Gabapentinoids and sodium-channel anticonvulsants for pain

Gabapentinoids are renally cleared, sedating and dangerous with opioids; dose them by creatinine clearance and taper rather than stop. Carbamazepine and oxcarbazepine lead for trigeminal neuralgia but bring HLA and sodium warnings.

1. Gabapentin absorption is saturable. Bioavailability falls from about 60% at 900 mg/day to about 34% at 2,400 mg/day, so exposure rises less than proportionally with dose. Gabapentin is not appreciably metabolized, is renally excreted and is not protein bound ¹.
2. Pregabalin is linear and renally dosed. Bioavailability is at least 90% regardless of dose. The daily range roughly halves with each step down in creatinine clearance, and hemodialysis patients get a reduced daily dose plus a supplement after each session ².
3. Both carry respiratory-depression warnings. Labels warn of serious respiratory depression with opioids and other CNS depressants, or with underlying respiratory impairment; CDC notes higher overdose risk when gabapentin is combined with an opioid ¹²³.
4. Carbamazepine or oxcarbazepine for trigeminal neuralgia. EAN names them the drugs of first choice; gabapentin, pregabalin, lamotrigine, baclofen and others are alternatives or add-ons ⁴.
5. Screen for HLA-B*15:02 before carbamazepine. The allele, found almost only in people with Asian ancestry, is strongly associated with Stevens-Johnson syndrome and toxic epidermal necrolysis; screen at-risk patients first, and do not give carbamazepine to carriers unless benefit clearly outweighs risk ⁵.
6. Oxcarbazepine lowers sodium. Clinically significant hyponatremia (below 125 mmol/L) occurred in about 2.5% of patients in epilepsy trials; monitor sodium, especially with other sodium-lowering drugs such as thiazides ⁶.

Stopping a gabapentinoid abruptly risks withdrawal and seizures, so taper it; in older adults, gabapentinoid plus opioid is a Beers combination to avoid, so reassess once the indication ends ¹⁷.

• Pregabalin with CrCl 30–60 mL/min: 75–300 mg/day; 15–30: 25–150 mg/day; below 15: 25–75 mg/day ².
• Switching gabapentin to pregabalin does not remove the opioid-interaction respiratory warning ².
• Gabapentinoids count toward the Beers criterion against three or more CNS-active drugs in older adults ⁷.
• Oxcarbazepine is not a safe workaround for HLA-B*15:02 carriers; its label warns of risk too ⁶.
• AAN lists gabapentinoids among four effective classes for painful diabetic neuropathy, with switching to another class if one fails ⁸.
• When trigeminal neuralgia is not controlled or drugs are poorly tolerated, EAN recommends offering surgery, with microvascular decompression first-line for classical disease ⁴.

• Doubling gabapentin and expecting double the blood level ¹.
• Holding pregabalin on dialysis days instead of giving a post-dialysis supplement ².
• Using oxcarbazepine as a "safe" alternative in an HLA-B*15:02 carrier ⁶.
• Missing hyponatremia when new nonspecific neurologic symptoms appear on oxcarbazepine, particularly with other sodium-lowering drugs ⁶.