Understanding Dose Titration: Overactive Bladder Treatment With Fesoterodine as an Example

Context: Individuals differ in their sensitivity to drug treatment, including that with muscarinic receptor antagonists used in the treatment of overactive bladder (OAB), due to a combination of pharmacodynamic and pharmacokinetic reasons. Objective: To discuss the variability in drug response among individual patients, the concept of the dose-response curve, and the selection of drug dosage as well as how these factors are integrated when optimising OAB treatment using the muscarinic receptor antagonist fesoterodine as an example. Evidence acquisition: Data sources were identified in 2010 using a nonsystematic search and included articles and abstracts selected using expert opinion of their relevance to drug response in OAB. Evidence synthesis: A given drug dose is unlikely to yield the same quantitative response in all patients, and undertreatment (too little efficacy) or overtreatment (too many side effects) may occur. The position and shape of the dose-response curve for a drug may differ between patients and within a patient for desired and adverse effects. The availability of two or more drug doses allows for titration (flexible dosing) to find the dose exhibiting the optimal clinical efficacy that is tolerable for an individual patient. Optimally, a patient would have symptom resolution with no adverse events (AEs). Realistically, an efficacy-to-tolerability ratio (therapeutic index) exists for each of the combinations of selected efficacy metrics and AE reports. Conclusions: Dose titration is important for selection of an effective dose of a treatment with minimal side effects. (C) 2011 European Association of Urology. Published by Elsevier B. V. All rights reserved.