Version June 2024
| Usual starting dose* | Metabolism and elimination¶ | Selected drug interactionsΔ | Adverse effects | |
| HMG CoA reductase inhibitors ("statins") | ||||
| Pravastatin | 10 or 20 mg once per day | Approximately 50% is renally cleared as unchanged drug. Smaller amounts are cleared by biliary excretion or undergo non-CYP and CYP 3A4 hepatic transformation. Pravastatin is a substrate of P-gp and OATP1B1/1B3. | Cyclosporine: increased risk of myopathy due to additive toxicity and elevation of statin serum level by competitive inhibition of CYP 3A4, BCRP, OATP1B1/1B3, and/or P-gp. Pravastatin and fluvastatin are less likely than other statins to interact significantly with cyclosporine. | Gastrointestinal intolerance, CK elevations, transaminase elevations, muscle toxicity, rhabdomyolysis (rare). Close monitoring of transaminases may provide early evidence of elevated statin levels and toxicity. |
| Fluvastatin | 20 mg once per day | Approximately 75% undergoes hepatic transformation by CYP 2C9 and 20% by CYP 3A4. Fluvastatin inhibits and can interact with other drugs metabolized by CYP 2C9. Fluvastatin is a substrate of OATP1B1/B3. | ||
| Rosuvastatin | 5 or 10 mg once per day. Maximum 5 mg per day with cyclosporine. | Most clearance occurs as unchanged drug. Approximately 10% undergoes CYP 2C9 transformation to a partially active metabolite. Rosuvastatin is a substrate of BCRP and OATP1B1/1B3. | ||
| Atorvastatin | 5 or 10 mg once per day. Maximum 10 mg per day with cyclosporine. | Undergoes extensive CYP 3A4 transformation to active metabolites. Atorvastatin is a substrate of P-gp, OATP1B1/1B3, and BCRP. | ||
| Simvastatin | 5 or 10 mg once per day. Avoid use with cyclosporine. | Undergoes extensive CYP 3A4 transformation to active and inactive metabolites. Simvastatin is a substrate of OATP1B1/1B3. | ||
| Cholesterol absorption inhibitor | ||||
| Ezetimibe | 10 mg once per day | Undergoes glucuronide conjugation in small intestine and liver to form active metabolite. Most clearance occurs by enterohepatic recycling and fecal excretion. | Statins: useful for added LDL lowering in combination with a statin or as single agent. Fibrate: increased serum level of ezetimibe; theoretic increased risk of cholelithiasis. Cyclosporine: increased serum level of ezetimibe and possible alteration of cyclosporine level. Ezetimibe 5 mg daily may suffice for LDL lowering effect in combination with cyclosporine. | Gastrointestinal intolerance, headache. In combination with statin, slightly higher incidence of serum aminotransferase elevations than statin monotherapy. |
| Refractory severe hypertriglyceridemia (≥500 mg/dL [5.6 mmol/L]) | ||||
| Gemfibrozil | 600 mg twice per day | Undergoes non CYP transformation by glucuronide conjugation with small amount of CYP 3A4 transformation. Gemfibrozil inhibits and can interact with other drugs metabolized by CYP 2C8 or transported by OATP1B1. | Statins: increased risks of hepatotoxicity, myopathy, and rhabdomyolysis due to additive toxicity and elevation of statin serum level. Avoid combining gemfibrozil with statins. Cyclosporine: additive risk of nephrotoxicity and altered serum concentration of cyclosporine. | Gastrointestinal intolerance, muscle toxicity, cholelithiasis, rhabdomyolysis (rare). |
| Fenofibrate | 30 to 67 mg once per day depending on preparation | Hydrolysed to active intermediary by plasma and tissue esterases. Undergoes non CYP metabolism by glucuronide conjugation. | Statins: increased risk of myopathy and rhabdomyolysis due to additive toxicity. If combination with a statin is unavoidable, fenofibrate with fluvastatin or pravastatin may be less likely to interact significantly than gemfibrozil with a statin. Cyclosporine: additive risk of nephrotoxicity and altered serum concentration of cyclosporine. Tacrolimus: additive risk of nephrotoxicity. | |
| Omega-3-acid ethyl esters◊ | 1 to 2 grams twice per day | Inadequately defined. | CYP-mediated interactions with immunosuppressive agents, statins, fibrates, or ezetimibe are not expected based on in vitro data. | Dyspepsia, fishy taste, modest increase in LDL-C (5%). Modest increase in bleeding time that is insignificant for patients with functional hemostasis. |
CYP: cytochrome P450; OATP1B1: organic anion transporting polypeptide 1B1; P-gp: P-glycoprotein transporter; BCRP: breast cancer resistance protein.
* This table notes usual starting doses for oral administration in adult liver transplant recipients, which may differ from usual starting doses in other patient populations. Post liver transplant patients with compromised kidney function are at elevated risk of adverse effects due to statins and other hypolipidemic drugs. Limited dose titration or dose reduction may be necessary.
¶ Shows disposition of drug reaching systemic circulation. Statins undergo extensive pre-systemic clearance in gastric mucosa and/or liver. Patients with hepatic insufficiency may have increased systemic exposure.
Δ For additional information, refer to the Lexicomp drug interactions database included with UpToDate.
◊ Potential option. Inadequate data and experience in patients with hepatic insufficiency and/or post liver transplant. If used, a licensed standardized preparation (eg, Lovaza or icosapent ethyl [Vascepa]) appears to be preferable.آیا می خواهید مدیلیب را به صفحه اصلی خود اضافه کنید؟
