pregabalin and Renal-Insufficiency

Gabapentin (GBP) and pregabalin (PGB) are FDA approved for adjunctive treatment of partial seizures and for treatment of post-herpetic neuralgia. Both drugs are primarily eliminated by renal excretion. However, PGB or GBP induced myoclonus has only been reported infrequently in case reports/series. It is not discussed with patients and its sudden occurrence can lead to anxiety because of "seizure-like" nature. In addition, first-contact physicians might treat it as seizures, leading to unnecessary tests and aggressive management. Medical records of patients who had myoclonus because of PGB or GBP seen by Neurology service between Jan & May 2017 in inpatient or outpatient setting at our tertiary care setting were reviewed. We identified six patients who were on either GBP or PGB or both who developed likely subcortical myoclonus in the setting of renal insufficiency and one patient who developed myoclonus independent of renal dysfunction. Our results indicate that myoclonus is commonly seen in patients in various clinical settings with or without renal insufficiency, and is independent of the severity of the renal failure. However, this is a reversible side effect of medication and it resolves either by discontinuing the medication, removing the medication with hemodialysis or by improvement of renal dysfunction. With a high index of suspicion, aggressive testing and treatment for other possible conditions like seizures (in non-epilepsy patients) or CNS infections can be avoided. In patients with renal failure and with decreased physiological renal clearance such as the elderly, GBP or PGB dose initiation and changes should be conservative.

Topics: Adult; Aged; Analgesics; Chronic Pain; Female; Gabapentin; Humans; Male; Middle Aged; Myoclonus; Pregabalin; Renal Dialysis; Renal Insufficiency

A population pharmacokinetic (PK) model was developed to characterize the properties of pregabalin extended-release (ER) in healthy volunteers and was subsequently applied to patient data from efficacy/safety studies investigating pregabalin ER for postherpetic neuralgia, fibromyalgia, and partial-onset seizures. The impact of demographic and other covariates on PK was assessed, and various dosing scenarios were simulated to inform pregabalin ER dosing/administration instructions. Phase 1 and 3 models were developed using data from 14 phase 1 studies (12 627 samples from 335 participants receiving pregabalin immediate-release [IR] or ER) and 3 phase 3 studies (2591 samples from 1235 patients receiving pregabalin ER), respectively. Final phase 1 and 3 models adequately characterized the data. Several covariates were statistically significant, but renal function (creatinine clearance) was considered the only clinically relevant covariate. The relationship between creatinine clearance and pregabalin clearance was reasonably consistent between phase 1 and 3 models and with that reported previously with pregabalin IR data alone. Patients with moderate renal impairment who received pregabalin ER 82.5 mg once daily (QD) had similar predicted area under the plasma concentration-time curve and peak plasma concentration values as patients with normal/mild renal impairment who received 165 mg QD. Ranges in predicted PK parameters after switching from pregabalin IR administered in the morning to ER after a meal at 3, 6, or 9 pm were similar. Administration of a missed evening dose at bedtime with food or the next morning with food did not result in clinically important changes in predicted PK parameters.

Topics: Adult; Aged; Cross-Over Studies; Female; Fibromyalgia; Healthy Volunteers; Humans; Male; Middle Aged; Neuralgia, Postherpetic; Pregabalin; Renal Insufficiency; Seizures; Sex Factors

The objectives of this study were to determine the single-dose pharmacokinetics of pregabalin in subjects with various degrees of renal function, determine the relationship between pregabalin clearance and estimated creatinine clearance (CLcr), and measure the effect of hemodialysis on plasma levels of pregabalin. Results form the basis of recommended pregabalin dosing regimens in patients with decreased renal function. Thirty-eight subjects were enrolled to ensure a wide range of renal function (CLcr < 30 mL/min, n = 8; 30-50, n = 5; 50-80, n = 7; and > 80, n = 6). Also enrolled were 12 subjects with renal impairment requiring hemodialysis. Each subject received 50 mg of pregabalin as two 25-mg capsules in this open-label, parallel-group study. Pregabalin concentrations were measured using previously validated liquid chromatographic methods. Pregabalin pharmacokinetic parameters were evaluated by established noncompartmental methods. Pregabalin was rapidly absorbed in all subjects. Total and renal pregabalin clearance were proportional (56% and 58%, respectively) to CLcr. As a result, area under the plasma concentration-time profile (AUC) and terminal elimination half-life (t1/2) values increased with decreasing renal function. Pregabalin dosage adjustment should be considered for patients with CLcr < 60 mL/min. A 50% reduction in pregabalin daily dose is recommended for patients with CLcr between 30 and 60 mL/min compared to those with CLcr > 60 mL/min. Daily doses should be further reduced by approximately 50% for each additional 50% decrease in CLcr. Pregabalin was highly cleared by hemodialysis. Supplemental pregabalin doses may be required for patients on chronic hemodialysis treatment after each hemodialysis treatment to maintain steady-state plasma pregabalin concentrations within desired ranges.

Topics: Administration, Oral; Adolescent; Adult; Aged; Anticonvulsants; Area Under Curve; Creatinine; Dose-Response Relationship, Drug; Female; gamma-Aminobutyric Acid; Half-Life; Humans; Male; Middle Aged; Pregabalin; Renal Dialysis; Renal Insufficiency