lomitapide + rosuvastatin

**Lomitapide + rosuvastatin** is a combination of two oral **small molecule** lipid-lowering drugs, not currently available as a fixed-dose combination product but sometimes used together in clinical practice to treat **homozygous familial hypercholesterolemia (HoFH)** or severe hypercholesterolemia. **Lomitapide** is a microsomal triglyceride transfer protein (MTP) inhibitor that reduces the assembly and secretion of ApoB-containing lipoproteins (VLDL, LDL, and chylomicrons) by inhibiting MTP in hepatocytes and enterocytes. **Rosuvastatin** is an HMG-CoA reductase inhibitor ("statin"), which lowers cholesterol by blocking the conversion of HMG-CoA to mevalonate, a key step in cholesterol biosynthesis, and also increases the uptake of LDL cholesterol by upregulating LDL receptors. Using lomitapide and rosuvastatin together can increase lipid lowering but also raises the risk of adverse effects due to pharmacokinetic interactions: lomitapide increases exposure to rosuvastatin via CYP-mediated mechanisms, necessitating close monitoring for myopathy and liver toxicity.