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Active ingredients
Pitavastatin
Release form
Pills
Composition
Pitavastatin calcium 4.18 mg,; which corresponds to the content of pitavastatin 4 mg; Excipients: lactose monohydrate - 252.34 mg, low-level hyprolosis - 50.16 mg, hypromellose - 5.32 mg, magnesium aluminometasilicate - 6.4 mg, magnesium stearate - 1.6 mg. Opadry white - 9 mg, including hypromellose - 5.952 mg, titanium dioxide - 2.409 mg, triethyl acetate - 0.594 mg, colloidal silicon dioxide - 0.045 mg.
Pharmacological effect
Pitavastatin is a competitive inhibitor of HMG-CoA (3-hydroxy-3-methylglutarycoenzyme A) reductase, an enzyme that catalyzes the initial stage of cholesterol synthesis, the formation of mevalonic acid from HMG-CoA. Since the conversion of HMG-CoA and mevalonic acid is the initial stage of cholesterol synthesis, the use of pitavastatin does not cause the accumulation of potentially toxic sterols in the body. HMG-CoA is easily metabolized to acetyl-CoA. which is involved in many processes of synthesis in the body. Clinical studies have shown the effectiveness of the drug Livazo in reducing the concentration of total cholesterol (total cholesterol) in plasma, low-density lipoprotein cholesterol (LDL cholesterol), very low-density lipoprotein cholesterol (cholesterol-VLDL). triglycerides (TG) and apolipoprotein B (Aro-B), as well as increasing the concentration of high-density lipoprotein cholesterol (HDL cholesterol) and apolipoprotein A1 (Aro-Al).
Pharmacokinetics
Absorption; Pitavastatin is rapidly absorbed in the upper gastrointestinal tract (GIT). the maximum concentration (Cax) in the blood plasma is reached within I hour after taking the drug. Reception write does not affect absorption. Pitavastatin spacing in plasma decreases by 43% when taken together with a fat niche, but the area under the concentration-time pharmacokinetic curve (AUC) remains unchanged. Unchanged drug undergoes enterohepatic circulation and is well absorbed from the jejunum and ileum. Absolute bioavailability of pitavastatin 51% .; Distribution; more than 99% of pitavastatin binds to plasma proteins, mainly albumin n alpha-1 acid glycoprotein. The average distribution of 133 liters. Pitavastatin actively penetrates hepatocytes with the help of OATP1BI and OATP1BZ transport proteins.AUC varies within 4-fold increase from minimum to maximum value. Pitavastatin is not a substrate for P-glycoprotein. ; Metabolism; Plasma contains mostly unchanged pitavastatin. The main metabolite is an inactive lactone, which is formed from a pitavastatin glucuronide ether-type conjugate with the participation of UDP-glucuronosyltransferase (UGT1A3 and 2B7). 1 (Cytochrome P450 affects the metabolism of pitavastatin is minimal. The isoenzyme CYP2C9 and (to a lesser extent the isoenzyme CYP2C8) are involved in the metabolism of pitavastatin to secondary metabolites; Excretion; Pitavastatin, in its unchanged form, is rapidly excreted from the liver with a bile, but is exposed to the excretion; pitavastatin in an unchanged form is quickly excreted from the liver, but is exposed to the metabolism of secondary metabolites; its long-lasting effect. Less than 5% of pitavastatin is excreted by the kidneys. The half-life from plasma varies from 5.7 hours (single dose) to 8.9 hours (in equilibrium), the mean clearance value is 43.4 l / hour e single intake.
Indications
Primary hypercholesterolemia, including heterozygous familial hypercholesterolemia (type II hyperlipidemia subjects, as of Fredrikson, or as a mixed-type hypercholesterolemia (Frederickson class II), hypertriglyceridemia (type IV hyperlipidemia, and Fredrikson's classification,), hypertriglyceridemia (type IV hyperlipidemia and Fredrikson's classification, but asymptoma, as a group of subjects, as a group of subjects, as a result of FDA; (for example, exercise, weight loss) are insufficient.
Contraindications
- hypersensitivity to pitavastatin, auxiliary components of the drug and other HMG-CoA reductase inhibitors (statins); - severe hepatic impairment (more than 9 points on the Child-Pugh scale) or class C according to the Child-Pugh classification, liver disease and the active phase, including a persistent increase in the activity of liver transaminases in the serum (more than 3 times compared with the upper the boundary of the norm (VGN)); - lactose intolerance, lactase deficiency or glucose-galactose malabsorption; - myopathy; - simultaneous administration of cyclosporine; - pregnancy, breastfeeding period, lack of adequate methods of contraception in women of childbearing age; - age up to 18 years (efficacy and safety have not been established); With caution; If there is a risk of myopathy / rhabdomyolysis - renal failure,hypothyroidism, personal or family history of hereditary muscular diseases and previous history of muscular toxicity with the use of other HMG-CoA inhibitors or fibrates, excessive alcohol consumption, age over 70 years, history of liver disease.
Dosage and administration
Inside, the pill must be swallowed whole. The pill is preferred at the same time of day, preferably in the evening, in accordance with the circadian rhythm of lipid metabolism. Patients should adhere to a cholesterol-lowering diet prior to treatment and in the process. The initial dose of the drug is 1 mg / day once. If necessary, the dose of the drug is increased at intervals of at least 4 weeks to 2 mg / day. The dose should be selected individually in accordance with the concentrations of LDL cholesterol, the purpose of treatment and the patient's response to treatment. Most patients require a dose of 2 mg. The maximum daily dose is 1 mg.; Patients with mild and moderately impaired liver function: the maximum daily dose of 2 mg is recommended. Patients with impaired renal function: with impaired renal function of a mild degree of heaviness (it is desirable to objectively evaluate this degree with a reflection of CC or glomerular velocity). filtration), Livazo should be used with caution. Data on the use of a maximum daily dose of 4 mg for kidney dysfunction of any severity are limited, therefore, it is necessary to prescribe a maximum daily dose of 4 mg only with careful monitoring of renal function after gradually increasing the dose. It is not recommended for patients with severely impaired renal function to prescribe a maximum daily dose of 4 mg; It is recommended to consider limiting the maximum daily dose to 2 mg in case of severe renal failure.; Patients of advanced age: dose adjustment is not required.
Side effects
In controlled clinical trials, when taking recommended doses, less than 4% of patients treated with Lnvazo. was excluded from the study due to the development of undesirable reactions. The most common was miapgia.; Depending on the frequency of occurrence, the following undesirable reactions are distinguished according to the WHO classification: very often: ≥10, often: from ≥1 / 100 to <1/10, infrequently: from ≥1 / 1000 to <1 / 100, rarely: from ≥1 / 10,000 to <1/10000,very rarely: <1/10000 n frequency unknown (available data do not allow to determine the frequency) .; From the side of hematopoietic organs: infrequently - anemia.; From the side of metabolism: infrequently - anorexia.; Mental disorder: often - insomnia.; nervous system: often - headache; infrequently - dizziness, taste disturbance, drowsiness. From the sense organs: infrequently - ringing in the ears; rarely - decreased visual acuity. From the skin: rarely - pruritus, soup; rarely - urticaria, erythema. From the musculoskeletal system: often - myalgia, arthralgia; infrequently - muscle spasms.; From the urinary system: infrequently - pollakiuria.; From the digestive system: often - constipation, diarrhea, dyspepsia, nausea; infrequently - abdominal pain, dry oral mucosa, vomiting; rarely - glossodynamia, acute pancreatitis, cholestatic jaundice.; Laboratory indicators: infrequently - increased activity of liver transaminases ACT, ALT, increased activity of creatine phosphokinase (CPH); 49 patients out of 2800 (1.8%). Elevated levels of VGN 10 times or more with concomitant muscle symptoms were rarely observed, and were observed in only one patient out of 2406 patients who received 4 mg of Livazo (0.04%) in the program of clinical studies.; Other: infrequent - asthenia, malaise, increased fatigue, peripheral edema; postmarketing experience; A two-year prospective post-registration follow-up study was conducted in approximately 20,000 patients in Japan. The vast majority of these patients received pitavastatin at a dose of 1 or 2 mg, and not 4 mg. In 10.4% of patients, undesirable reactions were reported, in which causal relationship with pitavastatin cannot be excluded, and 7.4% of patients discontinued treatment due to the development of adverse reactions. The incidence of myalgia was 1.08%. Most unwanted reactions were mild. For 2 years, the incidence of adverse reactions was higher in patients with a history of drug allergy (20.4%) or liver or kidney disease (13.5%) .; Adverse reactions and their incidence, observed in a prospective post-registration study,but not in international controlled clinical trials with the use of the drug and the recommended doses are given below. From the side of the liver and biliary tract: rarely - impaired liver function; From the musculoskeletal system: rarely - myopathy, rhabdomyolysis; In the study of post-registration observation there were two reports of rhabdomyolysis, in which patients required hospitalization (0.01% of patients); In addition, there are spontaneous reports of effects on the musculoskeletal system, including myalgia and myopathy in patients treated with Livazo in all recommended doses. Reports of rhabdomyolysis with and without acute renal failure, including lethal rhabdomyolysis, were also received; spontaneous reports of the following undesirable reactions (frequency based on cases observed in post-registration studies) were also received; nervous system side: infrequently - hypoesthesia; from the alimentary system: rarely - abdominal discomfort; undesirable effects when using other statins: - sleep disturbance, including nightmares; - amnesia; - sexual dysfunction; - depression; - intestitic lung disease; - diabetes mellitus: the frequency of onset depends on the presence or absence of risk factors (fasting blood glucose concentration ≥5 mmol / l, BMI> 30 kg / m2, elevated TG concentration, arterial hypertension in history); - increased glycated hemoglobin.