Pitavastatin
pitavastatin calcium · Tablet, Film Coated · Oral
Uses
Pitavastatin tablets are indicated as an adjunct to diet to reduce low-density lipoprotein cholesterol (LDL-C) in: Adults with primary hyperlipidemia. Adults and pediatric patients aged 8 years and older with heterozygous familial hypercholesterolemia (HeFH). Pitavastatin tablets is a HMG-CoA reductase inhibitor (statin) indicated as an adjunct to diet to reduce low-density lipoprotein cholesterol (LDL-C) in: ( 1 ) Adults with primary hyperlipidemia Adults and pediatric patients aged 8 years and older with heterozygous familial hypercholesterolemia (HeFH)
Dosage and administration
Take orally once daily with or without food at the same time each day. ( 2.1 ) For patients requiring a high-intensity statin or are unable to achieve their LDL-C goal receiving pitavastatin tablets 4 mg daily, prescribe alternative LDL-C-lowering treatment. ( 2.1 ) Assess LDL-C when clinically appropriate, as early as 4 weeks after initiation of pitavastatin tablets and adjust the dosage if necessary. ( 2.1 ) Recommended dosage is 2 mg to 4 mg once daily. Maximum recommended dosage is 4 mg once daily ( 2.2 ) Recommended starting dosage for patients with moderate and severe renal impairment and end-stage renal disease on hemodialysis is 1 mg once daily. Maximum recommended dosage is 2 mg once daily. ( 2.3 ) See full prescribing information for pitavastatin tablets dosage modifications due to drug interactions. ( 2.4 ) 2.1 Important Dosage and Administration Information Take pitavastatin tablets orally once daily with or without food at the same time each day. For patients that require a high-intensity statin or are unable to achieve their LDL-C goal receiving pitavastatin tablets 4 mg daily, prescribe alternative LDL-C-lowering treatment. Assess LDL-C when clinically appropriate, as early as 4 weeks after initiating pitavastatin tablets, and adjust the dosage if necessary. 2.2 Recommended Dosage for Adults and Pediatric Patients Aged 8 Years and Older The recommended dosage range of pitavastatin tablets is 2 mg to 4 mg daily. The maximum recommended dosage is pitavastatin tablets 4 mg once daily. 2.3 Recommended Dosage in Patients with Renal Impairment The recommended starting dosage for patients with moderate and severe renal impairment (estimated glomerular filtration rate 30 to 59 mL/minute/1.73 m 2 and 15 to 29 mL/minute/1.73 m 2 , respectively) and patients with end-stage renal disease receiving hemodialysis is pitavastatin tablets 1 mg once daily. The maximum recommended dose for these patients is pitavastatin tablets 2 mg once daily [see Use in Specific Populations (8.5) ] . There are no dosage adjustment recommendations for patients with mild renal impairment. 2.4 Pitavastatin Tablets Dosage Adjustments Due to Drug Interactions In patients taking erythromycin, do not exceed pitavastatin tablets 1 mg once daily [see Drug Interactions (7) ] . In patients taking rifampin, do not exceed pitavastatin tablets 2 mg once daily [see Drug Interactions (7) ] .
Dosage forms and strengths
Pitavastatin tablets are supplied as: 1 mg: Round, white to off-white, film-coated tablet, debossed with "P1" on one side. 2 mg: Round, white to off-white, film-coated tablet, debossed with "P2" on one side. 4 mg: Round, white to off-white, film-coated tablet, debossed with "P4" on one side. Tablets: 1 mg, 2 mg, and 4 mg ( 3 )
Contraindications
Pitavastatin tablets is contraindicated in the following conditions: Concomitant use of cyclosporine [see Drug Interactions (7) ] . Acute liver failure or decompensated cirrhosis [see Warnings and Precautions (5.3) ] . Hypersensitivity to pitavastatin or any excipients in pitavastatin tablets. Hypersensitivity reactions including angioedema, rash, pruritus, and urticaria have been reported with pitavastatin tablets [see Adverse Reactions (6) ] . Cyclosporine ( 4 , 7 ) Active liver failure or decompensated cirrhosis ( 4 , 5.3 ) Hypersensitivity to pitavastatin or any excipients in pitavastatin tablets ( 4 )
Warnings and precautions
Myopathy and Rhabdomyolysis: Risk factors include age 65 or greater, uncontrolled hypothyroidism, renal impairment, concomitant use with certain other drugs, and higher pitavastatin tablets dosage. Discontinue pitavastatin tablets if markedly elevated CK levels occur or myopathy is diagnosed or suspected. Temporarily discontinue pitavastatin tablets in patients experiencing an acute or serious condition at high risk of developing renal failure secondary to rhabdomyolysis. Inform patients of the risk of myopathy and rhabdomyolysis when starting or increasing the pitavastatin tablets dosage. Instruct patients to promptly report unexplained muscle pain, tenderness or weakness particularly if accompanied by malaise or fever. ( 5.1 , 7 , 8.5 , 8.6 ) Immune-Mediated Necrotizing Myopathy (IMNM): Rare reports of IMNM, an autoimmune myopathy, have been reported. Discontinue pitavastatin if IMNM is suspected. ( 5.2 ) Hepatic Dysfunction : Increases in serum transaminases have occurred, some persistent. Rare reports of fatal and non-fatal hepatic failure have occurred. Consider testing liver enzymes before initiating therapy and as clinically indicated thereafter. If serious hepatic injury with clinical symptoms and/or hyperbilirubinemia or jaundice occurs, promptly discontinue pitavastatin tablets. ( 5.3 ) 5.1 Myopathy and Rhabdomyolysis Pitavastatin tablets may cause myopathy (muscle pain, tenderness, or weakness associated with elevated creatine kinase [CK]) and rhabdomyolysis. Acute kidney injury secondary to myoglobinuria and rare fatalities have occurred as a result of rhabdomyolysis in patients treated with statins, including pitavastatin tablets. Risk Factors for Myopathy Risk factors for myopathy include age 65 years or greater, uncontrolled hypothyroidism, renal impairment, concomitant use of certain drugs (including other lipid-lowering therapies), and higher pitavastatin tablets dosage [see Dosage and Administration (2.2) , Drug Interactions (7) and Use in Specific Populations (8.5 , 8.6) ] . Dosages of pitavastatin tablets greater than 4 mg once daily were associated with an increased risk for severe myopathy in premarketing clinical studies. The maximum recommended dose of pitavastatin tablets is 4 mg once daily. Steps to Prevent or Reduce the Risk of Myopathy and Rhabdomyolysis Pitavastatin tablets is contraindicated in patients taking cyclosporine and not recommended in patients taking gemfibrozil [see Contraindications (4) and Drug Interactions (7) ] . There are pitavastatin tablets dosage restrictions for patients taking erythromycin or rifampin [see Dosage and Administration (2.4) ] . The following drugs when used concomitantly with pitavastatin tablets may also increase the risk of myopathy and rhabdomyolysis: lipid-modifying dosages of niacin (>1 grams/day), fibrates, and colchicine [see Drug Interactions (7) ] . Discontinue pitavastatin tablets if markedly elevated CK levels occur or if myopathy is either diagnosed or suspected. Muscle symptoms and CK elevations may resolve if pitavastatin tablets is discontinued. Temporarily discontinue pitavastatin tablets in patients experiencing an acute or serious condition at high risk of developing renal failure secondary to rhabdomyolysis (e.g., sepsis; shock; severe hypovolemia; major surgery; trauma; severe metabolic, endocrine, or electrolyte disorders; or uncontrolled epilepsy). Inform patients of the risk of myopathy and rhabdomyolysis when starting or increasing the pitavastatin tablets dosage. Instruct patients to promptly report any unexplained muscle pain, tenderness or weakness, particularly if accompanied by malaise or fever. 5.2 Immune-Mediated Necrotizing Myopathy There have been rare reports of immune-mediated necrotizing myopathy (IMNM), an autoimmune myopathy, associated with statin use, including reports of recurrence when the same or a different statin was administered. IMNM is characterized by proximal muscle weakness and elevated serum creatine kinase that persist despite discontinuation of statin treatment; positive anti-HMG CoA reductase antibody; muscle biopsy showing necrotizing myopathy; and improvement with immunosuppressive agents. Additional neuromuscular and serologic testing may be necessary. Treatment with immunosuppressive agents may be required. Discontinue pitavastatin tablets if IMNM is suspected. 5.3 Hepatic Dysfunction Increases in serum transaminases have been reported with pitavastatin tablets [see Adverse Reactions (6) ] . In most cases, these changes appeared soon after initiation, were transient, were not accompanied by symptoms, and resolved or improved on continued therapy or after a brief interruption in therapy. There have been rare postmarketing reports of fatal and non-fatal hepatic failure in patients taking statins, including pitavastatin. Patients who consume substantial quantities of alcohol and/or have a history of liver disease may be at increased risk for hepatic injury. Consider liver enzyme testing before the initiation of pitavastatin tablets and when clinically indicated thereafter. Pitavastatin tablets is contraindicated in patients with acute liver failure or decompensated cirrhosis [see Contraindications (4) ] . If serious hepatic injury with clinical symptoms and/or hyperbilirubinemia or jaundice occurs, promptly discontinue pitavastatin tablets. 5.4 Increases in HbA1c and Fasting Serum Glucose Levels Increases in HbA1c and fasting serum glucose levels have been reported with statins, including pitavastatin tablets. Optimize lifestyle measures, including regular exercise, maintaining a healthy body weight, and making healthy food choices.
Side effects
The following serious adverse reactions are discussed in other sections of the labeling: Myopathy and Rhabdomyolysis [see Warnings and Precautions (5.1) ] Immune-Mediated Necrotizing Myopathy [see Warning and Precautions (5.2) ] Hepatic Dysfunction [see Warning and Precautions (5.3) ] Increases in HbA1c and Fasting Serum Glucose Levels [see Warning and Precautions (5.4) ] . The most frequent adverse reactions (rate ≥ 2%) were myalgia, constipation, diarrhea, back pain, and pain in extremity. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Upsher-Smith Laboratories, LLC at 1-855-899-9180 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Studies Experience Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of one drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in practice. Adverse Reactions in Adults with Primary Hyperlipidemia In 10 controlled clinical studies and 4 subsequent open-label extension studies, 3,291 adult patients with primary hyperlipidemia were administered pitavastatin tablets 1 mg to 4 mg daily. The mean continuous exposure of pitavastatin (1 mg to 4 mg) was 36.7 weeks (median 51.1 weeks). The mean age of the patients was 60.9 years (range; 18 years to 89 years) and 52% were females. Approximately 93% of the patients were White, 7% were Asian/Indian, 0.2% were African American and 0.3% were Hispanic and other. In controlled clinical studies and their open-label extensions, 3.9% (1 mg), 3.3% (2 mg), and 3.7% (4 mg) of pitavastatin-treated patients were discontinued due to adverse reactions. The most common adverse reactions that led to treatment discontinuation were: elevated creatine phosphokinase (0.6% on 4 mg) and myalgia (0.5% on 4 mg). Adverse reactions reported in ≥ 2% of patients in controlled clinical studies and at a rate greater than or equal to placebo are shown in Table 1. These studies had treatment duration of up to 12 weeks. Table 1. Adverse Reactions (≥ 2% and ≥ placebo) in Adults with Primary Hyperlipidemia in Studies up to 12 Weeks Adverse Reactions Placebo (n=208) % Pitavastatin tablets 1 mg (n=309) % Pitavastatin tablets 2 mg (n=951) % Pitavastatin tablets 4 mg (n=1,540) % Myalgia 1.4 1.9 2.8 3.1 Constipation 1.9 3.6 1.5 2.2 Diarrhea 1.9 2.6 1.5 1.9 Back pain 2.9 3.9 1.8 1.4 Pain in extremity 1.9 2.3 0.6 0.9 Other adverse reactions reported from clinical studies were arthralgia, headache, influenza, and nasopharyngitis. Hypersensitivity reactions including rash, pruritus, and urticaria have been reported with pitavastatin tablets. The following laboratory abnormalities have been reported: elevated creatine phosphokinase, transaminases, alkaline phosphatase, bilirubin, and glucose. Adverse Reactions in Adult HIV-Infected Patients with Dyslipidemia In a double-blind, randomized, controlled, 52-week trial, 252 HIV-infected patients with dyslipidemia were treated with either pitavastatin tablets 4 mg once daily (n=126) or another statin (n=126). All patients were taking antiretroviral therapy (excluding darunavir) and had HIV-1 RNA less than 200 copies/mL and CD4 count greater than 200 cell/μL for at least 3 months prior to randomization. The safety profile of pitavastatin tablets was generally consistent with that observed in the clinical trials described above. One patient (0.8%) treated with pitavastatin tablets had a peak creatine phosphokinase value exceeding 10 times the upper limit of normal (ULN), which resolved spontaneously. Four patients (3%) treated with pitavastatin tablets had at least one ALT value exceeding 3 times but less than 5 times the ULN, none of which led to drug discontinuation. Virologic failure was reported for four patients (3%) treated with pitavastatin tablets, defined as a confirmed measurement of HIV-1 RNA exceeding 200 copies/mL that was also more than a 2-fold increase from baseline. Adverse Reactions in Pediatric Patients Aged 8 Years and Older with HeFH In a 12-week, double-blind, placebo-controlled trial of pitavastatin tablets 1 mg, 2 mg, and 4 mg once daily in 82 pediatric patients 8 years to 16 years of age with HeFH and a 52-week open-label trial in 85 pediatric patients with HeFH, the safety profile was similar to that observed in the adult population. 6.2 Postmarketing Experience The following adverse reactions have been identified during postapproval use of pitavastatin tablets. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Gastrointestinal disorders: abdominal discomfort, abdominal pain, dyspepsia, nausea General disorders: asthenia, fatigue, malaise, dizziness Hepatobiliary disorders: hepatitis, jaundice, fatal and non-fatal hepatic failure Immune system disorders: angioedema, immune-mediated necrotizing myopathy associated with statin use Metabolism and nutrition disorders: increases in HbA1c, fasting serum glucose levels Musculoskeletal and connective tissue disorders: muscle spasms, myopathy, rhabdomyolysis Nervous system disorders: hypoesthesia, peripheral neuropathy. There have been rare reports of new onset or exacerbation of myasthenia gravis, including ocular myasthenia, and reports of recurrence when the same or a different statin was administered. Rare reports of cognitive impairment (e.g., memory loss, forgetfulness, amnesia, memory impairment, confusion) associated with statin use. Cognitive impairment was generally nonserious, and reversible upon statin discontinuation, with variable times to symptom onset (1 day to years) and symptom resolution (median of 3 weeks). Psychiatric disorders: insomnia, depression.
Drug interactions
Table 2 includes a list of drugs that increase the risk of myopathy and rhabdomyolysis when administered concomitantly with pitavastatin and instructions for preventing or managing drug interactions [see Warnings and Precautions (5.1) , Clinical Pharmacology (12.3) ] . Table 2. Drug Interactions that Increase the Risk of Myopathy and Rhabdomyolysis with Pitavastatin Tablets Cyclosporine Clinical Impact: Cyclosporine significantly increases pitavastatin exposure and increases the risk of myopathy and rhabdomyolysis . Intervention: Concomitant use of cyclosporine with pitavastatin is contraindicated [see Contraindications (4) ] . Gemfibrozil Clinical Impact: Gemfibrozil may cause myopathy when given alone. The risk of myopathy and rhabdomyolysis is increased with concomitant use of gemfibrozil with statins, including pitavastatin. Intervention: Avoid concomitant use of gemfibrozil with pitavastatin. Erythromycin Clinical Impact: Erythromycin significantly increases pitavastatin exposure and increases the risk of myopathy and rhabdomyolysis . Intervention: In patients taking erythromycin, do not exceed pitavastatin tablets 1 mg once daily [see Dosage and Administration (2.4) ] . Rifampin Clinical Impact: Rifampin significantly increases peak pitavastatin exposure and increases the risk of myopathy and rhabdomyolysis . Intervention: In patients taking rifampin, do not exceed pitavastatin tablets 2 mg once daily [see Dosage and Administration (2.4) ] . Fibrates Clinical Impact: Fibrates may cause myopathy when given alone. The risk of myopathy and rhabdomyolysis is increased with concomitant use of fibrates with statins, including pitavastatin. Intervention: Consider if the benefit of using fibrates concomitantly with pitavastatin outweighs the increased risk of myopathy and rhabdomyolysis. Niacin Clinical Impact: The risk of myopathy and rhabdomyolysis may be increased with concomitant use of lipid-modifying doses (≥1 g/day) of niacin with pitavastatin. Intervention: Consider if the benefit of using lipid-modifying doses (>1 g/day) of niacin concomitantly with pitavastatin outweighs the increased risk of myopathy and rhabdomyolysis. Colchicine Clinical Impact: Cases of myopathy and rhabdomyolysis have been reported with concomitant use of colchicine with statins, including pitavastatin. Intervention: Consider the risk/benefit of concomitant use of colchicine with pitavastatin. See full prescribing information for details regarding concomitant use of pitavastatin tablets with other drugs that increase the risk of myopathy and rhabdomyolysis. ( 2.4 , 7 )
Use in specific populations
Pregnancy: May cause fetal harm. ( 8.1 ) Lactation: Breastfeeding not recommended during treatment with pitavastatin tablets. ( 8.2 ) 8.1 Pregnancy Risk Summary Discontinue pitavastatin tablets when pregnancy is recognized. Alternatively, consider the ongoing therapeutic needs of the individual patient. Pitavastatin decreases synthesis of cholesterol and possibly other biologically active substances derived from cholesterol; therefore, pitavastatin tablets may cause fetal harm when administered to pregnant patients based on the mechanism of action [see Clinical Pharmacology (12.1) ] . In addition, treatment of hyperlipidemia is not generally necessary during pregnancy. Atherosclerosis is a chronic process and the discontinuation of lipid-lowering drugs during pregnancy should have little impact on the outcome of long-term therapy of primary hyperlipidemia for most patients. Available data from case series and prospective and retrospective observational cohort studies over decades of use with statins in pregnant women have not identified a drug-associated risk of major congenital malformations. Published data from prospective and retrospective observational cohort studies with statin use in pregnant women are insufficient to determine if there is a drug associated risk of miscarriage [see Data ] . In animal reproduction studies, no embryo-fetal toxicity or congenital malformations were observed in pregnant rats and rabbits orally administered pitavastatin during the period of organogenesis at doses which were 22 and 4 times, respectively, the human exposure at the maximum recommended human dosage (MRHD) of 4 mg, based on AUC [see Data ] . The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. Adverse outcomes in pregnancy occur regardless of the health of the mother or the use of medications. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Human Data A Medicaid cohort linkage study of 1,152 statin-exposed pregnant women compared to 886,996 controls did not find a significant teratogenic effect from maternal use of statins in the first trimester of pregnancy, after adjusting for potential confounders – including maternal age, diabetes mellitus, hypertension, obesity, and alcohol and tobacco use – using propensity score-based methods. The relative risk of congenital malformations between the group with statin use and the group with no statin use in the first trimester was 1.07 (95% confidence interval 0.85 to 1.37) after controlling for confounders, particularly pre-existing diabetes mellitus. There were also no statistically significant increases in any of the organ-specific malformations assessed after accounting for confounders. In the majority of pregnancies, statin treatment was initiated prior to pregnancy and was discontinued at some point in the first trimester when pregnancy was identified. Study limitations include reliance on physician coding to define the presence of a malformation, lack of control for certain confounders such as body mass index, use of prescription dispensing as verification for the use of a statin, and lack of information on non-live births. Animal Data Embryo-fetal developmental studies were conducted in pregnant rats administered 3, 10, 30 mg/kg/day pitavastatin by oral gavage during organogenesis (gestation days 7 to 17). No adverse effects were observed at 3 mg/kg/day, systemic exposures 22 times human systemic exposure at 4 mg/day based on AUC. Embryo-fetal developmental studies were conducted in pregnant rabbits administered 0.1, 0.3, 1 mg/kg/day pitavastatin by oral gavage during the period of fetal organogenesis (gestation days 6 to 18). Maternal toxicity consisting of reduced body weight and abortion was observed at all doses tested (4 times human systemic exposure at 4 mg/day based on AUC). In perinatal/postnatal studies in pregnant rats given oral gavage doses of pitavastatin at 0.1, 0.3, 1, 3, 10, 30 mg/kg/day from organogenesis through weaning (gestation day 17 to lactation day 21), maternal toxicity consisting of mortality at ≥0.3 mg/kg/day and impaired lactation at all doses contributed to the decreased survival of neonates in all dose groups (0.1 mg/kg/day represents approximately 1 time human systemic exposure at 4 mg/day dose based on AUC). Reproductive toxicity studies have shown that pitavastatin crosses the placenta in rats and is found in fetal tissues at ≤36% of maternal plasma concentrations following a single dose of 1 mg/kg/day during gestation (at the end of organogenesis). 8.2 Lactation Risk Summary There is no available 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. However, it has been shown that another drug in this class passes into human milk. Statins, including pitavastatin, decrease cholesterol synthesis and possibly the synthesis of other biologically active substances derived from cholesterol and may cause harm to the breastfed infant. Because of the potential for serious adverse reactions in a breastfed infant, based upon the mechanism of action, advise patients that breastfeeding is not recommended during treatment with pitavastatin. [see Use in Specific Populations (8.1) , Clinical Pharmacology (12.1) ] . 8.4 Pediatric Use The safety and effectiveness of pitavastatin tablets as an adjunctive therapy to diet to reduce elevated LDL-C in pediatric patients aged 8 years and older with HeFH have been established. Use of pitavastatin tablets for this indication is supported by a 12-week, double-blind, placebo-controlled trial in 82 pediatric patients 8 to 16 years of age with HeFH [see Clinical Studies (14) ] and a 52-week open-label trial in 85 pediatric patients with HeFH.
Pregnancy
8.1 Pregnancy Risk Summary Discontinue pitavastatin tablets when pregnancy is recognized. Alternatively, consider the ongoing therapeutic needs of the individual patient. Pitavastatin decreases synthesis of cholesterol and possibly other biologically active substances derived from cholesterol; therefore, pitavastatin tablets may cause fetal harm when administered to pregnant patients based on the mechanism of action [see Clinical Pharmacology (12.1) ] . In addition, treatment of hyperlipidemia is not generally necessary during pregnancy. Atherosclerosis is a chronic process and the discontinuation of lipid-lowering drugs during pregnancy should have little impact on the outcome of long-term therapy of primary hyperlipidemia for most patients. Available data from case series and prospective and retrospective observational cohort studies over decades of use with statins in pregnant women have not identified a drug-associated risk of major congenital malformations. Published data from prospective and retrospective observational cohort studies with statin use in pregnant women are insufficient to determine if there is a drug associated risk of miscarriage [see Data ] . In animal reproduction studies, no embryo-fetal toxicity or congenital malformations were observed in pregnant rats and rabbits orally administered pitavastatin during the period of organogenesis at doses which were 22 and 4 times, respectively, the human exposure at the maximum recommended human dosage (MRHD) of 4 mg, based on AUC [see Data ] . The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. Adverse outcomes in pregnancy occur regardless of the health of the mother or the use of medications. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Human Data A Medicaid cohort linkage study of 1,152 statin-exposed pregnant women compared to 886,996 controls did not find a significant teratogenic effect from maternal use of statins in the first trimester of pregnancy, after adjusting for potential confounders – including maternal age, diabetes mellitus, hypertension, obesity, and alcohol and tobacco use – using propensity score-based methods. The relative risk of congenital malformations between the group with statin use and the group with no statin use in the first trimester was 1.07 (95% confidence interval 0.85 to 1.37) after controlling for confounders, particularly pre-existing diabetes mellitus. There were also no statistically significant increases in any of the organ-specific malformations assessed after accounting for confounders. In the majority of pregnancies, statin treatment was initiated prior to pregnancy and was discontinued at some point in the first trimester when pregnancy was identified. Study limitations include reliance on physician coding to define the presence of a malformation, lack of control for certain confounders such as body mass index, use of prescription dispensing as verification for the use of a statin, and lack of information on non-live births. Animal Data Embryo-fetal developmental studies were conducted in pregnant rats administered 3, 10, 30 mg/kg/day pitavastatin by oral gavage during organogenesis (gestation days 7 to 17). No adverse effects were observed at 3 mg/kg/day, systemic exposures 22 times human systemic exposure at 4 mg/day based on AUC. Embryo-fetal developmental studies were conducted in pregnant rabbits administered 0.1, 0.3, 1 mg/kg/day pitavastatin by oral gavage during the period of fetal organogenesis (gestation days 6 to 18). Maternal toxicity consisting of reduced body weight and abortion was observed at all doses tested (4 times human systemic exposure at 4 mg/day based on AUC). In perinatal/postnatal studies in pregnant rats given oral gavage doses of pitavastatin at 0.1, 0.3, 1, 3, 10, 30 mg/kg/day from organogenesis through weaning (gestation day 17 to lactation day 21), maternal toxicity consisting of mortality at ≥0.3 mg/kg/day and impaired lactation at all doses contributed to the decreased survival of neonates in all dose groups (0.1 mg/kg/day represents approximately 1 time human systemic exposure at 4 mg/day dose based on AUC). Reproductive toxicity studies have shown that pitavastatin crosses the placenta in rats and is found in fetal tissues at ≤36% of maternal plasma concentrations following a single dose of 1 mg/kg/day during gestation (at the end of organogenesis).
Pediatric use
8.4 Pediatric Use The safety and effectiveness of pitavastatin tablets as an adjunctive therapy to diet to reduce elevated LDL-C in pediatric patients aged 8 years and older with HeFH have been established. Use of pitavastatin tablets for this indication is supported by a 12-week, double-blind, placebo-controlled trial in 82 pediatric patients 8 to 16 years of age with HeFH [see Clinical Studies (14) ] and a 52-week open-label trial in 85 pediatric patients with HeFH. The safety and effectiveness of pitavastatin tablets have not been established in pediatric patients younger than 8 years of age with HeFH or in pediatric patients with other types of hyperlipidemia (other than HeFH).
Geriatric use
8.5 Geriatric Use In controlled clinical studies, 1,209 (43%) patients were 65 years and older. No overall differences in safety or effectiveness were observed between these patients and younger patients. Advanced age (≥65 years) is a risk factor for pitavastatin-associated myopathy and rhabdomyolysis. Dose selection for a geriatric patient should be cautious, recognizing the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy and the higher risk of myopathy. Monitor geriatric patients receiving pitavastatin tablets for the increased risk of myopathy [see Warnings and Precautions (5.1) ] .
Overdosage
No specific treatment for pitavastatin tablets overdose is known. Contact Poison Control (1-800-222-1222) for latest recommendations. Hemodialysis is unlikely to be of benefit due to high protein binding ratio of pitavastatin tablets.
Description
Pitavastatin tablets for oral use is an HMG-CoA reductase inhibitor. The chemical name for pitavastatin is (+)monocalcium bis {(3R, 5S, 6 E )-7-[2-cyclopropyl-4-(4-fluorophenyl)-3-quinolyl]-3,5- dihydroxy-6-heptenoate}. The structural formula is: The empirical formula for pitavastatin is C 50 H 46 CaF 2 N 2 O 8 and the molecular weight is 880.98. Pitavastatin is odorless and occurs as white to pale-yellow powder. It is freely soluble in pyridine, chloroform, dilute hydrochloric acid, and tetrahydrofuran, soluble in ethylene glycol, sparingly soluble in octanol, slightly soluble in methanol, very slightly soluble in water or ethanol, and practically insoluble in acetonitrile or diethyl ether. Pitavastatin is hygroscopic and slightly unstable in light. Each film-coated pitavastatin tablet contains 1.045 mg, 2.09 mg, or 4.18 mg of pitavastatin calcium, which is equivalent to 1 mg, 2 mg, or 4 mg, respectively of free base and the following inactive ingredients: lactose monohydrate, magnesium carbonate, low-substituted hydroxypropyl cellulose, hypromellose and magnesium stearate. The film coating contains: hypromellose, polyethylene glycol, talc and titanium dioxide. Chemical Structure
Mechanism of action
12.1 Mechanism of Action Pitavastatin is an inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, the enzyme that catalyzes the conversion of HMG-CoA to mevalonate, a rate-limiting step in the biosynthetic pathway for cholesterol. As a result, the expression of LDL-receptors followed by the uptake of LDL from blood to liver is accelerated and then the plasma TC decreases. Sustained inhibition of cholesterol synthesis in the liver also decreases levels of very low-density lipoproteins.
How supplied
Pitavastatin tablets, for oral administration are available as: 1 mg : Round, white to off-white, film-coated tablet, debossed with "P1" on one side. They are supplied as: Bottles of 90 with a child-resistant closure, NDC 0832-6048-90 2 mg : Round, white to off-white, film-coated tablet, debossed with "P2" on one side. They are supplied as: Bottles of 90 with a child-resistant closure, NDC 0832-6049-90 4 mg : Round, white to off-white, film-coated tablet, debossed with "P4" on one side. They are supplied as: Bottles of 90 with a child-resistant closure, NDC 0832-6050-90 Store at 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30°C (59° to 86°F) [See USP Controlled Room Temperature]. Protect from light. Dispense contents in a tight, light-resistant container with a child-resistant closure.
Storage
Store at 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30°C (59° to 86°F) [See USP Controlled Room Temperature]. Protect from light. Dispense contents in a tight, light-resistant container with a child-resistant closure.
Patient information
Myopathy and Rhabdomyolysis Advise patients that pitavastatin tablets may cause myopathy and rhabdomyolysis. Inform patients that the risk is increased when taking certain types of medication and they should discuss all medication, both prescription and over the counter, with their healthcare provider. Instruct patients to promptly report any unexplained muscle pain, tenderness or weakness particularly if accompanied by malaise or fever [see Warnings and Precautions (5.1) ] . Hepatic Dysfunction Inform patients that pitavastatin tablets may cause liver enzyme elevations and possibly liver failure. Advise patients to promptly report fatigue, anorexia, right upper abdominal discomfort, dark urine or jaundice [see Warnings and Precautions (5.3) ] . Increases in HbA1c and Fasting Serum Glucose Levels Inform patients that increases in HbA1c and fasting serum glucose levels may occur with pitavastatin tablets. Encourage patients to optimize lifestyle measures, including regular exercise, maintaining a healthy body weight, and making healthy food choices [see Warnings and Precautions (5.4) ] . Pregnancy Advise pregnant patients and patients who become pregnant of the potential risk to a fetus. Advise patients to inform their healthcare provider of a known or suspected pregnancy to discuss if pitavastatin tablets should be discontinued [see Use in Specific Populations (8.1) ] . Lactation Advise patients that breastfeeding is not recommended during treatment with pitavastatin tablets [see Use in Specific Populations (8.2) ] .
Label text from the FDA structured product label by Upsher-Smith Laboratories, LLC (revised Jun 8, 2026). Long sections are shortened; the complete label is on DailyMed.
Active ingredients
- Pitavastatin Calcium in 18 products
Pitavastatin NDC products (18)
| NDC | Strength & form | Labeler | Type |
|---|---|---|---|
| 65162-031 | Pitavastatin Calcium 4 mg/1 Tablet, Film Coated | Amneal Pharmaceuticals LLC | ANDA |
| 65162-030 | Pitavastatin Calcium 2 mg/1 Tablet, Film Coated | Amneal Pharmaceuticals LLC | ANDA |
| 65162-029 | Pitavastatin Calcium 1 mg/1 Tablet, Film Coated | Amneal Pharmaceuticals LLC | ANDA |
| 65862-814 | Pitavastatin Calcium 4 mg/1 Tablet, Film Coated | Aurobindo Pharma Limited | ANDA |
| 65862-813 | Pitavastatin Calcium 2 mg/1 Tablet, Film Coated | Aurobindo Pharma Limited | ANDA |
| 65862-812 | Pitavastatin Calcium 1 mg/1 Tablet, Film Coated | Aurobindo Pharma Limited | ANDA |
| 42291-905 | Pitavastatin Calcium 1.045 mg/1 Tablet, Film Coated | AvKARE | ANDA |
| 42291-906 | Pitavastatin Calcium 2.09 mg/1 Tablet, Film Coated | AvKARE | ANDA |
| 42291-907 | Pitavastatin Calcium 4.18 mg/1 Tablet, Film Coated | AvKARE | ANDA |
| 51407-956 | Pitavastatin Calcium 1 mg/1 Tablet | Golden State Medical Supply, Inc. | ANDA |
| 51407-958 | Pitavastatin Calcium 4 mg/1 Tablet | Golden State Medical Supply, Inc. | ANDA |
| 51407-957 | Pitavastatin Calcium 2 mg/1 Tablet | Golden State Medical Supply, Inc. | ANDA |
| 0480-3631 | Pitavastatin Calcium 1.045 mg/1 Tablet, Film Coated | Teva Pharmaceuticals, Inc. | ANDA |
| 0480-3633 | Pitavastatin Calcium 4.18 mg/1 Tablet, Film Coated | Teva Pharmaceuticals, Inc. | ANDA |
| 0480-3632 | Pitavastatin Calcium 2.09 mg/1 Tablet, Film Coated | Teva Pharmaceuticals, Inc. | ANDA |
| 0832-6050 | Pitavastatin Calcium 4 mg/1 Tablet | Upsher-Smith Laboratories, LLC | ANDA |
| 0832-6049 | Pitavastatin Calcium 2 mg/1 Tablet | Upsher-Smith Laboratories, LLC | ANDA |
| 0832-6048 | Pitavastatin Calcium 1 mg/1 Tablet | Upsher-Smith Laboratories, LLC | ANDA |
Pitavastatin recalls
- D-0526-2025 Jul 9, 2025 · Class III · Ongoing
Failed Impurities/Degradation Specifications. - D-0527-2025 Jul 9, 2025 · Class III · Ongoing
Failed Impurities/Degradation Specifications. - D-0528-2025 Jul 9, 2025 · Class III · Ongoing
Failed Impurity/Degradation Specifications - D-0529-2025 Jul 9, 2025 · Class III · Ongoing
Failed Impurity/Degradation Specifications
Frequently asked questions
What is Pitavastatin used for?
Pitavastatin tablets are indicated as an adjunct to diet to reduce low-density lipoprotein cholesterol (LDL-C) in: Adults with primary hyperlipidemia. Adults and pediatric patients aged 8 years and older with heterozygous familial hypercholesterolemia (HeFH). Pitavastatin tablets is a HMG-CoA reductase inhibitor (statin) indicated as an adjunct to diet to reduce low-density lipoprotein…
What are the side effects of Pitavastatin?
The following serious adverse reactions are discussed in other sections of the labeling: Myopathy and Rhabdomyolysis [see Warnings and Precautions (5.1) ] Immune-Mediated Necrotizing Myopathy [see Warning and Precautions (5.2) ] Hepatic Dysfunction [see Warning and Precautions (5.3) ] Increases in HbA1c and Fasting Serum Glucose Levels [see Warning and Precautions (5.4) ] . The most frequent… See the full label for the complete list.
Who makes Pitavastatin?
Pitavastatin is listed by 6 labelers in the FDA NDC directory, including Amneal Pharmaceuticals LLC, Aurobindo Pharma Limited, AvKARE, Golden State Medical Supply, Inc..
Has Pitavastatin been recalled?
The FDA enforcement database lists 4 recalls for Pitavastatin, most recently D-0526-2025 (class iii): Failed Impurities/Degradation Specifications.