What are the considerations for using Phenergan (promethazine) in the elderly?

Phenergan (Promethazine) Use in the Elderly

Phenergan should be avoided in elderly patients due to significant risks of CNS impairment, falls, anticholinergic toxicity, and respiratory depression, with safer alternatives available for most indications.

Primary Safety Concerns

First-generation antihistamines like promethazine cause substantial harm in older adults and should be avoided. The medication carries multiple high-risk adverse effects specific to the elderly population 1:

• CNS impairment including delirium, slowed comprehension, and over-sedation 1, 2
• Falls and fractures: First-generation antihistamines are associated with a significantly increased risk (OR 2.03,95% CI 1.49-2.76) of injurious falls or fractures 3
• Anticholinergic effects: impaired vision, urinary retention, constipation, and confusion 1
• Respiratory depression: particularly dangerous in elderly patients with compromised respiratory function (COPD, sleep apnea) 2

Guideline Recommendations

The 2019 AGS Beers Criteria and polypharmacy guidelines explicitly identify first-generation antihistamines, including promethazine, as potentially inappropriate medications for older adults 1. These medications are flagged for:

• Strong anticholinergic properties that worsen cognitive function 1
• Sedating effects that increase fall risk 1
• Enhanced sensitivity in elderly patients to psychomotor impairment 1

Age-Related Pharmacological Changes

Elderly patients experience altered drug responses that amplify promethazine's risks 2, 4:

• Decreased hepatic metabolism leads to drug accumulation and prolonged effects 4, 5
• Reduced renal clearance delays elimination 1, 5
• Increased CNS sensitivity to sedating and anticholinergic effects 1, 6
• Decreased plasma protein binding may intensify drug effects 5

FDA Labeling Warnings

The FDA label specifically warns about promethazine use in elderly patients 2:

• "Sedating drugs may cause confusion and over-sedation in the elderly"
• "Elderly patients generally should be started on low doses and observed closely"
• Dose selection should be cautious, "usually starting at the low end of the dosing range" 2

Clinical Pitfalls to Avoid

Common errors when prescribing to elderly patients include 1:

• Failing to recognize that normal serum creatinine may mask significant renal impairment due to reduced muscle mass 1
• Not accounting for polypharmacy and drug-drug interactions, particularly with other CNS depressants 1, 2
• Underestimating anticholinergic burden in patients with pre-existing cognitive impairment, benign prostatic hypertrophy, or glaucoma 1, 2
• Using promethazine for behavioral symptoms when non-pharmacological interventions should be prioritized 7

Safer Alternatives

When antihistamine therapy is necessary, second-generation agents are strongly preferred 1:

• Fexofenadine, loratadine, or desloratadine do not cause sedation at recommended doses and lack anticholinergic effects 1
• These agents have not been associated with performance impairment or increased fall risk in elderly patients 1

For nausea/vomiting specifically, if promethazine must be used 8:

• Start with the lowest dose (6.25 mg IV) which is as effective as higher doses with fewer adverse drug reactions 8
• Avoid doses exceeding 12.5 mg 8
• Monitor closely for sedation, confusion, and respiratory depression 2

Absolute Contraindications

Do not use promethazine in elderly patients with 2:

• Compromised respiratory function (COPD, sleep apnea) - risk of potentially fatal respiratory depression 2
• Concurrent use of other CNS depressants (opioids, benzodiazepines, alcohol) - amplified impairment 2
• Seizure disorders - lowers seizure threshold 2
• Bone marrow depression 2