Pregabalin and severe respiratory depression

Pregabalin and severe respiratory depression

Pregabalin has been associated with infrequent reports of severe respiratory depression, including some cases without the presence of concomitant opioid medicines.

Patients with compromised respiratory function, respiratory or neurological disease, renal impairment; those using concomitant central nervous system (CNS) depressants; and people older than 65 years might be at higher risk of experiencing these events and adjustments in dose or dosing regimen may be necessary.

Studies show use of high doses of pregabalin (over 300mg a day) alongside opioid medicines to be particularly associated with an increased risk of opioid-related death (1).

Advice for healthcare professionals (2):

• pregabalin has been associated with reports of respiratory depression, in some cases without concomitant opioid treatment
• consider whether adjustments in dose or dosing regimen are necessary for patients at higher risk of respiratory depression, this includes people:
  • with compromised respiratory function, respiratory or neurological disease, or renal impairment
  • taking other CNS depressants (including opioid-containing medicines)
  • aged older than 65 years
• report suspected adverse drug reactions associated with use of pregabalin on a Yellow Card

Advice for healthcare professionals (3):

• to reflect growing concern about abuse, both pregabalin and gabapentin are now classified as Class C controlled substances (under the Misuse of Drugs Act 1971) and scheduled under the Misuse of Drugs Regulations 2001 (as amended) as Schedule 3, but are exempt from the safe custody requirements (see new legal requirements and resources for prescribers and dispensers below)

• evaluate patients carefully for a history of drug abuse and dependence before prescribing pregabalin and gabapentin

• observe patients on pregabalin and gabapentin for possible signs of abuse and dependence, for example, drug-seeking behaviour, dose escalation, and development of tolerance

• ensure patients are aware of the risk of potentially fatal interactions with other medicines that cause CNS depression, particularly opioid medicines, and with alcohol

• report suspected adverse drug reactions to pregabalin and gabapentin on a Yellow Card, including cases of abuse and dependence

Pregabalin (Lyrica), gabapentin (Neurontin) and risk of abuse and dependence: new scheduling requirements from 1 April Drug Safety Update volume 12, issue 9: April 2019: 4.

Reference:

• Gomes T and others. Pregabalin and the risk for opioid-related death: a nested case-control study. Ann Intern Med. 2018; issue 169: 732–34
• Drug Safety Update volume 14, issue 7: February 2021: 2.
• Pregabalin (Lyrica), gabapentin (Neurontin) and risk of abuse and dependence: new scheduling requirements from 1 April Drug Safety Update volume 12, issue 9: April 2019: 4.