When the Solifenacin Label Lowers the Dose | Kidney and Liver Disease (Special Populations 13.3)

How do renal impairment and hepatic impairment change the dose on a US label? Lesson 13.3 of our special populations module covers three parts: renal impairment, hepatic impairment and the label. The worked example is solifenacin, with a study in renal impairment, a study in moderate hepatic impairment and the dose changes of its label. 0:00 Definitions and the Child-Pugh score 1:33 Renal impairment 2:16 Hepatic impairment 3:06 The label 3:47 Solifenacin dose changes 4:26 Renal impairment study 5:24 Hepatic impairment study 6:05 Summary Sources HEC Pharm USA Inc. Solifenacin succinate tablets: DailyMed label. 2026. https://dailymed.nlm.nih.gov/dailymed... Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron. 1976. PMID 1244564 Verbeeck RK, Musuamba FT. Pharmacokinetics and dosage adjustment in patients with renal dysfunction. Eur J Clin Pharmacol. 2009. PMID 19543887 Palmieri C, Macpherson IR. A review of the evidence base for utilizing Child-Pugh criteria for guiding dosing of anticancer drugs in patients with cancer and liver impairment. ESMO Open. 2021. PMID 34098229 Weersink RA, Bouma M, Burger DM, et al. Evaluating the safety and dosing of drugs in patients with liver cirrhosis by literature review and expert opinion. BMJ Open. 2016. PMID 27733414 Johnson TN, Boussery K, Rowland-Yeo K, et al. A semi-mechanistic model to predict the effects of liver cirrhosis on drug clearance. Clin Pharmacokinet. 2010. PMID 20170207 Verbeeck RK. Pharmacokinetics and dosage adjustment in patients with hepatic dysfunction. Eur J Clin Pharmacol. 2008. PMID 18762933 Weersink RA, Bouma M, Burger DM, et al. Evidence-based recommendations to improve the safe use of drugs in patients with liver cirrhosis. Drug Saf. 2018. PMID 29330714 Benet LZ, Liu S, Wolfe AR. The universally unrecognized assumption in predicting drug clearance and organ extraction ratio. Clin Pharmacol Ther. 2017. PMID 28762489 Dreisbach AW, Lertora JJ. The effect of chronic renal failure on drug metabolism and transport. Expert Opin Drug Metab Toxicol. 2008. PMID 18680441 Zhang Y, Zhang L, Abraham S, et al. Assessment of the impact of renal impairment on systemic exposure of new molecular entities: evaluation of recent new drug applications. Clin Pharmacol Ther. 2009. PMID 19020495 Matzke GR, Aronoff GR, Atkinson AJ, et al. Drug dosing consideration in patients with acute and chronic kidney disease: a clinical update from Kidney Disease: Improving Global Outcomes (KDIGO). Kidney Int. 2011. PMID 21918498 US Food and Drug Administration. Pharmacokinetics in patients with impaired renal function: study design, data analysis, and impact on dosing; guidance for industry; availability. Federal Register notice. 2024. https://www.govinfo.gov/content/pkg/F... US Food and Drug Administration. Pharmacokinetics in patients with impaired renal function: study design, data analysis, and impact on dosing. Guidance for industry. 2024. https://www.fda.gov/regulatory-inform... US Food and Drug Administration. Pharmacokinetics in patients with impaired hepatic function: study design, data analysis, and impact on dosing. Draft guidance for industry. 2026. https://www.fda.gov/regulatory-inform... US Code of Federal Regulations. 21 CFR 201.57: Specific requirements on content and format of labeling for human prescription drug and biological products. 2026. https://www.law.cornell.edu/cfr/text/... Munar MY, Singh H. Drug dosing adjustments in patients with chronic kidney disease. Am Fam Physician. 2007. PMID 17555141 Doroshyenko O, Fuhr U. Clinical pharmacokinetics and pharmacodynamics of solifenacin. Clin Pharmacokinet. 2009. PMID 19566112 Smulders RA, Smith NN, Krauwinkel WJ, et al. Pharmacokinetics, safety, and tolerability of solifenacin in patients with renal insufficiency. J Pharmacol Sci. 2007. PMID 17251687 Kuipers M, Smulders R, Krauwinkel W, et al. Open-label study of the safety and pharmacokinetics of solifenacin in subjects with hepatic impairment. J Pharmacol Sci. 2006. PMID 17170513 Illustrations adapted from Servier Medical Art (smart.servier.com), CC BY 4.0. Structures drawn with RDKit.