4 hours and a maximum total daily dose of 100 mg. 1, 2

Standard Dosing by Indication

Nausea and Vomiting

• Administer 12.5–25 mg every 4–6 hours as needed for acute nausea and vomiting, with dosing intervals not more frequent than every 4 hours. 1, 2
• The American Gastroenterological Association endorses this regimen as abortive therapy for conditions including cyclic vomiting syndrome and inflammatory bowel disease. 1
• Maximum daily dose is 100 mg in a 24-hour period for most indications. 2

Allergic Conditions

• Give 25 mg as the initial dose, which may be repeated within 2 hours if necessary. 2
• Transition to oral administration as soon as circumstances permit, as parenteral therapy should be limited. 2

Sedation

• For nighttime sedation in hospitalized adults, administer 25–50 mg. 2

Obstetric Use

• In early labor, 50 mg provides sedation and relieves apprehension. 2
• Once labor is established, give 25–75 mg (average 50 mg) with appropriately reduced narcotic doses, repeatable once or twice at 4-hour intervals. 2
• Maximum obstetric dose is 100 mg total in 24 hours. 2

Route-Specific Considerations

Oral Administration

• Oral promethazine 12.5–25 mg every 4–6 hours is the preferred route when gastrointestinal absorption is intact. 1
• Oral bioavailability is approximately 25%, yet dosing remains identical across routes in current practice. 1

Intravenous Administration

• When IV administration is necessary, infuse at a rate not exceeding 25 mg per minute to minimize hypotension risk. 3, 2
• Use a concentration no greater than 25 mg/mL and preferably inject through functioning IV tubing. 2
• Stop injection immediately if the patient complains of pain, as this may indicate arterial injection or extravasation. 2
• IV promethazine carries significant risks of thrombophlebitis, tissue necrosis, and gangrene with extravasation. 1, 3
• Onset of action is within 5 minutes IV, with duration of 4–6 hours. 1, 3

Intramuscular Administration

• Deep intramuscular injection is the preferred parenteral route. 2
• Subcutaneous injection is contraindicated due to tissue necrosis risk. 2
• Intra-arterial injection is absolutely contraindicated due to severe arteriospasm and gangrene risk. 2

Lower-Dose Strategy for Reduced Sedation

Consider using promethazine 6.25–12.5 mg for antiemetic purposes, as these lower doses are equally effective as 25 mg but cause significantly less sedation. 1, 4

• Research demonstrates that 6.25 mg IV provides equivalent nausea relief to 12.5 mg, with 97% of patients achieving complete symptom resolution. 5
• Lower doses result in significantly less sedation at 30 minutes post-administration and at discharge. 5
• In elderly hospitalized patients, 6.25 mg IV showed similar efficacy to higher doses with significantly fewer adverse drug reactions. 6

Critical Safety Limitations

Tissue Injury Risk

• Avoid repeated or prolonged courses of IV promethazine due to heightened risk of serious tissue injury. 1, 3
• Careful administration technique is essential to prevent extravasation. 3

Central Nervous System Effects

• Significant sedation occurs, particularly when combined with opioids or other CNS depressants. 1, 4
• Reduce doses of concomitant analgesics, barbiturates, and sedatives when using promethazine. 2
• Promethazine is inappropriate for chronic use due to risks of neuroleptic malignant syndrome and cumulative respiratory depression. 1, 4

High-Risk Populations

• Use with extreme caution in elderly patients due to increased risk of cognitive impairment, anticholinergic effects, and falls. 1
• Avoid in patients with prostatic hypertrophy, elevated intraocular pressure, or existing cognitive impairment. 1

Extrapyramidal Reactions

• Monitor for extrapyramidal symptoms including dystonia and akathisia, though these occur less commonly than with metoclopramide. 1, 4
• Have diphenhydramine 25–50 mg readily available for prompt treatment if extrapyramidal symptoms arise. 1

Anticholinergic Effects

• Counsel patients about dose-related anticholinergic effects including dry mouth, urinary retention, and constipation. 1

Pharmacokinetic Profile

• Duration of action is 4–6 hours after a single dose, though effects may persist up to 12 hours. 1
• Plasma half-life is 9–16 hours. 1
• Onset is within 5 minutes IV and within 20 minutes orally. 1