l impairment may be a risk factor for statin-associated myopathy. These patients merit closer monitoring for skeletal muscle effects [see Warnings and Precautions (5.1)].
In patients with renal impairment, no dosage adjustment of LIPTRUZET is necessary.
10 OVERDOSAGE
LIPTRUZET
No specific treatment of overdosage with LIPTRUZET can be recommended. In the event of an overdose, the patient should be treated symptomatically, and supportive measures instituted as required.
Ezetimibe
In clinical studies, administration of ezetimibe, 50 mg/day to 15 healthy subjects for up to 14 days, 40 mg/day to 18 patients with primary hyperlipidemia for up to 56 days, and 40 mg/day to 27 patients with homozygous sitosterolemia for 26 weeks, was generally well tolerated. One female patient with homozygous sitosterolemia took an accidental overdose of ezetimibe 120 mg/day for 28 days with no reported clinical or laboratory adverse events.
Atorvastatin
Due to extensive drug binding to plasma proteins, hemodialysis is not expected to significantly enhance atorvastatin clearance.
11 DESCRIPTION
LIPTRUZET contains ezetimibe, a selective inhibitor of intestinal cholesterol and related phytosterol absorption, and atorvastatin, a 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor.
The chemical name of ezetimibe is 1-(4-fluorophenyl)-3(R)-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4(S)-(4-hydroxyphenyl)-2-azetidinone. The empirical formula is C24H21F2NO3. Its molecular weight is 409.4.
Ezetimibe is a white, crystalline powder that is freely to very soluble in ethanol, methanol, and acetone and practically insoluble in water. Its structural formula is:
Atorvastatin is [R-(R*, R*)]-2-(4-fluorophenyl)-ß, δ-dihydroxy-5-(1-methylethyl)-3-phenyl-4-[(phenylamino) carbonyl]-1H-pyrrole-1-heptanoic acid, calcium salt (2:1).
Atorvastatin calcium is a white to off-white amorphous powder that is very slightly soluble in water, insoluble in acetonitrile, and soluble in methanol. The empirical formula of atorvastatin calcium is (C33H34FN2O5)2Ca. The molecular weight of atorvastatin calcium is 1155.37. Its structural formula is:
LIPTRUZET is available for oral use as tablets containing 10 mg of ezetimibe and: 10.34 mg of atorvastatin calcium, equivalent to 10 mg of atorvastatin (LIPTRUZET 10 mg/10 mg); 20.68 mg of atorvastatin calcium, equivalent to 20 mg of atorvastatin (LIPTRUZET 10 mg/20 mg); 41.37 mg of atorvastatin calcium, equivalent to 40 mg of atorvastatin (LIPTRUZET 10 mg/40 mg); or 82.73 mg of atorvastatin calcium, equivalent to 80 mg of atorvastatin (LIPTRUZET 10 mg/80 mg). Each film-coated tablet of LIPTRUZET contains the following inactive ingredients: lactose monohydrate, microcrystalline cellulose, croscarmellose sodium, povidone, sodium lauryl sulfate, magnesium stearate, lactose anhydrous, hydroxypropyl cellulose, and sodium bicarbonate. In addition, the film coating contains the following inactive ingredients: hydroxypropyl cellulose, hypromellose, titanium dioxide, and carnauba wax.
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
LIPTRUZET
Plasma cholesterol is derived from intestinal absorption and endogenous synthesis. LIPTRUZET contains ezetimibe and atorvastatin, two lipid-lowering compounds with complementary mechanisms of action.
Ezetimibe
Ezetimibe reduces blood cholesterol by inhibiting the absorption of cholesterol by the small i |
