Pitavastatin is a member of the HMG-CoA reductase inhibitor ('statin') class of lipid-lowering drugs with moderately potent LDL-lowering effects. It is used to lower cholesterol and triglycerides in adults with primary hyperlipidemia and adults and pediatric patients 8 years and older with heterozygous familial hypercholesterolemia (HeFH). In patients with primary hypercholesterolemia, doses of 1 mg, 2 mg, and 4 mg PO daily reduce LDL-cholesterol by 32%, 36%, and 43%, respectively; doses of 1 to 4 mg/day lower triglycerides by 15% to 19%. Similar to other statins, pitavastatin produces modest increases in HDL (5% to 8%). Clinical trials have been conducted in adult patients to compare pitavastatin with atorvastatin and simvastatin in patients with hypercholesterolemia, dyslipidemia, type 2 diabetes, and acute coronary syndrome (ACS). When compared to atorvastatin and simvastatin, pitavastatin was shown to be noninferior to either agent for reduction of LDL-C in patients with primary hyperlipidemia or mixed dyslipidemia, but when compared to equivalent doses of pravastatin, pitavastatin therapy resulted in a significantly greater reduction in LDL-C in patients with primary hyperlipidemia or mixed dyslipidemia. In a 12-week comparative trial with atorvastatin, pitavastatin did not reach the noninferiority objective for the treatment of patients with type 2 diabetes and combined dyslipidemia. Treatment with pitavastatin 4 mg/day has been shown to be as effective as atorvastatin 20 mg/day in patients with ACS for the regression of atherosclerosis. In a 12-week double-blind study (n = 82) in pediatric patients with HeFH, pitavastatin significantly reduced plasma LDL-C, non-HDL-C, total cholesterol, and Apo-B compared to placebo. The reductions were dose dependent.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Oral Administration
-Administer once daily without regard to food at the same time each day.
Hypersensitivity reactions, including angioedema, rash, pruritus, and urticaria, have been reported with pitavastatin. Lichen planus-like eruption has been reported during postmarketing surveillance of pitavastatin.
Constipation (1.5% to 3.6%) and diarrhea (1.5% to 2.6%) were reported during clinical trials for pitavastatin. Abdominal pain or discomfort, dyspepsia, and nausea have been reported with postmarketing use.
Back pain (1.4% to 3.9%), myalgia (1.9% to 3.1%), and extremity pain (0.6% to 2.3%) were reported during clinical trials for pitavastatin. Arthralgia was also reported; muscle cramps/spasms have been reported with postmarketing use. Myalgia and elevations in creatinine phosphokinase (CPK) were the most common adverse reactions that led to discontinuation of therapy.
Influenza and naso-pharyngitis were reported during pitavastatin clinical trials without frequency. Interstitial lung disease has been reported with postmarketing use.
Pitavastatin may cause myopathy (muscle pain, tenderness, or weakness with increases in creatine phosphokinase [CPK] values above 10 times the upper limit of normal [ULN]) and rhabdomyolysis. Acute kidney injury or renal failure secondary to myoglobinuria and rare fatalities have occurred as a result of rhabdomyolysis in patients treated with statins, including pitavastatin. Muscle symptoms and elevations in CPK may resolve with drug discontinuation. Instruct patients to promptly report any unexplained muscle pain, tenderness, or weakness, especially if accompanied by malaise or fever. Discontinue pitavastatin if markedly elevated CPK concentrations occur or if myopathy is diagnosed or suspected.
Immune-mediated necrotizing myopathy (IMNM), an autoimmune myopathy, has occurred rarely (1 to 3 of every 100,000 patients) with HMG-CoA reductase inhibitors, such as pitavastatin. Recurrence of IMNM has been reported following administration of the same or a different statin. IMNM is characterized by myalgia with symmetrical and proximal muscle weakness and elevated serum creatine phosphokinase, which persist despite discontinuation of HMG-CoA reductase inhibitor treatment. Some cases have occurred months to years after starting HMG-CoA reductase therapy and the myopathy progressed following therapy discontinuation. Other characteristics include positive anti-HMG-CoA reductase antibody, muscle biopsy showing necrotizing myopathy, and improvement with immunosuppressive agents. Dysphagia and respiratory failure have also been reported in patients with IMNM. Reported serum creatine phosphokinase levels have ranged from 576 to 35,000 International Units/L. Patients who develop IMNM may require additional neuromuscular and serologic testing. If IMNM develops, HMG-CoA reductase inhibitor therapy should be discontinued and treatment with immunosuppressants, such as high dose corticosteroids, intravenous immune globulin (IVIG), or other immunosuppressive agents, may be needed.
Elevated hepatic enzymes (transaminases, alkaline phosphatase, bilirubin) have been reported with pitavastatin use. In most cases, elevations appeared soon after initiation, were transient, were not associated with symptoms, and either resolved or improved with continued therapy or after a brief interruption of therapy. There have been rare postmarketing reports of fatal and non-fatal hepatic failure in patients taking statins, including pitavastatin. Hepatitis and jaundice have also been reported with postmarketing use of pitavastatin. Assess liver enzymes prior to treatment initiation and repeat as clinically indicated if signs or symptoms of hepatic injury occur. Promptly discontinue pitavastatin if hepatic injury with clinical symptoms, hyperbilirubinemia, or jaundice occur.
Peripheral neuropathy and hypoesthesia have been reported during postmarketing use of pitavastatin in adult patients. In a nested case-control study of a Danish population, the odds ratio for idiopathic peripheral neuropathy in 166 adult patients that ever or were currently taking a statin, was 3.7 (95% CI 1.8 to 7.6); similar results have been found in other population based studies, although the number of patients studied was significantly smaller. Case reports and series indicate that the onset of neuropathy is typically more than 1 year after drug initiation and is reversible with drug discontinuation. However, cases describing irreversible neuropathy are also reported. The adverse effect appears to be a class effect because, in all cases, when a patient is either rechallenged or treated with a different statin, the symptoms of neuropathy return. While the data appear to support an association between HMG-CoA reductase inhibitors and peripheral neuropathy, the incidence is rare and estimated to be approximately 1 per 14,000 person-years. Furthermore, a causal relationship cannot be definitively established based on the observational nature of the available data.
Increased hemoglobin A1C and fasting serum glucose (hyperglycemia) have been reported with statin use. A meta-analysis of 13 statin trials with 91,140 participants showed a 9% increase in the likelihood of the development of diabetes (OR 1.09; 95% CI 1.02 to 1.17). The incidence of diabetes was higher in high-risk patients (i.e., age 70 to 82 years with or at high risk of cardiovascular disease, myocardial infarction within the last 6 months, or heart failure) compared to patients with low diabetes risk (i.e., low BMI). Additionally, an analysis of the data from the Women's Health Initiative (WHI) trial found that statin use in postmenopausal women is associated with an increased risk of new-onset diabetes mellitus (multivariate-adjusted HR 1.48; 95% CI 1.38 to 1.59). No difference in the risk for diabetes between statins was detected in either analysis. Because the use of statins has been associated with significant benefits for cardiovascular risk reduction and all-cause mortality at comparable rates in diabetic and non-diabetic patients, no changes to clinical practice guidelines have been recommended in either population. However, the increased risk of diabetes should be considered when initiating pitavastatin therapy in patients at low risk for cardiovascular events and in patient groups where the cardiovascular benefit of statin therapy has not been established.
Headache was reported during pitavastatin clinical trials. Insomnia, depression, asthenia, fatigue, malaise, and dizziness have been reported with postmarketing use. Rare cases of cognitive impairment (e.g., memory loss, forgetfulness, amnesia, memory impairment, confusion) have been associated with statin use in adult patients. Cognitive impairment is generally nonserious and reversible upon drug discontinuation. Time to symptom onset (1 day to years) and resolution (median 3 weeks) is variable. There appears to be no association between the event and a specific statin, statin dose, concomitant medication, or age of the patient. In general, reports describe patients over the age of 50 years who experienced notable, but ill-defined memory loss or impairment that is reversible upon statin discontinuation. The cases do not appear to be associated with progressive or fixed dementia.
HMG-CoA reductase inhibitors, such as pitavastatin, inhibit the synthesis of mevalonate and decrease Co-Enzyme Q-10 concentrations, which may lead to Co-Enzyme Q-10 deficiency. Supplementation with Co-Enzyme Q-10 may limit potential adverse reactions.
Impotence (erectile dysfunction) has been reported with postmarketing use of pitavastatin.
Statin therapy, including pitavastatin, has been associated with rare reports of new-onset or exacerbation of myasthenia gravis (including ocular myasthenia) and reports of recurrence when the same or different statin was administered. In a review of adult patients enrolled at a neuromuscular disease clinic over a 4-year time period, 6 of 54 myasthenia gravis patients (11%) receiving statin therapy experienced worsening myasthenia gravis. In a disproportionality analysis of the World Health Organization's VigiBase pharmacovigilance database, 169 of 3,967 (4.2%) of adverse reactions with the term 'myasthenia gravis and related conditions' were related to statin therapy. The reporting odds ratio (ROR) of myasthenia gravis relative to all other adverse reactions was 2.66 [95% CI: 2.28, 3.1] for statin therapy. In addition, the ROR was greater than 1 and statistically significant for all individual statins except lovastatin. The onset of symptoms following initiation of statin therapy has ranged from 1 week to 4 months for exacerbation and 6 months to 6 years for induction of myasthenia gravis. Partial or complete recovery has been reported following discontinuation of statin therapy; however, some patients have required treatment with pyridostigmine or immunosuppressive agents. Though this appears to be a rare adverse reaction, clinicians should closely monitor patients with myasthenia gravis for disease exacerbation and encourage them to report any muscle-related symptoms.
Pitavastatin is contraindicated in patients with acute hepatic failure or decompensated cirrhosis (hepatic decompensation). Increases in hepatic transaminases have been reported with pitavastatin. In most cases, increases in hepatic transaminases occurred soon after initiation, were transient, were not associated with symptoms, and resolved or improved on continued therapy or after temporary discontinuation of therapy. There have been rare postmarketing reports of fatal and non-fatal hepatic failure in patients taking statins, including pitavastatin. Patients with alcoholism or those who consume substantial quantities of alcohol and/or have a history of hepatic disease (i.e., hepatitis) may be at increased risk for hepatic injury. Assess liver enzymes prior to treatment initiation and repeat as clinically indicated if signs or symptoms of hepatic injury occur. Promptly discontinue pitavastatin if hepatic injury with clinical symptoms, hyperbilirubinemia, or jaundice occurs.
Pitavastatin may cause myopathy (muscle pain, tenderness, or weakness associated with elevated creatine kinase above 10 times the upper limit of normal) and rhabdomyolysis. Acute renal failure secondary to myoglobinuria and rare fatalities have occurred as a result of rhabdomyolysis in patients treated with statins, including pitavastatin. Discontinue pitavastatin if markedly elevated creatinine phosphokinase (CPK) concentrations occur or if myopathy is diagnosed or suspected. Temporarily discontinue pitavastatin in patients experiencing an acute or serious condition putting them at increased risk of developing renal failure secondary to rhabdomyolysis (e.g., sepsis, shock, uncontrolled seizure disorder, severe hypovolemia, major surgery, trauma, severe metabolic disorders, severe endocrine disorder, or severe electrolyte imbalance). Risk factors for myopathy and/or rhabdomyolysis include severe endocrine disease, uncontrolled hypothyroidism, severe metabolic disorders, severe electrolyte imbalance, renal disease, hypotension, acute infection including sepsis, shock, severe hypovolemia, major surgery, trauma, uncontrolled seizure disorder, concomitant use of certain drugs, and higher statin dosage. In premarketing clinical studies, pitavastatin doses greater than 4 mg once daily were associated with an increased risk of severe myopathy. Monitor all patients with renal impairment for development of myopathy as these patients are at high risk due to drug accumulation; dosage adjustments of pitavastatin are recommended in patients with moderate to severe impairment and those with renal failure receiving dialysis. Inform patients of the increased risk of myopathy and rhabdomyolysis when starting or increasing the dosage of pitavastatin. Instruct patients to promptly report unexplained muscle pain, tenderness or weakness, especially if accompanied by malaise or fever.
Immune-mediated necrotizing myopathy (IMNM), an autoimmune myopathy, has occurred rarely (1 to 3 of every 100,000 patients) with HMG-CoA reductase inhibitors, such as pitavastatin. Recurrence of IMNM has been reported following administration of the same or a different statin. IMNM is characterized by myalgia with symmetrical and proximal muscle weakness and elevated serum creatine phosphokinase, which persist despite discontinuation of HMG-CoA reductase inhibitor treatment. Some cases have occurred months to years after starting HMG-CoA reductase therapy and the myopathy progressed following therapy discontinuation. Other characteristics include positive anti-HMG-CoA reductase antibody, muscle biopsy showing necrotizing myopathy, and improvement with immunosuppressive agents. Dysphagia and respiratory failure have also been reported in patients with IMNM. Reported serum creatine phosphokinase levels have ranged from 576 to 35,000 International Units/L. Patients who develop IMNM may require additional neuromuscular and serologic testing. If IMNM develops, HMG-CoA reductase inhibitor therapy should be discontinued and treatment with immunosuppressants, such as high dose corticosteroids, intravenous immune globulin (IVIG), or other immunosuppressive agents, may be needed.
If pitavastatin is initiated in a patient with diabetes, increased monitoring of blood glucose control may be warranted. Increased hemoglobin A1C, hyperglycemia, and worsening glycemic control have been reported during therapy with HMG-CoA reductase inhibitors. Because the use of statins has been associated with significant benefit for cardiovascular risk reduction and all-cause mortality at comparable rates in diabetic and non-diabetic patients, no changes to clinical practice guidelines have been recommended in either population. However, the increased risk of diabetes mellitus should be considered when initiating pitavastatin therapy in patients at low risk for cardiovascular events and in patient groups where the cardiovascular benefit of statin therapy has not been established. Although an analysis of participants from the JUPITER trial found an increased incidence of developing diabetes in patients allocated to rosuvastatin compared to placebo (270 reports of diabetes vs. 216 in the placebo group; HR 1.25, 95% CI 1.05 to 1.49, p = 0.01), the cardiovascular and mortality benefits of statin therapy exceeded the diabetes hazard even in patients at high risk for developing diabetes (i.e., patients with one or more major diabetes risk factor: metabolic syndrome, impaired fasting glucose, BMI 30 kg/m2 or more, or A1C greater than 6%). In patients at high risk for developing diabetes, treatment with rosuvastatin was associated with a 39% reduction in the primary endpoint (composite of non-fatal myocardial infarction, non-fatal stroke, unstable angina or revascularization, and cardiovascular death) (HR 0.61, 95% CI 0.47 to 0.79, p = 0.0001), nonsignificant reductions in venous thromboembolism (VTE) (HR 0.64, CI 0.39 to 1.06, p = 0.08) and total mortality (HR 0.83, CI 0.64 to 1.07, p = 0.15), and a 28% increase in diabetes (HR 1.28, CI 1.07 to 1.54, p = 0.01). In patients with no major diabetes risk factor, treatment with rosuvastatin was associated with a 52% reduction in the primary endpoint (HR 0.48, 95% CI 0.33 to 0.68, p = 0.0001), nonsignificant reductions in VTE (HR 0.47, CI 0.21 to 1.03, p = 0.05) and total mortality (HR 0.78, CI 0.59 to 1.03, p = 0.08), and no increase in diabetes (HR 0.99, CI 0.45 to 2.21, p = 0.99). For those at high risk for developing diabetes, 134 total cardiovascular events or deaths were avoided for every 54 new cases of diabetes diagnosed. In those without major risk factors, 86 total cardiovascular events or deaths were avoided with no excess new cases of diabetes diagnosed.
Pitavastatin therapy should be discontinued once pregnancy is identified in most patients. Alternatively, consider the ongoing therapeutic needs of the individual patient, particularly those at very high risk for cardiovascular events during pregnancy, such as those with homozygous familial hypercholesterolemia or with established cardiovascular disease. Based on the mechanism of action, pitavastatin may cause fetal harm when administered to pregnant patients due to decreases in the synthesis of cholesterol and possibly other biologically active substances derived from cholesterol. Cholesterol and other products of the cholesterol biosynthesis pathway are essential components for fetal development, including synthesis of steroids and cell membranes. The U.S. Food and Drug Administration (FDA) completed a review of data from case series, prospective and retrospective observational cohort studies over decades of statin use in pregnant patients and concluded that these studies have not identified a drug-associated risk of major congenital malformations associated with statin use during pregnancy. In a Medicaid cohort linkage study of 1,152 statin-exposed pregnant women, no significant teratogenic effects were observed following maternal statin use during the first trimester of pregnancy after adjusting for potential confounders (i.e., maternal age, diabetes mellitus, hypertension, obesity, alcohol use, and tobacco use); the relative risk (RR) of congenital malformations was 1.07 (95% confidence interval (CI), 0.85 to 1.37). In addition, after accounting for confounders, there were no statistically significant increases in organ-specific malformations. In the study, statin treatment was started prior to pregnancy and was discontinued within the first trimester after pregnancy was detected in a majority of patients. In another cohort study of 469 patients who were dispensed statins during pregnancy, it was determined that there was no increase in congenital anomalies after adjustment for maternal age and comorbidities; however, statin use was associated with an increased risk of preterm labor (RR, 1.99 [95% CI, 1.46 to 2.71]) and low birth weight (RR, 1.51 [95% CI, 1.05 to 2.16]). In a published, retrospective cohort study of 281 statin-exposed pregnant women, patients on statin therapy had a miscarriage rate of 25% compared to 21% for pregnant women not on statin therapy (n = 2,643); adjusted hazard ratio was 1.64 (95% CI, 1.1 to 2.46). The FDA also re-reviewed non-clinical, animal data statin development programs and concluded that statins have a limited potential to cause malformations or embryofetal lethality, and limited potential to affect nervous system development during embryofetal development during the pre- and post-natal period. No teratogenic effects were observed in pregnant rats and rabbits at doses up to 20 times and 4 times, respectively, the maximum recommended human dose (MRHD). Maternal toxicity, such as reduced body weight, abortion, mortality, and impaired lactation, was observed at pitavastatin 1 time and 4 times the MRHD in pregnant rats and rabbits, respectively. Overall, available data have not identified a drug-associated risk of major congenital malformations, but published data are insufficient to determine if there is a drug-associated risk of miscarriage. Temporary discontinuation of lipid-lowering therapy, such as pitavastatin, should have minimal impact on the long-term therapy of primary hyperlipidemia, as atherosclerosis is a chronic process. Advise pregnant patients and patients of child-bearing potential of the potential risk of statin therapy to the fetus and the importance of informing their health care provider of known or suspected pregnancy.
Safe and effective use of pitavastatin in infants and children younger than 8 years with heterozygous familial hypercholesterolemia (HeFH) or in pediatric patients with other types of hyperlipidemia has not been established. Because cholesterol plays a crucial role in growth and development, the clinical implications of using pharmacologic therapy to alter the normal production of cholesterol in young children is not clear. Because of these potential safety concerns and lack of safety data, most experts generally recommend delaying cholesterol-lowering medications until the child is at least 8 to 10 years old. In some cases of severe familial hypercholesterolemia, however, HMG-CoA reductase inhibitors have been used in younger children with careful monitoring of growth and development.
Pitavastatin is not recommended for use during breast-feeding. There is no information about the presence of pitavastatin in human or animal milk, the effects of the drug on the breastfed infant, or the effects of the drug on milk production. Cholesterol and other products of the cholesterol biosynthesis pathway are essential components for infant growth and development, including synthesis of steroids and cell membranes. HMG-CoA reductase inhibitors decrease the synthesis of cholesterol and possibly other products of the cholesterol biosynthesis pathway. Based on the mechanism of action of pitavastatin, there is potential for development of serious adverse reactions in a breastfed infant. Advise patients that breastfeeding is not recommended during treatment with pitavastatin. If pharmacotherapy for hypercholesterolemia is necessary in the nursing mother, an alternative agent such as a nonabsorbable resin (cholestyramine, colesevelam, or colestipol) may be considered. These agents do not enter the bloodstream and will not be excreted during lactation. However, resins bind fat-soluble vitamins and prolonged use may result in deficiencies of these vitamins in the mother and her nursing infant.
Advanced age (65 years of age or more) is a risk factor for myopathy and rhabdomyolysis due to statins; therefore use pitavastatin with caution in geriatric adults. Monitor geriatric patients receiving pitavastatin for the increased risk of myopathy. During clinical trials, no overall differences in safety or efficacy have been observed between older and younger adult patients receiving pitavastatin. Some older adults may be more sensitive to the effects of the usual adult dosage of pitavastatin due to a higher frequency of decreased hepatic, renal, or cardiac function, concomitant disease, or other drug therapy; individualize dosage to achieve serum lipoprotein goals.
Pitavastatin may cause fetal harm when administered to a pregnant woman. Contraception requirements are advised; females of child-bearing potential should be counseled regarding appropriate methods of contraception while receiving pitavastatin.
Use pitavastatin with caution in persons with myasthenia gravis. Closely monitor for myasthenia gravis exacerbation and encourage reporting of any muscle-related symptoms. Exacerbation of myasthenia gravis, including ocular myasthenia gravis, has been reported during treatment with statins, including pitavastatin. Reports of recurrence have been noted when the same or a different statin was administered. The onset of symptom exacerbation following initiation of statin therapy has ranged from 1 week to 4 months. Partial or complete recovery has been reported following discontinuation of statin therapy; however, some patients have required treatment with pyridostigmine or immunosuppressive agents.
General dosing information:
-Pitavastatin 1 to 4 mg once daily is considered to be a moderate-intensity statin (expected to lower low-density lipoprotein cholesterol (LDL-C) by 30% to 49%).
-Choice of moderate-intensity statin therapy is dependent on patient age, baseline LDL-C, ASCVD risk factors, and concomitant diseases. High-intensity therapy provides greatest LDL-C reductions and is associated with a significantly greater reduction in ASCVD events vs. moderate-intensity therapy.
-Monitor lipid concentrations at 4 to 12 weeks after initiation or dose adjustment, and then every 3 to 12 months as necessary.
For general dosing information in persons requiring moderate-intensity statin therapy:
Oral dosage:
Adults: 1 to 4 mg PO once daily.
For the treatment of primary hyperlipidemia, including hypercholesterolemia, as an adjunct to dietary control:
Oral dosage:
Adults: 2 to 4 mg PO once daily. Individualize dose based on patient characteristics, goals of therapy, and response. Analyze lipid concentrations 4 weeks after initiation or dosage titration and adjust dose as necessary. Maximum is 4 mg/day. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. Patients who are taking 4 mg and are unable to achieve desired LDL reduction should be switched to an alternative agent.
For the treatment of heterozygous familial hypercholesterolemia (HeFH) as an adjunct to dietary control:
Oral dosage:
Adults: 2 to 4 mg PO once daily. Individualize dose based on patient characteristics, goals of therapy, and response. Analyze lipid concentrations 4 weeks after initiation or dosage titration and adjust dose as necessary. Maximum is 4 mg/day. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. Patients who are taking 4 mg and are unable to achieve desired LDL reduction should be switched to an alternative agent.
Children and Adolescents 8 to 17 years: 2 to 4 mg PO once daily. Individualize dose based on patient characteristics, goals of therapy, and response. Analyze lipid concentrations 4 weeks after initiation or dosage titration and adjust dose as necessary. Maximum is 4 mg/day. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. Patients who are taking 4 mg and are unable to achieve desired LDL reduction should be switched to an alternative agent.
For the regression of coronary atherosclerosis in patients with acute coronary syndrome (ACS)*:
Oral dosage:
Adults: 4 mg PO once daily resulted in significant regression of non-culprit coronary plaque volume (PV) in patients with acute coronary syndrome (ACS). In a prospective, open-label, parallel group study with blind endpoint evaluation, patients with ACS were randomized within 72 hours after percutaneous coronary intervention (PCI) to pitavastatin 4 mg/day or atorvastatin 20 mg/day to determine the effect on PV. After 8 to 12 months of therapy, coronary PV was significantly reduced in both groups (pitavastatin: -16.9 +/- 13.9%, p less than 0.001 compared to baseline; atorvastatin: -18.1 +/- 14.2%, p less than 0.001 compared to baseline) with associated negative vessel remodeling. Percent PV and normalized PV were also significantly reduced in both groups. There was no significant difference in treatment effect between the 2 drugs. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.
Maximum Dosage Limits:
-Adults
4 mg/day PO.
-Geriatric
4 mg/day PO.
-Adolescents
4 mg/day PO.
-Children
8 to 12 years: 4 mg/day PO.
1 to 7 years: Safety and efficacy have not been established.
-Infants
Safety and efficacy have not been established.
Patients with Hepatic Impairment Dosing
Contraindicated in patients with active hepatic disease including unexplained persistent elevations of hepatic transaminase concentrations.
Patients with Renal Impairment Dosing
eGFR 60 mL/minute or more: No dosage adjustment is required.
eGFR 15 to 59 mL/minute/1.73 m2: 1 mg PO once daily initially; do not exceed 2 mg/day.
eGFR less than 15 mL/minute/1.73 m2: Specific guidelines are not available.
Intermittent hemodialysis
1 mg PO once daily initially; do not exceed 2 mg/day.
*non-FDA-approved indication
Abiraterone: (Moderate) Use abiraterone and pitavastatin together cautiously. Monitor closely for symptoms of pitavastatin toxicity such as myopathy (muscle pain or weakness). Patients should be instructed to report any complaints of muscle pain, tenderness, or weakness to their health care professional immediately. Pitavastatin is marginally metabolized by CYP2C9 and to a lesser extent by CYP2C8; it is possible that abiraterone, a weak CYP2C8 inhibitor, could increase pitavasstatin concentrations.
Abrocitinib: (Moderate) Monitor for an increase in pitavastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with abrocitinib is necessary. Concomitant use may increase pitavastatin exposure. Pitavastatin is a P-gp substrate; abrocitinib is a P-gp inhibitor.
Adagrasib: (Moderate) Monitor for an increase in pitavastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with adagrasib is necessary. Concomitant use may increase pitavastatin exposure. Pitavastatin is a P-gp substrate; adagrasib is a P-gp inhibitor.
Amiodarone: (Moderate) Monitor for an increase in pitavastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with amiodarone is necessary. Concomitant use may increase pitavastatin exposure. Pitavastatin is a P-gp substrate; amiodarone is a P-gp inhibitor.
Aprepitant, Fosaprepitant: (Minor) Use caution if pitavastatin and aprepitant are used concurrently and monitor for a possible decrease in the efficacy of pitavastatin. After administration, fosaprepitant is rapidly converted to aprepitant and shares the same drug interactions. Pitavastatin is a CYP2C9 substrate and aprepitant is a CYP2C9 inducer. Administration of a CYP2C9 substrate, tolbutamide, on days 1, 4, 8, and 15 with a 3-day regimen of oral aprepitant (125 mg/80 mg/80 mg) decreased the tolbutamide AUC by 23% on day 4, 28% on day 8, and 15% on day 15. The AUC of tolbutamide was decreased by 8% on day 2, 16% on day 4, 15% on day 8, and 10% on day 15 when given prior to oral administration of aprepitant 40 mg on day 1, and on days 2, 4, 8, and 15. The effects of aprepitant on tolbutamide were not considered significant. When a 3-day regimen of aprepitant (125 mg/80 mg/80 mg) given to healthy patients on stabilized chronic warfarin therapy (another CYP2C9 substrate), a 34% decrease in S-warfarin trough concentrations was noted, accompanied by a 14% decrease in the INR at five days after completion of aprepitant.
Asciminib: (Moderate) Monitor for an increase in pitavastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with asciminib is necessary. Concomitant use may increase pitavastatin exposure. Pitavastatin is an OATP1B1 substrate; asciminib is an OATP1B1 inhibitor.
Atazanavir; Cobicistat: (Major) The plasma concentrations of pitavastatin may be elevated when administered concurrently with cobicistat. Clinical monitoring for adverse effects, such as rhabdomyolysis or GI effects, is recommended during coadministration. Cobicistat is a organic anion transporting polypeptide (OATP) inhibitor, while pitavastatin is a OATP1B1 substrate.
Bortezomib: (Minor) Monitor patients for the development of peripheral neuropathy when receiving bortezomib in combination with other drugs that can cause peripheral neuropathy like HMG-CoA reductase inhibitors; the risk of peripheral neuropathy may be additive.
Cannabidiol: (Moderate) Monitor for an increase in pitavastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with cannabidiol is necessary. Concomitant use may increase pitavastatin exposure. Pitavastatin is a P-gp substrate; cannabidiol is a P-gp inhibitor.
Capmatinib: (Moderate) Monitor for an increase in pitavastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with capmatinib is necessary. Concomitant use may increase pitavastatin exposure. Pitavastatin is a P-gp substrate; capmatinib is a P-gp inhibitor.
Cimetidine: (Moderate) Use HMG-CoA reductase inhibitors with caution with concomitant drugs that may decrease the levels or activity of endogenous steroids, such as cimetidine. Evaluate patients with signs and symptoms of endocrine dysfunction appropriately. HMG-CoA reductase inhibitors interfere with cholesterol synthesis and theoretically might blunt adrenal and/or gonadal steroid production.
Clofarabine: (Moderate) Concomitant use of clofarabine, a substrate of OAT1 and OAT3, and pitavastatin, a substrate of OAT protein (OATP), may result in altered clofarabine levels. Therefore, monitor for signs of clofarabine toxicity such as gastrointestinal toxicity (e.g., nausea, vomiting, diarrhea, mucosal inflammation), hematologic toxicity, and skin toxicity (e.g., hand and foot syndrome, rash, pruritus) in patients also receiving OATP substrates.
Cobicistat: (Major) The plasma concentrations of pitavastatin may be elevated when administered concurrently with cobicistat. Clinical monitoring for adverse effects, such as rhabdomyolysis or GI effects, is recommended during coadministration. Cobicistat is a organic anion transporting polypeptide (OATP) inhibitor, while pitavastatin is a OATP1B1 substrate.
Colchicine: (Moderate) Concomitant use of colchicine and HMG-CoA reductase inhibitors (statins) may increase the risk for myopathy and rhabdomyolysis. If concomitant use is necessary, monitor for signs and symptoms of muscle pain, tenderness, or weakness especially following therapy initiation and upward dose titration. The use of low dose colchicine may further reduce the risk for myopathy.
Cyclosporine: (Contraindicated) Coadministration of pitavastatin and cyclosporine is contraindicated due to significantly increased pitavastatin exposure and risk for myopathy or rhabdomyolysis. In a drug interaction study, concurrent use of cyclosporine increased the pitavastatin Cmax and AUC by 6.6- and 4.6-fold, respectively.
Daclatasvir: (Moderate) Caution and close monitoring is advised if daclatasvir is administered with HMG-CoA reductase inhibitors (Statins). Use of these drugs together may result in elevated Statin serum concentrations, potentially resulting in adverse effects such as myopathy and rhabdomyolysis.
Daptomycin: (Major) Temporarily suspend HMG-CoA reductase inhibitors in patients taking daptomycin as cases of rhabdomyolysis have been reported with concomitant use. Both agents can cause myopathy and rhabdomyolysis when given alone and the risk may be increased when given together.
Daridorexant: (Moderate) Monitor for an increase in pitavastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with daridorexant is necessary. Concomitant use may increase pitavastatin exposure. Pitavastatin is a P-gp substrate; daridorexant is a P-gp inhibitor.
Darolutamide: (Moderate) Monitor for an increase in pitavastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with darolutamide is necessary. Concomitant use may increase pitavastatin exposure. Pitavastatin is an OATP1B1 substrate; darolutamide is an OATP1B1 inhibitor.
Darunavir; Cobicistat: (Major) The plasma concentrations of pitavastatin may be elevated when administered concurrently with cobicistat. Clinical monitoring for adverse effects, such as rhabdomyolysis or GI effects, is recommended during coadministration. Cobicistat is a organic anion transporting polypeptide (OATP) inhibitor, while pitavastatin is a OATP1B1 substrate.
Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Major) The plasma concentrations of pitavastatin may be elevated when administered concurrently with cobicistat. Clinical monitoring for adverse effects, such as rhabdomyolysis or GI effects, is recommended during coadministration. Cobicistat is a organic anion transporting polypeptide (OATP) inhibitor, while pitavastatin is a OATP1B1 substrate.
Elacestrant: (Moderate) Monitor for an increase in pitavastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with elacestrant is necessary. Concomitant use may increase pitavastatin exposure. Pitavastatin is a P-gp substrate; elacestrant is a P-gp inhibitor.
Elexacaftor; tezacaftor; ivacaftor: (Moderate) Monitor for an increase in pitavastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with elexacaftor is necessary. Concomitant use may increase pitavastatin exposure. Pitavastatin is an OATP1B1 substrate; elexacaftor is an OATP1B1 inhibitor.
Eltrombopag: (Moderate) Use caution and monitor for adverse reactions if eltrombopag and pitavastatin are coadministered. Eltrombopag is an inhibitor of the transporter OATP1B1. Drugs that are substrates for this transporter, such as pitavastatin, may exhibit an increase in systemic exposure if coadministered with eltrombopag.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Major) The plasma concentrations of pitavastatin may be elevated when administered concurrently with cobicistat. Clinical monitoring for adverse effects, such as rhabdomyolysis or GI effects, is recommended during coadministration. Cobicistat is a organic anion transporting polypeptide (OATP) inhibitor, while pitavastatin is a OATP1B1 substrate.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) The plasma concentrations of pitavastatin may be elevated when administered concurrently with cobicistat. Clinical monitoring for adverse effects, such as rhabdomyolysis or GI effects, is recommended during coadministration. Cobicistat is a organic anion transporting polypeptide (OATP) inhibitor, while pitavastatin is a OATP1B1 substrate.
Enasidenib: (Moderate) Monitor for an increase in pitavastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with enasidenib is necessary. Concomitant use may increase pitavastatin exposure. Pitavastatin is a P-gp and OATP1B1 substrate; enasidenib is a P-gp and OATP1B1 inhibitor.
Encorafenib: (Moderate) Monitor for an increase in pitavastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with encorafenib is necessary. Concomitant use may increase pitavastatin exposure. Pitavastatin is an OATP1B1 substrate; encorafenib is an OATP1B1 inhibitor.
Erdafitinib: (Moderate) Monitor for an increase in pitavastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with erdafitinib is necessary. Concomitant use may increase pitavastatin exposure. Pitavastatin is a P-gp substrate; erdafitinib is a P-gp inhibitor.
Erythromycin: (Major) Do not exceed a daily dose of 1 mg PO for pitavastatin if used concomitantly with erythromycin due to increased pitavastatin exposure and risk for myopathy or rhabdomyolysis. When coadministered with erythromycin 500 mg 4 times daily for 6 days, the pitavastatin AUC increased by 2.8-fold and the Cmax increased by 3.6-fold.
Everolimus: (Major) Guidelines recommend avoiding coadministration of pitavastatin with everolimus due to the potential for increased risk of myopathy/rhabdomyolysis. Consider use of an alternative statin such as atorvastatin, fluvastatin, pravastatin, or rosuvastatin with dose limitations in patients receiving everolimus.
Fenofibrate: (Moderate) Clinical practice guidelines state the concurrent use of fenofibrate and pitavastatin is reasonable and preferred over gemfibrozil if statin/fibrate combination therapy is indicated. However, because combination therapy increases the risk of myopathy, caution is advised.
Fenofibric Acid: (Moderate) Clinical practice guidelines state the concurrent use of fenofibric acid and pitavastatin is reasonable and preferred over gemfibrozil if statin/fibrate combination therapy is indicated. However, because combination therapy increases the risk of myopathy, caution is advised.
Fostemsavir: (Moderate) Use the lowest possible starting dose for pitavastatin when administered concurrently with fostemsavir and monitor for signs of pitavastatin-associated adverse events, such as rhabdomyolysis. Use of these drugs together may increase the systemic exposure of pitavastatin. Pitavastatin is a substrate for the transporters OATP1B1/3 and fostemsavir is an inhibitor of OATP1B1/3.
Futibatinib: (Moderate) Monitor for an increase in pitavastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with futibatinib is necessary. Concomitant use may increase pitavastatin exposure. Pitavastatin is a P-gp substrate; futibatinib is a P-gp inhibitor.
Gemfibrozil: (Major) Although FDA approved labeling recommends avoiding coadministration of pitavastatin and gemfibrozil, clinical practice guidelines state the concurrent use of gemfibrozil and pitavastatin is acceptable to use if clinically indicated and fenofibrate or fenofibric acid is not an option. Initiate pitavastatin at a reduced dosage of 1 mg/day not to exceed 2 mg/day if coadministered with gemfibrozil. The risk of myopathy/rhabdomyolysis increases when HMG-CoA reductase inhibitors are administered concurrently with gemfibrozil. The serious risk of myopathy or rhabdomyolysis should be weighed carefully against the benefits of combined statin and gemfibrozil therapy; there is no assurance that periodic monitoring of CK will prevent the occurrence of severe myopathy and renal damage.
Gilteritinib: (Moderate) Monitor for an increase in pitavastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with gilteritinib is necessary. Concomitant use may increase pitavastatin exposure. Pitavastatin is a P-gp substrate; gilteritinib is a P-gp inhibitor.
Glecaprevir; Pibrentasvir: (Major) Use the lowest approved pitavastatin dose (i.e., 1 mg PO once daily) when coadministered with glecaprevir due to an increased risk of myopathy, including rhabdomyolysis. If a higher dose is necessary, use the lowest necessary dose based on a risk/benefit assessment. Coadministration may increase the plasma concentrations of pitavastatin. Pitavastatin is a substrate of the drug transporters OATP1B1 and OATP1B3. Glecaprevir is an inhibitor of these transporters. (Major) Use the lowest approved pitavastatin dose (i.e., 1 mg PO once daily) when coadministered with pibrentasvir due to an increased risk of myopathy, including rhabdomyolysis. If a higher dose is necessary, use the lowest necessary dose based on a risk/benefit assessment. Coadministration may increase the plasma concentrations of pitavastatin. Pitavastatin is a substrate of the drug transporters OATP1B1 and OATP1B3; pibrentasvir is an inhibitor of these transporters.
Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Major) Do not exceed a daily dose of 2 mg PO for pitavastatin if used concomitantly with rifampin due to increased pitavastatin exposure and risk for myopathy or rhabdomyolysis. When coadministered with rifampin 600 mg daily for 5 days, the pitavastatin AUC increased by 29% and the Cmax increased by 2-fold.
Isoniazid, INH; Rifampin: (Major) Do not exceed a daily dose of 2 mg PO for pitavastatin if used concomitantly with rifampin due to increased pitavastatin exposure and risk for myopathy or rhabdomyolysis. When coadministered with rifampin 600 mg daily for 5 days, the pitavastatin AUC increased by 29% and the Cmax increased by 2-fold.
Lanthanum Carbonate: (Major) To limit absorption problems, HMG-CoA reductase inhibitors ("statins") should not be taken within 2 hours of dosing with lanthanum carbonate. Oral drugs known to interact with cationic antacids, like statin cholesterol treatments, may also be bound by lanthanum carbonate. Separate the times of administration appropriately. Monitor the patient's lipid profile to ensure the appropriate response to statin therapy is obtained.
Lasmiditan: (Moderate) Monitor for an increase in pitavastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with lasmiditan is necessary. Concomitant use may increase pitavastatin exposure. Pitavastatin is a P-gp substrate; lasmiditan is a P-gp inhibitor.
Leflunomide: (Major) Consider reducing the dose of HMG-CoA reductase inhibitors ("Statins" including atorvastatin, fluvastatin, lovastatin, pitavastatin, pravastatin, rosuvastatin, or simvastatin) during use of leflunomide and monitor patients closely for signs and symptoms of myopathy. For a patient taking leflunomide, the dose of rosuvastatin should not exceed 10 mg once daily. Patients should be advised to report promptly unexplained muscle pain, tenderness, or weakness, particularly if accompanied by malaise or fever. Following oral administration, leflunomide is metabolized to an active metabolite, teriflunomide, which is responsible for essentially all of leflunomide's in vivo activity. Teriflunomide is an inhibitor of the organic anion transporting polypeptide OATP1B1, and some statins are substrates for the OATP transporters. Teriflunomide may increase the exposure (AUC) of these statins. Increased concentrations of the statins increases the risk for myopathy and other statin-related side effects.
Leniolisib: (Moderate) Monitor for an increase in pitavastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with leniolisib is necessary. Concomitant use may increase pitavastatin exposure. Pitavastatin is an OATP1B1 substrate; leniolisib is an OATP1B1 inhibitor.
Letermovir: (Major) Use of pitavastatin with letermovir is not recommended due to increased pitavastatin exposure. Concurrent use is contraindicated if the patient is also receiving cyclosporine. Administering letermovir with pitavastatin significantly increases pitavastatin concentration and risk for myopathy or rhabdomyolysis. The magnitude of this interaction may be increased in patients who are also receiving cyclosporine. Pitavastatin is a substrate of the organic anion-transporting polypeptides 1B1 and 1B3 (OATP1B1/3). Both letermovir and cyclosporine are inhibitors of OATP1B1; letermovir is also an OATP1B3 inhibitor.
Maralixibat: (Minor) Maralixibat may reduce the oral absorption of HMG-CoA reductase inhibitors, also known as statins, which may reduce their efficacy. This risk is greatest with maralixibat doses greater than 4.75 mg. Monitor statin therapy and adjust the dose as needed based on clinical response. Maralixibat is a OATP2B1 inhibitor and statins are OATP2B1 substrates.
Maribavir: (Moderate) Monitor for an increase in pitavastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with maribavir is necessary. Concomitant use may increase pitavastatin exposure. Pitavastatin is a P-gp substrate; maribavir is a P-gp inhibitor.
Midostaurin: (Moderate) Monitor for an increase in pitavastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with midostaurin is necessary. Concomitant use may increase pitavastatin exposure. Pitavastatin is an OATP1B1 substrate; midostaurin is an OATP1B1 inhibitor.
Mitapivat: (Moderate) Monitor for an increase in pitavastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with mitapivat is necessary. Concomitant use may increase pitavastatin exposure. Pitavastatin is a P-gp substrate; mitapivat is a P-gp inhibitor.
Nanoparticle Albumin-Bound Sirolimus: (Major) Guidelines recommend avoiding coadministration of pitavastatin with sirolimus due to the potential for increased risk of myopathy/rhabdomyolysis. Consider use of an alternative statin such as atorvastatin, fluvastatin, pravastatin, or rosuvastatin with dose limitations in patients receiving sirolimus.
Neratinib: (Moderate) Monitor for an increase in pitavastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with neratinib is necessary. Concomitant use may increase pitavastatin exposure. Pitavastatin is a P-glycoprotein (P-gp) substrate; neratinib is a P-gp inhibitor.
Niacin, Niacinamide: (Major) There is no clear indication for routine use of niacin in combination with pitavastatin. The addition of niacin to a statin has not been shown to reduce cardiovascular morbidity or mortality. In addition, lipid-modifying doses (1 g/day or more) of niacin increase the risk of myopathy and rhabdomyolysis when combined with pitavastatin. If coadministered, consider lower starting and maintenance does of pitavastatin. Monitor patients closely for myopathy or rhabdomyolysis, particularly in the early months of treatment or after upward dose titration of either drug. Consider monitoring serum creatinine phosphokinase (CPK) and potassium periodically in such situations. Discontinue pitavastatin immediately if myopathy is diagnosed or suspected.
Niraparib; Abiraterone: (Moderate) Use abiraterone and pitavastatin together cautiously. Monitor closely for symptoms of pitavastatin toxicity such as myopathy (muscle pain or weakness). Patients should be instructed to report any complaints of muscle pain, tenderness, or weakness to their health care professional immediately. Pitavastatin is marginally metabolized by CYP2C9 and to a lesser extent by CYP2C8; it is possible that abiraterone, a weak CYP2C8 inhibitor, could increase pitavasstatin concentrations.
Oritavancin: (Moderate) Pitavastatin is metabolized by CYP2C9; oritavancin is a weak CYP2C9 inhibitor. Coadministration may result in elevated pitavastatin plasma concentrations. If these drugs are administered concurrently, monitor patients for signs of pitavastatin toxicity, such as muscle aches, muscle pain or tenderness, general weakness or fatigue, side or back pain, or decreased urination.
Pacritinib: (Moderate) Monitor for an increase in pitavastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with pacritinib is necessary. Concomitant use may increase pitavastatin exposure. Pitavastatin is a P-gp substrate; pacritinib is a P-gp inhibitor.
Pirtobrutinib: (Moderate) Monitor for an increase in pitavastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with pirtobrutinib is necessary. Concomitant use may increase pitavastatin exposure. Pitavastatin is a P-gp substrate; pirtobrutinib is a P-gp inhibitor.
Pretomanid: (Moderate) Monitor for an increase in pitavastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with pretomanid is necessary. Concomitant use may increase pitavastatin exposure. Pitavastatin is a P-gp substrate; pretomanid is a P-gp inhibitor.
Probenecid; Colchicine: (Moderate) Concomitant use of colchicine and HMG-CoA reductase inhibitors (statins) may increase the risk for myopathy and rhabdomyolysis. If concomitant use is necessary, monitor for signs and symptoms of muscle pain, tenderness, or weakness especially following therapy initiation and upward dose titration. The use of low dose colchicine may further reduce the risk for myopathy.
Raltegravir: (Moderate) Raltegravir use has been associated with elevated creatinine kinase concentrations; myopathy and rhabdomyolysis have been reported. Use raltegravir cautiously with drugs that increase the risk of myopathy or rhabdomyolysis such as HMG-CoA reductase inhibitors (Statins).
Red Yeast Rice: (Contraindicated) Since compounds in red yeast rice claim to have HMG-CoA reductase inhibitor activity, red yeast rice should not be used in combination with HMG-CoA reductase inhibitors. The administration of more than one HMG-CoA reductase inhibitor at one time would be duplicative therapy and perhaps increase the risk of drug-related toxicity including myopathy and rhabdomyolysis.
Rifampin: (Major) Do not exceed a daily dose of 2 mg PO for pitavastatin if used concomitantly with rifampin due to increased pitavastatin exposure and risk for myopathy or rhabdomyolysis. When coadministered with rifampin 600 mg daily for 5 days, the pitavastatin AUC increased by 29% and the Cmax increased by 2-fold.
Selpercatinib: (Moderate) Monitor for an increase in pitavastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with selpercatinib is necessary. Concomitant use may increase pitavastatin exposure. Pitavastatin is a P-gp substrate; selpercatinib is a P-gp inhibitor.
Sirolimus: (Major) Guidelines recommend avoiding coadministration of pitavastatin with sirolimus due to the potential for increased risk of myopathy/rhabdomyolysis. Consider use of an alternative statin such as atorvastatin, fluvastatin, pravastatin, or rosuvastatin with dose limitations in patients receiving sirolimus.
Sodium Phenylbutyrate; Taurursodiol: (Moderate) Monitor for an increase in pitavastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with taurursodiol is necessary. Concomitant use may increase pitavastatin exposure. Pitavastatin is a P-gp substrate; taurursodiol is a P-gp inhibitor.
Sofosbuvir; Velpatasvir; Voxilaprevir: (Major) Avoid concurrent administration of pitavastatin and voxilaprevir. Taking these drugs together is expected to increase pitavastatin plasma concentrations; thereby increasing the risk for side effects such as myopathy and rhabdomyolysis. Pitavastatin is a substrate of the Organic Anion Transporting Polypeptides 1B1/1B3 (OATP1B1/1B3). Voxilaprevir is an OATP1B1/1B3 inhibitor.
Sotorasib: (Moderate) Monitor for an increase in pitavastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with sotorasib is necessary. Concomitant use may increase pitavastatin exposure. Pitavastatin is a P-gp substrate; sotorasib is a P-gp inhibitor.
Sparsentan: (Moderate) Monitor for an increase in pitavastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with sparsentan is necessary. Concomitant use may increase pitavastatin exposure. Pitavastatin is a P-gp substrate; sparsentan is a P-gp inhibitor.
Sulfacetamide; Sulfur: (Moderate) HMG-CoA reductase inhibitors have been administered safely with niacin (nicotinic acid) in some patients; however the risk of potential myopathy should be considered. Rare cases of rhabdomyolysis have been reported in patients taking niacin (nicotinic acid) in lipid-altering doses (i.e., >=1 g/day) and HMG-CoA reductase inhibitors (Statins) concurrently. The serious risk of myopathy or rhabdomyolysis should be carefully weighed against the potential risks. Patients undergoing combined therapy should be carefully monitored for myopathy or rhabdomyolysis, particularly in the early months of treatment or during periods of upward dose titration of either drug. Chinese patients receiving concomitant lipid-altering doses of niacin-containing products should not receive the 80 mg dose of simvastatin due to increased risk of myopathy.
Tacrolimus: (Major) Guidelines recommend avoiding coadministration of pitavastatin with tacrolimus due to the potential for increased risk of myopathy/rhabdomyolysis. Consider use of an alternative statin such as atorvastatin, fluvastatin, pravastatin, or rosuvastatin with dose limitations in patients receiving tacrolimus.
Tepotinib: (Moderate) Monitor for an increase in pitavastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with tepotinib is necessary. Concomitant use may increase pitavastatin exposure. Pitavastatin is a P-gp substrate; tepotinib is a P-gp inhibitor.
Teriflunomide: (Major) Consider reducing the dose of HMG-CoA reductase inhibitors ("Statins" including atorvastatin, fluvastatin, lovastatin, pitavastatin, pravastatin, rosuvastatin, or simvastatin) during use of teriflunomide and monitor patients closely for signs and symptoms of myopathy. For a patient taking teriflunomide, the dose of rosuvastatin should not exceed 10 mg once daily. Patients should be advised to report promptly unexplained muscle pain, tenderness, or weakness, particularly if accompanied by malaise or fever. Teriflunomide is an inhibitor of the organic anion transporting polypeptide OATP1B1, and some statins are substrates for the OATP transporters. Teriflunomide may increase the exposure (AUC) of these statins. Increased concentrations of the statins increases the risk for myopathy and other statin-related side effects.
Trofinetide: (Moderate) Monitor for an increase in pitavastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with trofinetide is necessary. Concomitant use may increase pitavastatin exposure. Pitavastatin is an OATP1B1 substrate; trofinetide is an OATP1B1 inhibitor.
Vitamin B Complex Supplements: (Major) There is no clear indication for routine use of niacin in combination with pitavastatin. The addition of niacin to a statin has not been shown to reduce cardiovascular morbidity or mortality. In addition, lipid-modifying doses (1 g/day or more) of niacin increase the risk of myopathy and rhabdomyolysis when combined with pitavastatin. If coadministered, consider lower starting and maintenance does of pitavastatin. Monitor patients closely for myopathy or rhabdomyolysis, particularly in the early months of treatment or after upward dose titration of either drug. Consider monitoring serum creatinine phosphokinase (CPK) and potassium periodically in such situations. Discontinue pitavastatin immediately if myopathy is diagnosed or suspected.
Voclosporin: (Moderate) Monitor for an increase in pitavastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with voclosporin is necessary. Concomitant use may increase pitavastatin exposure. Pitavastatin is a P-gp and OATP1B1 substrate; voclosporin is a P-gp and OATP1B1 inhibitor.
Warfarin: (Minor) Although no clinically significant interaction has been demonstrated with warfarin and pitavastatin, the manufacturer of pitavastatin recommends patients receiving warfarin have their PT and INR monitored when pitavastatin is added to therapy.
Pitavastatin competitively inhibits hydroxymethylglutaryl-CoA (HMG-CoA) reductase, an enzyme necessary for the intracellular synthesis of cholesterol. HMG-CoA reductase is the rate-limiting hepatic enzyme responsible for converting HMG-CoA to mevalonate, a precursor of sterols including cholesterol. Inhibition of HMG-CoA reductase lowers the amount of mevalonate and subsequently reduces cholesterol levels in hepatic cells. This, in turn, results in upregulation of LDL-receptors and increased hepatic uptake of LDL-cholesterol from the circulation. Additionally, VLDL is decreased due to the sustained inhibition of cholesterol synthesis in the liver.
HMG-CoA reductase inhibitors have also been reported to decrease endogenous CoQ10 serum concentrations; the clinical significance of these effects is unknown.
Pitavastatin is administered orally. It is more than 99% protein bound, with a mean Vd of approximately 148 L and minimal penetration into red blood cells. There is only marginal metabolism by CYP2C9 and, to a lesser extent, CYP2C8. The major metabolite is the lactone, which is formed via an ester-type pitavastatin glucuronide conjugate by uridine 5'-diphosphate (UDP) glucuronosyltransferase (UGT1A3 and UGT2B7). Approximately 15% of an orally administered dose is excreted in the urine, whereas 79% is excreted in the feces within 7 days. The mean plasma elimination half-life is approximately 12 hours.
Affected cytochrome P450 isoenzymes and drug transporters: CYP2C9, CYP2C8, UGT1A3, UGT2B7, OATP1B1
Pitavastatin undergoes minimal hepatic metabolism and is expected to have less potential for drug interactions than 'statins' metabolized by CYP450 isoenzymes. Pitavastatin is marginally metabolized by CYP2C9 and, to a lesser extent, CYP2C8. The lactone metabolite is formed via an ester-type pitavastatin glucuronide conjugate by uridine 5'-diphosphate (UDP) glucuronosyltransferase (UGT1A3 and UGT2B7). Pitavastatin is taken up into human hepatocytes mainly by organic anion transporting polypeptide (OATP)1B1.
-Route-Specific Pharmacokinetics
Oral Route
Peak plasma concentrations are achieved approximately 1 hour after oral administration. Extent of absorption increases in proportion to the dose of pitavastatin. Absolute bioavailability of the oral solution is 51%. Administration with a high fat meal decreases Cmax by 43% but does not significantly reduce AUC. Plasma concentrations do not differ with evening or morning administration, although the percent change from baseline for LDL-C after evening dosing is slightly greater than that after morning dosing.
-Special Populations
Hepatic Impairment
Cmax and AUC were 2.7- and 3.8-fold higher, respectively, in patients with moderate (Child-Pugh B) hepatic impairment compared to healthy volunteers during pharmacokinetic trials. In patients with mild (Child-Pugh A) hepatic impairment, Cmax and AUC were 30% and 60% higher. Mean half-life was 15 and 10 hours for those with moderate and mild impairment, respectively, compared to 8 hours for healthy volunteers.
Renal Impairment
AUC was 102% and 86% higher in adult patients with moderate renal impairment (eGFR 30 to 59 mL/minute/1.73m2) and end stage renal disease receiving hemodialysis, respectively, compared to healthy patients during pharmacokinetic studies; Cmax was 60% and 40% higher. Hemodialysis patients had 33% and 36% increases in the mean unbound fraction of pitavastatin as compared to healthy volunteers and those with moderate renal impairment, respectively. In adult patients with severe renal impairment (eGFR 15 to 29 mL/minute/1.73 m2) not receiving hemodialysis, AUC and Cmax were 36% and 18% higher, respectively, compared with those of healthy volunteers. For both patients with severe renal impairment and healthy volunteers, the mean percentage of protein-unbound pitavastatin was approximately 0.6%.
Pediatrics
In pediatric patients 8 to 16 years treated with pitavastatin 1 mg, 2 mg, and 4 mg once daily in a 12-week study (n = 82), a dose-dependent increase in pitavastatin plasma concentrations at trough (for 2 mg and 4 mg doses) and 1 hour post dose was observed.
Geriatric
Cmax and AUC were 10% and 30% higher, respectively, in geriatric patients compared to younger adult patients during pharmacokinetic trials.
Gender Differences
Cmax and AUC were 60% and 54% higher, respectively, in females compared to male subjects during pharmacokinetic trials.
Ethnic Differences
Cmax and AUC were 21% and 5% lower, respectively, in healthy Black or African American subjects compared to healthy Caucasian subjects during pharmacokinetic trials.