Introduction The Role of the Kidneys Drugs used in Renal Disease Drugs and Dialysis Renal Pharmacy Team

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2 Introduction The Role of the Kidneys Drugs used in Renal Disease Drugs and Dialysis Renal Pharmacy Team

3 Drugs play a major role in both treating and causing renal disease Doses of some drugs need to be changed in renal disease Clearance of drugs is different again in dialysis Renal pharmacists can help with doses and drug choice

4 Controls the water and electrolyte content of the body By filtration, secretion and reabsorption Keeps vital substances (e.g. protein) in the body Maintains the acid-base balance Excretes waste products, toxins and drugs Endocrine functions Activates Vitamin D Produces hormones (e.g. Erythropoeitin)

5 Acute Kidney Injury (AKI) Can be caused by drugs, sepsis, trauma Chronic Kidney Disease (CKD) Staged according to renal function Causes Inherited disease (e.g. polycystic kidneys) Acquired disease (e.g. nephrotic syndrome) Hypertension Diabetes

6 Treatment can be for the underlying disease e.g. cyclophosphamide to treat vasculitis Most drugs are aimed at treating the complications of renal disease EPO for renal anaemia Phosphate binders for renal bone disease ACE-I for protein loss in nephrotic syndrome Renal patients often have multiple comorbidities, so we need to consider their other treatments too

7 In renal failure, drugs are handled differently by the body Reduced absorption Increased permeability of the blood brain barrier Reduced protein binding Reduced metabolism Reduced clearance of drugs Doses of some drugs need to be altered in renal failure

8 Is the drug nephrotoxic? Avoid where possible e.g. Ciprofloxacin instead of Gentamicin Less of an issue if anuric Is the drug excreted unchanged in the urine? Ideally <25% Risk of accumulation Lower dose needed for same effect

9 How are metabolites excreted? Very little significant metabolism by the kidney Active metabolites may accumulate in ESRF E.g. Morphine-6-glucuronide Is there significant non-renal toxicity? If wide therapeutic window, e.g. Penicillins, dose adjustment may not be necessary Caution with LMWHs as CKD patients already at higher bleeding risk

10 The degree that the dose needs to be adjusted is according to an estimation of the patient s renal function Resources Renal Drug Handbook BNF Manufacturer s information Renal Pharmacist

11 MDRD Equation Reported on the VitalData/ CWS Not validated for drug dosing BSA = 1.73m 2 Cockcroft and Gault Equation Used for drug dosing Esp when narrow therapeutic index CrCl = (140 Age) x Weight(kg) x g Serum Creatinine g... Men = 1.23 Women = 1.04

12 Is the drug removed by dialysis? If not it doesn t matter when you give it If it is, give after if it is a ONCE daily drug This information is in the Renal Drug Handbook Peritoneal dialysis does not remove drugs, Dose as in ESRF

13 The extent to which drugs are removed by haemodialysis depends on Size of the drug (MW<500) Protein binding In plasma or tissue? High water solubility Low volume of distribution If the drug is only removed by HD, it should be only be given after dialysis e.g. Vancomycin (see ward protocol)

14 Dose 1 HD day or non-hd day Vancomycin 1g (patient <70kg) Vancomycin 1.5g (patient kg) Vancomycin 2g (patient >100kg) Dose 2 With next HD session And plan to give vancomycin with every subsequent haemodialysis session Dose 3 With next HD session Dose 4 With next HD session Vancomycin 750mg (patient <70kg) Vancomycin 1g (patient kg) Vancomycin 1.5g (patients >100kg) Check vancomycin level prior to next HD session Do not wait for levels before giving vancomycin Dose 3 Vancomycin 750mg (patient <70kg) Vancomycin 1g (patient kg) Vancomycin 1.5g (patients >100kg) Prescribe Dose 4, 5 and 6 according to vancomycin levels (mg/l) taken prior to Dose 3 Aim to maintain vancomycin levels of 15-20mg/L Vancomycin administration: 500mg or 750mg infuse in 100ml sodium chloride 0.9% during last 60 minutes of HD 1g infuse in 250ml sodium chloride 0.9% during last 90 mins 1.5g infuse in 250ml sodium chloride 0.9% during last 120 mins 2g infuse in 250ml sodium chloride 0.9% during last 150 mins < 5 Vanc 1.5g (1g if <70kg) Seek advice for subsequent antibiotic plan 5 to 9 Vanc 1.5g (1g if <70kg) 10 to 14 Vanc 1g 15 to 20 Vanc 750mg 21 to 25 Vanc 500mg > 25 Hold dose Dose 5 and Dose 6 With next two HD sessions Repeats of Dose 4 (except when vancomycin level >25mg/L prior to Dose 3) Vanc 1.5g (1g if <70kg) Vanc 1g Vanc 750mg Vanc 500mg Check vancomycin level prior to Dose 6 (take level before starting the HD session) Do not wait for levels before giving vancomycin Dose 6 Vanc 500mg Dose 7 With next HD session Prescribe Dose 7, 8 and 9 according to vancomycin levels (mg/l) taken prior to Dose 6 (see above) Aim to maintain vancomycin levels of 15-20mg/L Dose 8 and beyond Continue to prescribe vancomycin according to this guidance Check vancomycin levels prior to every 3 rd HD session (generally once weekly)

15 Uraemia Toxins can displace drugs from binding sites Leads to increased free drug levels Proteinuria Low plasma albumin levels an issue with drugs which are highly protein bound Leads to increased free drug levels Poor urine concentrating ability Nitrofurantoin relies on this, therefore ineffective when egfr <45ml/min

16 Tubular dysfunction Avoid thiazide diuretics when egfr <30ml/min Fluid restriction Consider volume of IV drugs Sodium content (e.g. Disp paracetamol) Drugs requiring constant fluid status (e.g. Li) Oedema Gut oedema can reduce GI drug absorption

17 Erythropoeitin deficiency Occurs early in CKD Replace with synthetic ESA Need to ensure adequate iron stores prior to starting Eprex First line ESA for haemodialysis patients Short acting, 1-3x/week dosing Start at units two-three times a week Mircera First line ESA for pre-dialysis, RTx and PD Long acting; monthly dosing Start around 50-75mcg (depending on wt)

18 Iron deficiency NICE 2015 put more emphasis on iron status Ferritin and TSATs Unit HD patients get Venofer on HD Others get TDI (Ferinject or Monofer) Vitamin B 12 deficiency Folate deficiency

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20 Phosphate Binders No point taking them if not with food! First line... Calcium containing binders Calcichew, Calcium acetate If Calcium high, concerns re calcification... Alucaps, Lanthanum, Sevelamer Vitamin D analogues Alfacalcidol, calcitriol Colecalciferol??? Hyperparathyroidism Parathyroidectomy Cinacalcet

21 Calcification of blood vessels and soft tissue Treatment Pain relief Stop warfarin As much dialysis as possible Sodium thiosulphate 50ml of 50% solution (25g) after HD

22 Tinzaparin first line across N&T Doses according to time on HD initially Adjusted to clinical signs (e.g streaking, bleeding) Check with satellite unit on admission Some patients on heparin/ fondaparinux If on treatment dose Clexane, don t need extra anticoagulation on HD First line line lock = Citralock All should be prescribed on drug chart

23 AVF is best access option Better pump speeds Less risk of infection Blocked lines Algorithm... Check for mechanical issues Urokinase Protocol 3 push locks and 1 infusion = senior review Line sepsis Vancomycin for empirical treatment Blood cultures guide further treatment

24 Antibiotic stickers MicroGuide Includes N&T guidance and dosing Restricted antibiotics vuhb/adult Sepsis bundle

25 Guidance on MicroGuide Empirical treatment IP Vancomycin in one bag every 5-7 days PO Ciprofloxacin Further Abx guided by PD fluid/ blood cultures Should be prescribed on main drug chart as well as on PD chart Disconnection/ contamination of line

26 Types of donors Live donor Donors after Brain Death (DBD) Donors after Cardiac Death (DCD) Anti-rejection drugs Reduce risk of acute rejection i.e immune system attacking new kidney Doses must not be missed

27 Tacrolimus Prescribed by brand Adoport, Prograf, Advagraf, Envarsus Doses 12 hours apart (empty stomach) Pre-dose level Lots of drug-drug interactions Mycophenolate mofetil Doses 12 hours apart GI side effects (may switch to Myfortic) Increased risk of cancer SPF 50

28 Prednisolone Best taken in morning with breakfast Gradual reduction (unless short course) Often given omeprazole for gastroprotection Ciclosporin Only used in transplants from ages ago Similar issues to Tacrolimus Azathioprine Likewise, unless once daily preferable or pregnancy (in place of MMF) Sirolimus Used in place of tacrolimus to avoid nephrotoxicity Also needs pre-dose levels

29 Increased risk of infection if taking immunosuppression Pneumocystis jirovecii (PJP AKA PCP) Co-trimoxazole for 6 months 480mg daily (960mg MWF if cyclophosphamide) Cytomegalovirus (CMV) Valganciclovir for 3 months Dose depends on renal function Other prophylaxis given if patient at risk Donor history Hep B/C history in donor or recipient Either from area where TB endemic

30 Ward based roles Medicines reconciliation for all new patients Daily review of all charts Technician led non-stock top up TTHs at ward level Don t send down to pharmacy, bleep us Transplant clinic Prescription and supply of all anti-rejection drugs for all transplant patients Annual review, medication counselling, queries re drug choice

31 Home therapies Iron prescribing, nocturnal HD medication review Renal medication queries Via ward, HD units, Drs, nurses, other pharmacists, patients Directorate level roles Expenditure reporting Service development

32 Used for medicines management Drs now do electronic TTHs Signed off by pharmacist on WCP Ward view to see which TTHs have been seen by pharmacy team Can t tell you whether they have been dispensed though! Can also access old TTHs, GP record

33 Rob Bradley Bleep 5707 Helen Thomas Bleep 6351 Hayley Jones Bleep 6360 Jenna Walker Bleep 6359 Gareth Bryant Bleep???? Edwina Jenkins Bleep 6523 Clinic pharmacy Ext 41222

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