What is the proper dosage and usage of Phenergan (promethazine)?

Phenergan (Promethazine) Dosage and Usage

Promethazine should be administered at the lowest effective dose for the specific indication, with particular caution in children under 2 years (contraindicated) and careful attention to route of administration due to serious limb-threatening complications with IV use. 1, 2

Critical Safety Considerations

Black Box Warning and Age Restrictions

• Contraindicated in children under 2 years of age due to risk of fatal respiratory depression 1
• Use with extreme caution in children 2 years and older, adjusting to the smallest effective dose 1
• Significant sedation, agitation, hallucinations, seizures, dystonic reactions, and possible sudden infant death syndrome have been reported 3

Route of Administration Safety

• Intramuscular (IM) administration is preferred over intravenous (IV) due to rare but serious limb-threatening adverse effects from extravasation or inadvertent intra-arterial injection 2
• If IV administration is necessary, proper dilution and slow administration are critical 2
• The FDA changed product labeling in December 2023 to emphasize IM preference and add specific dilution/administration recommendations 2

Dosing by Indication

Allergic Conditions

• Adults: 25 mg at bedtime, or 12.5 mg before meals and at bedtime if necessary 1
• Alternative adult dosing: 6.25-12.5 mg three times daily 1
• Children ≥2 years: Adjust to smallest effective dose after initiation 1
• For minor transfusion reactions: 25 mg controls allergic-type reactions 1

Motion Sickness

• Adults: 25 mg twice daily; initial dose 30-60 minutes before travel, repeat in 8-12 hours 1
• On subsequent travel days: 25 mg on arising and before evening meal 1
• Children ≥2 years: 12.5-25 mg twice daily 1

Nausea and Vomiting

• Adults: 25 mg as the average effective dose 1
• Children ≥2 years: 0.5 mg per pound of body weight, adjusted for age, weight, and severity 1
• Repeat doses: 12.5-25 mg every 4-6 hours as necessary 1
• Important: Antiemetics should not be used for vomiting of unknown etiology in children and adolescents 1
• For hyperemesis gravidarum: Promethazine has similar efficacy to metoclopramide and ondansetron, though drowsiness, dizziness, and dystonia are more frequent than with metoclopramide 4

Sedation

• Children ≥2 years: 12.5-25 mg at bedtime 1
• Adults: 25-50 mg for nighttime, presurgical, or obstetrical sedation 1

Pre- and Postoperative Use

• Preoperative (night before surgery):
  • Children: 12.5-25 mg 1
  • Adults: 50 mg 1
• Preoperative medication:
  • Children: 0.5 mg per pound body weight with reduced narcotic/barbiturate and atropine-like drug 1
  • Adults: 50 mg with reduced narcotic/barbiturate and belladonna alkaloid 1
• Postoperative sedation:
  • Children: 12.5-25 mg 1
  • Adults: 25-50 mg 1

Low-Dose IV Promethazine Evidence

For antiemetic use, low-dose IV promethazine (6.25-12.5 mg) is as effective as standard 25 mg dosing or ondansetron 4 mg, with comparable sedation profiles. 5

• 6.25 mg IV relieved nausea/vomiting in 74% at 1 hour, 67% at 3 hours 5
• 12.5 mg IV relieved nausea/vomiting in 68% at 1 hour, 80% at 3 hours 5
• Ondansetron 4 mg IV: 59% at 1 hour, 71% at 3 hours 5
• No statistically significant differences in efficacy or sedation scores 5
• This challenges traditional dosing references that suggest identical dosing regardless of route, despite oral bioavailability being only 25% 5

Contraindications and Precautions

Absolute Contraindications

• Children under 2 years of age 1
• Concomitant use with monoamine oxidase inhibitors (MAOIs) 4, 6
• Pregnancy and lactation (use with extreme caution, especially first trimester) 4, 6

Use With Caution

• Angle-closure glaucoma 4, 6
• Prostatic hypertrophy and urinary retention 4, 6
• Severe hepatic disease (may require dose adjustment) 6
• Moderate renal insufficiency (creatinine clearance 10-20 mL/min): consider dose reduction 6
• Elderly patients: start with lower doses due to increased anticholinergic sensitivity 6
• Cardiovascular disease, hyperthyroidism, seizure disorders 4

Common Adverse Effects

• Central nervous system: Drowsiness, dizziness, restlessness, dystonic reactions, akathisia, pseudo-parkinsonism, tardive dyskinesia 4, 7
• Cardiovascular: Hypotension, tachycardia, arrhythmias 4
• Gastrointestinal: Xerostomia, constipation 4
• Other: Urinary retention, blurred vision, nasal congestion, decreased diaphoresis 4
• Extrapyramidal adverse effects may occur; withdraw drug if symptoms develop 4

Drug Interactions

• Avoid concomitant use with: MAOIs, medications with anticholinergic effects 6
• Enhanced sedation with: Narcotic analgesics, barbiturates, other CNS depressants 1
• Increased risk of adverse events when combined with caffeine and stimulants (e.g., ADHD medications) 4

Misuse Potential

Promethazine has documented misuse/abuse potential, particularly in adolescents, often in combination with opioids ("purple drank"). 8

• European Monitoring Agency data (2003-2019) showed 557 abuse/misuse/dependence cases out of 1543 total adverse drug reactions 8
• 55.6% of abuse cases resulted in fatalities, mostly involving concomitant opioid use 8
• Healthcare professionals should be vigilant, especially where promethazine is available over-the-counter 8