Pitavastatin

Pharmacological properties

Pharmacodynamic parameters. pitavastatin is a synthetic lipid-lowering agent that controls cholesterol (xc) synthesis by competitively inhibiting the liver enzyme 3-hydroxy-3-methylglutaryl-coenzyme a (hmg-koa) reductase. as a result, there is a compensatory increase in the expression of LDL receptors, which contributes to increased LDL catabolism.

The structure of pitavastatin, which is different from other representatives of this group, determines its high affinity for HMG-CoA reductase and a pronounced effect on the level of LDL cholesterol and HDL cholesterol in blood plasma.

Livazo lowers elevated levels of LDL cholesterol, total cholesterol, TG, apolipoproteins (Apo) B, as well as the ratio of TG / HDL and Apo-B / Apo-A1 and increases the content of HDL cholesterol and Apo-A1.

The magnitude of the decrease in LDL cholesterol with pitavastatin (2 and 4 mg) is comparable to that with atorvastatin (10 and 20 mg) and simvastatin (20 and 40 mg).

Pitavastatin also increases the level of adiponectin in the blood plasma, a protein with anti-atherosclerotic and anti-inflammatory properties, and contributes to the regression of atherosclerotic plaque (approximately 17%).

Pharmacokinetic parameters. Pitavastatin absorption occurs mainly in the small intestine. Eating does not affect this process. Bioavailability is 51%; time to reach C_max in blood plasma - 1 h.

Over 99% of pitavastatin binds to plasma proteins, mainly albumin and α₁-acid glycoprotein.

Pitavastatin is mainly metabolized in the liver. It undergoes glucuronidization with uridine-5-diphosphate-glucuronyl transferases (UGT1A3 and UGT2B7) to form the main circulating metabolite, pitavastatin lactone.

The cytochrome P450 system is practically not involved in the metabolism of pitavastatin. Exposure is provided by CYP 2C9 and to a lesser extent - CYP 2C8.

T_½ from plasma in steady state is almost 9 hours

It is excreted mainly with feces (79%) and 15% with urine.

AIT of pitavastatin increases in females, as well as in patients over the age of 65, which does not affect the safety and effectiveness of the drug.

The content of pitavastatin in blood plasma 1 hour after administration depends on the dose and has a feedback with body weight, which may indicate higher concentrations of the substance in children.

In the study, the pharmacokinetics of pitavastatin in healthy volunteers of different races (Mongoloids and Caucasoids) were similar.

Indications

Elevated levels of total cholesterol and cholesterol of LDL in the blood of patients (age 6 years) with primary hypercholesterolemia and mixed dyslipidemia in case of insufficient response to compliance with dietary restrictions and the use of other non-drug methods.

Application

It is necessary to adhere to the restriction of the content of cholesterol in the diet both before and during treatment with the drug.

Apply exclusively per os without violating the integrity of the pill. It is more advisable in the evening, at the same time. Eating does not affect the effectiveness of the drug.

If it is impossible to swallow a tablet without violating its integrity, it should be dissolved in water (1 glass) and immediately drink it. And then immediately drink the volume of water used to rinse the indicated container.

As a rule, the starting dose of the drug is 1 mg once a day. With dose adjustment, the interval between changes is ≥4 weeks. Dose selection is carried out individually and is determined by the content of LDL cholesterol in the blood, the clinical condition of the patient and the treatment regimen. The maximum daily dose is 4 mg.

In elderly patients, the dose is not adjusted.

With caution, they are used without dose adjustment in patients with mild renal failure.

In patients with minor and moderate renal failure, pitavastatin is used in a dose of 4 mg exclusively against the background of careful monitoring of renal function after a gradual increase in dose.

Pitavastatin in a dose of 4 mg is not used in patients with severe renal impairment.

In patients with mild to moderate hepatic insufficiency, 4 mg pitavastatin is not used. It is possible to use pitavastatin at a dose of 2 mg / day against the background of scrupulous monitoring of liver function indices.

Children aged 6 years and adolescents with heterozygous familial hypercholesterolemia: initial dose - 1 mg / day. The maximum daily dose: children aged 6–9 years - 2 mg; ≥10 years - 4 mg.

Contraindications

• Hypersensitivity to the active substance or to any of the auxiliary ingredients of the drug, as well as to other statins;

• severe impaired liver function; active stage of hepatic pathology or a persistent increase in 3 values ​​of the upper limit of normal (VGN) activity of aminotransferases in blood serum;

• myopathy
• combined use with cyclosporine;

• pregnancy;

• lactation period.

Side effects

• Anemia; a complete lack of appetite with an objective need for nutrition; insomnia cephalgia, dizziness, violation of taste perception, drowsiness, decreased sensitivity to irritants; decreased visual acuity; tinnitus; nausea, vomiting, dyspeptic symptoms, diarrhea, constipation, abdominal pain, xerostomia, glossodynia, acute pancreatitis, gastrointestinal discomfort; increased levels of aminotransferases, intrahepatic cholestasis, impaired liver function, liver pathology; rashes, itching, erythema, urticaria; muscle pain (the most common effect), joints, muscle cramps; myopathy (including immuno-mediated necrotic), rhabdomyolysis; frequent urination; weakness, fatigue, malaise, peripheral edema.

There is also the possibility of developing negative effects inherent in the class of statins.

special instructions

The patient should immediately inform the doctor regarding any disturbance that has arisen in him from the muscular system. in any case, with the development of muscle weakness, pain or soreness, especially against the background of an increase in body temperature or malaise, it is required to establish the content of creatine kinase in the blood.

Assign with caution to patients with a high probability of rhabdomyolysis.

Therapy does not start in the case of creatinine clearance values ​​of 5 values ​​of VGN.

Discontinue therapy if there is an increase in the content of creatine kinase in the blood of 5 values ​​of VGN, as well as if the content of creatine kinase in the blood is 5 values ​​of VGN, but there are pronounced muscle disorders. In case of regression of symptoms and normalization of creatine kinase content, it is possible to resume taking the drug (daily dose of 1 mg) with careful monitoring of the patients condition.

The use of pitavastatin is resumed 1 week after the withdrawal of fusidic acid. As an exception, if necessary, prolonged use of fusidic acid after careful analysis may be combined with pitavastatin against the background of careful medical monitoring of the patients condition.

With caution, patients with liver pathology or alcohol abusers are prescribed.

Monitoring of hepatic function is required before and during pitavastatin therapy.

The therapy is canceled in the case of a persistent increase in plasma activity of aminotransferases of 3 values ​​of VGN.

With caution, patients with moderate and severe renal impairment are prescribed. The dose is increased gradually and exclusively against the background of scrupulous monitoring of renal function. Pitavastatin in a dose of 4 mg is not used in patients with severe renal impairment.

Monitoring of the clinical condition and biochemical parameters in patients who have an increased likelihood of hyperglycemia is required.

If the patient is expected to develop diffuse parenchymal lung disease, it is necessary to cancel treatment with the drug.

Due to the lactose content in Livazo tablets, the drug should not be taken in patients with galactosemia, Lapp lactase deficiency or glucose-galactose malabsorption syndrome.

Do not use in pregnant women and during lactation.

There is currently no information on the effects on fertility.

During the period of taking Livazo, you should avoid driving or working with other mechanisms.

Therapy of patients aged 6-18 years is carried out exclusively under the supervision of a specialist with experience in the treatment of such lipid metabolism disorders and with constant monitoring of the patients condition.

Girls and women of childbearing age should observe contraception against the background of the use of Livazo.

There has been no study of the safety and effectiveness of Livazo in children under the age of 6 years.

Interactions

Do not combine with cyclosporine.

In the case of antibiotics of the macrolide group, as well as fusidic acid, Livazo therapy should be discontinued for this period.

Used with caution in combination with vitamin B₃ and derivatives of fibroic acid.

AIT of pitavastatin increases in case of simultaneous use with rifampicin and slightly changes when combined with protease inhibitors.

In case of combined use with warfarin, monitoring of the hemostatic system (prothrombin time or INR) is required.

There is no interaction with the substrate of P-glycoprotein digoxin and clinically pronounced changes in the content of pitavastatin in blood plasma when combined with CYP 3A4 inhibitors.

Overdose

In case of taking an excessive dose, an increase in the manifestations of undesirable effects is likely. there is no specific treatment and antidote, as well as the effect of hemodialysis. symptomatic therapy, as needed - supportive. monitoring of liver function and creatine kinase levels in the blood should be ensured.

Storage conditions

In a place inaccessible to children, in packaging at a temperature of ≤25 ° c.