• 28
    Nov
  • Estimating Renal Function for Drug Dosing: Rewriting the Gospel? part 5

THE “GOSPEL” OF PATIENT ASSESSMENT

We feel that any potential new “gospel” for pharmacists should not be based on the debate between the CG and MDRD equations, but rather should focus on enhancing the overall approach to drug use and dosing assessment in individual patients. In our experience, too many pharmacists make dosing recommendations according to an assessment of renal function alone, rather than relying on the overall clinical picture.

Clinical factors are arguably the most important determinants of whether a dose is “appropriate” for a particular patient. In addition, chronic renal insuffi­ciency can create pharmacokinetic changes (e.g., in volume of distribution or methods of elimination) that further complicate renal drug dosing, which makes the clinical parameters all the more important. Calculated estimates of renal function do not take these factors into consideration, so adjusting doses solely on the basis of renal function estimates may lead to inappropriate recommendations. cialis super active

Assuming that the drug selected is the correct drug for the patient, with an appropriate balance of efficacy and toxicity, the next assessment should be a determination of the acuity of the patient’s situation. If an immediate response is not required, and the dose can be titrated to response, then assessment of renal function is almost unnecessary. The patient should be started at a dose lower than that typically recommended, and the dose should be modified according to response and/or toxicity. For instance, if an angiotensin-converting enzyme inhibitor such as lisinopril (primarily eliminated by the kidneys) is being used to treat high blood pressure in a renally impaired patient, it would be reasonable to start with one-quarter to one-half of the typical starting dose (i.e., one-quarter of a 5-mg tablet) and increase the dose as needed.

If an immediate effect is required, one should attempt to obtain a therapeutic response within minutes to hours, regardless of renal function. This can be accomplished by administering a loading dose or by starting with a regular dose and reducing the dose accordingly once a response has been observed. Use of this method depends on the medication in question and its potential toxic effects. For example, for a patient needing ceftazidime, a relatively nontoxic medication, the initial dose decision is whether to administer 1 or 2 g. If the patient has a life-threatening infection, it would make sense to start with 2 or 3 doses of 2 g each, and then (particularly if a response has occurred) reduce the total daily dose, using the patient’s renal function to guide selection of a reasonable dosing regimen. However, pharmacists should be mindful of medications with well-known dose-related side effects, such as aminoglycosides. In patients with renal dysfunction, potentially nephrotoxic medications such as aminoglycosides should be avoided wherever possible, and safer alternatives should be used instead. For medications with a narrow therapeutic index, an overall assessment of the patient’s renal function, and of the potential benefits and harms associated with the medication, is needed. If the potential benefits outweigh the potential harms, the pharmacist should make an informed dosage recommendation but should be meticulous in monitoring for adverse events. Finally, if a clinical trial has shown that a specific dose is effective and safe for patients with renal insufficiency, this evidence should supersede empiric dosing recommen­dations.
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If dosages are based on clinical parameters as well as on renal function estimates, the clinical impact of any miscategorization resulting from the use of dosing tables will be minimized. An antibiotic dose that is too low for the patient may be apparent from persistence of fever, elevation of white cell count, or persistence of positive culture results. Similarly a dose that is too high will be apparent because of adverse effects. For medications with delayed adverse effects or adverse effects that are difficult to monitor, pharmacists should remain proactive in considering dosage adjustment with changes in renal function. They should also be aware that a lack of efficacy and/or the occurrence of toxic effects can occur even at recommended doses; again, the clinical picture remains more important when it comes to dosing recommendations than doses empirically chosen on the basis of renal function estimates.

THE “NEW GOSPEL”

In summary, evidence is available to show that dosages may differ depending on which method of assessing renal function is used, but no studies have shown which method provides “correct” estimates for clinical dosing, probably because no dosage estimate is “wrong”. Estimates are by definition imprecise, and the clinical significance of dosage adjustments can be determined only after the dose has been given.

Whether any of the equations discussed in this article is superior for predicting appropriate dosage adjustments remains to be determined. Clinicians should therefore make sure that they understand the difference between absolute and relative renal function, and should use renal function assessments only in conjunction with clinical assessments. kamagra soft tablets

Choosing the initial dose is really only a small part of the work that a pharmacist needs to do. Monitoring the patient’s response to the medication is the best way to evaluate if the dose is appropriate and should be the pharmacist’s primary role in renal drug dosing. Indicators of efficacy and toxicity should be followed, and dosage changes should be made according to these factors, in addition to serum creatinine, estimated GFR, and literature recommendations. Proactively determin­ing rational starting doses and monitoring a patient’s response to the dose chosen should be the new gospel for pharmacists who adjust drug dosages on the basis of renal function. If they do so, the debate about which formula to use could seem somewhat trivial.

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