Can promethazine (Phenergan) be a culprit in the development of extrapyramidal symptoms?

Promethazine Can Cause Extrapyramidal Symptoms

Yes, promethazine (Phenergan) is definitely a culprit in the development of extrapyramidal symptoms, ranging from restlessness to oculogyric crises, as explicitly stated in multiple guidelines and its FDA drug label. 1

Mechanism of Action and Risk

• Promethazine is a phenothiazine that blocks postsynaptic dopaminergic receptors in the brain, which is the primary mechanism responsible for extrapyramidal symptoms 2
• As a dopamine receptor antagonist with antihistaminergic and anticholinergic effects, promethazine can disrupt the balance of neurotransmitters in the basal ganglia, leading to movement disorders 2, 3

Types of Extrapyramidal Symptoms Associated with Promethazine

Promethazine can cause several forms of extrapyramidal symptoms:

• Acute dystonia: Involuntary muscle contractions affecting the face, neck, back, and limb muscles 2
• Oculogyric crisis: A specific form of dystonia involving abnormal eye movements 2, 1
• Akathisia: A sense of restlessness and inability to remain still 2
• Torticollis: Abnormal neck positioning due to muscle contractions 1
• Tongue protrusion: Involuntary movement of the tongue 1

Clinical Considerations

• The FDA drug label explicitly lists extrapyramidal symptoms among promethazine's adverse reactions 1
• Extrapyramidal symptoms can range in severity from mild restlessness to severe oculogyric crises 2
• These symptoms can be confused with the central nervous system signs of undiagnosed primary disease (e.g., encephalopathy or Reye's syndrome) in pediatric patients 1
• The risk of extrapyramidal symptoms appears to be dose-dependent, with higher doses increasing the risk 2

Comparison with Other Medications

• In a randomized trial comparing different interventions for psychomotor agitation, the combination of haloperidol with promethazine showed a higher risk for extrapyramidal symptoms compared to other regimens 4
• While all phenothiazines can cause extrapyramidal symptoms, promethazine's dopamine-blocking properties make it particularly problematic compared to pure antihistamines like diphenhydramine 3

Management of Promethazine-Induced Extrapyramidal Symptoms

• If extrapyramidal symptoms occur, the first step should be to discontinue promethazine 1
• Anticholinergic medications may be used to treat acute dystonic reactions 2
• For severe cases, benzodiazepines may help manage akathisia 2
• In cases where promethazine is necessary, using the lowest effective dose may reduce the risk of extrapyramidal symptoms 2

Special Warnings

• Promethazine can also cause neuroleptic malignant syndrome, a potentially fatal complication characterized by hyperpyrexia, muscle rigidity, altered mental status, and autonomic instability 1, 5
• Peripheral IV administration of promethazine requires careful attention as it can cause tissue injury, including gangrene or thrombophlebitis 2
• Promethazine is contraindicated in children under 2 years of age due to the risk of fatal respiratory depression 1

Recognizing the potential for promethazine to cause extrapyramidal symptoms is crucial for clinicians, as early identification and management can prevent more serious complications and improve patient outcomes.