Dosing and uses of Zetia (ezetimibe)
Adult dosage forms and strengths
tablets
- 10mg
Hypercholesterolemia
10 mg PO qDay
Dosing Considerations
Overdose management: Treatment should be supportive
Dosing Modifications
Renal impairment
- Monotherapy: No dosage adjustment required
- Moderate to severe: Renal impairment is a risk factor for statin-associated myopathy; caution when coadministered with doses of simvastatin exceeding 20 mg
Hepatic impairment
- Mild (Child-Pugh class A): Dose adjustment not necessary
- Moderate to severe (Child-Pugh class B or C): Not recommended
Pediatric dosage forms and strengths
tablets
- 10mg
Hypercholesterolemia
<10 years: Safety and efficacy not established
>10 years: 10 mg PO qDay
Zetia (ezetimibe) adverse (side) effects
1-10%
Diarrhea (4%)
Upper respiratory tract symptoms (2-4%)
Cough (2-4%)
Pain in extremity (3%)
Sinusitis (3%)
Arthralgia (2-3%)
Fatigue (2%)
Influenza (2%)
Increased liver transaminases (with HMG-CoA reductase inhibitors; ≥3 x ULN; 1%)
Postmarketing Reports
Hepatitis/liver function test abnormalities (LFTs elevated slightly higher in combination with statin than with statin alone)
Hypersensitivity reactions (including anaphylaxis, angioedema, rash, urticaria)
Erythema multiforme
Elevated creatine phosphokinase
Myopathy/rhabdomyolysis
Thrombocytopenia
Back pain
Abdominal pain
Pancreatitis
Nausea
Dizziness
Paresthesia
Depression
Headache
Cholelithiasis and cholecystitis
Warnings
Contraindications
Hypersensitivity
Coadministration with a statin in the presence of active liver disease or persistent, unexplained elevations of hepatic transaminase levels
Cautions
Use caution in patients with mild hepatic impairment or severe renal impairment
Cholelithiasis reported (when coadministered with fibric acid derivatives)
Rule out secondary causes of hyperlipidemia prior to therapy
Pregnancy and lactation
Pregnancy category: C
Lactation: Excretion in milk unknown; use with caution
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Zetia (ezetimibe)
Mechanism of action
Inhibits sterol transporter at brush border and, consequently, intestinal absorption of cholesterol, which in turn decreases delivery of cholesterol to the liver and reduces hepatic cholesterol stores
Absorption
Bioavailability: Variable
Peak plasma time: 4-12 hr (parent drug); 1-2 hr (metabolite)
Peak plasma concentration: 3.4-5.5 ng/mL (parent drug); 45-71 ng/mL (metabolite)
Distribution
Protein bound: >90%
Metabolism
Metabolized by glucuronide conjugation
Metabolites: Ezetimibe-glucuronide (80-90%)
Elimination
Half-life: 22 hr
Excretion: Bile (78%), urine (11%)
