What are the new warnings about gabapentin (Neurontin)?

New Warnings About Gabapentin (Neurontin)

The FDA has issued new warnings about gabapentin, highlighting serious risks including Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)/multiorgan hypersensitivity, anaphylaxis, and increased risk of falls or fractures, particularly at higher doses. 1, 2

Key Safety Concerns

Serious Hypersensitivity Reactions

• DRESS syndrome (Drug Reaction with Eosinophilia and Systemic Symptoms), which can be fatal or life-threatening, has been reported with gabapentin use 1
• DRESS typically presents with fever, rash, and/or lymphadenopathy, along with other organ system involvement such as hepatitis, nephritis, hematological abnormalities, myocarditis, or myositis 1
• Anaphylaxis and angioedema can occur after the first dose or at any time during treatment, with signs including difficulty breathing, swelling of the lips, throat, and tongue, and hypotension requiring emergency treatment 1

Neurological and Psychiatric Concerns

• Suicidal thoughts and behavior have been reported in patients taking gabapentin 1
• Somnolence, sedation, and dizziness are common side effects that can impair driving ability and operation of complex machinery 1
• Increased risk of falls or fractures, with a clear dose-response relationship showing highest risk at doses ≥2,400 mg/day (relative risk 1.90) 2
• Altered mental status has been observed, particularly at doses between 600-2,399 mg/day 2

Withdrawal Risk

• Abrupt discontinuation may increase seizure frequency or precipitate status epilepticus 1
• Gabapentin should not be stopped without first consulting a healthcare provider 1

Abuse Potential

• Growing evidence of gabapentin misuse and abuse, particularly among individuals with a history of substance use disorders 3, 4
• Some states have reclassified gabapentin as a Schedule V controlled substance and implemented prescription monitoring programs 5
• Individuals with opioid abuse, mental illness, or previous history of prescription drug abuse are at highest risk for gabapentin misuse 5

Monitoring Recommendations

• Patients should be carefully observed for signs of central nervous system depression when gabapentin is used with other sedative medications 1
• Dosage adjustment is required for patients with renal insufficiency 6
• Healthcare providers should evaluate patients for signs of:
  • Hypersensitivity reactions (fever, rash, lymphadenopathy) 1
  • Suicidal thoughts or behavior 1
  • Changes in behavior, mood, or thinking 1
  • Falls risk, especially in elderly patients or at higher doses 2

Dosing Considerations

• Treatment should be initiated at low dosages with gradual titration to minimize adverse effects 6
• Starting dose: 100-300 mg at bedtime or 100-300 mg three times daily 6
• Titration: Increase by 100-300 mg every 1-7 days as tolerated 6
• Dose-dependent side effects (dizziness, sedation) can be reduced by starting with lower dosages and titrating cautiously 6
• Consider lower starting dosages and slower titration in geriatric patients 6

Patient Counseling

• Patients should be instructed to seek immediate medical care if they experience signs of hypersensitivity reactions 1
• Patients should be advised not to drive until they have gained sufficient experience to assess whether gabapentin impairs their ability to drive 1
• Patients should be monitored for mood changes, suicidal thoughts, or unusual behavior changes, especially when starting treatment 1
• Patients should be informed about the risk of abuse and dependence, particularly those with a history of substance use disorders 3, 5

Despite these warnings, gabapentin remains an effective first-line medication for certain conditions like neuropathic pain when used appropriately and with proper monitoring 7, 6.