Nustendi (Ezetimibe, Bempedoic Acid)

Nustendi is a combination lipid‑lowering agent that acts on cholesterol metabolism pathways. It is indicated for:

• Primary hyperlipidemia: reduces low‑density lipoprotein cholesterol (LDL‑C) when added to statin therapy.
• Heterozygous familial hypercholesterolemia (HeFH): helps achieve LDL‑C targets in patients who are statin‑intolerant or need additional lowering.
• Secondary prevention of cardiovascular events: used as part of a regimen to lower LDL‑C after myocardial infarction or stroke.
• Statin‑intolerant patients: provides an alternative mechanism to lower cholesterol when statins cannot be used.
• Patients with mixed dyslipidemia: lowers non‑HDL‑C and triglycerides in addition to LDL‑C.

• Ezetimibe inhibits the intestinal Niemann‑Pick C1‑like 1 (NPC1L1) transporter, reducing absorption of dietary and biliary cholesterol. Bempedoic acid is a pro‑drug activated in the liver that inhibits ATP‑citrate lyase, a key enzyme upstream of HMG‑CoA reductase in the cholesterol synthesis pathway. Together, they lower hepatic cholesterol pools, up‑regulate LDL receptors and increase clearance of LDL‑C from the bloodstream.

Nustendi may cause a range of adverse reactions. Monitoring and reporting are recommended.

Common Side Effects

• Headache: mild to moderate intensity.
• Upper respiratory tract infection: symptoms such as sore throat or nasal congestion.
• Diarrhea: loose stools that are usually self‑limiting.
• Muscle pain (myalgia): occasional discomfort without severe weakness.
• Elevated liver enzymes: mild increases in ALT/AST.
• Abdominal discomfort: mild pain or cramping.

Serious or Rare Side Effects

• Rhabdomyolysis: severe muscle breakdown, often with marked CK elevation.
• Acute liver injury: significant rise in liver enzymes with jaundice.
• Severe hypersensitivity: rash, angioedema or anaphylaxis.
• Tendon rupture: rare but serious musculoskeletal event.
• Kidney injury: acute renal impairment in susceptible individuals.
• Hyperuricemia: elevated uric acid levels leading to gout flares.

Before prescribing Nustendi, clinicians should consider several safety aspects.

• Liver function monitoring: assess baseline ALT/AST and repeat periodically.
• Renal function assessment: evaluate eGFR in patients with chronic kidney disease.
• Pregnancy and lactation: avoid use unless benefits outweigh risks.
• Concomitant statin therapy: monitor for muscle‑related symptoms.
• Drug interactions: review patient’s medication list for potential interactions.
• Store at ambient temperature: keep in original packaging, protect from moisture and direct sunlight.

Nustendi can interact with several medicines, requiring attention to dosing and monitoring.

Major Interactions (Avoid)

• Strong CYP3A4 inhibitors (e.g., itraconazole, clarithromycin): may increase bempedoic‑acid levels.
• Cyclosporine: raises ezetimibe concentrations, increasing risk of liver enzyme elevation.
• High‑intensity statins (e.g., rosuvastatin >20 mg): heightened risk of myopathy.

Moderate Interactions (Monitor Closely)

• Bile‑acid sequestrants (e.g., cholestyramine): may reduce ezetimibe absorption.\n- Fibrates (gemfibrozil, fenofibrate): increase risk of muscle toxicity when combined with statins.
• Anticoagulants (warfarin): may require INR monitoring adjustments.
• Niacin (nicotinic acid): additive effect on liver enzymes.
• Antidiabetic ​