DRUG PRESCRIBING IN RENAL FAILURE PDF
The data base for rational guidelines to safe, efficacious drug prescribing in adults with renal insufficiency are presented in tabular form. Current medical. Drugs or drug metabolites may accumulate in renal failure, leading to toxicity. When prescribing oral strong opioids, the immediate release forms are preferred. . Available from: yazik.info [Last. Chronic kidney disease affects renal drug elimination and other phar- . Drug Prescribing in Renal Failure: Dosing Guidelines for Adults.
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in the care of patients. Each of us needs to be wary of prescribing for renal patients . Drug Prescribing in Renal Failure: Dosing guidelines for adults. 4th ed. continuous renal replacement therapy; drug dosing; hemodialysis; pharmaco- kinetics . developed to enhance drug prescribing for patients with AKI and CKD ? library/Scientific_guideline//09/WCpdf. Drug or class of drug Dose adjustment required in renal impairment (including age related). Adjust Prescribe antiproteinuric drugs (ACE inhibitors and/or.
Google Scholar Barza, M.
Drug Prescribing in Renal Failure: Dosing Guidelines for Adults.
Journal of Infectious Diseases — Dialysis and Transplantation 6: 22—23 a. Google Scholar Bennett, W. Clinical Pharmacology and Therapeutics — b. British Medical Journal 4: 83—86 Annals of Internal Medicine — c.
Clinical Pharmacokinetics 1: — Annals of Internal Medicine — Nephron 31—41 Clinical Pharmacokinetics 1: 99— Medical Journal of Australia 1: — Clinical Pharmacokinetics 2: — American Journal of Medicine — New England Journal of Medicine — Tetracycline and Chlortetracycline.
Journal of Clinical Investigation — A complete list of the medications subject to intervention is shown in Table 1. The percentage of the global acceptance of the recommendation was Of the interventions, Internal Medicine The distribution of the interventions per unit is included in Table 2.
In the Falconnier et al. One of the main causes of high prevalence of kidney failure in the patients who were admitted was due to old age3. The population included in this survey was elderly patients, The consensus document by S. This was backed by the EPIRCE study in , in which it was concluded that the most evident predictive factor for chronic kidney failure was age, with an odds ratio of The average glomerular filtration rate of the patients included in the study suffered moderate renal failure, in accordance with clinical guidelines by the National Kidney Foundation in The percentage of the drug interventions in comparison with the total number of drugs that were reviewed is high, which highlights the relevance of the process carried out by doctors and pharmacists.
The pharmaco-therapeutic group with the highest number of interventions was the antimicrobial drugs, like in other publications3, Levofloxacin was the most frequent drug. However, the Devesa et al.
Nonetheless, we must bear in mind that aforementioned study included all drugs dosages that could be intervened, and pharmacokinetic monitoring which came from the intervention. We must highlight that a high percentage of interventions recommends the suspension of drug. In the Devesa et al. The results we obtained in our study are similar.
Non-acceptance of these recommendations is usually caused by improvements in the kidney function. The evidence grade and recommendation strength for the various treatment options can be derived from Cochrane Reviews and published meta-analyses table 4.
Because renal insufficiency is associated with sodium retention 13 , diuretic treatment is usually necessary; for this purpose, the best strategy is usually sequential nephron blockade with furosemide and hydrochlorothiazide.
The opioid drug pethidine should not be given to patients with renal insufficiency, because its renal-dependent metabolite, normeperidine, can cause cerebral convulsions.
Before an erythropoietic hormone is given, iron should be given first. Iron is poorly taken up by patients with renal insufficiency when given orally, because of the elevated hepcidin level 15 ; it is thus best to give iron IV.
Pethidine, cefepime, lithium, gilbenclamide, gimepiride, metformin, spironolactone, eplerenone, methotrexate, gadolinium, enoxaparin. Large-scale observational studies have revealed that the additional administration of active vitamin D e. Paricalcitol and cinacalcet should remain in reserve for the treatment of severe, clinically manifest hyperparathyroidism.
Oral neutralization of acidosis with bicarbonate in the predialysis phase protects the bones, lessens malnutrition, and slows the progressive loss of renal function A stepwise algorithm for the use of phosphate binders has been published e7: The treatment begins with calcium acetate.
If this is ineffective or poorly tolerated, sevelamer or the newly available sevelamer carbonate should be given instead as a powder. The authors use lanthanum and phosphate binders containing aluminum only for short times, and only in otherwise intractable cases.
Drugs for which this is true are excreted more slowly than normal and can, therefore, accumulate to toxic levels if given repeatedly. Not only is every patient different, every drug is different as well. Nonetheless, there are simple rules of pharmacokinetics and pharmacodynamics that apply to every drug and every patient.
With the aid of these rules, the dosage of any drug can be adjusted for any patient. The renally eliminated fraction of a drug is a key to predicting its pharmacokinetics in patients with renal insufficiency. The renally eliminated fraction of a drug f ren is the key to predicting its pharmacokinetics in patients with renal insufficiency. Drug elimination and renal function. The drug dose D is adjusted to renal function proportionally to the elimination rate constant, and therefore inversely proportionally to the half-life e Like the serum creatinine level, the half-life has a hyperbolic dependence on renal function figure 2.
Half-life and renal function.
Drug Therapy in Patients With Chronic Renal Failure
The dependence is stronger with a higher renal elimination fraction f ren. Many drugs must have their doses adjusted to renal function in patients with CKD stage 3 or higher, i. In the absence of dose adjustment, aciclovir and valaciclovir can be neurotoxic, ganciclovir and valganciclovir myelotoxic, foscavir nephrotoxic, and cidofovir both myelo- and nephrotoxic.
Dose adjustment has proved to be outstandingly useful for these vitally indicated drugs. Further drugs whose doses need to be adjusted are oseltamivir, which is effective against the H1N1 virus, and intravenous zanamivir. Drugs for which dose adjustment is often forgotten include the newer antiepileptic drugs, such as gabapentin 19 , pregabalin, lamotrigine, and levetiracetam.
For these drugs, half the normal dose or an even smaller amount will often suffice table 2. More and more commonly, cancer patients with renal insufficiency undergo treatment with cytostatic and other chemotherapeutic drugs. It is helpful to distinguish cytostatic agents that depend on, or are independent of, renal function Unlike the authors of an article on this topic that was published in 20 , the authors of the current article consider gemcitabin to depend on renal function because of its active metabolite dFdU table 2.
The dose of gemcitabin, platinum derivatives, or of cyclophosphamide need not be lowered if the patient undergoes hemodialysis on three consecutive days, one to twelve hours after the administration of either of these dialyzable drugs. For carboplatin and cisplatin, dialysis must begin one to two hours after the infusion in order to be effective.
Drug Prescribing in Renal Failure
Etoposide and epirubicin are not dialyzable. It should not be forgotten that patients with renal insufficiency need a higher starting dose! Begin with the normal dose. The maintenance dose is adjusted to renal function depending on its half-life. Cumulation kinetics implies that there are separate considerations for the starting dose and the maintenance dose, as Augsberger already pointed out with respect to the digitalis glycosides e If the effect of the drug must have a rapid onset, then the treatment should begin with a normal starting dose, so that an effective drug concentration can be established at once.
With antibiotics, in particular, one should never commit the capital error of forgetting the starting dose. The second innovative idea of Luzius Dettli was to realize e10 that the necessary dose adjustment could be calculated proportionally to the changed elimination rate and thus inversely proportionally to the half-life figure 1. These two rules can also be applied in combination.
If the dose is thus reciprocally lowered and the interval between doses is unchanged, then the area under the curve will be the same as in the normal case, but with higher trough values figure 3 , which are what is customarily measured in drug monitoring. This can easily lead physicians unfamiliar with the relevant pharmacokinetics to draw false conclusions and then reduce the dose of the drug still further, e.
Dose adjustment in renal insufficiency e The Kunin rule e12 with halving of the starting dose leads to higher trough values and more frequent peak values than the Dettli-2 rule with the same dose given at longer intervals e The Dettli-1 rule, with a reduced dose and a constant interval, results in lower peaks and higher troughs than normal e If the half-life is shorter than the dosing interval, dose adjustment is usually unnecessary.
In the case of ampicillin, for example, one would have to reduce the dose of ampicillin from mg every 8 hours to mg every 8 hours, or perhaps mg every 80 hours. The main benefit of this scheme is to achieve effective peak levels. The halving rule results in peak drug levels that are the same as those in patients with normal renal function, but markedly higher trough levels; the area under the curve is greater than with the Dettli rule figure 3.
This larger area under the curve can, however, be associated with more frequent adverse effects. The authors prefer to use the Kunin rule in the intensive care unit for pharmacodynamic reasons 4 , and we have published corresponding dosing recommendations in tabular form www.
Underdosing of antibiotics, in comparison to overdosing, can have much worse, indeed potentially fatal effects. The importance of pharmacodynamics also becomes clear in the use of loop diuretics such as furosemide and torasemide. Starting in CKD stage 5, i. Dose adjustment is a question not just of pharmacokinetics, but also of pharmacodynamics, i.
Pharmacodynamics involves a formulation of the relationship between the concentration of a drug and its effect, most commonly described in terms of the so-called sigmoid E max model. In this mode, the effect is a non-linear function of the concentration of the drug at its site of action C and of the concentration that produces a half-maximal effect CE The examples of furosemide and torasemide show that pharmacodynamic parameters can also change in renal insufficiency.
Sigmoid effect-concentration curve. For a Hill coefficient of 1. On the other hand, when the Hill coefficient equals 4.
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The therapeutically effective range of a drug thus depends on its Hill coefficient: Antibiotics provide a good illustration of the explanatory power of pharmacodynamics. Antibiotics can be classified into those whose effect depends on concentration, and those whose effect depends on time Aminoglycosides such as gentamicin and fluoroquinolones such as levofloxacin are examples of antibiotics whose effect is concentration-dependent and for which the ceiling concentration CE 95 should be reached to make the treatment effective—even if the treating physician often does not know the value of CE 95 or CE 50 with any precision.
Beta-lactams, such as cefazolin, and antiviral drugs, such as valganciclovir, are examples of antibiotics whose effect is time-dependent and for which the concentration should not become any lower than the threshold concentration CE These two classes of antibiotics, distinguished by the concentration- or time-dependency of their effects, differ in the height of their Hill coefficients figure 4: The starting dose is important for both types of antibiotic, those whose effect is concentration-dependent and those whose effect is time-dependent.
After the starting dose is given, the important consideration for antibiotics of the former type is the drug concentration at the beginning of each dosing interval, while that for the latter type is the drug concentration at the end of each dosing interval. Thus, for drugs of the former type, such as ciprofloxacin or levofloxacin, there is less reason to reduce the dose 23 ; it would seem to be better to prolong the interval between doses for patients with renal insufficiency, while keeping the individual dose the same as usual figure 5.
Further examples of drugs of this pharmacodynamic type are cytostatic agents such as cyclophosphamide, melphalan, and daunoblastin For cytostatic agents with a narrow therapeutic window, careful consideration of pharmacodynamics is needed, because adverse effects may be correlated with the area under the curve and might arise even after the administration of a single dose.
Dose adjustment for ciprofloxacin, a drug whose effect is concentration-dependent, according to a mechanistic model If renal failure causes a doubling of the half-life from four to eight hours, the dose should not be halved upper graph ; rather, the interval between doses should be doubled lower graph.
If half the normal dose is given, it will take hours for E. On the other hand, for antibiotics whose effect depends on time, such as ceftazidime a beta-lactam and the virustatic agents, it is less important to achieve peak levels that are well above CE 50 , but it is absolutely necessary to ensure that the trough level at the end of each dosing interval does not drop below CE 05 , as this might lead to loss of the antimicrobial effect. It follows that a continuous infusion might be a better administration strategy for beta-lactams, as has been shown in the case of oxacillin The same consideration often applies in antiviral HIV therapy: For antibiotics whose effect depends on time, such as cefotaxime or aciclovir, it makes more sense to lower the dose rather than prolong the interval between doses, as is done in the case of ciprofloxacin or daptomycin.
On the other hand, there is a much older principle that has been, to some extent, forgotten over the years: This remains an important principle in nephropharmacology today, particularly for antibiotics and antiviral drugs, but also for oncological cytostatic drugs.
Above all, one must not make the mistake of dosing anti-infective or cytostatic drugs too low at the start, or of forgetting the starting dose entirely.
This mistake should be avoided in all patients, including those with renal insufficiency. CME points of the Medical Associations can be acquired only through the Internet, not by mail or fax, by the use of the German version of the CME questionnaire within 6 weeks of publication of the article. See the following website: The EFN must be entered in the appropriate field in the cme. Diagnosis, Treatment, and Prevention. With what glomerular filtration rate does it usually become necessary to adjust drug doses to renal function?
Which of the following drugs can cause long-lasting bone marrow toxicity four to six weeks after it is given to a patient with renal insufficiency? Which of the following drugs is unsuitable for the treatment of comorbidity in patients with renal insufficiency? Which of the following anti-infective drugs exerts its effect in time-dependent fashion? Which of the following drugs must be given at a higher dose than normal in the setting of renal insufficiency?
The threshold concentration produces what percentage of the maximal effect?Factors that may reduce the extent to which a drug is dialysed include large molecular size of the drug, high protein binding, large volume of distribution and high lipid solubility.
Renal function declines steadily with age in adults, but this is not reflected in the serum creatinine, which remains steady or may only increase slightly with age in the absence of overt renal disease, where it may rise more obviously. Drugs usually eliminated by the kidneys require the most modification. Dose adjustment Many drugs must have their doses adjusted to renal function in patients with CKD stage 3 or higher, i.
There are various references to consult in Australia including the approved product information and the Australian Medicines Handbook.
Creatinine clearance The serum creatinine concentration represents a balance between its production in the body from muscle and its excretion by the kidneys. In interpreting these levels, recognition of decreased plasma protein binding and prolonged elimination half-lives in renal failure is imperative.
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