What is the appropriate dosing of Gabapentin (Gabapentin) for a patient with Impaired renal function undergoing Hemodialysis (HD)?

From the Guidelines

For hemodialysis patients, gabapentin should be dosed at 200-300 mg after each hemodialysis session, as this population requires significant dose reduction due to impaired renal function 1.

Key Considerations

• Gabapentin is primarily eliminated by the kidneys, and its accumulation can lead to toxic levels in patients undergoing hemodialysis, causing adverse effects such as excessive sedation, dizziness, and ataxia.
• The standard dosing for patients with normal renal function, as outlined in studies such as 1, involves starting doses of 100-300 mg nightly and increasing to 900-3600 mg daily in divided doses, but this must be adjusted for those with renal insufficiency.
• For patients on a typical three-times-weekly hemodialysis schedule, administering gabapentin only after each dialysis treatment, rather than daily, is recommended to avoid accumulation and potential toxicity.

Dosing Adjustments

• If the patient experiences breakthrough pain or neuropathic symptoms between dialysis sessions, a small maintenance dose (100 mg) on non-dialysis days may be considered, but this should be done with caution and close monitoring for side effects.
• Regular assessment of patients for efficacy and adverse effects is crucial, with particular attention to neurological symptoms that might indicate toxicity, and dose adjustments may be necessary based on individual patient response and tolerability.

Clinical Context

• The management of gabapentin dosing in hemodialysis patients requires careful consideration of the drug's pharmacokinetics and the patient's renal function to balance efficacy with the risk of adverse effects.
• Studies like 1 provide guidance on the use of anticonvulsants, including gabapentin, in managing pain, but the specific context of hemodialysis necessitates a tailored approach to dosing.

From the FDA Drug Label

Dosage adjustment in patients 12 years of age and older with compromised renal function or undergoing hemodialysis is recommended, as follows

TABLE 1 Gabapentin Tablets Dosage Based on Renal Function

Renal Function Creatinine Clearance (mL/min) Total Daily Dose Range (mg/day) Dose Regimen (mg)

...

Post-Hemodialysis Supplemental Dose (mg)b

Hemodialysis 125b 150b 200b 250b 350b

TID = Three times a day; BID = Two times a day; QD = Single daily dose

a For patients with creatinine clearance <15 mL/min, reduce daily dose in proportion to creatinine clearance (e.g., patients with a creatinine clearance of 7. 5 mL/min should receive one-half the daily dose that patients with a creatinine clearance of 15 mL/min receive).

b Patients on hemodialysis should receive maintenance doses based on estimates of creatinine clearance as indicated in the upper portion of the table and a supplemental post-hemodialysis dose administered after each 4 hours of hemodialysis as indicated in the lower portion of the table

The appropriate dosing of Gabapentin for a patient with impaired renal function undergoing Hemodialysis (HD) is as follows:

• The patient should receive a maintenance dose based on their creatinine clearance, as indicated in the table.
• A supplemental post-hemodialysis dose should be administered after each 4 hours of hemodialysis.
• The supplemental dose can range from 125mg to 350mg, depending on the patient's creatinine clearance. 2

From the Research

Gabapentin Dosing for Patients with Impaired Renal Function Undergoing Hemodialysis

• The appropriate dosing of Gabapentin for a patient with impaired renal function undergoing hemodialysis (HD) is crucial to avoid toxicity and ensure therapeutic efficacy 3.
• A study published in the Journal of Clinical Pharmacology in 1995 recommends an initial 300-mg to 400-mg gabapentin loading dose for patients with end-stage renal disease maintained on hemodialysis 3.
• To maintain plasma gabapentin concentrations, it is suggested to give 200 to 300 mg of gabapentin after every 4 hours of hemodialysis 3.
• Another study published in the American Journal of Kidney Diseases in 2017 found that continuous peritoneal dialysis provides significant clearance of gabapentin, with an apparent elimination half-life of 41.33 hours 4.
• However, the study notes that this method is slow and may not be suitable for all patients 4.
• A review of the literature by the EXTRIP workgroup in 2022 suggests that hemodialysis is effective in removing gabapentin and pregabalin from the body, but the clinical benefit of extracorporeal treatment is unclear 5.
• The workgroup recommends against performing extracorporeal treatment in addition to standard care for patients with normal kidney function, but suggests it may be considered for patients with decreased kidney function and coma requiring mechanical ventilation 5.
• A study published in the Journal of the American Society of Nephrology in 2018 found that gabapentin and pregabalin use is associated with adverse outcomes, including altered mental status, falls, and fractures, in hemodialysis patients 6.
• The study suggests that these medications should be used judiciously in patients on hemodialysis, and research is needed to identify the most optimal dosing 6.