What liver, muscle, renal, pregnancy, and drug‑interaction safety concerns and monitoring are required when prescribing Nexlizet (ezetimibe 10 mg/rosuvastatin)?

Nexlizet (Ezetimibe 10 mg/Rosuvastatin) Safety Monitoring

When prescribing Nexlizet, you must monitor hepatic transaminases before and during treatment, assess for myopathy/rhabdomyolysis symptoms, avoid use in pregnancy and moderate-to-severe hepatic impairment, and be vigilant for specific drug interactions with cyclosporine, fibrates, and bile acid sequestrants. 1

Hepatic Monitoring Requirements

• Measure ALT, AST, alkaline phosphatase, and total bilirubin before initiating therapy 1
• Monitor hepatic transaminases during treatment based on statin monitoring recommendations 1
• Persistent elevations in hepatic transaminases may occur with the ezetimibe-statin combination 1
• The incidence of consecutive elevations (≥3× ULN) of hepatic transaminases is 1.3% with ezetimibe plus statins versus 0.4% with statins alone 2
• Nexlizet is not recommended in patients with moderate or severe hepatic impairment 1
• Ezetimibe has been associated with mild elevations of liver transaminases, mainly in combination with statins 3

Muscle Toxicity Surveillance

• Cases of myopathy and rhabdomyolysis have been reported when ezetimibe was used alone or in combination with statin therapy 1
• Monitor patients for unexplained muscle pain, tenderness, or weakness, particularly during the first months of therapy 1, 2
• Rosuvastatin treatment is associated with relatively low rates of severe myopathy, rhabdomyolysis, and renal failure 4
• The combination of ezetimibe with rosuvastatin has been generally well tolerated with no significant increase in myopathy rates in clinical trials 5, 6
• Avoid rigorous physical activity if muscle symptoms develop 1

Renal Function Considerations

• No dosage adjustment is necessary in patients with mild-to-severe renal insufficiency for the ezetimibe component 7
• Higher doses of rosuvastatin have been associated with cases of renal failure 4
• Proteinuria induced by rosuvastatin is likely associated with statin-provoked inhibition of low-molecular-weight protein reabsorption by renal tubules 4
• Monitor renal function when using higher rosuvastatin doses or in patients with pre-existing renal disease 4

Pregnancy and Lactation Contraindications

• All lipid-lowering drugs, including ezetimibe and rosuvastatin, should be avoided during pregnancy and nursing 8
• Women on lipid-lowering drugs for primary prevention should discontinue therapy at least 1 month and preferably 3 months before attempted conception, or immediately if already pregnant 8
• There are no safety data in humans for ezetimibe use during pregnancy 1
• Preconception counseling in women of childbearing age taking lipid-lowering therapy is necessary 8
• Bile acid sequestrants are the only lipid-lowering agents approved for use during pregnancy if treatment is absolutely necessary 8

Critical Drug Interactions

High-Risk Interactions Requiring Caution:

• Cyclosporine: Higher ezetimibe exposures occur with concomitant cyclosporine, and ezetimibe causes a small but statistically significant effect on ciclosporin levels; carefully monitor ciclosporin levels 1, 7
• Gemfibrozil: Coadministration increases ezetimibe bioavailability, though clinical significance is thought to be minor 1, 7
• Fenofibrate: Increases ezetimibe bioavailability but appears safe with no evidence of significant pharmacokinetic or pharmacodynamic interaction with rosuvastatin 7, 4
• Bile acid sequestrants (cholestyramine): Significantly decrease ezetimibe oral bioavailability; administer ezetimibe either ≥2 hours before or ≥4 hours after bile acid sequestrants 1, 7

Interactions Requiring Monitoring:

• Vitamin K antagonists (warfarin): Rosuvastatin may interact; monitor INR when co-administering 4
• Antiretroviral agents: Potential pharmacokinetic interaction may increase risk of toxicity with rosuvastatin 4

Safe Combinations:

• Fenofibrate, omega-3-fatty acids, antifungal azoles, rifampin, and clopidogrel appear safe with rosuvastatin 4
• No clinically significant effects with digoxin, glipizide, or oral contraceptives when combined with ezetimibe 7
• Food, antacids, and cimetidine have no significant effect on ezetimibe bioavailability 7

Common Adverse Effects to Monitor

Ezetimibe Component:

• Upper respiratory tract infection, diarrhea, arthralgia, sinusitis, pain in extremities (monotherapy) 1
• Nasopharyngitis, myalgia, upper respiratory tract infection, arthralgia, diarrhea (in combination with statin) 1

Rosuvastatin Component:

• Gastrointestinal tract symptoms and central nervous system effects 4
• Asymptomatic liver enzyme elevations occur at similarly low incidence as with other statins 4

Special Population Considerations

• No dosage adjustment necessary based on age, sex, or race for ezetimibe 7
• For very high-risk patients with established ASCVD, multiple risk factors, or homozygous familial hypercholesterolemia, individual discussions are advised regarding ongoing therapeutic needs during pregnancy 8
• Referral to a lipid specialist and registered dietitian is strongly recommended for high-risk pregnant patients 8

Key Clinical Pitfalls to Avoid

• Do not continue Nexlizet in women planning pregnancy without careful risk-benefit assessment and discussion 8
• Do not co-administer with strong or moderate CYP3A4 inhibitors when using higher rosuvastatin doses 4
• Do not ignore unexplained muscle symptoms—these require immediate evaluation and possible discontinuation 1, 2
• Do not prescribe in patients with moderate-to-severe hepatic impairment 1
• Do not administer ezetimibe simultaneously with bile acid sequestrants—separate dosing by at least 2-4 hours 1, 7