Liptruzet, a New Combination Therapy for Hyperlipidemia, Approved
Merck announced that the FDA has approved Liptruzet (ezetimibe and atorvastatin) tablets for the treatment of elevated low-density lipoprotein (LDL) cholesterol in patient with primary or mixed hyperlipidemia as adjunctive therapy to diet when diet alone is not enough. Liptruzet is also approved 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 or if no treatments are available. Liptruzet is a once daily combination drug containing ezetimibe, a cholesterol absorption inhibitor and atorvastatin, a HMG-CoA reductase inhibitor.
In a multicenter, double-blind, placebo-controlled study in which 628 patients with hyperlipidemia were treated for up to 12 weeks, Liptruzet reduced LDL cholesterol by a mean 56% across all doses (eztimibe/atorvastatin 10mg/10mg, 10mg/20mg, 10mg/40mg) compared to 44% for all atorvastatin doses pooled; P<0.01.
A six-week study, with 556 high risk patients taking atorvastatin 40mg but not at LDL cholesterol <70mg/dL were randomized to either Liptruzet 10mg/40mg coadministered as ezetimibe and atorvastatin (n=277) or atorvastatin 80mg (n=279). Results demonstrated that Liptruzet 10mg/40mg further lowered LDL cholesterol by an average of 27% vs 11% when titrating atorvastatin 80mg (P<-0.05). This additional reduction resulted in 74% of patient achieving LDL cholesterol <70mg/dL compared to 32% of patient taking atorvastin 80mg.
In a separate six-week study, 184 moderately high-risk patients taking atorvastatin 20mg but not at LDL cholesterol <100mg/dL were randomized to either ezetimibe 10mg plus atorvastatin 20mg (N=92) or atorvastatin 40mg (N=92). Results demonstrated that Liptruzet 10mg/20mg further lowered LDL cholesterol by an average of 31% compared to 11% when titrating to atorvastatin 40mg (P<0.05). This additional reduction resulted in 84% of patients treated with Luptruzet 10mg/20mg achieving LDL cholesterol <100mg/dL compared to 49% of patients taking atorvastatin 40mg.
Liptruzet is available as a once-daily tablet containing ezetimibe/atorvastatin in fixed 10mg/10mg, 10mg/20mg, 10mg/40mg, or 10mg/80mg dosage strengths. It will be available the week of May 6.


Liptruzet
Generic Name: atorvastatin and ezetimibe (a TOR va STAT in and e ZET i mibe)
Brand Names: Liptruzet
Pharmacological Class:
Cholesterol absorption inhibitor + HMG-CoA reductase inhibitor.

Active Ingredient(s):
Ezetimibe/atorvastatin; 10mg/10mg, 10mg/20mg, 10mg/40mg, 10mg/80mg; tabs.

Company
Merck & Co., Inc.

Indication(s):

To reduce elevated total-C, LDL-C, Apo B, TG, and non-HDL-C, and to increase HDL-C in primary (heterozygous familial and non-familial) or mixed hyperlipidemia. To reduce elevated total-C and LDL-C in homozygous familial hypercholesterolemia (HoFH), as an adjunct to other lipid-lowering treatments (eg, LDL apheresis) or if such treatments are unavailable. Limitations of use: No incremental benefit on cardiovascular morbidity/mortality over and above that demonstrated for atorvastatin has been established. Not studied in Fredrickson type I, III, IV, and V dyslipidemias.

Pharmacology:

Ezetimibe reduces blood cholesterol by inhibiting cholesterol absorption by the small intestine. Atorvastatin lowers plasma cholesterol and lipoprotein levels by inhibiting HMG-CoA reductase and cholesterol synthesis.

Clinical Trials:

In a clinical study, 628 patients were randomized to placebo, ezetimibe, atorvastatin, or coadminstered ezetimibe and atorvastatin equivalent to Liptruzet in a 12-week study.
 
Patients receiving all doses of the ezetimibe/atorvastatin combination were compared to those receiving all doses of atorvastatin. Results at 12 weeks demonstrated that the ezetimibe/atorvastatin combination treatment significantly reduced total-C (-41% vs. -32%), LDL-C (-56% vs. -44%), Apo B (-45% vs. -36%), TG (-33% vs. -24%), and non-HDL-C (-52% vs. -41%), and significantly increased HDL-C (7% vs. 4%) compared to all doses of atorvastatin pooled, respectively.

For more information on clinical studies: see full labeling.
 

Legal Classification:

Rx

Adults:

Swallow whole. Usual range: 10mg/10mg to 10mg/80mg. Initially 10mg/10mg or 10mg/20mg; for LDL-C reduction >55%: may start at 10mg/40mg; monitor lipids within ≥2wks and adjust dose as needed. HoFH: 10mg/40mg or 10mg/80mg. Concomitant bile acid sequestrants: give Liptruzet dose either ≥2hrs before or ≥4hrs after bile acid sequestrant administration. Concomitant lopinavir/ritonavir: use lowest dose. Concomitant clarithromycin, itraconazole, saquinavir/ritonavir, darunavir/ritonavir, fosamprenavir, or fosamprenavir/ritonavir: max 10mg/20mg. Concomitant nelfinavir or boceprevir: max 10mg/40mg.

Children:

Not established.

Contraindication(s):

Active liver disease. Unexplained persistent elevated hepatic transaminases. Pregnancy (Category X). Nursing mothers.

Warnings/Precautions:

Increased risk of myopathy/rhabdomyolysis (with high doses). Discontinue if elevated CPK (>10 X ULN) levels occur or myopathy is diagnosed or suspected; withhold if a predisposition in renal failure secondary to rhabdomyolysis develops. Monitor liver function prior to starting therapy and repeat as clinically indicated. History of liver disease or renal impairment; monitor closely. Substantial alcohol consumption. Elderly.

Interaction(s)

See Adult dose. Avoid with concomitant cyclosporine, tipranavir/ritonavir, telaprevir, gemfibrozil. Potentiated by strong CYP3A4 inhibitors, grapefruit juice (>1.2L/day). Caution with lopinavir/ritonavir, colchicine, fenofibrates, niacin ≥1g/day; consider dose reduction of Liptruzet. May increase serum levels of digoxin (monitor), oral contraceptives. May be antagonized by cholestyramine, CYP3A4 inducers (eg, efavirenz, rifampin); coadminister rifampin simultaneously. Monitor oral anticoagulants. Caution with drugs that decrease levels or activity of endogenous steroid hormones (eg, ketoconazole, spironolactone, cimetidine).

Adverse Reaction(s)

Increased ALT/AST, musculoskeletal pain, arthralgia, abdominal pain, nausea; increased in HbA1c or fasting serum glucose; myopathy, rhabdomyolysis; rare: immune-mediated necrotizing myopathy.

How Supplied:

Tabs—30, 90