Safety Alert:
Health Authority:
Pharmacovigilance Risk Assessment Committee (PRAC) of the European Medicines Agency (EMA)
Pregabalin-containing medicinal products are marketed under various brand names for the treatment of following conditions:
- Generalized anxiety disorder in adults
- Neuropathic pain in adults
- As adjunctive therapy in adults for specific forms of epilepsy
Safety profile of pregabalin is already documented with respiratory depression risk in association with concomitant use of-
- Opioids such as Codeine, Fentanyl (Actiq, Abstral, Duragesic, Fentora), Hydrocodone (Hysingla, Zohydro ER), Hydrocodone/acetaminophen (Lorcet, Lortab, Norco, Vicodin), Hydromorphone (Dilaudid, Exalgo), Meperidine (Demerol), Methadone (Dolophine, Methadose), Morphine (Kadian, MS Contin, Morphabond),
and/or
- CNS depressant medications like diazepam (Valium®), clonazepam, (Klonopin®), alprazolam (Xanax®), triazolam (Halcion®), estazolam (Prosom®)
With the reports of respiratory failure, coma and deaths, the product information for pregabalin-containing medicinal products reflected this risk and advised caution when prescribing pregabalin concomitantly with opioids due to the risk of CNS depression, noting that a case-control study of opioid users found that concomitant use of pregabalin with an opioid was associated with an increased risk for opioid related death compared to opioid use alone.
Recent PRAC review of safety data:
Revealed case reports of respiratory depression in patients even without concomitant use of opioids or CNS depressants, with and without other risk factors for respiratory depression.
Based on the emerging safety evidence from post-marketing sources, PRAC concluded that pregabalin has also been associated with severe respiratory depression even in the absence of concomitant opioid and/or other CNS depressant use in patients with and without risk factors for respiratory depression.
Important note for Healthcare professionals:
Awareness: Pregabalin is contraindicated in patients with risk factors for respiratory depression even without concomitant use of opioids & CNS depressants.
Individual Benefit-risk analysis: It is recommended to consider this product use ONLY when alternative treatments are not available, exhausted, or not tolerated and unsuitable for addressing the patient medical condition.
Transparency: Please discuss with patients/care providers about both the risks & benefits of using this medicine and advise for close monitoring of any signs/symptoms/adverse events for early reporting and early implementations of actions for a better patient safety and public health.
The product information (summary of product characteristics (SmPC) and package leaflet (PL)) for pregabalin-containing medicinal products are being updated to include this new safety information in below specific sections-
- Warnings on respiratory depression
- Addition of respiratory depression a possible adverse reaction with a frequency of ‘not known’
Important note for Public (Patients/patient care providers):
Be aware of this potential risk for pregabalin, and consider using alternative treatment options having favorable benefit-risk profile before use.
Inform your respective doctor or healthcare professional about your underlying medical conditions and concurrent use of other medications. This facilitates the effective assessment of benefit-risk ratio and identification of suitability of the medicine for use/or looking for alternative medicine with the favorable benefit risk ratio. Be conscious of below signs and symptoms this potential risk and inform your respective healthcare professional or report to your national ADR reporting system.
Patients with the following risk factors may be at higher risk of experiencing respiratory depression with pregabalin and dose adjustment may be necessary:
- Older age (> 65 years)
- Compromised respiratory function
- Respiratory or neurological disease
- Renal impairment
- Concomitant use of CNS depressants
Please avoid drinking alcohol while consuming pregabalin medication.
Please contact your respective doctors (who prescribed this medicine), if patient experiences trouble in breathing or having shallow breaths.
Voluntary ADR reporting:
Every medicinal product has both benefits and risks. Medicines are authorized to market based on the favorable benefit-risk profile anticipated at the time of regulatory approval/entry into market. However, the safety profile of medicine would continuously updates owing to safety data from the post marketing experience from public. If the rate of reporting of suspected adverse drug reactions (ADR) from public is line with the actual occurrence of ADRs, the time lapse for taking regulatory action can be reduced and thereby improving patient safety.
All health care professionals and consumers of pharmaceutical medicinal products are encouraged to be aware of this fact and observe/monitor for any possible adverse events, reactions, medication errors, or quality complaints of medicinal products and report the same to your respective national health authority.
This would accumulate safety evidence for medicinal products which in turn help health authorities to take regulatory actions at the earliest possibility for a better patient safety and overall public health.