Date of approval.
Date of revision.
Pitavastatin Calcium Tablets Instructions
Please read the instructions carefully and use under the guidance of a physician
Drug Name]
Generic name: Pitavastatin Calcium Tablets
English name: Pitavastatin Calcium Tablets
Hanyu Pinyin: Pifatatinggai Pian
Ingredients
The main ingredient of this product is Pitavastatin Calcium.
Chemical name: Bis{(3R,5S,6E)-7-[2-cyclopropyl-4-(4-fluorophenyl)quinolin-3-yl]-3,5-dihydroxy-6-heptenoic acid} monocalcium salt pentahydrate
Chemical structure formula.
Molecular formula: C50H46CaF2N2O8-5H2O
Molecular weight: 971.06
【Properties】.
This product 1mg is white film-coated tablet, 2mg and 4mg are white film-coated tablets with one side “one” indentation; after removing the film coating, they all appear white or off-white.
Indications
Hypercholesterolemia, familial hypercholesterolemia.
Precautions.
1. Adequate examination must be performed before use to confirm the presence of hypercholesterolemia and familial hypercholesterolemia before considering the use of this preparation.
2. Since there is no experience with the use of pure congeners in familial hypercholesterolemia, this preparation should be considered as an adjunct to non-pharmacological therapy such as partial removal of LDL-blood components only when it is judged to be necessary for treatment.
Specification
According to C50H46CaF2N2O8 (1) 1mg (2) 2mg (3) 4mg
Dosage]
Usually, adults take 1 to 2mg orally once a day.
The dose can be increased or decreased according to age and treatment response, and the maximum daily dose is 4mg in case of insufficient LDL-cholesterol reduction.
Precautions.
1. When administered to patients with liver disease, the initial dose is 1 mg daily and the maximum dose is 2 mg daily. (Refer to [caution in administration] [pharmacokinetics])
2. Since adverse events related to rhabdomyolysis may occur as the dose (blood concentration) increases, when increasing the dose to 4 mg, pay adequate attention to the pre-myocardial symptoms of rhabdomyolysis such as elevated CK (CPK), myoglobinuria, muscle pain and weakness. [Dosing above 8 mg in foreign clinical trials was terminated due to the occurrence of rhabdomyolysis and related adverse events].
3. When administered to patients with moderate and severe renal insufficiency (glomerular filtration rate of 30-59 ml/min/1.73m2 and 15-29 ml/min/1.73m2 not receiving hemodialysis, respectively) and end-stage renal disease receiving hemodialysis, the initial dose is 1 mg once a day and the maximum dose is 2 mg once a day.
[Adverse Reactions].
In clinical trials conducted before pitavastatin calcium was approved for marketing in Japan, 197 out of 886 cases (22.2%) showed adverse reactions. There were 50 cases (5.6%) of adverse reactions with autonomic (other) symptoms, the main symptoms included abdominal pain, rash, feeling of tiredness, numbness and itching. There were 167 cases (18.8%) with abnormal clinical examination values, mainly elevated γ-GTP, elevated CK (CPK), elevated serum ALT (GPT), elevated serum AST (GOT), etc.
Adverse reactions were reported in 1,082 (5.4%) of 19,921 safety analysis subjects in post-marketing safety monitoring. (At the end of the re-examination)
In the clinical trial of pitavastatin calcium imported into China, adverse reactions were observed in 23 (10.1%) of the 227 patients taking pitavastatin. Among them, the main manifestation was gastrointestinal dysfunction, and the incidence of gastrointestinal dysfunction in the 2 mg dose group was 6.3%. 0.9% of patients had more than 3-fold elevation of hepatic transaminases during use, and 1 case (1/109) had >10-fold elevation of CK in the 4 mg group.
1. Serious adverse reactions
(1) Rhabdomyolysis (incidence unknown): rhabdomyolysis characterized by muscle pain, weakness, elevated CK (CPK), and elevated myoglobin in blood and urine may occur. Along with rhabdomyolysis, serious renal dysfunction such as acute renal failure may occur, and the administration of the drug should be stopped when this occurs.
(2) Myopathy (incidence unknown): Myopathy may occur, so administration must be stopped if widespread muscle pain, muscle induration or marked CK (CPK) elevation occurs.
(3) Liver dysfunction and jaundice (less than 0.1%): Liver dysfunction and jaundice accompanied by significant elevation of AST (GOT) and ALT (GPT) may occur, so liver function tests should be performed regularly and administration should be discontinued for proper management if abnormalities are detected.
(4) Thrombocytopenia (incidence unknown): Thrombocytopenia may occur, so blood tests should be performed, and if abnormalities are found, drug administration should be stopped and proper treatment should be carried out.
(5) Interstitial pneumonia (incidence unknown): Interstitial pneumonia may occur, so even if the drug is given for a long time, if fever, cough, dyspnea and chest X-ray abnormalities are found, the drug should be stopped immediately and properly managed by giving corticosteroid drugs, etc.
(6) Immune necrotizing myopathy (incidence unknown): Since the occurrence of immune necrotizing myopathy has been observed, the drug should be discontinued immediately after adequate observation and appropriate treatment when abnormalities are detected.
2. Other adverse reactions: (Japanese data)
0.1% to 2.0% Less than 0.1% incidence Unknown allergiesNote 1) Rash, pruritus urticaria erythema digestive system belching, nausea, stomach upset thirst, dyspepsia, abdominal pain, bloating, constipation, endostomatitis, vomiting, loss of appetite, tongue inflammation, diarrhea liverNote 2) Elevated AST (GOT), elevated ALT (GPT), elevated γ-GTP, elevated LDH elevated bilirubin, elevated Elevated cholinesterase, elevated ALP Kidney Frequent urination, elevated BUN, elevated serum creatinine MuscleNote 3CK (CPK) elevated, muscle pain, feeling of weakness muscle cramps, elevated myoglobin Psychoneurology Headache, feeling of heavy head, numbness, feeling of vertigo and stiffness, sleepiness, insomnia Blood Anemia Thrombocytopenia, granulocytopenia, leukopenia, eosinophilia, leukocytosis, elevated globulin Positive serum antiglobulin test Endocrine testosterone decrease Aldosterone decrease, aldosterone increase, ACTH increase, cortisol increase Other tiredness, antinuclear antibody positive Palpitations, fatigue, skin pain, hot flashes, arthralgia, swelling, blurred vision, visual flicker, ear occlusion, urine occult blood, uric acid value increase, serum K increase, serum P increase, abnormal taste, coloring urine hair loss Note 1) At this time, stop administration of drugs.
(Note 2) Observe the patient adequately and stop administration of the drug if abnormalities occur.
(Note 3) Pre-existing symptoms of rhabdomyolysis may occur, so adequate observation should be made and drug administration should be stopped if necessary.
The frequency of occurrence is calculated based on the total at the time of approval and safety monitoring.
3. Adverse reactions of statin drugs in other reports
1) Hyperglycemic reactions, abnormal glucose tolerance, elevated glycosylated hemoglobin levels, new-onset diabetes, and deterioration of glycemic control have been reported in post-marketing surveillance of statins, and hypoglycemic reactions have been reported in some statins.
2) Post-marketing experience: There are rare reports of cognitive impairment in the post-marketing surveillance of statin drugs abroad, manifesting as memory loss, memory loss, confusion, etc. Most of these reactions are non-serious and reversible, and can generally be recovered after discontinuation of the drug.
Contraindications
The following patients are prohibited to administer the drug.
1) Patients with previous history of hypersensitivity to the ingredients of this preparation.
2) Patients with severe liver disease or biliary tract occlusion [these patients may have increased blood levels and increased frequency of adverse reactions. and the possibility of further deterioration of liver function]. (Refer to [Pharmacokinetics] item)
3) Patients taking cyclosporine [May lead to increased blood levels and increased frequency of adverse reactions. Serious adverse reactions such as rhabdomyolysis may occur] (Refer to [Drug Interactions][Pharmacokinetics] item)
4) Pregnant women and women who may become pregnant or lactating. (Refer to [Pregnant and lactating women])
Precautions]
1. Administer with caution
(The following patients should be administered with caution)
1) Patients with liver disease or previous history, alcoholics (This drug is mainly distributed and acts on the liver, and there is a possibility of further deterioration of liver function. In addition, in alcoholics, there are reports of susceptibility to rhabdomyolysis.)
2) Patients with renal disease or a previous history of (Most of the reported cases of rhabdomyolysis are in patients with renal dysfunction, and additionally it has been found that dramatic deterioration of renal function can occur with rhabdomyolysis.)
3) Patients who are taking fibrates (benzofibrate, etc.), niacin [susceptible to rhabdomyolysis] (refer to [drug interactions] item).
4) Patients with hypothyroidism, patients with hereditary muscle diseases (myotonic disorders, etc.) or a family history of them, and patients with a past history of drug-related muscle disorders [predisposition to rhabdomyolysis has been reported].
5) Elderly patients (refer to [medication for elderly patients])
2. Important basic precautions
The following points should be fully noted in the case of using this product.
1) Before using this product, first use the basic therapy for hypercholesterolemia – food therapy, as well as reducing risk factors such as hypertension, smoking, etc. that cause ischemic heart disease and further exercise therapy.
2) For patients with abnormal values of clinical tests related to renal function, use this product only if it is judged that it is clinically necessary to combine it with fibrates. Rhabdomyolysis with acute renal function deterioration is likely to occur. In the event that a combination is necessary, periodic renal function tests should be performed and the drug should be discontinued immediately if any deterioration in renal function is detected, such as spontaneous symptoms (e.g. muscle pain, weakness), elevated CK (CPK), elevated blood and urine myoglobin, or elevated serum creatinine.
3) Liver function should be checked at least once between the start of drug administration and 12 weeks, and periodically (e.g. once every six months) thereafter.
4) Blood lipid values should be checked regularly while taking the drug, and administration should be stopped if no response to treatment is found.
3. Precautions for use
When delivering this preparation to the patient, instruct the patient to take the PTP-packaged agent after removing it from the PTP plate. (There have been reports of serious comorbidities such as perforation and complications such as mediastinitis due to the accidental administration of PTP plates with hard corners piercing the esophageal mucosa.)
4. Other precautions
(1) There are reported cases showing that immune necrotizing myopathy characterized by proximal muscle weakness, elevated CK (CPK), non-inflammatory muscle fiber necrosis, and positive anti-HMG-CoA reductase (HMGCR) antibodies persists even after discontinuation of the drug, so attention should be paid to adequately observe the patient’s status. In addition, there are reports of improvement in the condition after administration of immunosuppressive drugs. (Refer to [Serious Adverse Reactions])
(2) The development of cataracts was found in oral administration trials in dogs (3 mg/kg/day for more than 3 months and 1 mg/kg/day for more than 12 months). However, similar occurrences were not observed in other animals (rats, monkeys).
[Pregnant and lactating women use].
1. Administration to pregnant women or women who may become pregnant is prohibited. [The safety of administration in pregnancy has not been confirmed. In animal experiments (rats) during perinatal and lactation administration (1 mg/kg or more), death occurred in females before and after delivery. Deaths in females were also observed in rabbits during the organogenesis period (0.3 mg/kg or more). Fetal skeletal malformations have been reported in rats given large amounts of other HMG-CoA reductase inhibitors. Fetal congenital malformations have also been reported in humans following administration of other HMG-CoA reductase inhibitors during the third trimester of pregnancy].
2. Administration during lactation is prohibited. [Animal studies (rats) found transfer to breast milk].
[Pediatric Use].
The safety of the drug in children has not been confirmed (no experience with its use).
Use in elderly patients
In general, the physiological function of elderly patients is reduced, and care should be taken to reduce the dosage if adverse reactions are detected. [There are reports of susceptibility to rhabdomyolysis]
[Drug Interactions].
This agent is barely metabolized by the hepatic drug metabolizing enzyme P450 (CYP) (CYP2C9 has minimal metabolism).
1. Contraindications to combined drug use (not to be combined)
Drug name and other clinical symptoms – Treatment mechanism – Risk factors cyclosporine (bacteriophage)
Susceptible to serious adverse events such as rhabdomyolysis accompanied by rapid deterioration of renal function. The blood concentration of this drug is increased due to cyclosporine. (Cmax 6.6 times, AUC 4.6 times) 2. Precautions for combined use of drugs (matters to be noted when combining drugs)
Drug name and other clinical symptoms – Treatment mechanism – Risk factors Betablockers
Benzafibrate and others are prone to rhabdomyolysis accompanied by rapid renal deterioration. Stop using this drug immediately if you notice any deterioration of renal function such as self-induced symptoms (muscle pain, feeling of weakness), elevated CK (CPK), elevated myoglobin in blood and urine, and elevated serum creatinine. Both drugs have been reported to cause rhabdomyolysis.
Risk factor: The presence of abnormal clinical test values related to renal function. Niacin risk factor: The presence of renal disease. Kolalenamide
Because of the possibility of lowering the blood concentration of this drug, it is necessary to take koleleneamine after a sufficient time interval before taking this drug. Simultaneous administration may reduce the absorption of this drug. Erythromycin has the potential to cause rhabdomyolysis with dramatic renal deterioration. Stop using this drug immediately if you notice any deterioration in renal function such as spontaneous symptoms (e.g. muscle pain, weakness), elevated CK (CPK), elevated blood and urine myoglobin, and elevated serum creatinine. Combination doses of this drug should not exceed 1 mg per day. left may inhibit hepatic uptake of this agent (refer to [Pharmacokinetics]) When rifampin is combined, an increase in Cmax and AUC of up to 2.0-fold has been reported for pitavastatin. The combined dose of this product should not exceed 2 mg per day.[Overdose
There is no specific treatment for overdose. In case of overdose, symptomatic treatment and supportive treatment measures should be taken as needed. Hemodialysis does not significantly accelerate the clearance of pitavastatin due to the binding of large amounts of pitavastatin to plasma proteins.
Pharmacology and Toxicology
Pitavastatin calcium prevents the synthesis of cholesterol in the liver by antagonistically inhibiting HMG-CoA reductase, the rate-limiting enzyme necessary for the synthesis of the cholesterol pathway. The result promotes LDL receptor expression in the liver, resulting in increased uptake of LDL from the blood to the liver and therefore a decrease in total plasma cholesterol. In addition, the persistent impairment of cholesterol synthesis in the liver also leads to a decrease in the secretion of VLDL into the blood and thus a decrease in plasma triglycerides.
1. Inhibition of HMG-CoA reductase
Pitavastatin calcium had an antagonistic blocking effect on HMG-CoA reductase in an assay using rat liver microsomes, with an IC50 value of 6.8 nM for the blocking effect (in vitro assay).
2. Inhibition of cholesterol synthesis
Pitavastatin calcium showed a concentration-dependent inhibition of cholesterol synthesis in a test using human hepatocellular carcinoma derived cells (HepG2) (in vitro test). In addition, when administered orally, the cholesterol synthesis inhibition effect was selective in the liver (rats).
3. Hypolipidemic effect
Oral administration of pitavastatin calcium significantly reduced total plasma cholesterol and triglycerides (dog, guinea pig).
4. Inhibition of lipid accumulation and endothelial hypertrophy
Pitavastatin calcium inhibited the accumulation of cholesteryl esters in macrophages containing oxidized LDL (mouse monoglobular by-coming strain cells) (in vitro test). In addition, transoral administration also showed a significant inhibition of intimal hypertrophy in a model of carotid artery wear (rabbits).
5. Mechanism of action
1) Promotion of LDL receptor expression
Pitavastatin calcium promotes LDL receptor mRNA expression in HepG2 cells, increasing LDL binding, uptake, and ApoB catabolism (in vitro test). In addition, when administered orally, the expression of LDL receptor was promoted positively correlated with the dosage (guinea pigs).
2) VLDL secretion-lowering effect
Oral administration of pitavastatin calcium significantly reduced VLDL-triglyceride secretion (guinea pigs).
6. Effect on electrocardiographic QTc
In a randomized, double-blind, placebo-controlled, 4-group parallel and moxifloxacin-positive controlled trial involving 174 healthy subjects, this product did not result in clinically significant QTc interval prolongation or heart rate changes at doses up to 16 mg daily (4 times the maximum recommended daily dose).
7. Non-clinical toxicology
(1) Carcinogenicity, mutagenicity, reproductive impairment
In a 92-week carcinogenicity study in mice given pitavastatin at a maximum tolerated dose of 75 mg/kg/day, the maximum systemic exposure (based on AUC) was 26 times greater than at the maximum clinical dose of 4 mg/day, and no drug-associated tumors occurred. In a 92-week carcinogenicity study in rats, the incidence of thyroid follicular cell tumors was significantly increased at 25 mg/kg/day (295 times the maximum human dose of 4 mg/day based on AUC systemic exposure) when pitavastatin was administered by gavage at 1, 5, and 25 mg/kg/day. In a 26-week carcinogenicity study in transgenic mice (Tg rasH2) given pitavastatin at 30, 75 and 150 mg/kg/day by gavage, no clinically significant tumors were found. Pitavastatin was not mutagenic in the Ames test with or without metabolic activation of Salmonella typhimurium and Escherichia coli, the micronucleus test in mice after single and multiple doses in rats, the rat non-programmed DNA synthesis test, and the mouse comet test, and in the chromosomal aberration test, chromosomal aberrations were observed only at the highest dose tested, a dose that also induced high levels of cytotoxicity. Pitavastatin administered orally to male and female rats at 10 mg and 30 mg/kg/day, respectively, had no adverse effects on fertility when systemic exposure was 56 and 354 times the clinical exposure (based on AUC) of 4 mg/day, respectively. In a fertility study, pitavastatin administered to rabbits, male and female rabbits given 1 mg/kg/day (30 times the clinical systemic exposure of 4 mg/day based on AUC) and higher doses died. Although the cause of death has not been determined, rabbits had carnal signs of nephrotoxicity (whitening of the kidneys) suggestive of possible anemia. Low doses (15 times human whole-body exposure) did not show significant toxicity in adult males and females. However, reduced implantation, increased reabsorption, and reduced viability of fetal litters were observed.
2) Central nervous system toxicity
CNS vasculopathy, characterized by perivascular hemorrhage, edema, and perivascular space mononuclear cell infiltration, has been observed in experiments with other similar drugs in dogs. In dogs, at plasma drug concentration levels about 30 times higher than the average drug level taken at the highest recommended dose in humans, chemically similar analogs produced dose-dependent optic nerve degeneration (Wallerian Wallerian degeneration of retinal geniculate nerve fibers). In contrast, Wallerian degeneration was not observed with pitavastatin. Cataracts and lens clouding were observed at a therapeutic dose of 1 mg/kg/day (9 times the clinical exposure level based on the maximum AUC human dose of 4 mg/day) administered to dogs for 52 weeks.
Pharmacokinetics]
1. In vivo dynamics in healthy adults
(1) Blood concentration of a single oral dose (Japanese data)
When single oral doses of pitavastatin calcium 2 mg and 4 mg were administered to each of six healthy adult males on an empty stomach, the prodrug and its major metabolite, endosomes, were mainly present in the plasma. the pharmacokinetic parameters of the prodrug after 2 mg administration are shown in the table below. The effect of food on the pharmacokinetics of the prodrug was that a delay in Tmax and a decrease in Cmax occurred with a single postprandial dose compared to a single fasting dose, but there was no significant difference between pre- and postprandial dosing on AUC.
Tmax(hr)Cmax(ng/ml)AUC(ng.hr/ml)Fasting0.826.158.8Postprandial1.816.854.3
In a phase I clinical trial of pitavastatin calcium in the dosage range of 1 to 8 mg in healthy adult Chinese men, compared with Japanese, either dosage of pitavastatin entered plasma rapidly after administration and decayed in a 2- or 3-phase fashion after reaching the highest blood concentration, although the blood concentration was slightly lower. In this trial, no significant differences in pharmacokinetic parameters were found between Chinese and Japanese, and no effect of diet on pharmacokinetic parameters was found.
2) Blood concentrations at repeated oral administration (Japanese data)
Six healthy adult males received pitavastatin calcium 4 mg orally once daily after breakfast and repeated dosing for 7 consecutive days. The pharmacokinetic parameters are shown in the table below, with minimal variation caused by repeated dosing and a T 1/2 of approximately 11 hours.
Tmax (hr) Cmax (ng/ml) Cmin (ng/ml) AUC (ng.hr/ml) T 1/2 (hr) on the first day of administration 1.755.61.417410.5 on the seventh day of administration 1.159.52.222111.6 In addition, when pitavastatin calcium 2 mg was administered orally once daily for five consecutive days in six senior versus five non-senior individuals There were no significant differences in pharmacokinetic parameters between the two groups.
In a phase I clinical trial of 7 consecutive days of oral repeated administration of pitavastatin calcium 1-4 mg dosage range in healthy adult Chinese males, pitavastatin reached steady state on days 2-3 of administration with little to no accumulation. In this trial, no significant differences in pharmacokinetic parameters were found between Chinese and Japanese.
2. In vivo dynamics in patients with hepatic dysfunction
1) Patients with cirrhosis (non-Japanese data)
When 12 patients with cirrhosis and 6 healthy adults received a single oral dose of pitavastatin calcium 2 mg, the concentration in plasma was 1.3 times the Cmax and 1.6 times the AUC in patients with Child-Pugh grade A and 2.7 times the Cmax and 3.9 times the AUC in patients with Child-Pugh grade B compared to healthy adults.
2) Fatty liver (Japanese data)
Six patients with hepatic dysfunction (fatty liver) versus six patients with normal liver function received pitavastatin calcium 2 mg orally once a day for 7 consecutive days, with minimal effect on drug dynamics.
3. in vivo dynamics in patients with renal dysfunction
(Japanese data)
In 6 hypercholesterolemic patients with renal dysfunction (blood creatinine 1.5 to 3 times the upper limit of normal) versus 6 hypercholesterolemic patients with normal renal function, oral administration of pitavastatin calcium 2 mg once a day for 7 consecutive days resulted in a 1.7-fold higher Cmax and 1.9-fold higher AUC on day 7 of administration in patients with renal dysfunction compared to patients with normal renal function.
4. Drug interactions
1) In vitro tests
Pitavastatin calcium had no effect on the metabolism of toluenesulfonylurea, a substrate for CYP2C9, and testosterone, a substrate for CYP3A4, in an injury test on a model substrate for CYP molecular classes. In addition, the organic anion-transporting polypeptide OATP1B1 (OATP-C/OATP2) was involved in the intrahepatic uptake of pitavastatin calcium, and cyclosporine, erythromycin and rifampicin impeded the uptake.
2) Clinical trials
(1) Cyclosporine (bacteriocin) (Japanese data)
In 6 healthy adult males, pitavastatin calcium 2 mg was administered orally once a day for 6 days repeatedly, and the Cmax and AUC of pitavastatin in plasma increased to 6.6-fold and 4.6-fold when cyclosporine 2 mg/kg was administered orally as a single dose 1 hour before pitavastatin calcium administration on the 6th day.
(2) Erythromycin (non-Japanese data)
In 18 healthy adults, erythromycin 500 mg was administered orally four times a day for 6 days. On the morning of the fourth day, 4 mg of pitavastatin calcium was administered in combination with pitavastatin calcium, and the plasma Cmax and AUC of pitavastatin increased to 3.6-fold and 2.8-fold, respectively, compared with those of pitavastatin calcium alone.
(3) Rifampin (non-Japanese data)
In 18 healthy adults, rifampicin 600 mg was administered orally once a day for 15 days, and when 4 mg of pitavastatin calcium was combined once a day on days 11 to 15, the Cmax in plasma concentration of pitavastatin increased to 2.0-fold and the AUC increased to 1.3-fold compared with that of pitavastatin calcium alone.
(4) Betablockers (non-Japanese data)
In 24 healthy adults, pitavastatin calcium 4 mg was administered orally once a day for 6 days, and when a 7-day co-administration of fenofibrate or gemfibrozil was performed from day 8, the plasma concentration (AUC) of pitavastatin increased to 1.2-fold with co-administration of fenofibrate and to 1.4-fold with co-administration of gemfibrozil.
5. Urinary excretion (Japanese data)
Urinary excretion of single oral doses of pitavastatin calcium 2 mg and 4 mg in each of 6 healthy adult males was low, with less than 0.6% of the drug in its original form and less than 1.3% of the endosomes, and less than 2% in total. Urinary excretion rates of prodrugs and endosomes in six healthy Japanese adult males given once daily oral pitavastatin calcium 4 mg for 7 consecutive days did not increase from the first dose to the 7th day of administration and decreased rapidly with discontinuation of dosing.
6. Metabolism
Pitavastatin calcium is metabolized in vivo by cyclization to lactosomes, beta-oxidation of the side chain, hydroxylation of the quinoline ring, and glucuronide or aminoethanesulfonic acid internalization, and is excreted primarily in the feces (rats, dogs). In humans, the prodrug and its main metabolite, lactosomes, were found in blood, while other metabolites such as derivatives of propionic acid, and 8-position hydroxylates were only found in very small amounts. Similarly only very small amounts of prodrugs, lactones, dehydrolactones, 8-position hydroxylates and their ligands were found in urine.
7. Drug metabolizing enzymes
Pitavastatin calcium was only rarely metabolized in metabolism assays using human liver microsomes and was mainly produced by CYP2C9 to produce the 8-site hydroxamer (in vitro assay).
8. Plasma protein binding rate
The plasma protein binding rate of pitavastatin calcium is very high, 99.5%~99.6% in human plasma and 4% human serum albumin, and 94.3%~94.9% in 0.06% human α1 acidic glycoprotein binding rate (in vitro test).
Storage
Store under shade and seal.
Package
Aluminum-plastic packaging, 7 tablets x 1 plate/box, 7 tablets x 2 plates/box, 10 tablets x 1 plate/box, 10 tablets x 2 plates/box, 12 tablets x 1 plate/box, 12 tablets x 2 plates/box.
【Validity】 18 months
【Execution standard
【Approval number】
【Drug marketing license holder
Company name: Shandong Qidu Pharmaceutical Co.
Registered address: No. 17, Hongda Road, Linzi District, Zibo City, Shandong Province
Postal code: 255400
Telephone number: 0533-7150888 7152367
Fax number: 0533-7155078
Web
Address: http://www.qidu-pharma.com
Manufacturer
Company name: Shandong Qidu Pharmaceutical Co.
Address: No.17 Hongda Road, Linzi District, Zibo City, Shandong Province
Postal code: 255400
Telephone number: 0533-7150888 7152367
Fax number: 0533-7155078
Web
Address: http://www.qidu-pharma.com