Date of approval.
Date of revision.
Pitavastatin Calcium Dispersible Tablets Instructions
Please read the instructions carefully and use under the guidance of a physician
Drug Name
Generic name: Pitavastatin Calcium Dispersible Tablets
English name: Pitavastatin Calcium Dispersible Tablets
Hanyu Pinyin: Pifatatinggai Fensanpian
Ingredients
The active ingredient of this product is pitavastatin calcium.
Chemical name: (+)-Bis{(3R,5S,6E)-7-[2-cyclopropyl-4-(4-fluorophenyl)-3-quinolinyl]-3,5-dihydroxy-6-heptenoic acid} calcium.
The chemical structure formula is
Molecular formula: C50H46CaF2N2O8
Molecular weight: 880.98
【Properties】.
This product is white or off-white film-coated tablets, with a single-sided inscription, and appears white or off-white after removing the coating.
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]
2 mg
Dosage]
This product can be swallowed directly or taken orally, or it can be put into an appropriate amount of warm water and dispersed well before taking it orally.
Usually, adults take 1 to 2 mg orally once a day.
The dose may be increased or decreased according to age and treatment response, and the maximum daily dose is 4 mg 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 [Precautions] [Pharmacokinetics] item).
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-rhabdomyolysis symptoms such as elevated CK (CPK), myoglobinuria, muscle pain and weakness. Dosing above 8 mg in foreign clinical trials was discontinued 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. The main symptoms included abdominal pain, rash, tiredness, numbness, itching, etc. There were 50 cases (5.6%) of adverse reactions with autonomic symptoms. 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 occurred in 1082 of 19921 safety analysis subjects (5.4%) in post-marketing safety monitoring (at the end of the reexamination).
In the imported clinical trial of pitavastatin calcium in China, adverse reactions occurred in 23 (10.1%) of 227 patients taking pitavastatin. The main manifestation was gastrointestinal dysfunction, with an incidence of 6.3% in the 2 mg dose group, 0.9% of patients with more than 3-fold elevation of hepatic transaminases during use, and 1 case (1/109) with >10-fold elevation of CK in the 4 mg group.
1. serious adverse reactions
1) Rhabdomyolysis (incidence unknown): rhabdomyolysis characterized by muscle pain, feeling of weakness, elevated CK (CPK), and elevated myoglobin in blood and urine may occur, and along with rhabdomyolysis, severe renal dysfunction such as acute renal failure may occur, and administration of the drug should be discontinued 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 a significant increase in AST (GOT) and ALT (GPT) may occur, so liver function tests should be performed periodically, and if abnormalities are found, drug administration should be discontinued for proper management.
(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 when adequate observation is made and abnormalities are detected, and appropriate disposition should be made.
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, endophthalmitis, 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 3) elevated CK (CPK), muscle pain, feeling of weakness muscle cramps, elevated myoglobin mental nervous system headache, feeling of heavy head, numbness, feeling of dizziness 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 Frequency of occurrence based on approval The frequency is calculated at the time of approval and the sum of safety monitoring.
(Note 1) At this time, the administration of the drug should be stopped.
(Note 2) Adequate observation should be made and appropriate treatment such as discontinuation of drug administration should be made in case of abnormalities.
(Note 3) Pre-existing symptoms of rhabdomyolysis may occur, so adequate observation should be made and drug administration should be stopped if necessary.
3. Other reported adverse reactions to statin drugs
(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 statin drugs, and hypoglycemic reactions have also been reported for some statin drugs.
(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 and confusion, etc. Most of them are non-serious and reversible reactions, which can generally be recovered after stopping 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. Administration of pitavastatin calcium to these patients may result in increased blood levels and an increased frequency of adverse reactions. And there is a possibility of further deterioration of liver function (refer to item [Pharmacokinetics]).
(3) Patients taking cyclosporine: May result in increased blood levels and increased frequency of adverse reactions. Serious adverse reactions such as rhabdomyolysis may occur (refer to [Drug Interactions] [Pharmacokinetics]).
(4) Pregnant women and women who may be pregnant and lactating (refer to [Pregnancy and Lactation] item).
Precautions]
1. The following patients should be administered with caution.
(1) Patients with liver disease or previous history, alcoholics. Pitavastatin calcium is mainly distributed and acts on the liver, and there is a possibility of further deterioration of liver function. In addition, rhabdomyolysis has been reported in alcoholics who are prone to develop 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 a sharp deterioration in renal function can occur with rhabdomyolysis.
(3) Patients who are taking fibrates (benzofibrate, etc.) and niacin are susceptible to rhabdomyolysis (refer to [Drug Interactions] item).
(4) Patients with hypothyroidism, patients with hereditary muscle diseases (myotonic disorders, etc.) or family history, and patients with a past history of drug-related muscle disorders have been reported to be prone to rhabdomyolysis.
(5) Elderly patients (refer to [Geriatric Use]).
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 to be 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 pitavastatin calcium should be discontinued immediately if deterioration in renal function is detected, such as spontaneous symptoms (e.g. muscle pain, weakness), elevated CK (CPK), elevated blood and urine myoglobin, and 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 during dosing and dosing 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 the hard horn 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) antibody persists even after discontinuation of the drug, so attention should be paid to adequately observe the patient’s status. In addition, there are reported columns showing improvement of the condition after administration of immunosuppressive drugs (refer to [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 studies (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 organogenesis trials (0.3 mg/kg or more) in rabbits. 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) have found transfer to breast milk.
[Pediatric Use].
The safety of the drug in children has not been confirmed (no experience with its use).
[Geriatric use].
In general, the physiological function of elderly patients is reduced, so care should be taken to reduce the dosage if adverse reactions are found. Rhabdomyolysis has been reported to occur.
Drug Interactions]
Pitavastatin calcium is barely metabolized by the hepatic drug metabolizing enzyme P450 (CYP) (CYP2C9 has very little metabolism).
1. Contraindications to combined drug use (not to be combined)
Drug name and other clinical symptoms – Treatment mechanism – Risk factors Cyclosporine (bacteriophage) is prone to serious adverse events such as rhabdomyolysis accompanied by acute deterioration of renal function. As cyclosporine increases the blood concentration of pitavastatin calcium. (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, etc. are prone to rhabdomyolysis accompanied by rapid deterioration of renal function. Stop using pitavastatin calcium immediately if you notice 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. Because of the potential for lower blood levels of pitavastatin calcium, a sufficient interval between doses of colesevelam is required before administration of pitavastatin calcium. Simultaneous administration may reduce the absorption of pitavastatin calcium. Erythromycin has the potential to develop rhabdomyolysis accompanied by a rapid deterioration in renal function. Discontinue pitavastatin calcium immediately if worsening renal function such as spontaneous symptoms (e.g. muscle pain, feeling of weakness), elevated CK (CPK), elevated blood and urine myoglobin, and elevated serum creatinine are observed. Combination doses of pitavastatin should not exceed 1 mg/day. left may inhibit hepatic uptake of this agent (refer to “Pharmacokinetics”) When rifampin is combined, an increase in plasma Cmax and AUC of up to 2.0-fold has been reported for pitavastatin. The combined dose of pitavastatin should not exceed 2 mg per day.[Overdose
There is no specific treatment for overdose. In case of overdose, symptomatic 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 impaired 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 the expression of LDL receptor mRNA 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 pig).
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, pitavastatin calcium at doses up to 16 mg daily (4 times the maximum recommended daily dose) did not result in clinically significant QTc interval prolongation or heart rate changes.
7. Non-clinical toxicology
1) Carcinogenicity, mutagenicity, and 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 clinical maximum 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 detected. 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 rat multiple dosing, 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 greater than 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, the rabbits had visual 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, chemically similar analogues produced dose-dependent optic nerve degeneration (Wallerian Wallerian degeneration of retinal geniculate nerve fibers) at plasma drug concentration levels about 30 times higher than the average drug level taken at the highest recommended dose in humans. 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 AUC human maximum dose of 4 mg/day) administered to dogs for 52 weeks.
Pharmacokinetics]
1. Pharmacokinetic characteristics of healthy adults
(1) Blood concentration of a single oral dose
When single oral doses of pitavastatin calcium 2 mg and 4 mg were administered to each of six healthy adult Japanese males on an empty stomach, the prodrug and its major metabolite, endosomes, were mainly present in plasma. 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 with 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 1-8 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 manner 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 dosing
Six healthy adult Japanese males received pitavastatin calcium 4 mg orally once daily after breakfast and repeatedly administered for 7 consecutive days. The pharmacokinetic parameters are shown in the table below, with minimal changes caused by repeated dosing and a T1/2 of approximately 11 hours.
Tmax(hr)Cmax(ng/ml)Cmin(ng/ml)AUC(ng.hr/ml)T1/2(hr)First day of dosing 1.755.61.417410.5 Seventh day of dosing 1.159.52.222111.6 In addition, when pitavastatin calcium 2 mg was administered orally once daily for 5 consecutive days in 6 senior versus 5 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 accumulation. In this trial, no significant differences in pharmacokinetic parameters were found between Chinese and Japanese.
2. Pharmacokinetic characteristics 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. pharmacokinetic characteristics of 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 1.7 times the Cmax and 1.9 times the AUC on day 7 of dosing in patients with renal dysfunction compared with patients with normal renal function.
4. Drug interactions
1) In vitro tests
Pitavastatin calcium had no effect on the metabolism of toluenesulfonylurea, a substrate of CYP2C9, and testosterone, a substrate of CYP3A4, in an injury test on a model substrate of the CYP molecule class. 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 hindered 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 six days, and on the morning of the fourth day, 4 mg of pitavastatin calcium was combined with pitavastatin calcium, at which time the plasma Cmax of pitavastatin increased to 3.6 times and the AUC increased to 2.8 times compared with 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 on days 11-15, when 4 mg of pitavastatin calcium was administered once a day in combination, the Cmax and AUC of pitavastatin increased to 2.0-fold compared with those 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 when co-administered with fenofibrate and 1.4-fold when co-administered with 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 oral pitavastatin calcium 4 mg once daily 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 metabolic assays using human liver microsomes and was mainly produced by CYP2C9 as an 8-site hydroxylator (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】
Polyamide/aluminum/polyvinyl chloride cold pressed solid pharmaceutical compound hard tablets and pharmaceutical aluminum foil, 6 tablets/box, 12 tablets/box, 7 tablets/box, 14 tablets/box, 10 tablets/box, 20 tablets/box, 28 tablets/box.
[Expiration date
12 months
【Execution standard
Approval number】
State Drug Certificate H20130115
[Drug Marketing Licensee
Name: Zhejiang Jingxin Pharmaceutical Co.
Registered address: No. 800 East Xinchang Avenue, Yulin Street, Xinchang County, Zhejiang Province
Zip code: 312500
Contact: Sales Hotline (0575)86096832 Complaint Telephone (0575)86098209
Fax: (0575)86096898
Website: www.jingxinpharm.com
【Manufacturer】
Company name: Zhejiang Jingxin Pharmaceutical Co.
Production Address: No. 800 East Xinchang Avenue, Yulin Street, Xinchang County, Zhejiang Province
Postal Code: 312500
Contact：Sales Hotline (0575)86096832 Complaint Telephone (0575)86098209
Fax: (0575)86096898
Website: www.jingxinpharm.com