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- There are a number of inter-dependent factors that need to be considered when dosing patients on RRT. Consider the drug, the patient and the type of RRT.
- Alteration of drug dosage is usually only necessary if renal clearance exceeds 25% of total body clearance.
- Drugs which are cleared by the kidneys are usually dialysed, and vice versa, although there are some anomalies.
- Dose adjustment for RRT is normally only necessary for drugs that require dose adjustment because of the presence of renal failure. No RRT is as effective as the normal kidney – so for most drugs, doses used will never be larger than those recommended in normal renal function.
- Physicochemical drug characteristics affecting drug removal include protein binding, volume of distribution, water/lipid solubility, and molecular weight. Drugs that are highly protein bound (>80%) and/or have a large Vd (>1L/kg), are unlikely to be removed to a significant degree. In general, very large molecules are less likely to be removed than smaller ones.
- Pharmacokinetic studies that formed the basis for many of the drug dosing recommendations used today were performed in the 1980s and 1990s using less efficient techniques of RRT than those employed currently. These studies varied in design, used different haemofilters, blood, dialysate and ultrafiltration rates and calculated drug clearance by different methods. Advice on drug dosage in CRRT from the literature should therefore be applied cautiously to individual patients. Dosing recommendations based on this older data may result in underdosing of drugs e.g. antibiotics.
- In patients on HD, dose after the dialysis session otherwise a proportion of the drug may be removed during the HD session and its duration of action reduced. For CRRT and CAPD, since these are continuous processes, there is no need to schedule doses around RRT sessions.
- For toxic drugs, and for drugs with a narrow therapeutic index, drug monitoring with measurements of plasma concentrations, where available, and monitoring of the patient for therapeutic response and adverse effects, are essential