Can inhaling particles of pregabalin (lyrica) lead to an overdose?

Can Inhaling Particles of Pregabalin Lead to an Overdose?

Yes, inhaling particles of pregabalin can potentially lead to an overdose, as pregabalin can be absorbed through the respiratory tract and cause systemic toxicity similar to oral ingestion. 1

Mechanism of Pregabalin Overdose

• Pregabalin is an anticonvulsant medication widely used for epilepsy and neuropathic pain that can cause significant central nervous system depression when taken in excessive amounts 2
• When inhaled, pregabalin particles can be absorbed through the respiratory mucosa and enter systemic circulation, potentially leading to toxic effects similar to those seen with oral overdose 1
• The drug works by binding to calcium channels, reducing the release of excitatory neurotransmitters, and is thought to possess GABA-mimetic properties that contribute to its CNS effects 3

Clinical Manifestations of Pregabalin Overdose

• The most commonly reported adverse events in pregabalin overdose include reduced consciousness, depression/anxiety, confusional state, agitation, and restlessness 1
• More severe manifestations can include:
  • Seizures and heart block 1
  • Significant neurological depression and coma, which may develop several hours post-exposure 4
  • Respiratory depression, particularly when combined with other CNS depressants 5
• Deaths have been reported with pregabalin overdose, especially when combined with other CNS depressants such as opioids 1, 5

Risk Factors for Severe Toxicity

• Concomitant use of other central nervous system depressants significantly increases overdose risk 1, 5
• Particularly dangerous combinations include:
  • Pregabalin with opioids (79% of gabapentinoid-related deaths also involved opioids) 5
  • Pregabalin with alcohol or benzodiazepines 3
• History of substance use disorders increases risk of misuse and potential overdose 2, 3
• Renal impairment can lead to drug accumulation and increased toxicity 6

Management of Pregabalin Overdose

• There is no specific antidote for pregabalin overdose 1
• Management primarily consists of supportive care:
  • Airway protection and mechanical ventilation if needed for respiratory depression 4
  • Cardiovascular support as needed 1
  • Elimination of unabsorbed drug may be attempted by emesis or gastric lavage with appropriate airway protection 1
• Hemodialysis can effectively remove pregabalin from circulation (approximately 50% clearance in 4 hours) and should be considered in severe cases 1, 4
• Contact a Certified Poison Control Center for up-to-date management guidance 1

Special Considerations

• Pregabalin has become increasingly misused, with users often taking doses 3-20 times higher than clinically recommended 3
• Individuals with a history of recreational polydrug use are at particular risk for pregabalin misuse 3
• High doses of pregabalin are surprisingly well tolerated with fewer acute toxicological consequences than might be expected, though lethal cases have been reported 7
• Withdrawal symptoms can occur with abrupt discontinuation after chronic use or abuse 7