Can a patient with diabetes (diabetes mellitus), peripheral neuropathy, and impaired renal function safely take gabapentin in combination with temazepam (Restoril, benzodiazepine)?

Can Gabapentin Be Taken with Temazepam?

Yes, gabapentin can be taken with temazepam, but this combination requires dose adjustment for gabapentin due to impaired renal function and heightened monitoring for central nervous system depression, particularly sedation and confusion. 1

Critical Renal Function Considerations

Gabapentin requires mandatory dose reduction in renal impairment because it is almost exclusively eliminated by the kidneys. 1

• In patients with creatinine clearance <30 mL/min, gabapentin half-life extends from 6.5 hours to 52 hours, and plasma clearance drops from 190 mL/min to 20 mL/min 1
• Gabapentin toxicity in renal impairment manifests as confusion, myoclonus, tremulousness, altered mental status, and even coma 2
• The standard dose of 300 mg three times daily used for diabetic peripheral neuropathy must be reduced based on creatinine clearance 1

Drug Interaction Profile

There is no direct pharmacokinetic interaction between gabapentin and benzodiazepines, but additive central nervous system depression is the primary concern. 1

• Gabapentin does not inhibit cytochrome P450 enzymes (CYP1A2, CYP2A6, CYP2C9, CYP2C19, CYP2D6, CYP2E1, CYP3A4) even at concentrations 15 times higher than therapeutic levels 1
• Gabapentin is not metabolized hepatically, eliminating concerns about metabolic drug interactions 1
• The combination of gabapentin (which causes somnolence in 23% and confusion in 8% of patients) with temazepam (a sedative-hypnotic) increases risk of excessive sedation, falls, and cognitive impairment 3

Practical Dosing Algorithm for This Patient

Start with reduced gabapentin dosing and monitor closely:

1. Determine creatinine clearance to guide gabapentin dosing (not provided in question, but essential) 1
2. If CrCl 30-60 mL/min: Start gabapentin 300 mg once daily at bedtime, increase to 300 mg twice daily after 1 week if tolerated 1
3. If CrCl 15-30 mL/min: Start gabapentin 300 mg once daily, may increase to 300 mg twice daily only if closely monitored 1
4. If CrCl <15 mL/min: Start gabapentin 100-300 mg once daily; if on hemodialysis, give supplemental dose after each dialysis session 1

Monitoring Requirements

Monitor for gabapentin toxicity signs weekly during titration:

• Confusion, hallucinations, or altered mental status (early signs of toxicity in renal impairment) 2
• Myoclonus or tremulousness (indicates supratherapeutic levels) 2
• Excessive sedation beyond expected temazepam effects (additive CNS depression) 3
• Dizziness (occurs in 24% on gabapentin) and ataxia (increases fall risk when combined with benzodiazepines) 3
• Peripheral edema (occurs in 7% and may worsen with renal impairment) 3

Evidence-Based Efficacy for Diabetic Neuropathy

Gabapentin at 1200-3600 mg/daily provides substantial pain relief (≥50% reduction) in 38% of patients with painful diabetic peripheral neuropathy versus 21% with placebo (NNT 5.9). 4

• However, this patient with renal impairment will likely require doses well below 1200 mg/day, potentially limiting efficacy 1
• Moderate benefit (≥30% pain relief) occurs in 52% versus 37% with placebo (NNT 6.6) 4
• Gabapentin is recommended as first-line therapy for diabetic peripheral neuropathy by multiple guidelines 5, 6

Alternative Considerations if Combination is Poorly Tolerated

If excessive sedation occurs with gabapentin plus temazepam:

• Switch to duloxetine 60 mg daily (FDA-approved for diabetic neuropathy, no renal dose adjustment needed unless severe renal impairment, does not interact with benzodiazepines) 7, 6
• Switch to pregabalin (similar efficacy to gabapentin but more predictable pharmacokinetics; however, also requires renal dose adjustment) 5, 4
• Consider discontinuing temazepam and using gabapentin's sedative properties for sleep benefit (23% experience somnolence, which may be therapeutic for insomnia) 3

Common Pitfalls to Avoid

• Do not use standard gabapentin dosing (900-3600 mg/day) without assessing renal function—this will cause toxicity 1, 2
• Do not assume gabapentin is safe simply because it lacks drug-drug interactions—the additive CNS depression with benzodiazepines is clinically significant 3
• Do not overlook the need for post-hemodialysis supplemental dosing if the patient progresses to dialysis 1
• Do not continue escalating gabapentin if confusion or myoclonus develops—these are signs of toxicity requiring immediate dose reduction or discontinuation 2