From the Guidelines
Pravastatin can be used in patients with a creatinine clearance (CrCl) of 20 mL/min without the need for dose adjustment, as indicated by the KDOQI clinical practice guidelines 1. When considering the use of pravastatin in patients with severe renal impairment, it is essential to weigh the benefits of lipid management against the potential risks. According to the guidelines, pravastatin has a dosing range of 10-40 mg daily, with no dosage adjustment needed for patients with chronic kidney disease (CKD) 1. Key points to consider when prescribing pravastatin in this context include:
- The patient's renal function should be closely monitored, as well as their liver enzymes and muscle symptoms, due to the increased risk of adverse effects in severe renal impairment.
- Pravastatin is preferred in renal impairment because it has minimal renal excretion (approximately 20%) and undergoes extensive hepatic metabolism, making it safer than some other statins that rely more heavily on renal clearance.
- If the patient develops unexplained muscle pain or weakness, pravastatin should be temporarily discontinued and creatine kinase levels checked to rule out myopathy or rhabdomyolysis, which can be particularly dangerous in those with pre-existing kidney disease. Overall, the use of pravastatin in patients with a CrCl of 20 mL/min is supported by the guidelines, with no dose adjustment required 1.
From the FDA Drug Label
A single 20 mg oral dose of pravastatin was administered to 24 patients with varying degrees of renal impairment (as determined by creatinine clearance) No effect was observed on the pharmacokinetics of pravastatin or its 3α-hydroxy isomeric metabolite (SQ 31,906). Compared to healthy subjects with normal renal function, patients with severe renal impairment had 69% and 37% higher mean AUC and Cmax values, respectively, and a 0. 61 hour shorter t½ for the inactive enzymatic ring hydroxylation metabolite (SQ 31,945) [see Use in Specific Populations (8. 6)].
The pharmacokinetics of pravastatin are not significantly affected in patients with renal impairment, including those with a creatinine clearance (CrCL) of 20. However, patients with severe renal impairment had higher mean AUC and Cmax values.
- Key points:
- No significant effect on pharmacokinetics
- Higher AUC and Cmax values in severe renal impairment
- No specific dosage adjustment recommended for CrCL of 20 2
From the Research
Pravastatin and Renal Function
- Pravastatin is a statin medication used to lower cholesterol and prevent cardiovascular disease.
- The dosage of pravastatin may need to be adjusted in patients with renal impairment, as it is partially excreted by the kidneys.
- A creatinine clearance (CrCl) of 20 mL/min indicates severe renal impairment.
Estimating Renal Function
- The Cockcroft-Gault equation is a commonly used method to estimate CrCl, which takes into account serum creatinine, age, weight, and sex 3.
- The Mawer method is another equation that can be used to estimate CrCl, which is similar to the Cockcroft-Gault equation 3.
- A 2-hour creatinine clearance (CrCl-2h) can be used as a substitute for 24-hour creatinine clearance (CrCl-24h) in intensive care unit patients, especially when a 24-hour collection is impossible 4.
Considerations for Patients with Renal Impairment
- Patients with severe renal impairment (CrCl < 30 mL/min) may require dose adjustments for medications that are renally cleared, such as pravastatin.
- The volume-to-creatinine clearance ratio (V/CrCl) can be used to predict the risk of contrast-induced nephropathy in patients undergoing coronary angiography or percutaneous coronary intervention 5.
- Augmented renal clearance (ARC) is a condition where renal filtration is heightened, and can affect the dosing of antibiotics and other medications in critically ill patients 6.