Do pregabalin and gabapentin have warnings for cerebral edema, cardiac arrhythmia, respiratory depression, or nephrotoxic effects on their labels?

Label Warnings for Pregabalin and Gabapentin

No, pregabalin and gabapentin do not have identical label warnings for these specific adverse effects—only pregabalin carries an FDA black box-level warning for respiratory depression, while neither medication has formal label warnings for cerebral edema, cardiac arrhythmia, or nephrotoxic effects. 1

Respiratory Depression

Pregabalin has an explicit FDA label warning for serious, life-threatening, or fatal respiratory depression, particularly when co-administered with CNS depressants (including opioids) or in patients with underlying respiratory impairment. 1 The FDA mandates that prescribers monitor patients for respiratory depression symptoms and consider initiating pregabalin at low doses in these high-risk scenarios. 1

• Evidence from case reports, human studies, and animal studies directly links pregabalin to respiratory depression, with more limited evidence showing this can occur even without co-administered CNS depressants or underlying respiratory disease. 1
• The 2019 Lancet Psychiatry guidelines emphasize that when gabapentinoids are taken with opioids, dangerous respiratory depression can occur. 2
• Gabapentin does not have the same explicit FDA label warning for respiratory depression as pregabalin, though clinical evidence suggests similar risks exist in practice. 2

Cardiac Effects

Neither pregabalin nor gabapentin carries FDA label warnings for cardiac arrhythmias. However, both medications have documented associations with peripheral edema and potential cardiac complications:

• Pregabalin commonly causes peripheral edema (10% of patients), which is dose-dependent. 3
• Case reports describe heart failure development in patients treated with pregabalin, particularly in elderly patients with chronic disease, though the FDA label does not include a formal arrhythmia warning. 4
• The New York Heart Association issued warnings about using caution when prescribing pregabalin to type III-IV heart failure patients, despite lack of published evidence establishing direct causation. 4
• Both medications may affect cardiac function through calcium channel mechanisms, though this is not well-characterized on their labels. 4

Cerebral Edema

Neither medication has FDA label warnings for cerebral edema. The primary CNS warnings for both drugs focus on:

• Dizziness (30% with pregabalin vs 8% with placebo) 1
• Somnolence (23% with pregabalin vs 8% with placebo) 1
• Cognitive impairment and confusion, particularly in elderly patients 3

Nephrotoxic Effects

Neither pregabalin nor gabapentin has FDA label warnings for nephrotoxicity. Instead, both medications require dose adjustments in renal impairment because they are eliminated unchanged by the kidneys:

• Pregabalin is 95% renally excreted unchanged, requiring mandatory dose reduction: approximately 50% reduction for creatinine clearance 30-60 mL/min, 75% for 15-30 mL/min, and 85-90% for <15 mL/min. 3
• Gabapentin has similar renal elimination characteristics requiring dose adjustment in renal dysfunction. 5
• The concern is drug accumulation and toxicity in renal impairment, not direct nephrotoxic injury. 3

Critical Clinical Pitfalls

Do not assume equivalent safety profiles between these medications—pregabalin has more stringent FDA warnings for respiratory depression, making it particularly hazardous when combined with opioids or other CNS depressants. 1

• The FDA strengthened warnings for both gabapentinoids in 2018 to emphasize CNS side effects and respiratory depression risk, but pregabalin's label is more explicit. 6
• Never combine pregabalin and gabapentin—this therapeutic duplication causes additive sedation, dizziness, visual disturbances, and ataxia without additional benefit. 7
• Both medications require gradual tapering over minimum 1 week to avoid withdrawal symptoms (insomnia, nausea, headache, anxiety, hyperhidrosis, diarrhea). 1