Nustendi (Ezetimibe, Bempedoic Acid)

Nustendi combines two lipid‑modifying agents that act on cholesterol metabolism pathways. It is indicated for:

• Primary hypercholesterolaemia: helps lower LDL‑cholesterol when diet and statins alone are insufficient.
• Heterozygous familial hypercholesterolaemia (HeFH): provides additional LDL‑cholesterol reduction in genetically predisposed patients.
• Statin‑intolerant patients: offers an alternative LDL‑cholesterol‑lowering option for those who cannot tolerate adequate statin doses.

• Ezetimibe blocks the Niemann‑Pick C1‑like 1 (NPC1L1) transporter in the intestinal brush‑brush border, decreasing dietary and biliary cholesterol uptake. Bempedoic acid is a pro‑drug that is converted in the liver to an active metabolite that inhibits ATP‑citrate lyase, a key enzyme upstream of HMG‑CoA reductase, thereby reducing hepatic cholesterol synthesis. The combined effect results in lower circulating LDL‑cholesterol.

Side‑effect profiles reflect the actions of both components.

Common Side Effects

• Gastrointestinal discomfort: mild abdominal pain or dyspepsia.
• Elevated liver enzymes: transient increases in ALT/AST.
• Muscle pain: mild myalgia without weakness.
• Headache: occasional tension‑type headache.
• Fatigue: general tiredness reported by some patients.

Serious or Rare Side Effects

• Rhabdomyolysis: severe muscle breakdown, especially with concurrent statins.
• Acute liver injury: marked elevation of transaminases with jaundice.
• Severe hypersensitivity: rash, angio‑edema or anaphylaxis.
• Kidney impairment: acute renal failure in rare cases.
• Hyperuricaemia: gout flares in predisposed individuals.

When prescribing Nustendi, clinicians should consider several safety aspects.

• Liver function monitoring: check ALT/AST before initiation and periodically thereafter.
• Statin co‑administration: assess risk of myopathy and adjust statin dose if needed.
• Renal function: evaluate baseline creatinine in patients with chronic kidney disease.
• Pregnancy and lactation: avoid use unless the potential benefit outweighs risk.
• Drug interactions: review concomitant medications for CYP‑related effects.
• Store at below 25°C: keep in the original container, protect from moisture and direct sunlight.

Nustendi may interact with several medicines that share metabolic pathways or affect muscle tissue.

Major Interactions (Avoid)

• Strong CYP3A4 inducers (e.g., rifampicin, carbamazepine) may reduce bempedoic‑acid exposure.
• High‑intensity statins (atorvastatin >40 mg) increase risk of rhabdomyolysis.
• Cyclosporine: may raise ezetimibe concentrations.

Moderate Interactions (Monitor Closely)

• Fibrates (gemfibrozil, fenofibrate) – additive risk of myopathy.
• Warfarin – potential alteration of INR values.
• Niacin – may increase flushing and liver enzyme changes.