Drug Prescription in Chronic Kidney Disease
Selection of drugs and their dosing in patients with CKD is a challenging but unavoidable task as the number of patients suffering from CKD is increasing worldwide and exceeds 15 % of the population in industrialized countries. In the United States 62.2 %
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Jan T. Kielstein
Before You Start: Facts You Need to Know
• Less is more – the lower the pill count, the higher the adherence and the smaller the likelihood of dosing errors and interactions. • Every drug has potential side effects; thus, the indication for every prescription has to be based on an individual benefit/risk ratio. • Chronic pharmacotherapy has to be reassessed on a regular basis considering the current risk/benefit ratio, the persistence of indications, and current kidney (and hepatic) function. • Physicians should educate patients and caregivers about potentially severe adverse
events, like hyperkalemia in case of diarrhea under double blockade of the reninangiotensin-aldosterone system. • Renal replacement therapy comes in different modes (peritoneal dialysis, hemodialysis), treatment intensities, and accompanying effects (e.g., hypotension) – all have to be considered for adequate timing and drug dose. • There is little evidence from randomized controlled trials to guide the decisions mentioned above, let alone considering age, comorbidities, and other therapies.
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J.T. Kielstein, MD Department of Nephrology and Hypertension, Hannover Medical School, Carl-Neuberg-Str. 1, Hannover 30625, Germany Abteilung für Nieren- und Hochdruckerkrankungen, Medizinische Hochschule Hannover, Carl-Neuberg-Strasse 1, Hannover 30625, Germany e-mail: [email protected]
Scio Nescio1 Paucity of Dosing Studies in CKD
The determination of kidney function is one cornerstone of dosing drugs in CKD patients. Chapter 2 summarizes details to this task. Frequently this alone is of little help as corresponding pharmacokinetic and pharmacodynamic studies of drugs that would allow converting a specific GFR in a specific dose or dosing interval are missing. Based on the linear relationship between the overall drug elimination rate constant and the GFR, individual drug elimination in patients with renal impairment can be estimated from the patient’s GFR. 1
Scio Nescio = I know that I know nothing (Socrates)
M. Arici (ed.), Management of Chronic Kidney Disease, DOI 10.1007/978-3-642-54637-2_27, © Springer-Verlag Berlin Heidelberg 2014
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Dettli did this for the first time by means of a simple nomogram according to which either a dose reduction or an increase in the dosing interval has to occur [1]. This can however not be routinely done at the bedside, where dosing is frequently based on package inserts of the manufacturer. Occasionally this information in the official US Food and Drug Administration (FDA) or European Medicines Agency (EMA) product labeling which can also be found in some yearly reissued but not updated pocket books is in sharp conflict with the recommendations derived from post-marketing studies [2]. Why is there insufficient evidence to guide dosing on many commonly used drugs? For decades the industry had neither guidance nor pressure from the regulatory agencies to deal with this matter. Not until 1998 did the FDA (2004 EMA) provide frameworks to help companies decide when to conduct pha
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