Nustendi (Ezetimibe, Bempedoic Acid)

Nustendi is indicated for disorders of lipid metabolism that require additional cholesterol reduction beyond statin therapy.

• Primary hyperlipidemia: provides additional lowering of LDL‑cholesterol when statins alone are inadequate.
• Heterozygous familial hypercholesterolemia: helps achieve target LDL‑cholesterol levels in patients with this genetic condition.
• Secondary prevention of cardiovascular disease: reduces LDL‑cholesterol as part of a comprehensive risk‑reduction strategy after myocardial infarction or stroke.

• Ezetimibe blocks the Niemann‑Pick C1‑like 1 (NPC1L1) transporter in the intestinal brush‑border, reducing dietary and biliary cholesterol absorption. Bempedoic acid is a pro‑drug activated in the liver that inhibits ATP‑citrate lyase, a key enzyme upstream of HMG‑CoA reductase, decreasing hepatic cholesterol synthesis. The combined actions lower circulating LDL‑cholesterol without affecting statin metabolism.

Adverse reactions reported with the ezetimibe/bempedoic acid combination are generally mild to moderate.

Common Side Effects

• Headache: mild, transient headache.
• Muscle pain: occasional myalgia without significant CK elevation.
• Gastrointestinal discomfort: nausea, abdominal pain or dyspepsia.
• Elevated liver enzymes: mild, reversible increases in ALT/AST.
• Fatigue: general tiredness reported by some patients.

Serious or Rare Side Effects

• Rhabdomyolysis: rare severe muscle breakdown, especially with concurrent statins.
• Severe liver injury: uncommon but may present with jaundice or marked enzyme rise.
• Allergic reactions: rash, pruritus, or angio‑edema in hypersensitive individuals.
• Acute kidney injury: rare cases of renal function decline.
• Tendon rupture: isolated reports in patients on concomitant statin therapy.

When prescribing Nustendi, clinicians should consider several safety aspects.

• Liver function monitoring: check ALT/AST before initiating therapy and periodically thereafter.
• Statin co‑administration: assess risk of myopathy when used with high‑intensity statins.
• Renal impairment: use caution in patients with severe kidney disease.
• Pregnancy and lactation: avoid use unless benefits clearly outweigh risks.
• Drug interactions: review concomitant medications for potential CYP or transporter effects.
• Store at ambient temperature: keep below 25°C, retain original packaging, and protect from moisture.

Nustendi may interact with several drug classes; interactions are categorized by clinical relevance.

Major Interactions (Avoid)

• Strong CYP3A4 inducers (e.g., rifampicin): may reduce bempedoic‑acid exposure.
• High‑intensity statins (e.g., rosuvastatin >20 mg): increase risk of myopathy.

Moderate Interactions (Monitor Closely)

• Bile‑acid sequestrants: may lower ezetimibe absorption; separate dosing by at least 2 h.
• Fibrates: additive risk of liver enzyme elevation.
• Anticoagulants (warfarin): potential alteration of INR; monitor coagulation parameters.
• Antidiabetic agents: monitor glucose control as lipid‑lowering may affect glycaemia.