General Information

Liptruzet (ezetimibe and atorvastatin) treats two sources of cholesterol by inhibiting both the absorption of cholesterol in the digestive tract - through ezetimibe - and the production of cholesterol in the liver - through atorvastatin.

Liptruzet is specifically indicated for the reduction of elevated total cholesterol (total-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein B (Apo B), triglycerides (TG), and non-high-density lipoprotein cholesterol (non-HDL-C), and to increase high-density lipoprotein cholesterol (HDL-C) in patients with primary (heterozygous familial and non-familial) hyperlipidemia or mixed hyperlipidemia. It is also indicated for the reduction of elevated total-C and LDL-C in patients with homozygous familial hypercholesterolemia, as an adjunct to other lipid-lowering treatments (e.g., LDL apheresis) or if such treatments are unavailable.

Liptruzet is supplied as a tablet for oral administration. The recommended dose range is 10/10 mg/day to 10/80 mg/day. The recommended starting dose of Liptruzet is 10/10 mg/day or 10/20 mg/day. Liptruzet can be administered as a single dose at any time of the day, with or without food. The recommended starting dose for patients who require a larger reduction in LDL-C (greater than 55%) is 10/40 mg/day. After initiation and/or upon titration of Liptruzet, lipid levels should be analyzed within 2 or more weeks and dosage adjusted accordingly.

Clinical Results

FDA Approval
The FDA approval of Liptruzet was based on the following studies:
A on a multicenter, double-blind, placebo-controlled clinical study in 628 subjects:
The subjects were treated for up to 12 weeks. Liptruzet provided LDL cholesterol reductions of 53% at the lowest dose (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, Liptruzeyt 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< 0.01. 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).
Two six-week studies:
In one six-week study, 556 high risk patients taking atorvastatin 40 mg but not at LDL cholesterol < 70 mg/dL were randomized to either Liptruzet 10/40 mg coadministered as ezetimibe and atorvastatin (n = 277; mean baseline LDL-C 89 mg/dL) or atorvastatin 80 mg (n= 279; mean baseline LDL-C 90 mg/dL). Results showed that Liptruzet 10/40 mg further lowered LDL cholesterol by an average of 27 % compared to 11% when titrating to atorvastatin 80 mg (p<0.05).This greater additional LDL cholesterol reduction resulted in 74% of patients achieving LDL cholesterol <70 mg/dL as compared to 32% of patients taking atorvastatin 80 mg.
In a separate six-week study, 184 moderately-high risk patients taking atorvastatin 20 mg but not at LDL cholesterol < 100 mg/dL were randomized to either Liptruzet 10/20 mg coadministered as ezetimibe and atorvastatin (n = 92; mean baseline LDL-C 120 mg/dL) or atorvastatin 40 mg (n = 92; mean baseline LDL-C 118 mg/dL). Results showed that Liptruzet 10/20 mg further lowered LDL cholesterol by an average of 31% compared to 11% when titrating to atorvastatin 40 mg (p<0.05). This greater additional LDL cholesterol reduction resulted in 84% of patients treated with Liptruzet 10/20 mg achieving LDL cholesterol <100 mg/dL as compared to 49% of patients taking atorvastatin 40 mg.

Mechanism of Action

Liptruzet contains ezetimibe and atorvastatin, two lipid-lowering compounds with complementary mechanisms of action. Ezetimibe reduces blood cholesterol by inhibiting the absorption of cholesterol by the small intestine. Atorvastatin lowers plasma cholesterol and lipoprotein levels by inhibiting HMG-CoA reductase and cholesterol synthesis in the liver and by increasing the number of hepatic LDL receptors on the cell-surface to enhance uptake and catabolism of LDL; atorvastatin also reduces LDL production and the number of LDL particles.