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Pharmacology. Gabapentin and pregabalin are commonly used first-line agents for diabetic peripheral neuropathy and other common neuropathies. Pharmacologically, both agents inhibit alpha-2-delta (α2δ) subunit of N-type voltage-gated calcium channels, a key receptor involved in regulating the excitability of neurons. 3 Peripheral nerve injury results in the upregulation of α2δ-1 receptors Accumulation can cause renal failure resulting in adverse effects. Formulations. Gabapentin is available in two extended-release formulations in addition to the immediate release: a gastric retentive formulation (GBP-GR) and a gastro-retentive prodrug gabapentin enacarbil that are approved for the management of postherpetic neuralgia. Pain is one of the most common and distressing symptoms among patients with chronic kidney disease (CKD) . The prevalence of pain has been associated with substantially lower health-related quality of life and greater psychosocial distress, insomnia, and depressive symptoms [ 2-9 ]. In patients with normal renal function, the maximum dose of gabapentin is 3600mg daily in divided doses. However, gabapentin is renally cleared and so the dose needs to be adjusted according to the GFR. For patients on dialysis, the recommended dose is 100-300mg post dialysis on dialysis days only. Nonopioid analgesics, including acetaminophen, topical analgesics, gabapentinoids, serotonin-norepinephrine reuptake inhibitors, and tricyclic antidepressants may be considered based on pain etiology and type, with careful dose considerations in kidney disease. NSAIDs may be used in CKD and ESKD for short durations with careful monitoring. Child 6–11 years 10 mg/kg once daily (max. per dose 300 mg) on day 1, then 10 mg/kg twice daily (max. per dose 300 mg) on day 2, then 10 mg/kg 3 times a day (max. per dose 300 mg) on day 3; usual dose 25–35 mg/kg daily in 3 divided doses, some children may not tolerate daily increments; longer intervals (up to weekly) may be more appropriate, daily dose maximum to be given in 3 divided Affiliations 1 VA Tennessee Valley Healthcare System, Murfreesboro, Nashville, TN.; 2 Stratton VA Medical Center; Albany College of Pharmacy and Health Sciences, Albany, NY; Western New England University College of Pharmacy, Springfield, MA; Scientific and Clinical Affairs, Remitigate LLC, Delmar, NY, USA. Gabapentin dosing guidelines for adult with renal impairment are summarized in Table 3. Dosing guidelines for gabapentin immediate-release are also applicable for adolescents 12 years of age and older with renal impairment. Gabapentin Dosage Based on Renal Function. 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). Gabapentin has a favorable pharmacokinetic profile, because it is not protein-bound or metabolized and has no known drug–drug interactions. 10 Gabapentin has been widely used in elderly patients with multiple comorbidities, including chronic kidney disease. However, gabapentin is eliminated solely through the kidney, and kidney impairment The short answer is: yes, gabapentin can be problematic for individuals with kidney failure and chronic kidney disease (CKD). Gabapentin Dosage Based on Renal Function. TID = Three times a day; BID = Two times a day; QD = Single daily dose. a. I currently take gabapentin for trigeminal neuralgia and have CKD stage 3. Take 900-1200 gabapentin daily over past 20 years. Experiencing severe side effects of gabapentin that Im beginning to think correlate with decreased kidney function. It’s becoming cyclic. Take normal dose of gabapentin until start to become confused and lethargic. Detailed Gabapentin dosage information for adults and children. Includes dosages for Restless Legs Syndrome, Epilepsy and Postherpetic Neuralgia; plus renal, liver and dialysis adjustments. 4. Renal Dosing Recommendations. Mild Kidney Problems (CrCl 60-90 mL/min): Dose Adjustment: 900 - 3600 mg/day TID. How Often to Take: 3 times a day. Notes: Monitor for dizziness or double vision. Moderate Kidney Problems (CrCl 30-59 mL/min): Dose Adjustment: 400-1400 mg/day BID; How Often to Take: Twice a Day; Notes: Your doctor will decide the Loading dose of 300–400 mg in patients who have never received gabapentin. Maintenance dose of 100–300 mg after each HD : session and increase according to tolerability. Gabapentin toxicity in patients with chronic kidney disease is underrecognized. Patients with chronic kidney disease often receive inappropriately high gabapentin dosage for their kidney function, occasioning overt toxicity; advanced age and comorbidity predispose these patients for toxicity. Gabapentin’s apparent total clearance is 100 mL/min in adults with normal renal function, which is essentially equivalent to CrCl and does not suggest the involvement of tubular reabsorption. 1 Some evidence suggest that active tubular secretion mediated by organic cation transporter-1 (OCT-1) may play a role in gabapentin’s renal clearance. Gabapentin is widely used in the management of pain. It is entirely excreted through the renal system so this needs to be considered in any patient becoming acutely ill and developing renal failure. We describe a patient who developed significant deterioration in her conscious level due to iatrogenic gabapentin overdose. Conclusion.
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