What are the contraindications for Phenergan (promethazine)?

Contraindications for Phenergan (Promethazine)

Promethazine is absolutely contraindicated in children under 2 years of age, comatose patients, individuals with known hypersensitivity to promethazine or phenothiazines, and for treatment of lower respiratory tract symptoms including asthma. 1

Absolute Contraindications

Age-Related Restrictions

• Pediatric patients less than 2 years of age: This is an FDA black box contraindication due to risk of fatal respiratory depression 1
• The American Academy of Pediatrics specifically warns of fatal respiratory depression in this age group 2

Medical Conditions

• Comatose states: Promethazine is contraindicated in any patient with altered consciousness or comatose state 1
• Lower respiratory tract disease: Antihistamines including promethazine are contraindicated for treatment of lower respiratory tract symptoms, specifically asthma 1

Hypersensitivity

• Known hypersensitivity or idiosyncratic reaction to promethazine or other phenothiazines 1

Critical Warnings and High-Risk Situations

Respiratory Compromise

• Avoid use in patients with compromised respiratory function including COPD and sleep apnea, as promethazine may lead to potentially fatal respiratory depression 1
• Concomitant use with other respiratory depressants (narcotics, sedatives, barbiturates, general anesthetics) significantly increases respiratory depression risk and has been associated with death in pediatric patients 1

Neurological Conditions

• Use with extreme caution in seizure disorders: Promethazine lowers seizure threshold, particularly when combined with narcotics or local anesthetics 1
• Should be avoided in pediatric patients with signs suggesting Reye's syndrome or hepatic disease, as extrapyramidal symptoms may mask underlying CNS pathology 1

Hematologic Concerns

• Use cautiously with bone marrow depression: Leukopenia and agranulocytosis have been reported, especially when combined with other marrow-toxic agents 1

Cardiovascular and Other Conditions

• Closed-angle glaucoma: Anticholinergic effects make this a high-risk situation 3
• Prostatic hypertrophy and bladder neck obstruction: Anticholinergic effects can worsen urinary retention 3
• Hyperthyroidism: Use with caution due to potential cardiovascular effects 3

Special Population Considerations

Pediatric Patients (≥2 years)

• Even in children 2 years and older, use the lowest effective dose and avoid concomitant respiratory depressants 1
• Risk is increased in acutely ill, dehydrated children who have increased susceptibility to dystonic reactions 1
• Excessively large doses may cause sudden death 1
• Antiemetics should not be used for uncomplicated vomiting; reserve for prolonged vomiting of known etiology 1

Drug Interactions Requiring Avoidance

• Monoamine oxidase inhibitors (MAOIs): Contraindicated for concurrent use 3
• Central nervous system depressants should be eliminated or given in reduced dosage when promethazine is used 1

Administration-Related Contraindications

Route-Specific Risks

• Avoid subcutaneous administration: Risk of tissue necrosis and gangrene with extravasation 4, 5
• Avoid inadvertent intra-arterial injection: Can cause limb-threatening complications including possible amputation 4, 5
• The FDA now recommends intramuscular administration as preferred over intravenous when injectable promethazine is necessary 4

Clinical Pitfalls to Avoid

• Do not confuse promethazine-induced extrapyramidal symptoms with signs of primary CNS disease 1
• Be aware that promethazine can cause false-positive urine amphetamine results on certain immunoassays 6
• Cholestatic jaundice has been associated with promethazine administration 1
• Neuroleptic malignant syndrome, though rare, is a potentially fatal complication requiring immediate discontinuation 1