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Pitavastatin

Pronunciation: PIT-a-va-STAT-in
Class: HMG-CoA reductase inhibitor

Trade Names

Livalo
- Tablets 1 mg
- Tablets 2 mg
- Tablets 4 mg

Pharmacology

Increases rate at which body removes cholesterol from blood and reduces production of cholesterol by inhibiting enzyme that catalyzes early rate-limiting step in cholesterol synthesis.

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Pharmacokinetics

Absorption

Rapidly absorbed; T max is 1 h. Absolute bioavailability of oral solution is 51%. Food decreases C max by 43% but does not significantly reduce AUC.

Distribution

Vd is approximately 148 L. More than 99% protein bound.

Metabolism

Major metabolite is the lactone, formed by glucuronidation. Marginally metabolized by CYP2C9 and 2C8.

Elimination

Urine (15%), feces (79%); half-life of approximately 12 h

Special Populations

Renal Function Impairment

AUC and C max were 79% and 60% higher in patients with CrCl 30 to 60 mL/min and 86% and 40% higher in patients with ESRD on hemodialysis, respectively. The effect of mild and severe renal impairment on exposure is not known. Do not use in patients with severe renal impairment not yet on hemodialysis.

Hepatic Function Impairment

Half-life was 15, 10, and 8 h for patients with moderate hepatic impairment, mild hepatic impairment, and healthy hepatic function, respectively.

Elderly

C max and AUC were 10% and 30% higher, respectively, in elderly patients compared with younger patients.

Gender

C max and AUC were 60% and 54% higher, respectively, in women compared with men.

Race

C max and AUC were 21% and 5% lower, respectively, in black patients compared with white patients.

Indications and Usage

Adjunct to diet to reduce elevated total cholesterol, LDL-C, apolipoprotein B, and triglycerides, and to increase HDL-C in adults with primary hyperlipidemia or mixed dyslipidemia.

Contraindications

Active liver disease; women who are pregnant or may become pregnant; breast-feeding mothers; coadministration with cyclosporine; hypersensitivity to any component.

Dosage and Administration

Primary Hyperlipidemia or Mixed Dyslipidemia
Adults

PO Start with 2 mg once daily (max, 4 mg/day; range, 1 to 4 mg/day).

Coadministration with erythromycin

PO Do not exceed 1 mg/day.

Coadministration with rifampin

PO Do not exceed 2 mg/day.

Renal Function Impairment

PO Mild renal impairment (CrCl 30 to less than 60 mL/min) or ESRD on hemodialysis, start with 1 mg once daily (max, 2 mg/day). Severe renal impairment (CrCl less than 30 mL/min and not on hemodialysis), use is not recommended.

General Advice

  • Starting and maintenance dose should be individualized according to patient characteristics (eg, goal of therapy, response).
  • Administer once daily at any time of day with or without food.

Storage/Stability

Store at 59° to 86°F. Protect from light.

Drug Interactions

Cyclosporine

Pitavastatin C max and AUC may be increased more than 6- and 4-fold, respectively. Coadministration is contraindicated.

Digoxin

Digoxin and pitavastatin exposure may be decreased slightly. These changes are not likely to be clinically important.

Enalapril

Pitavastatin plasma concentrations may be decreased slightly and enalapril exposure may be decreased slightly. These changes are not likely to be clinically important.

Erythromycin

Pitavastatin C max and AUC may be increased more than 3- and 2-fold, respectively. The pitavastatin dosage should not exceed 1 mg once daily.

Ezetimibe

Ezetimibe and pitavastatin exposure may be increased slightly. These changes are not likely to be clinically important.

Fibric acids (eg, fenofibrate, gemfibrozil)

Pitavastatin exposure may be increased. The risk of myopathy may be increased. Use with caution, monitoring serum creatine kinase.

Grapefruit juice

Concomitant use of grapefruit juice and pitavastatin decreased the pitavastatin C max slightly and increased the AUC slightly. The changes are not likely to be clinically important.

Itraconazole

Pitavastatin exposure may be reduced about 20%. A clinically important interaction is unlikely. However, monitor the clinical response of the patient and adjust the pitavastatin dose as needed.

Niacin

The risk of myopathy may be increased. Use with caution. Consider reducing the pitavastatin dose.

Protease inhibitors (eg, atazanavir, ritonavir/lopinavir)

Protease inhibitor exposure may be increased. Avoid coadministration of pitavastatin and ritonavir/lopinavir. Monitor the clinical response of the patient when starting or stopping atazanavir. Adjust the pitavastatin dose as needed.

Rifampin

Pitavastatin C max may be reduced approximately 2-fold and the AUC approximately 29%, while rifampin exposure may be decreased approximately 15%. The pitavastatin dosage should not exceed 2 mg once daily.

Warfarin

Monitoring PT and INR is recommended when starting pitavastatin in patients receiving warfarin.

Laboratory Test Interactions

None well documented.

Adverse Reactions

GI

Constipation (4%); diarrhea (3%).

Lab Tests

Elevated alkaline phosphatase, bilirubin, creatine phosphokinase, glucose, and transaminases.

Musculoskeletal

Back pain (4%); myalgia (3%); arthralgia, pain in extremity (2%).

Other

Headache, hypersensitivity reactions (eg, rash, pruritis, urticaria), influenza, nasopharyngitis.

Precautions

Monitor

Analyze lipid levels 4 weeks after initiation of therapy or dosage titration. Monitor liver enzymes before and 12 wk after initiation of therapy or dosage titration, and periodically (eg, semiannually) thereafter. Monitor patients who develop increased transaminases until the abnormalities resolve.


Pregnancy

Category X .

Lactation

Contraindicated.

Children

Safety and effectiveness not established.

Elderly

Greater sensitivity of some older individuals cannot be ruled out.

Renal Function

Patients with moderate renal impairment (CrCl 30 to less than 60 mL/min) and ESRD on hemodialysis should receive decreased initial and maintenance dosages.

Hepatic Function

Contraindicated in patients with active liver disease.

Liver enzyme abnormalities

Increases in transaminases have been reported. Use with caution in patients who consume substantial quantities of alcohol and/or have a history of chronic liver disease.

Skeletal muscle effects

Rhabdomyolysis with renal dysfunction secondary to myoglobinuria has been reported. The risk of myopathy may be increased if coadministered with fibrates or lipid-modifying doses of niacin. Temporarily withhold therapy in any patient experiencing an acute or serious condition predisposing to the development of renal failure secondary to rhabdomyolysis (eg, hypotension, sepsis). Discontinue therapy if markedly elevated creatine kinase levels occur or if myopathy is diagnosed or suspected.

Overdosage

Symptoms

Not known.

Patient Information

  • Inform patients that pitavastatin can be taken at any time of the day with or without food.
  • Advise patients to promptly notify their health care provider of any unexplained muscle pain, tenderness, or weakness, particularly if accompanied by malaise or fever.
  • Advise patients to discuss all medicines, both prescription and OTC, with their health care provider.
  • Advise women of childbearing age to use an effective method of birth control to prevent pregnancy while using pitavastatin and discuss future pregnancy plans with their health care provider. If the patient becomes pregnant, advise her to stop taking pitavastatin and call her health care provider.
  • Instruct breast-feeding women not to use pitavastatin.
  • Advise patients that liver enzymes be checked before and 12 wk following initiation of therapy and any titration of dose, and periodically (eg, semiannually) thereafter.
  • Caution patient to avoid or decrease alcohol intake.
  • Advise patient that pitavastatin helps control, but does not cure, cholesterol abnormality and to continue taking as prescribed when cholesterol goals have been reached.
  • Emphasize to patient the importance of other modalities for cholesterol control: dietary changes (eg, reduced saturated fat intake, increased soluble fiber intake), weight control, regular exercise, and smoking cessation.

Copyright © 2009 Wolters Kluwer Health.

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