Total Cost
Free shipping on all orders

Powered by GeniusRx

brand livalo 2 mg tablet

In stock Manufacturer KOWA PHARMACEUT 66869020490
$10.63 / Tablet

Select Quantity

Prescription is required

Uses

Dyslipidemias

Pitavastatin is used as an adjunct to nondrug therapies (e.g., dietary management) to decrease elevated serum total cholesterol, low-density lipoprotein (LDL)-cholesterol, apolipoprotein B (apo B), and triglyceride concentrations, and to increase high-density lipoprotein (HDL)-cholesterol concentrations in the management of primary hypercholesterolemia or mixed dyslipidemia. Safety and efficacy of pitavastatin have not been established in patients with Fredrickson type I, III, or V dyslipidemia. The effect of pitavastatin on cardiovascular morbidity and mortality has not been established.

Nondrug therapies and measures specific for the type of hyperlipoproteinemia (therapeutic lifestyle changes) are the initial treatments of choice, including dietary management (e.g., restriction of saturated fat and cholesterol intake, addition of plant stanol/sterols and viscous fiber to diet), weight control, an appropriate program of physical activity, and management of potentially contributory disease. Drug therapy is not a substitute for but an adjunct to these nondrug therapies and measures, which should be continued when drug therapy is initiated.

Primary Hypercholesterolemia or Mixed Dyslipidemia

Pitavastatin is used as an adjunct to nondrug therapies (e.g., dietary management) to decrease elevated serum total cholesterol, LDL-cholesterol, apo B, and triglyceride concentrations, and to increase HDL-cholesterol concentrations in the management of primary hypercholesterolemia or mixed dyslipidemia. Safety and efficacy of pitavastatin in patients with primary hypercholesterolemia or mixed dyslipidemia have been established in placebo-controlled studies and in comparative studies with other statins (e.g., atorvastatin, pravastatin, simvastatin). Statins such as pitavastatin also are used in combination with fenofibrate to decrease triglyceride concentrations and increase HDL-cholesterol concentrations in patients with mixed dyslipidemia and coronary heart disease (CHD) (or CHD risk equivalents) who are receiving optimal statin therapy; however, no additional benefit on cardiovascular morbidity and mortality has been demonstrated with such combination therapy beyond that already established with statin monotherapy.

Reductions in total cholesterol, LDL-cholesterol, apo B, and triglyceride concentrations achieved with usual dosages of pitavastatin substantially exceed those with placebo or compared with baseline values. In a randomized, double-blind, placebo-controlled, dose-ranging study in 251 patients 21-75 years of age with primary hypercholesterolemia, mean reductions of 23-31% in total cholesterol, 32-43% in LDL-cholesterol, 25-35% in apo B, and 15-19% in triglyceride concentrations were reported in patients receiving pitavastatin 1-4 mg daily for 12 weeks. Modest and variable increases in HDL-cholesterol concentrations (5-8%) also were observed in these patients.

Data from comparative studies indicate that reductions in LDL-cholesterol concentrations achieved with usual dosages (1-4 mg daily) of pitavastatin are similar to or greater than those achieved with low to medium dosages of certain other statins (i.e., atorvastatin, pravastatin, simvastatin). In a double-blind, active-controlled, noninferiority phase 3 study in which 817 patients 18-75 years of age with primary hypercholesterolemia or mixed dyslipidemia were randomized to receive either pitavastatin or atorvastatin for 12 weeks, reductions in LDL-cholesterol concentrations achieved with pitavastatin 2 or 4 mg daily (38 or 45%, respectively) were noninferior to those achieved with atorvastatin 10 mg or 20 mg daily (38 or 44%, respectively). In another double-blind, active-controlled, noninferiority phase 3 study in which 843 patients 18-75 years of age with primary hypercholesterolemia or mixed dyslipidemia were randomized to receive either pitavastatin or simvastatin for 12 weeks, reductions in LDL-cholesterol concentrations achieved with pitavastatin 2 mg daily (39%) were greater than those achieved with simvastatin 20 mg daily (35%), and reductions achieved with pitavastatin 4 mg daily (44%) were noninferior to those achieved with simvastatin 40 mg daily (43%). In a third double-blind, active-controlled, noninferiority phase 3 study in which 942 geriatric patients (65 years of age or older) with primary hypercholesterolemia or mixed dyslipidemia were randomized to receive either pitavastatin or pravastatin for 12 weeks, reductions in LDL-cholesterol concentrations achieved with pitavastatin 1, 2, or 4 mg daily (31, 39, or 44%, respectively) were greater than those achieved with pravastatin 10, 20, or 40 mg daily (22, 29, or 34%, respectively).

In patients who have risk factors for CHD, reductions in LDL-cholesterol concentrations achieved with the maximum dosage (4 mg daily) of pitavastatin are similar to or less than those achieved with low to medium dosages of certain other statins (i.e., atorvastatin, simvastatin). In a double-blind, active-controlled, noninferiority phase 3 study in which 351 patients with primary hypercholesterolemia or mixed dyslipidemia and 2 or more risk factors for CHD were randomized to receive either pitavastatin or simvastatin for 12 weeks, reductions in LDL-cholesterol concentrations achieved with pitavastatin 4 mg daily were noninferior to those achieved with simvastatin 40 mg daily (44 versus 44%). In another double-blind, active-controlled, noninferiority phase 3 study in which 410 patients with mixed dyslipidemia and type 2 diabetes mellitus were randomized to receive either pitavastatin or atorvastatin for 12 weeks, reductions in LDL-cholesterol concentrations achieved with pitavastatin 4 mg daily (41%) were not noninferior to those achieved with atorvastatin 20 mg daily (43%).

Antilipemic effects of pitavastatin appear to be sustained during long-term (i.e., up to 2 years) therapy. In an open-label extension study in 1353 patients with primary hypercholesterolemia or mixed dyslipidemia who had previously received pitavastatin, atorvastatin, or simvastatin for 12 weeks in double-blind phase 3 studies, treatment with pitavastatin 4 mg daily for up to 52 weeks resulted in reductions of approximately 30% in total cholesterol, 43% in LDL-cholesterol, 36% in apo B, and 17% in triglyceride concentrations, and increases of approximately 14% in HDL-cholesterol concentrations; with the exception of substantially greater increases in HDL-cholesterol concentrations, these antilipemic effects were similar to those observed at the end of the 12-week double-blind phase 3 studies. In another extension study in 545 geriatric patients (65 years of age or older) who had previously received pitavastatin or pravastatin for 12 weeks in a double-blind phase 3 study, treatment with pitavastatin 2 mg daily (titrated to 4 mg daily after 8 weeks as needed to achieve target LDL-cholesterol goal) for 60 weeks resulted in reductions of approximately 43-44 or 19-20% in LDL-cholesterol or triglyceride concentrations, respectively, and an increase of approximately 10% in HDL-cholesterol concentrations, compared with baseline concentrations (i.e., prior to initiation of the 12-week double-blind phase 3 study); at week 60, approximately 99 or 70% of patients receiving pitavastatin 2 or 4 mg daily, respectively, achieved their LDL-cholesterol goals. In an uncontrolled, observational postmarketing surveillance study in which most patients (approximately 99% of the study population) with hypercholesterolemia received pitavastatin 1 or 2 mg daily, LDL-cholesterol concentrations were reduced by approximately 31% at 4 weeks or 29% at 2 years following initiation of pitavastatin therapy.

Prevention of Cardiovascular Events

The American College of Cardiology (ACC)/American Heart Association (AHA) cholesterol management guideline recommends statins as first-line therapy for the prevention of atherosclerotic cardiovascular disease (ASCVD) in adults. There is extensive evidence demonstrating that statins can substantially reduce ASCVD risk when used for secondary prevention or primary prevention (in high-risk patients). Because the relative reduction in ASCVD risk is correlated with the degree of LDL-cholesterol lowering, the maximum tolerated statin intensity should be used to achieve optimum ASCVD benefits. ACC/AHA considers pitavastatin 1 mg daily to be a low-intensity statin (producing approximate LDL-cholesterol reductions of less than 30%) and pitavastatin 2-4 mg daily to be a moderate-intensity statin (producing approximate LDL-cholesterol reductions of 30% to less than 50%); these dosages and approximate LDL reductions are based on FDA-labeled dosages only since pitavastatin was not evaluated in the randomized controlled studies reviewed by the guideline expert panel. Individual patient response may vary in clinical practice.

According to the ACC/AHA cholesterol management guidelines, pitavastatin may be considered for primary or secondary prevention in adults when moderate-intensity statin therapy is indicated.(See Prevention of Cardiovascular Events under Dosage and Administration: Dosage.) Nonstatin therapies do not provide acceptable ASCVD risk reduction benefits compared to their potential for adverse effects in the routine prevention of ASCVD. For additional details on prevention of ASCVD, and also consult the most recent ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults (available at http://www.cardiosource.org or http://my.americanheart.org).

For additional information on the role of pitavastatin or other statins in the treatment of lipoprotein disorders, prevention of cardiovascular events, or other uses, see General Principles of Antilipemic Therapy and also Uses in the HMG-CoA Reductase Inhibitors General Statement 24:06.08.

Dosage and Administration

Administration

Pitavastatin is administered orally once daily at any time of day, without regard to food. Patients should be placed on a standard cholesterol-lowering diet before receiving pitavastatin and should continue on this diet during treatment. For recommendations on dietary and other nondrug therapies (i.e., lifestyle modifications), consult the most recent American Heart Association (AHA)/American College of Cardiology (ACC) Guideline on Lifestyle Management to Reduce Cardiovascular Risk (available at http://www.cardiosource.org or http://my.americanheart.org).

The manufacturer states that serum lipoprotein concentrations should be determined 4 weeks after initiation and/or titration of pitavastatin, and that dosage should be adjusted accordingly. The ACC/AHA cholesterol management guideline states that lipoprotein concentrations should be determined within 4-12 weeks following initiation of statin therapy (to determine the patient's response to therapy and adherence) and monitored every 3-12 months thereafter as clinically indicated.

Dosage

Dosage of pitavastatin calcium is expressed in terms of pitavastatin and should be carefully adjusted according to individual requirements (i.e., percent reduction in low-density [LDL]-cholesterol concentrations) and response.

Prevention of Cardiovascular Events

The ACC/AHA cholesterol management guideline states that the appropriate intensity of statin therapy should be used to reduce atherosclerotic cardiovascular disease (ASCVD) risk in patients most likely to benefit. Giving a maximally tolerated statin intensity should be emphasized over giving lower statin dosages and adding nonstatin drugs to address low high-density lipoprotein (HDL)-cholesterol or high triglyceride concentrations, a strategy that has not yet been shown to reduce ASCVD risk. It should be noted that although dosages of 1-4 mg once daily are FDA-labeled dosages of pitavastatin, these dosages were not evaluated in randomized controlled studies reviewed by the ACC/AHA expert panel.

Primary Prevention

For primary prevention of cardiovascular disease in patients 21 years of age and older without clinical ASCVD who have primary, severe elevations in LDL-cholesterol concentration (190 mg/dL or greater), the ACC/AHA cholesterol management guideline recommends that high-intensity statin therapy (i.e., with atorvastatin or rosuvastatin) be initiated unless contraindicated. ( or 24:06.08.)

For primary prevention of cardiovascular disease in patients 40-75 years of age with type 1 or 2 diabetes mellitus and LDL-cholesterol concentrations of 70-189 mg/dL, the ACC/AHA cholesterol management guideline recommends that moderate-intensity statin therapy (e.g., pitavastatin 2-4 mg once daily) be initiated or continued. In those with an estimated 10-year ASCVD risk of 7.5% or higher, it is reasonable to consider high-intensity statin therapy (i.e., with atorvastatin or rosuvastatin) unless contraindicated. In patients with diabetes mellitus who are younger than 40 or older than 75 years of age, it is reasonable to evaluate the potential benefits, adverse effects, drug interactions, and patient preferences when deciding to initiate, continue, or intensify statin therapy.

For primary prevention of cardiovascular disease in patients 40-75 years of age without clinical ASCVD or diabetes mellitus who have LDL-cholesterol concentrations of 70-189 mg/dL and an estimated 10-year ASCVD risk of 7.5% or higher, the ACC/AHA cholesterol management guideline recommends that moderate- (e.g., pitavastatin 2-4 mg once daily) to high-intensity statin therapy (i.e., with atorvastatin or rosuvastatin) be initiated or continued. In those with an estimated 10-year ASCVD risk of 5 to less than 7.5%, it is reasonable to offer treatment with moderate-intensity statin therapy. Before initiating statin therapy for primary prevention of ASCVD in patients 40-75 years of age without clinical ASCVD or diabetes mellitus who have LDL-cholesterol concentrations of 70-189 mg/dL, it is reasonable for clinicians and patients to discuss the potential benefits, adverse effects, drug interactions, and patient preferences for such therapy.

Secondary Prevention

For secondary prevention of cardiovascular disease in patients 21-75 years of age with clinical ASCVD, the ACC/AHA cholesterol management guideline recommends that high-intensity statin therapy (i.e., with atorvastatin or rosuvastatin) be initiated or continued unless contraindicated. ( or 24:06.08.) For secondary prevention in patients 21-75 years of age with clinical ASCVD who are at increased risk for developing statin-associated adverse effects or in whom high-intensity statin therapy is inappropriate or contraindicated, moderate-intensity statin therapy (e.g., pitavastatin 2-4 mg once daily) should be given if tolerated. In patients older than 75 years of age with clinical ASCVD, use of statin therapy should be individualized based on the potential benefits, adverse effects, drug interactions, and patient preferences; it is reasonable to consider initiating or continuing moderate-intensity statin therapy in such patients if tolerated.

Dyslipidemias

Hypercholesterolemia or Mixed Dyslipidemia

The recommended initial adult dosage of pitavastatin for the management of primary hypercholesterolemia or mixed dyslipidemia is 2 mg once daily. The usual maintenance dosage is 1-4 mg once daily. The maximum dosage of pitavastatin is 4 mg once daily.

Concomitant Drug Therapy

Concomitant use of pitavastatin with certain drugs (e.g., erythromycin, fibric acid derivatives, antilipemic dosages of niacin, rifampin) may alter pitavastatin concentrations and/or increase the risk of myopathy or rhabdomyolysis.For specific recommendations (including dosage recommendations) for such concomitant use, see Drug Interactions.

Dosage Modification

The ACC/AHA cholesterol management guideline states that decreasing the statin dosage in adults may be considered when LDL-cholesterol concentrations are less than 40 mg/dL on 2 consecutive measurements; however, there are no data to suggest that LDL-cholesterol concentrations below 40 mg/dL would increase the risk of adverse effects.

Special Populations

The manufacturer makes no specific dosage recommendations at this time for patients with hepatic impairment.(See Cautions: Contraindications and also Hepatic Impairment under Warnings/Precautions: Specific Populations, in Cautions.)

The recommended initial adult dosage of pitavastatin in patients with moderate or severe renal impairment (glomerular filtration rate [GFR] 30-59 mL/minute per 1.73 m or 15-29 mL/minute per 1.73 m not undergoing hemodialysis, respectively) or in patients with end-stage renal disease who are undergoing hemodialysis is 1 mg once daily. The maximum recommended dosage in these patients is 2 mg once daily.

Cautions

Contraindications

Active liver disease, including unexplained, persistent elevations in serum aminotransferase (transaminase) concentrations.

Women who are or may become pregnant.(See Fetal/Neonatal Morbidity and Mortality under Cautions: Warnings/Precautions.)

Nursing women.(See Lactation under Warnings/Precautions: Specific Populations, in Cautions.)

Concomitant use with cyclosporine.(See Drug Interactions: Immunosuppressive Agents.)

Known hypersensitivity to pitavastatin or any ingredient in the formulation.(See Sensitivity Reactions under Cautions: Warnings/Precautions.)

Warnings/Precautions

Fetal/Neonatal Morbidity and Mortality

Serum cholesterol and triglyceride concentrations increase during normal pregnancy, and cholesterol products are essential for fetal development; therefore, suppression of cholesterol biosynthesis by pitavastatin during pregnancy may cause fetal harm. Atherosclerosis is a chronic process, and discontinuance of antilipemic drugs during pregnancy should have little impact on long-term outcomes of primary hypercholesterolemia therapy. There is no known clinical benefit for continued use during pregnancy.

Congenital anomalies following intrauterine exposure to statins have been reported rarely.

Women of childbearing potential should use effective contraceptive methods during pitavastatin therapy.(See Advice to Patients.) If the patient becomes pregnant while taking the drug, pitavastatin should be discontinued and the patient apprised of the potential fetal hazard and the lack of known clinical benefit with continued use during pregnancy.

Musculoskeletal Effects

Myopathy and rhabdomyolysis with acute renal failure secondary to myoglobinuria have been reported in patients receiving statins, including pitavastatin. These adverse effects can occur at any dosage, but the risk increases with increasing dosage; in clinical studies, the risk of severe myopathy increased with pitavastatin dosages exceeding 4 mg daily.

Pitavastatin should be used with caution in patients with predisposing factors for myopathy (e.g., advanced age [older than 65 years of age], renal impairment, inadequately-treated hypothyroidism) and in patients receiving concomitant therapy with certain antilipemic agents (i.e., fibric acid derivatives, antilipemic dosages of niacin).(See Drug Interactions.)

The American College of Cardiology (ACC)/American Heart Association (AHA) cholesterol management guideline does not recommend routine monitoring of CK concentrations in adults receiving statin therapy. However, the guideline states that it is reasonable to obtain baseline CK concentrations in adults at increased risk of developing adverse musculoskeletal effects (e.g., patients with personal or family history of statin intolerance or muscle disease, patients receiving concomitant therapy with myotoxic drugs) before initiating statin therapy. During statin therapy, it is reasonable to measure CK concentrations in adults experiencing muscle symptoms (e.g., pain, tenderness, stiffness, cramping, weakness, generalized fatigue).

Pitavastatin should be discontinued if CK concentrations become markedly elevated or if myopathy is diagnosed or suspected. Pitavastatin therapy should be temporarily withheld in patients experiencing an acute, serious condition suggestive of myopathy or predisposing to the development of renal failure secondary to rhabdomyolysis (e.g., sepsis; hypotension; dehydration; major surgery; trauma; severe metabolic, endocrine, or electrolyte disorders; uncontrolled seizures).(See Advice to Patients.)

For additional details on management of musculoskeletal effects in adults, and also consult the most recent ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults (available at http://www.cardiosource.org or http://my.americanheart.org).

Hepatic Effects

Increases in serum aminotransferase (i.e., AST [SGOT], ALT [SGPT]) concentrations have been reported in patients receiving statins, including pitavastatin. These increases usually were transient and resolved or improved with continued therapy or after temporary interruption of therapy. In phase 2, placebo-controlled studies, increases in serum ALT concentrations exceeding 3 times the upper limit of normal occurred in 0.5% of patients receiving pitavastatin 4 mg daily.

Cases of fatal and nonfatal hepatic failure have been reported rarely in patients receiving statins, including pitavastatin, during postmarketing surveillance.

Liver function tests should be performed prior to initiation of pitavastatin therapy and repeated as clinically indicated (e.g., presence of manifestations suggestive of liver damage). Although the manufacturer previously recommended more frequent monitoring of liver function (i.e., at 12 weeks following initiation of therapy or any increase in dosage, then periodically [e.g., semiannually] thereafter), the US Food and Drug Administration (FDA) concluded that serious statin-related liver injury is rare and unpredictable in individual patients, and that routine periodic monitoring of liver enzymes does not appear to be effective in detecting or preventing serious liver injury. The ACC/AHA cholesterol management guideline states that, during statin therapy, it is reasonable to obtain liver function tests in adults experiencing symptoms of hepatotoxicity (e.g., unusual fatigue or weakness, loss of appetite, abdominal pain, dark colored urine, yellowing of the skin or sclera).

If serious liver injury with clinical manifestations and/or hyperbilirubinemia or jaundice occurs, pitavastatin therapy should be promptly interrupted. If an alternate etiology is not found, pitavastatin therapy should not be restarted.

Pitavastatin should be used with caution in patients who consume substantial amounts of alcohol. The drug is contraindicated in patients with active liver disease, including unexplained, persistent elevations in serum aminotransferase concentrations.

Endocrine Effects

Increases in glycosylated hemoglobin (hemoglobin A1c [HbA1c]) and fasting serum glucose concentrations have been reported in patients receiving statins, including pitavastatin. Data from clinical trials and meta-analyses indicate that statin therapy may increase the risk of developing diabetes mellitus. Despite these findings, FDA continues to believe that the cardiovascular benefits of statins outweigh these small increased risks. The ACC/AHA cholesterol management guideline states that patients receiving statin therapy should be evaluated for new-onset diabetes mellitus according to current diabetes screening guidelines. If diabetes mellitus develops during statin therapy, patients should be encouraged to adhere to a heart-healthy diet, engage in physical activity, achieve and maintain a healthy body weight, cease tobacco use, and continue statin therapy to reduce the risk of atherosclerotic cardiovascular disease (ASCVD).

Sensitivity Reactions

Hypersensitivity reactions, including rash, pruritus, and urticaria, have been reported in patients receiving pitavastatin.

Cognitive Impairment

Cognitive impairment (e.g., memory loss, forgetfulness, amnesia, memory impairment, confusion) has been reported rarely with all statins during postmarketing surveillance. This adverse CNS effect generally was nonserious and reversible, with variable times to symptom onset (1 day to years) and symptom resolution (median of 3 weeks following discontinuance of statin therapy). Following review of available data (i.e., from the Adverse Event Reporting System [AERS] database, randomized clinical trials, observational studies, case reports), FDA concluded that cases of cognitive impairment did not appear to be associated with fixed or progressive dementia (e.g., Alzheimer's disease) or result in clinically important cognitive decline. Development of cognitive impairment did not appear to be associated with any specific statin, age of the patient, statin dosage, or concomitant drug therapy. Therefore, FDA continues to believe that the cardiovascular benefits of statins outweigh this small increased risk of cognitive impairment. The National Lipid Association (NLA) statin safety assessment task force recommends that patients experiencing manifestations consistent with cognitive impairment be evaluated and managed appropriately. The ACC/AHA cholesterol management guideline states that, in patients presenting with confusion or memory impairment, it is reasonable to evaluate the patient for statin as well as nonstatin causes (e.g., exposure to other drugs, systemic or neuropsychiatric causes).

Specific Populations

Pregnancy

Category X.(See Cautions: Contraindications and also Fetal/Neonatal Morbidity and Mortality under Cautions: Warnings/Precautions.)

Lactation

Pitavastatin is distributed into milk in rats. It is not known whether pitavastatin is distributed into human milk; however, a small amount of another statin is distributed into human milk. Because of the potential for serious adverse reactions from pitavastatin in nursing infants, the drug is contraindicated in nursing women. Women who require pitavastatin therapy should be advised not to breast-feed their infants or advised to discontinue pitavastatin.(See Cautions: Contraindications.)

Pediatric Use

Safety and efficacy of pitavastatin have not been established in pediatric patients younger than 18 years of age.

Geriatric Use

In clinical studies of pitavastatin, approximately 43% of patients were 65 years of age or older. No substantial differences in safety or efficacy relative to younger adults were observed, but increased sensitivity in some older patients cannot be ruled out. Data from a pharmacokinetic study indicate that peak plasma concentrations and area under the plasma concentration-time curve (AUC) of pitavastatin were 10 or 30% higher, respectively, in geriatric individuals (65 years of age or older) compared with younger adults.

The ACC/AHA cholesterol management guideline states that initiation of statin therapy for primary prevention of ASCVD in patients older than 75 years of age requires consideration of additional factors, including increasing comorbidities, safety considerations, and priorities of care. Therefore, the potential for an ASCVD risk reduction benefit, adverse effects, and drug interactions, along with patient preferences, must be considered before initiating statin therapy in patients older than 75 years of age.

Hepatic Impairment

Patients with aminotransferase (i.e., AST, ALT) concentrations exceeding 1.5 times the upper limit of normal were excluded from phase 3 clinical studies.

Results of a pharmacokinetic study indicate that peak plasma concentrations or AUC of pitavastatin were 1.3- or 1.6-fold higher, respectively, in patients with mild (Child-Pugh class A) hepatic impairment compared with those in healthy individuals. In patients with moderate (Child-Pugh class B) hepatic impairment, peak plasma concentrations or AUC of pitavastatin were 2.7- or 3.8-fold higher, respectively, compared with those in healthy individuals. In this study, the mean elimination half-life of pitavastatin in healthy individuals, patients with mild hepatic impairment, or patients with moderate hepatic impairment was 8, 10, or 15 hours, respectively.

Pitavastatin is contraindicated in patients with active liver disease, including unexplained, persistent elevations in serum aminotransferase concentrations.

Renal Impairment

Peak plasma concentrations or AUC of pitavastatin were 60 or 102% higher, respectively, in patients with moderate renal impairment (glomerular filtration rate [GFR] 30-59 mL/minute per 1.73 m) compared with healthy individuals. In patients with severe renal impairment (GFR 15-29 mL/minute per 1.73 m) not undergoing hemodialysis, peak plasma concentrations or AUC of pitavastatin were 18 or 36% higher, respectively, compared with those in healthy individuals following a single 4-mg dose of pitavastatin; the mean percentage of non-protein bound pitavastatin was approximately 0.6% in both groups. In patients with end-stage renal disease (ESRD) undergoing hemodialysis, peak plasma concentrations or AUC of pitavastatin were 40 or 86% higher, respectively, compared with those in healthy individuals. Patients undergoing hemodialysis have a 33 or 36% increase in the mean unbound fraction of pitavastatin compared with healthy individuals or patients with moderate renal impairment, respectively. The effect of mild renal impairment on pitavastatin exposure has not been established.

Dosage adjustments are required in patients with moderate renal impairment, patients with severe renal impairment not undergoing hemodialysis, and patients with ESRD undergoing hemodialysis.(See Dosage and Administration: Special Populations.)

Common Adverse Effects

Adverse effects reported in 2% or more of patients receiving pitavastatin include myalgia, back pain, diarrhea, constipation, and pain in extremity. Other adverse effects reported in clinical studies include arthralgia, headache, influenza, and nasopharyngitis. Laboratory abnormalities, including increases in concentrations of CK, aminotransferases, alkaline phosphatase, bilirubin, and glucose, also have been reported.

Drug Interactions

Pitavastatin is minimally metabolized by cytochrome P-450 (CYP) isoenzyme 2C9 and, to a lesser extent, by CYP2C8.

Drugs Transported by Organic Anion Transport Polypeptide 1B1

Pitavastatin is a substrate of organic anionic transport polypeptide (OATP) 1B1 (OATP2). Drugs that inhibit OATP1B1 (e.g., cyclosporine, erythromycin, rifampin) can increase bioavailability of pitavastatin.

Colchicine

Myopathy, including rhabdomyolysis, has been reported in patients receiving various statins concomitantly with colchicine. Caution is advised when pitavastatin is used concomitantly with colchicine.

Digoxin

Concomitant use of pitavastatin (4 mg once daily) and digoxin (0.25 mg once daily for 7 days) decreased pitavastatin peak plasma concentration by 9%, increased pitavastatin area under the plasma concentration-time curve (AUC) by 4%, and decreased digoxin peak plasma concentration and AUC by 4 and 3%, respectively.

Diltiazem

Concomitant use of pitavastatin (4 mg once daily on days 1-5 and 11-15) and extended-release diltiazem hydrochloride (240 mg on days 6-15) increased pitavastatin peak plasma concentration and by 15 and 10%, respectively, and decreased diltiazem peak plasma concentration and AUC by 7 and 2%, respectively.

Enalapril

Concomitant use of pitavastatin (4 mg once daily) and enalapril (20 mg once daily for 5 days) increased AUC of pitavastatin by 6% and decreased peak plasma concentrations of the drug by 7%. Peak plasma concentrations and AUC of enalapril were increased by 12%.

Erythromycin

Erythromycin substantially increases pitavastatin exposure. Following concomitant use of pitavastatin (4 mg as a single dose on day 4) and erythromycin (500 mg 4 times daily for 6 days), pitavastatin peak plasma concentration and AUC were increased by 3.6- and 2.8-fold, respectively; such effects were considered clinically important. The interaction between pitavastatin and erythromycin probably resulted partly from erythromycin-induced inhibition of OATP1B1-mediated hepatic uptake of pitavastatin. If used concomitantly with erythromycin, dosage of pitavastatin should not exceed 1 mg once daily.

Ezetimibe

Concomitant use of pitavastatin (2 mg once daily) and ezetimibe (10 mg for 7 days) decreased pitavastatin peak plasma concentration and AUC by 0.2 and 2%, respectively, and increased ezetimibe peak plasma concentration and AUC by 2 and 9%, respectively.

Fibric Acid Derivatives

Concomitant use of statins and gemfibrozil increases the risk of myopathy or rhabdomyolysis. Following concomitant use of pitavastatin (4 mg once daily) and gemfibrozil (600 mg twice daily for 7 days), pitavastatin peak plasma concentration and AUC were increased by 31 and 45%, respectively.

Concomitant use of statins and other fibric acid derivatives (e.g., fenofibrate) increases the risk of myopathy. Following concomitant use of pitavastatin (4 mg once daily) and fenofibrate (160 mg once daily for 7 days), pitavastatin peak plasma concentration and AUC were increased by 11 and 18%, respectively.

The manufacturer states that concomitant use of pitavastatin and gemfibrozil should be avoided, and concomitant use with other fibric acid derivatives (e.g., fenofibrate) should be employed with caution. The ACC/AHA cholesterol management guideline states that the combination of fenofibrate and low- or moderate-intensity statin therapy may be considered only if the benefits from atherosclerotic cardiovascular disease (ASCVD) risk reduction or triglyceride lowering (when triglyceride concentrations exceed 500 mg/dL) outweigh the potential risk of adverse effects.

Grapefruit Juice

Concomitant use of pitavastatin (2 mg as a single dose on day 3) and grapefruit juice (for 4 days) decreased pitavastatin peak plasma concentration by 12% and increased pitavastatin AUC by 15%.

HIV Protease Inhibitors

Atazanavir

Concomitant use of pitavastatin (4 mg once daily) and atazanavir (300 mg once daily for 5 days) increased peak plasma concentrations and AUC of pitavastatin by 60 and 31%, respectively, and atazanavir by 13 and 6%, respectively. Some experts state that dosage adjustments are not necessary when pitavastatin is used concomitantly with atazanavir.

Darunavir

Concomitant use of pitavastatin (4 mg once daily on days 1-5 and 12-16) and ritonavir-boosted darunavir (darunavir 800 mg with ritonavir 100 mg once daily on days 6-16) decreased peak plasma concentration and AUC of pitavastatin by 4 and 26%, respectively, while increasing peak plasma concentration and AUC of darunavir by 6 and 3%, respectively, and ritonavir by 2 and 8%, respectively. Some experts state that dosage adjustments are not necessary when pitavastatin is used concomitantly with ritonavir-boosted darunavir.

Lopinavir

Concomitant use of pitavastatin (4 mg once daily on days 1-5 and 20-24) and the fixed combination of lopinavir and ritonavir (lopinavir/ritonavir; lopinavir 400 mg/ritonavir 100 mg twice daily on days 9-24) decreased peak plasma concentration and AUC of pitavastatin by 4 and 20%, respectively, lopinavir by 7 and 9%, respectively, and ritonavir by 11 and 11%, respectively. Some experts state that dosage adjustments are not necessary when pitavastatin is used concomitantly with lopinavir/ritonavir.

Immunosuppressive Agents

Cyclosporine substantially increases pitavastatin exposure. Following concomitant use of pitavastatin (2 mg once daily for 6 days) and cyclosporine (2 mg/kg on day 6), pitavastatin peak plasma concentration and AUC were increased by 6.6- and 4.6-fold, respectively; such effects were considered clinically important. The interaction between pitavastatin and cyclosporine probably resulted partly from cyclosporine-induced inhibition of OATP1B1-mediated hepatic uptake of pitavastatin. Because of the potential for substantial increases in pitavastatin exposure, concomitant use of pitavastatin with cyclosporine is contraindicated.

Although data are more limited with everolimus, sirolimus, and tacrolimus, the drug interaction potential of these other immunosuppressive agents is expected to be similar to that of cyclosporine because of similar metabolism; therefore, some experts recommend that these drugs should also be avoided in patients receiving pitavastatin.

Itraconazole

Concomitant use of pitavastatin (4 mg as a single dose) and itraconazole (200 mg once daily for 5 days) decreased pitavastatin peak plasma concentration and AUC by 22 and 23%, respectively.

Niacin

Concomitant use of pitavastatin and antilipemic dosages (1 g daily or higher) of niacin increases the risk of myopathy. Data from several large randomized studies indicate that concomitant use of niacin (1.5-2 g daily) with another statin (i.e., simvastatin 40-80 mg once daily, with or without ezetimibe) resulted in an increased risk of severe adverse effects, including disturbances in glycemic control requiring hospitalization, development of diabetes mellitus, adverse GI effects, myopathy, gout, rash, skin ulceration, infection, and bleeding.

If pitavastatin is used concomitantly with antilipemic dosages of niacin, caution is advised, and reduction in pitavastatin dosage should be considered.

Rifampin

Rifampin substantially increases pitavastatin exposure. Following concomitant use of pitavastatin (4 mg once daily) and rifampin (600 mg once daily for 5 days), pitavastatin peak plasma concentration and AUC were increased by twofold and 29%, respectively, and rifampin peak plasma concentration and AUC were decreased by 18 and 15%, respectively. The increase in pitavastatin concentrations probably resulted partly from inhibition of OATP1B1-mediated hepatic uptake of pitavastatin. If used concomitantly with rifampin, dosage of pitavastatin should not exceed 2 mg once daily.

Warfarin

Pitavastatin had no clinically important pharmacokinetic interaction with R- and S-warfarin. Following concomitant use of pitavastatin (4 mg once daily for 9 days) and an individualized maintenance dosage of warfarin sodium (2-7 mg for 8 days), R-warfarin peak plasma concentration and AUC increased by 3 and 7%, respectively, and S-warfarin peak plasma concentration and AUC increased by 3 and 6%, respectively. In addition, pitavastatin (4 mg once daily) had no clinically important effect on prothrombin time (PT) and international normalized ratio (INR) in patients receiving long-term warfarin therapy; however, the manufacturer and some experts recommend close monitoring of PT and INR after pitavastatin is initiated and whenever there is a change in the statin dosage in patients receiving warfarin.

Write Your Own Review

Your meds on autopilot. Forever.