Pitavastatin suppresses the development of a panel of ovarian cancer cells cultured as spheroids (IC50 = 0.6-4 μM) or as monolayers (IC50 = 0.4-5 μM), including those thought to most likely represent HGSOC[4]. The increased activity of executioner caspases-3,7, as well as caspase-8 and caspase-9 in Ovcar-8 cells and Ovcar-3 cells, indicates that pitavastatin (one microgram; 48 hours) triggers apoptosis[4]. Ovcar-8 cells cleave PARP when exposed to 1 μM pitavastatin for 48 hours[4]. In TNF-stimulated human saphenous vein endothelial cells, pitavastatin (0.1 and 1 μM; 1 h, followed by 6 h of TNF-α incubation) enhances the production of ICAM-1 mRNA by inhibiting the NF-κB pathway[6].

Depressant pitavastatin (59 mg/kg; po; twice daily for 28 days) significantly reduces tumor growth[4]. In a rabbit model of diet-induced severe hyperlipidemia, pitavastatin (0.1 mg/kg; po; daily for 12 weeks) slows the development of atherosclerosis and increases NO bioavailability through eNOS up-regulation and O2-depletion[7].

Western Blot Analysis[4]
Cell Types: Ovcar-8 cells
Tested Concentrations: 1 μM
Incubation Duration: 48 hrs (hours)
Experimental Results: Induced PARP cleavage.

Animal/Disease Models: 4 week old female NCR Nu/Nu female mice (bearing Ovcar-4 tumours)[4]
Doses: 59 mg/kg
Route of Administration: po ; twice (two times) daily for 28 days
Experimental Results: Caused significant tumor regression.

---

Animal/Disease Models: Female New Zealand white rabbits (diet induced severe hyperlipidemia)[7]
Doses: 0.1 mg/kg
Route of Administration: po; daily for 12 weeks
Experimental Results: Retarded the progression of atherosclerosis formation and improved NO bioavailability by eNOS up-regulation and decrease of O2-.

Absorption, Distribution and Excretion
Pitavastatin peak plasma concentrations are achieved about 1 hour after oral administration. Both Cmax and AUC0-inf increased in an approximately dose-proportional manner for single pitavastatin doses from 1 mg to 24 mg once daily. The absolute bioavailability of pitavastatin oral solution is 51%. The Cmax and AUC of pitavastatin did not differ following evening or morning drug administration. In healthy volunteers receiving 4 mg pitavastatin, the percent change from baseline for LDL-C following evening dosing was slightly greater than that following morning dosing. Pitavastatin was absorbed in the small intestine but very little in the colon. Administration of pitavastatin with a high fat meal (50% fat content) decreases pitavastatin Cmax by 43% but does not significantly reduce pitavastatin AUC. Compared to other statins, pitavastatin has a relatively high bioavailability, which has been suggested to occur due to enterohepatic reabsorption in the intestine following intestinal absorption. Genetic differences in the OATP1B1 (organic-anion-transporting polypeptide 1B1) hepatic transporter encoded by the SCLCO1B1 gene (Solute Carrier Organic Anion Transporter family member 1B1) have been shown to impact pitavastatin pharmacokinetics. Evidence from pharmacogenetic studies of the c.521T>C single nucleotide polymorphism (SNP) in the gene encoding OATP1B1 (SLCO1B1) demonstrated that pitavastatin AUC was increased 3.08-fold for individuals homozygous for 521CC compared to homozygous 521TT individuals. Other statin drugs impacted by this polymorphism include [simvastatin], [pitavastatin], [atorvastatin], and [rosuvastatin]. Individuals with the 521CC genotype may be at increased risk of dose-related adverse effects including myopathy and rhabdomyolysis due to increased exposure to the drug.
A mean of 15% of radioactivity of orally administered, single 32 mg ¹⁴C-labeled pitavastatin dose was excreted in urine, whereas a mean of 79% of the dose was excreted in feces within 7 days.L48616]
The mean volume of distribution is approximately 148 L.
Following a single dose, the apparent mean oral clearance of pitavastatin is 43.4 L/h.
/MILK/ It is not known whether pitavastatin is excreted in human milk, however, it has been shown that a small amount of another drug in this class passes into human milk. Rat studies have shown that pitavastatin is excreted into breast milk.
This study was addressed to understand the underlying mechanism of the substrate-dependent effect of genetic variation in SLCO1B1, which encodes OATP1B1 (organic anion transporting polypeptide) transporter, on the disposition of two OATP1B1 substrates, pravastatin and pitavastatin, in relation to their transport activities. The uptake of pravastatin, pitavastatin, and fluvastatin was measured in oocytes overexpressing SLCO1B1*1a and SLCO1B1*15 to compare the alterations of in-vitro transporting activity. After 40-mg pravastatin or 4-mg pitavastatin was administered to 11 healthy volunteers with homozygous genotypes of SLCO1B1*1a/*1a and SLCO1B1*15/*15, the pharmacokinetic parameters of pravastatin and pitavastatin were compared among participants with SLCO1B1*1a/*1a and SLCO1B1*15/*15 genotypes. The uptake of pravastatin and pitavastatin in SLCO1B1*15 overexpressing oocytes was decreased compared with that in SLCO1B1*15, but no change occurred with fluvastatin. The fold change of in-vitro intrinsic clearance (Clint) for pitavastatin in SLCO1B1*15 compared with SLCO1B1*1a was larger than that of pravastatin (P<0.0001). The clearance (Cl/F) of pitavastatin was decreased to a greater degree in participant with SLCO1B1*15/*15 compared with that of pravastatin in vivo (P<0.01), consistent with in-vitro study. As a result, Cmax and area under the plasma concentration-time curve of these nonmetabolized substrates were increased by SLCO1B1*15 variant. The greater decrease in the transport activity for pitavastatin in SLCO1B1*15 variant compared with SLCO1B1*1a was, however, associated with the greater effect on the pharmacokinetics of pitavastatin compared with pravastatin in relation to the SLCO1B1 genetic polymorphism. This study suggests that substrate dependency in the consequences of the SLCO1B1*15 variant could modulate the effect of SLCO1B1 polymorphism on the disposition of pitavastatin and pravastatin.
A pharmacokinetics study was conducted in 12 Chinese volunteers following a single dose of 1 mg, 2 mg and 4 mg of pitavastatin calcium in an open-label, randomized, three-period crossover design. Plasma concentrations of pitavastatin acid and pitavastatin lactone were determined by a HPLC method. Single-nucleotide polymorphisms (SNPs) in ABCB1, ABCG2, SLCO1B1, CYP2C9 and CYP3A5 were determined by TaqMan (MGB) genotyping assay. An analysis was performed on the relationship between the aforementioned SNPs and dose-normalized (based on 1 mg) area under the plasma concentration-time curve extrapolated to infinity [AUC(0-infinity)] and peak plasma concentration (Cmax) values of the acid and lactone forms of pitavastatin. Pitavastatin exhibited linear pharmacokinetics and great inter-subject variability. Compared to CYP2C9*1/*1 carriers, CYP2C9*1/*3 carriers had higher AUC(0-infinity) and Cmax of pitavastatin acid and AUC(0-infinity) of pitavastatin lactone (P<0.05). With respect to ABCB1 G2677T/A, non-G carriers had higher Cmax and AUC(0-infinity) of pitavastatin acid, and Cmax of pitavastatin lactone compared to GT, GA or GG genotype carriers (P<0.05). Gene-dose effects of SLCO1B1 c.521T> C and g.11187G > A on pharmacokinetics of the acid and lactone forms were observed. Compared to non-SLCO1B1*17 carriers, SLCO1B1*17 carriers had higher Cmax and AUC(0-infinity) of the acid and lactone forms (P<0.05). Significant sex difference was observed for pharmacokinetics of the lactone. Female SLCO1B1 521TT subjects had higher Cmax and AUC(0-infinity) of pitavastatin lactone compared to male 521TT subjects, however, such gender difference disappeared in 521 TC and 521CC subjects. Pitavastatin pharmacokinetics was not significantly affected by ABCB1 C1236T, ABCB1C3435T, CYP3A5*3, ABCG2 c.34G > A, c.421C > A, SLCO1B1 c.388A>G, c.571T>C and c.597C>T. We conclude that CYP2C9*3, ABCB1 G2677T/A, SLCO1B1 c.521T>C, SLCO1B1 g.11187G > A, SLCO1B1*17 and gender contribute to inter-subject variability in pitavastatin pharmacokinetics. Personalized medicine should be necessary for hypercholesterolemic patients receiving pitavastatin.
Pitavastatin is more than 99% protein bound in human plasma, mainly to albumin and alpha 1-acid glycoprotein, and the mean volume of distribution is approximately 148 L. Association of pitavastatin and/or its metabolites with the blood cells is minimal.
For more Absorption, Distribution and Excretion (Complete) data for Pitavastatin (12 total), please visit the HSDB record page.

---

Metabolism / Metabolites
The principal route of pitavastatin metabolism is glucuronidation via liver uridine 5'-diphosphate glucuronosyltransferase (UGT) with subsequent formation of pitavastatin lactone. There is only minimal metabolism by the cytochrome P450 system. Pitavastatin is marginally metabolized by CYP2C9 and to a lesser extent by CYP2C8. The major metabolite in human plasma is the lactone, which is formed via an ester-type pitavastatin glucuronide conjugate by UGTs (UGT1A3 and UGT2B7).
Pitavastatin has been studied for its effects on hepatic microsomal drug metabolism in rats, and the activities of several drug-metabolizing enzymes have been measured. No induction of the drug metabolizing enzymes (aniline hydroxylase, aminopyrine N-demethylase, 7-ethoxycoumarin O-deethylase and UDP-glucuronic acid transferase) was found in the pitavastatin group compared to the control after the multiple administrations of pitavastatin at the dosage of 1-10 mg/kg per day for 7 days. Based on several different in vitro approaches, it is concluded that CYP2C9 is the enzyme responsible for the metabolism of pitavastatin and no metabolite is present in renal and intestinal microsomes. The CYP2C9 polymorphism was not involved in the pitavastatin metabolism. No inhibitory effect in CYP-mediated metabolism was detected on the tolbutamide 4-hydroxylation (CYP2C9) and testosterone 6 beta-hydroxylation (CYP3A4) in the presence of pitavastatin. The results suggested that pitavastatin did not affect the drug-metabolizing systems.
Pitavastatin is marginally metabolized by CYP2C9 and to a lesser extent by CYP2C8. The major metabolite in human plasma is the lactone which is formed via an ester-type pitavastatin glucuronide conjugate by uridine 5'-diphosphate (UDP) glucuronosyltransferase (UGT1A3 and UGT2B7).
To elucidate any potential species differences, the in vitro metabolism of pitavastatin and its lactone was studied with hepatic and renal microsomes from rats, dogs, rabbits, monkeys and humans. With the addition of UDP-glucuronic acid to hepatic microsomes, pitavastatin lactone was identified as the main metabolite in several animals, including humans. Metabolic clearances of pitavastatin and its lactone in monkey hepatic microsome were much greater than in humans. M4, a metabolite of pitavastatin with a 3-dehydroxy structure, was converted to its lactone form in monkey hepatic microsomes in the presence of UDP-glucuronic acid as well as to pitavastatin. These results implied that lactonization is a common pathway for drugs such as 5-hydroxy pentanoic acid derivatives. The acid forms were metabolized to their lactone forms because of their structural characteristics. UDP-glucuronosyltransferase is the key enzyme responsible for the lactonization of pitavastatin, and overall metabolism is different compared with humans owing to the extensive oxidative metabolism of pitavastatin and its lactone in monkey.

---

Biological Half-Life
The mean plasma elimination half-life is approximately 12 hours.L48616]
A mean of 15% of radioactivity of orally administered, single 32 mg (14)C-labeled pitavastatin dose was excreted in urine, whereas a mean of 79% of the dose was excreted in feces within 7 days. The mean plasma elimination half-life is approximately 12 hours.

Toxicity Summary
IDENTIFICATION AND USE: Pitavastatin, a hydroxymethylglutaryl-CoA (HMG-CoA) reductase inhibitor (i.e., statin), is an antilipemic agent. It is used as an adjunct to lifestyle modifications for the management of dyslipidemias. HUMAN EXPOSURE AND TOXICITY: Pitavastatin is contraindicated for use in pregnant women or patients with active liver disease, including unexplained, persistent elevations in serum aminotransferase concentrations. Cases of myopathy and rhabdomyolysis with acute renal failure secondary to myoglobinuria have been reported with HMG-CoA reductase inhibitors, including pitavastatin. These risks can occur at any dose level, but increase in a dose-dependent manner. Cases of fatal and nonfatal hepatic failure have also been reported rarely in patients receiving pitavastatin. ANIMAL STUDIES: In a 92-week carcinogenicity study in mice given pitavastatin, at the maximum tolerated dose of 75 mg/kg/day there was an absence of drug-related tumors. However, in a 92-week carcinogenicity study in rats given pitavastatin at 1, 5, 25 mg/kg/day by oral gavage, there was a significant increase in the incidence of thyroid follicular cell tumors at 25 mg/kg/day. Embryo-fetal developmental studies were conducted in pregnant rats treated with 3, 10, 30 mg/kg/day pitavastatin by oral gavage during organogenesis. No adverse effects were observed at 3 mg/kg/day. Embryo-fetal developmental studies were conducted in pregnant rabbits treated with 0.1, 0.3, 1 mg/kg/day pitavastatin by oral gavage during the period of fetal organogenesis. Maternal toxicity consisting of reduced body weight and abortion was observed at all doses tested. 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, 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. Pitavastatin had no adverse effects on male and female rat fertility at oral doses of 10 and 30 mg/kg/day, respectively. Pitavastatin was not mutagenic in the Ames test with Salmonella typhimurium and Escherichia coli with and without metabolic activation, the micronucleus test following a single administration in mice and multiple administrations in rats, the unscheduled DNA synthesis test in rats, and a Comet assay in mice. In the chromosomal aberration test, clastogenicity was observed at the highest doses tested which also elicited high levels of cytotoxicity.

---

Hepatotoxicity
Less information is available on the potential hepatotoxicity of pitavastatin in comparison to other more widely used statins. In large clinical trials, pitavastatin therapy was associated with mild, asymptomatic and usually transient serum aminotransferase elevations in approximately 1% of patients, but levels above 3 times the upper limit of normal (ULN) were infrequent and no cases of clinically apparent hepatitis were reported from the preregistration clinical trials. Since marketing of pitavastatin, however, the sponsor has received reports of jaundice, hepatitis and hepatic failure including fatal cases. However, the clinical features and typical course of the liver injury associated with pitavastatin have not been defined in the published literature. On the other hand, the other statins have all been implicated in cases of clinically apparent acute liver injury that typically arise after 1 to 6 months of therapy with either a cholestatic or hepatocellular pattern of serum enzyme elevations. Rash, fever and eosinophilia are uncommon, but some cases have been marked by autoimmune features including autoantibodies, chronic hepatitis on liver biopsy and a clinical response to corticosteroid therapy. This pattern has yet to be shown to apply to pitavastatin.
Likelihood score: D (possible rare cause of clinically apparent liver injury).

---

Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
No published information exists on the use of pitavastatin during breastfeeding. It is 99% bound to plasma proteins, so amounts in milk are likely low. Because of a concern with disruption of infant lipid metabolism, the consensus is that pitavastatin should not be used during breastfeeding. However, others have argued that children homozygous for familial hypercholesterolemia are treated with statins beginning at 1 year of age, that statins have low oral bioavailability, and risks to the breastfed infant are low, especially with rosuvastatin and pravastatin. Until more data become available, an alternate drug may be preferred, especially while nursing a newborn or preterm infant.
◉ Effects in Breastfed Infants
Relevant published information was not found as of the revision date.
◉ Effects on Lactation and Breastmilk
Relevant published information was not found as of the revision date.

---

Protein Binding
Pitavstatin is more than 99% protein bound in human plasma, mainly to albumin and alpha 1-acid glycoprotein.

---

Interactions
Pitavastatin is a substrate of organic anionic transport polypeptide (OATP) 1B1 (OATP2). Drugs that inhibit OATP1B1 (e.g., cyclosporine, erythromycin, rifampin) can increase bioavailability of pitavastatin.
Concomitant use of pitavastatin (2 mg once daily) and ezetimibe (10 mg for 7 days) decreased pitavastatin peak plasma concentration and AUC by 2 and 0.2%, respectively, and increased ezetimibe peak plasma concentration and AUC by 9 and 2%, respectively.
Erythromycin substantially increases pitavastatin exposure.1 Following concomitant use of pitavastatin (4 mg as a single dose on day 4) and erythromycin (500 mg 4 times daily for 6 days), pitavastatin peak plasma concentration and AUC were increased by 3.6- and 2.8-fold, respectively; such effects were considered clinically important. The interaction between pitavastatin and erythromycin probably resulted partly from erythromycin-induced inhibition of organic anionic transport polypeptide (OATP)1B1-mediated hepatic uptake of pitavastatin. If used concomitantly with erythromycin, dosage of pitavastatin should not exceed 1 mg once daily.
Concomitant use of pitavastatin (4 mg once daily on days 1-5 and 11-15) and extended-release diltiazem hydrochloride (240 mg on days 6-15) increased pitavastatin peak plasma concentration and AUC by 15 and 10%, respectively, and decreased diltiazem peak plasma concentration and AUC by 7 and 2%, respectively.
For more Interactions (Complete) data for Pitavastatin (20 total), please visit the HSDB record page.

[1]. Relative induction of mRNA for HMG CoA reductase and LDL receptor by five different HMG-CoA reductase inhibitors in cultured human cells. J Atheroscler Thromb. 2000;7(3):138-44.

[2]. Nanoparticle-mediated delivery of pitavastatin inhibits atherosclerotic plaque destabilization/rupture in mice by regulating the recruitment of inflammatory monocytes. Circulation. 2014 Feb 25;129(8):896-906.

[3]. Pitavastatin regulates helper T-cell differentiation and ameliorates autoimmune myocarditis in mice. Cardiovasc Drugs Ther. 2013 Oct;27(5):413-24.

[4]. Pitavastatin decreases tau levels via the inactivation of Rho/ROCK. Neurobiol Aging. 2012 Oct;33(10):2306-20.

[5]. Dietary geranylgeraniol can limit the activity of pitavastatin as a potential treatment for drug-resistant ovarian cancer.Sci Rep. 2017 Jul 14;7(1):5410.

[6]. The Effects of Pitavastatin on Nuclear Factor-Kappa B and ICAM-1 in Human Saphenous Vein Graft Endothelial Culture. Cardiovasc Ther. 2019 May 2;2019:2549432.

[7]. A new HMG-CoA reductase inhibitor, pitavastatin remarkably retards the progression of high cholesterol induced atherosclerosis in rabbits. Atherosclerosis. 2004 Oct;176(2):255-63.

[8]. A comprehensive review on the lipid and pleiotropic effects of pitavastatin. Prog Lipid Res. 2021 Nov;84:101127.

Therapeutic Uses
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Livalo is indicated as an adjunctive therapy to diet to reduce elevated total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), apolipoprotein B (Apo B), triglycerides (TG), and to increase HDL-C in adult patients with primary hyperlipidemia or mixed dyslipidemia. /Included in US product label/
The American College of Cardiology (ACC)/American Heart Association (AHA) cholesterol management guideline recommends statins as first-line therapy for prevention of atherosclerotic cardiovascular disease (ASCVD) in adults. Pitavastatin may be used for primary or secondary prevention in adults when moderate-intensity statin therapy is indicated. /NOT included in US product label/
/EXPL THER/ Pitavastatin classically functions as a blood cholesterol-lowering drug. Previously, it was discovered with antiglioma stem cell properties through drug screening. However, whether it can be used for liver cancer cell therapy has never been reported. In this study, the cell viability and colony formation assay were utilized to analyze the cytotoxicity of pitavastatin on liver cancer cells. The cell cycle alteration was checked after pitavastatin treatment. Apoptosis-related protein expression and the effect of caspase inhibitor were also checked. The in vivo inhibitory effect of pitavastatin on the growth of liver tumor was also tested. It was found that pitavastatin inhibited growth and colony formation of liver cancer Huh-7 cells and SMMC7721 cells. It induced arrest of liver cancer cells at the G1 phase. Increased proportion of sub-G1 cells was observed after pitavastatin treatment. Pitavastatin promoted caspase-9 cleavage and caspase-3 cleavage in liver cancer cells. Caspase inhibitor Z-VAD-FMK reversed the cleavage of cytotoxic effect of pitavastatin. Moreover, pitavastatin decreased the tumor growth and improved the survival of tumor-bearing mice. This study suggested the antiliver cancer effect of the old drug pitavastatin. It may be developed as a drug for liver cancer therapy.

---

Drug Warnings
Increases in serum aminotransferase (i.e., AST [SGOT], ALT [SGPT]) concentrations have been reported in patients receiving statins, including pitavastatin. These increases usually were transient and resolved or improved with continued therapy or after temporary interruption of therapy. In phase 2, placebo-controlled studies, increases in serum ALT concentrations exceeding 3 times the upper limit of normal occurred in 0.5% of patients receiving pitavastatin 4 mg daily. Cases of fatal and nonfatal hepatic failure have been reported rarely in patients receiving statins, including pitavastatin, during postmarketing surveillance.
Immune-mediated necrotizing myopathy (IMNM), an autoimmune myopathy, has been reported rarely in patients receiving statins. Immune-mediated necrotizing myopathy is characterized by proximal muscle weakness and elevated creatine kinase (CK, creatine phosphokinase, CPK) concentrations that persist despite discontinuance of statin therapy, necrotizing myopathy without substantial inflammation, and improvement following therapy with immunosuppressive agents. Pitavastatin should be used with caution in patients with predisposing factors for myopathy (e.g., advanced age [older than 65 years of age], renal impairment, inadequately-treated hypothyroidism) and in patients receiving concomitant therapy with certain antilipemic agents (i.e., fibric acid derivatives, antilipemic dosages of niacin).
Cases of myopathy and rhabdomyolysis with acute renal failure secondary to myoglobinuria have been reported with HMG-CoA reductase inhibitors, including Livalo. These risks can occur at any dose level, but increase in a dose-dependent manner.
Pitavastatin is distributed into milk in rats. It is not known whether pitavastatin is distributed into human milk; however, a small amount of another statin is distributed into human milk. Because of the potential for serious adverse reactions from pitavastatin in nursing infants, the drug is contraindicated in nursing women. Women who require pitavastatin therapy should be advised not to breast-feed their infants or advised to discontinue pitavastatin.
For more Drug Warnings (Complete) data for Pitavastatin (26 total), please visit the HSDB record page.

---

Pharmacodynamics
Pitavastatin is an oral antilipemic agent which inhibits HMG-CoA reductase. It is used to lower total cholesterol, low density lipoprotein-cholesterol (LDL-C), apolipoprotein B (apoB), non-high density lipoprotein-cholesterol (non-HDL-C), and trigleride (TG) plasma concentrations while increasing HDL-C concentrations. High LDL-C, low HDL-C and high TG concentrations in the plasma are associated with increased risk of atherosclerosis and cardiovascular disease. The total cholesterol to HDL-C ratio is a strong predictor of coronary artery disease and high ratios are associated with higher risk of disease. Increased levels of HDL-C are associated with lower cardiovascular risk. By decreasing LDL-C and TG and increasing HDL-C, rosuvastatin reduces the risk of cardiovascular morbidity and mortality. Elevated cholesterol levels, and in particular, elevated low-density lipoprotein (LDL) levels, are an important risk factor for the development of CVD. Use of statins to target and reduce LDL levels has been shown in a number of landmark studies to significantly reduce the risk of development of CVD and all-cause mortality. Statins are considered a cost-effective treatment option for CVD due to their evidence of reducing all-cause mortality including fatal and non-fatal CVD as well as the need for surgical revascularization or angioplasty following a heart attack. Evidence has shown that even for low-risk individuals (with <10% risk of a major vascular event occurring within 5 years) statins cause a 20%-22% relative reduction in major cardiovascular events (heart attack, stroke, coronary revascularization, and coronary death) for every 1 mmol/L reduction in LDL without any significant side effects or risks. **Skeletal Muscle Effects** Pitavastatin may cause myopathy (muscle pain, tenderness, or weakness with creatine kinase (CK) above ten times the upper limit of normal) and rhabdomyolysis (with or without acute renal failure secondary to myoglobinuria). Rare fatalities have occurred as a result of rhabdomyolysis with statin use, including pitavastatin. Predisposing factors for myopathy include advanced age (≥65 years), female gender, uncontrolled hypothyroidism, and renal impairment. In most cases, muscle symptoms and CK increases resolved when treatment was promptly discontinued. As dosages of pitavastatin greater than 4mg per day were associated with an increased risk of severe myopathy, the product monograph recommends a maximum daily dose of 4mg once daily. The risk of myopathy during treatment with pitavstatin may be increased with concurrent administration of interacting drugs such as [fenofibrate], [niacin], [gemfibrozil], and [cyclosporine]. Cases of myopathy, including rhabdomyolysis, have been reported with HMG-CoA reductase inhibitors coadministered with [colchicine], and caution should therefore be exercised when prescribing these two medications together. Real-world data from observational studies has suggested that 10-15% of people taking statins may experience muscle aches at some point during treatment. **Hepatic Dysfunction** Increases in serum transaminases have been reported with pitavastatin. In most cases, the elevations were transient and either 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. **Increases in HbA1c and Fasting Serum Glucose Levels** Increases in HbA1c and fasting serum glucose levels have been reported with statins, including pitavastatin. Optimize lifestyle measures, including regular exercise, maintaining a healthy body weight, and making healthy food choices. An in vitro study found that [atorvastatin], [pravastatin], [rosuvastatin], and [pitavastatin] exhibited a dose-dependent cytotoxic effect on human pancreas islet β cells, with reductions in cell viability of 32, 41, 34 and 29%, respectively, versus control. Moreover, insulin secretion rates were decreased by 34, 30, 27 and 19%, respectively, relative to control.

C25H24FNO4

421.46

421.168

147511-69-1

Pitavastatin Calcium;147526-32-7;Pitavastatin-d4;2070009-71-9;Pitavastatin-d5 sodium;Pitavastatin sodium;574705-92-3

5282452

White to off-white solid powder

1.4±0.1 g/cm3

692.0±55.0 °C at 760 mmHg

372.3±31.5 °C

0.0±2.3 mmHg at 25°C

1.680

3.45

3

6

8

31

631

2

C1CC1C2=NC3=CC=CC=C3C(=C2/C=C/[C@H](C[C@H](CC(=O)O)O)O)C4=CC=C(C=C4)F

VGYFMXBACGZSIL-MCBHFWOFSA-N

InChI=1S/C25H24FNO4/c26-17-9-7-15(8-10-17)24-20-3-1-2-4-22(20)27-25(16-5-6-16)21(24)12-11-18(28)13-19(29)14-23(30)31/h1-4,7-12,16,18-19,28-29H,5-6,13-14H2,(H,30,31)/b12-11+/t18-,19-/m1/s1

(E,3R,5S)-7-[2-cyclopropyl-4-(4-fluorophenyl)quinolin-3-yl]-3,5-dihydroxyhept-6-enoic acid

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ~100 mg/mL (~237.27 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (5.93 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

---

Solubility in Formulation 2: ≥ 2.5 mg/mL (5.93 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

---

 (Please use freshly prepared in vivo formulations for optimal results.)