1. Use of drugs in children with impaired renal function: what is to worry about? Augustina Jankauskien ė , Vilnius university children hospital, Lithuania

10. Table : Classification of various drugs based on pathophysiologic categories of acute kidney injury deBroe ME et all (2003) Clinical nephrotoxins: Renal injury from drugs and chemicals, 2 edn.Kluwer Academic, Dordrecht Pathophysiology Drugs known to cause acute kidney injury Prerenal failure NSAIDs, ACE inhibitors, cyclosporine A (CyA), norepinephrine, AT2-receptor antagonists, diuretics, interleukins, cocaine, mitomycin C, tacrolimus, estrogen, quinine Acute tubular necrosis Antibiotics: aminoglycosides, cephalosporins, amphotericin B, rifampicin, vancomycin, foscarnet, pentamidine NSAIDs, glaphemin, contrast media, acetaminophen, CyA, cisplatinum, i.v. immunoglobulin, dextran, maltose, sucrose, mannitol, heavy metals Acute interstitial nephritis Antibiotics: ciprofloxacin, methicillin, penicillin G, ampicillin, cephalosporins, oxacillin, rifampicin NSAIDs, glaphenin, acetylsalicylic acid (ASA), fenoprofen, naproxen, phenylbutazone, piroxicam, tolmetin, zomepirac, contrast media, sulfonamides, thiazides, phenytoin, furosemide, allopurinol, cimetidine, omeprazole, phenindione Tubular obstruction Sulfonamides, methotrexate, methoxyflurane, glaphenin, triamterene, acyclovir, ethylene glycol, protease inhibitors Hypersensitivity angiitis Penicillin G, ampicillin, sulfonamides Trombotic microangiopathy Mitomycin C, CyA, oral contraceptives

12. Dosage guideline based on renal e xcretion . From: Bartelink I.H et al. Guidelines on Paediatric dosing on the basis of Developmental Physiology and Pharmacokinetic Considerations. Clin Pharmacokin 2006:45(11):1077-1097 AS – Active Tubular Secretion. A marker for AS is p -aminohippuric acid

14. Table: Drug doses for children with normal and reduced kidney function. All doses are given for normal renal function, for a glomerular filtration rate (GFR) of 40 and 10 ml/ min / 1,73 m 2 , and for anuric patients. The doses for reduced renal function are calculated as a percentage of the normal dose and divided into the indicated number of single doses (for example: normal dose 100 mg/ kg / day in two single doses = 2 x 50 mg/ kg daily; dose at a GFR of 10 ml / min / 1,73 m 2 : 30 % in one single dose = 1 x 30 mg/ kg daily) Daschner M. Pediatr Nephrol (2005)20: 1675-1686 Group / subgroup Normal daily dose, number of single doses Dose at GFR (ml/min/1 . 73m 2 ) Dialysis 40 10 Anuric Aldosterone antagonists Spironolactone PO: 1-5 mg / kg in 2 single doses IV: -5mg / kg in 4 single doses 50 % (1 single dose) 25 % (1 single dose) Contraindicated Analgesics / anti-inflammatory agents Acetylsalicylic acid 5(-10) mg / kg as single dose (max. 4x / day) 75 % 50 % (increase dose interval) 50 % (increase d ose interval) Ibuprofen 20-30 mg / kg in 3-4 single doses Max. daily dose 1.2 g Normal dose Normal dose Normal dose Paracetamol 10-20 mg / kg as single dose (max.4x / day) . Max. daily dose 4g Normal dose 50 % (increase dose interval) 50 % increase d ose interval) Antibiotics aminoglycosides Gentamicin 3-5 mg / kg / day in 3 single doses Peak level 5-10 mg / ml Trough level 0.5-2 mg / l Max. daily dose 360 mg 60 % (2 single doses) Reduce loading dose 10 % (1 single doses) Reduce loading dose 5 % (1 single d ose), loading dose 1-2 mg / kg 15 % after hemodialysis; Intraperitonea loading dose 8 mg / l, Maintenance dose 4mg / l Antivirals Ganciclovir IV: initial (14 days) 10 mg / kg / day in 2 single doses, then 5 mg / kg / day in 1 single PO: 100 mg / kg / day in 3 single doses PO dose at GFR < 40: mg / kg = GFR; max. daily dose 3g PO IV: 40 % (2 single doses) 10 % (1 single dose); orally in 2 single doses 1.25mg.kg afte r Each hemodialysis(or 5 % during Peritoneal dialysis); PO in 2 single doses 1.25 mg / kg after each Hemodialysis (or 5 % during Peritoneal dialysis); PO in 2 single doses

19. Resources for More Information About Dosing Adjustments in Patients with Chronic Kidney Disease Drug Prescribing in Renal Failure: Dosing Guidelines for Adults Publisher: American College of Physicians PDA download: http://acp.pdaorder.com/pdaorder/-/605920537541/ item?oec-catalog-item-id=1028 FDA Center for Food Safety and Applied Nutrition Web site: http://www.cfsan.fda.gov/ FDA MedWatch Web site: http://www.fda.gov/medwatch/index.html Medline Plus (herbal medicine) Web site: http://www.nlm.nih.gov/medlineplus/herbalmedicine.html National Center for Complementary and Alternative Medicine Web site: http://www.nccam.nih.gov/ National Kidney Disease Education Program Web site: http://www.nkdep.nih.gov National Kidney Foundation Web site: http://www.kidney.org/

20. Guidelines must run the gaun t let between being too general to be useful and too specific to be excl u sive Baber N.S. Paediatric regulatory guidelines: do they help in optimising dose selection for children? Br J Clin Pharmacol, 2 00 5