FDA approves combination agent to help lower LDL cholesterol

FDA has approved ezetimibe and atorvastatin (Liptruzet, Merck) tablets for the treatment of elevated low-density lipoprotein (LDL) cholesterol in patients with primary or mixed hyperlipidemia as adjunctive therapy to diet, according to the manufacturer.

Liptruzet, administered once daily, targets cholesterol in two areas of the body by inhibiting: both the absorption of cholesterol in the digestive tract with ezetimibe and the production of cholesterol in the liver with atorvastatin. 

“FDA’s approval of Liptruzet serves as another milestone in FDA’s efforts to provide a wide array of drug therapies for individuals who are not able to achieve goal LDL levels with diet and exercise alone,” said Formulary advisor Abimbola Farinde, PharmD, MS, clinical staff pharmacist at Clear Lake Regional Medical Center, Webster, Texas. “The combination of ezetimibe and atorvastatin may be viewed as a more aggressive approach toward cholesterol management, and also a potential increase in the probability of achieving positive therapeutic outcomes.”

“For those patients who need a multipronged approach to lipid control, especially those who are unable to achieve a therapeutically meaningful lowering of low-density lipoproteins, Liptruzet offers an interesting option in that it controls both absorption from the gut and synthesis in the liver in product intended for a once-a-day administration,” Michael S. Ewer, MD, MPH, professor, division of internal medicine, University of Texas System Cancer Center, M.D. Anderson Hospital and Tumour Institute, Houston, told Formulary.

Liptruzet is indicated as adjunctive therapy to diet for the reduction of elevated total cholesterol, LDL cholesterol, apolipoprotein B, triglycerides, and non-high-density lipoprotein cholesterol and to increase high-density lipoprotein (HDL) cholesterol in patients with primary (heterozygous familial and non-familial) hyperlipidemia or mixed hyperlipidemia. It is also indicated for the reduction of elevated total cholesterol and LDL cholesterol in patients with homozygous familial hypercholesterolemia (HoFH), as an adjunct to other lipid-lowering treatments (eg, LDL apheresis) or if such treatments are unavailable. No incremental benefit of Liptruzet on cardiovascular morbidity and mortality over and above that demonstrated for atorvastatin has been established.

Liptruzet should not be taken by anyone who has active liver disease or unexplained persistent elevations in hepatic transaminases or who is hypersensitive to any component of Liptruzet. Women who are pregnant, nursing, or who may become pregnant should not take Liptruzet.

Liptruzet’s efficacy for primary hyperlipidemia was demonstrated in a multicenter, double-blind, placebo-controlled clinical study of 628 patients who underwent treatment for up to 12 weeks. Patients received placebo, ezetimibe (10 mg), atorvastatin (10, 20, 40, or 80 mg), or the coadministratration of ezetimibe and atorvastatin that was equivalent to Liptruzet (10/10 mg, 10/20 mg, 10/40 mg, or 10/80 mg). Patients achieved LDL cholesterol reductions of 53% at the lowest dose of Liptruzet (10/10 mg; mean baseline LDL-C 177 mg/dL), 54% at the 10/20 mg dose (mean baseline LDL-C 184 mg/dL), 56% at the 10/40 mg dose (mean baseline LDL-C 184 mg/dL) and 61% at the maximum dose (10/80 mg; mean baseline LDL-C 183 mg/dL). 

Pooled across doses, Liptruzet reduced LDL cholesterol by a mean 56% (mean baseline LDL-C 182 mg/dL) compared with 44% for all atorvastatin doses pooled (mean baseline LDL-C 181 mg/dL); P<.01. In the atorvastatin groups, the LDL cholesterol reductions seen by atorvastatin dose were 37% at 10 mg (mean baseline LDL-C 185 mg/dL), 42% at 20 mg (mean baseline LDL-C 177 mg/dL), 45% at 40 mg (mean baseline LDL-C 180 mg/dL), and 54% at 80 mg (mean baseline LDL-C 184 mg/dL). The clinical impact of these comparative differences in lipid changes between Liptruzet and atorvastatin is not known.

In two separate clinical studies, Liptruzet 10/40 mg and 10/20 mg provided significantly greater LDL cholesterol reductions and  helped more patients reach their target LDL cholesterol levels (<70 mg/dL or < 100 mg/dL) compared to doubling the dose of atorvastatin to 80 mg or 40 mg, respectively.

The recommended starting doses of Liptruzet are 10/10 mg or 10/20 mg once daily. Drug dosage strengths, available as 10/10 mg, 10/20 mg, 10/40 mg, and 10/80 mg, should be individualized and based on therapeutic response.