Europe’s medicines regulator has issued guidance limiting the use of Tegretol (carbamazepine) 100 mg/5 mL oral suspension in neonates due to propylene glycol concentrations that exceed recommended safety thresholds for newborns. 

Tegretol is used to treat various conditions, including epilepsy, and liquid formulations are important for precise dosing in pediatric patients. However, this oral suspension contains 25 mg of propylene glycol per 1 mL, significantly exceeding the recommended threshold of 1 mg/kg/day for neonates. At such levels, propylene glycol can accumulate in neonates, whose immature liver and kidneys are unable to effectively metabolize or eliminate the excipient. 

At its recent meeting, the European Medicines Agency’s Pharmacovigilance Risk Assessment Committee discussed a direct healthcare professional communication (DHPC) that will alert clinicians and other healthcare professionals across the European Union to these restrictions and the need for careful monitoring.

Safe Use and Monitoring

Tegretol 100 mg/5 mL oral suspension should not be used in neonates younger than 4 weeks of age for term babies or 44 weeks post-menstrual age for pre-term babies, unless no other treatment option is available and the expected benefit outweighs the risks. 

Healthcare professionals must be aware that propylene glycol accumulation can lead to serious adverse reactions, including metabolic acidosis, renal dysfunction with acute tubular necrosis, acute renal failure, and liver dysfunction. When treatment with Tegretol 100 mg/5 mL is deemed necessary in neonates, intensive monitoring is required, including measurements of osmolarity and/or anion gap to assess fluid balance and detect abnormal acid levels in the blood. 

Clinicians should exercise particular caution when co-administering other medicines containing propylene glycol or substances metabolized by alcohol dehydrogenase, such as ethanol, as this increases the risk of propylene glycol accumulation and toxicity. 

Revised Product Information

The product information for Tegretol 100 mg/5 mL will be updated to reflect the restricted use in neonates and inform about the risk of serious adverse reactions due to propylene glycol concentration. 

These restrictions apply specifically to Tegretol 100 mg/5 mL oral suspension and do not affect other liquid formulations of carbamazepine that do not contain propylene glycol. The guidance ensures continued access to carbamazepine therapy while protecting the most vulnerable patient population from preventable excipient-related toxicity.

The DHPC will be disseminated to healthcare professionals by the marketing authorization holders and published on the DHPCs page or in national registers in EU Member States.