Livazo film-coated tablets 2 mg blister No. 100

Instructions for Livazo film-coated tablets 2 mg blister No. 100

Composition

active ingredient: pitavastatin calcium;

1 film-coated tablet contains 1.045 mg of pitavastatin calcium equivalent to 1 mg of pitavastatin, or

1 film-coated tablet contains 2.09 mg of pitavastatin calcium equivalent to 2 mg of pitavastatin, or

1 film-coated tablet contains 4.18 mg of pitavastatin calcium equivalent to 4 mg of pitavastatin;

Excipients: lactose monohydrate, low-substituted hydroxypropylcellulose, hypromellose, magnesium aluminum silicate, magnesium stearate, titanium dioxide (E 171), triethyl citrate, colloidal anhydrous silicon dioxide.

Dosage form

Film-coated tablets.

Main physicochemical properties: round white tablets, film-coated, with the letters “KS” embossed on one side, and “1” (for Livazo 1 mg), or “2” (for Livazo 2 mg), or “4” (for Livazo 4 mg) on the other side.

Pharmacotherapeutic group

Lipid-lowering agents. HMG-CoA reductase inhibitors.

ATX code C10A A08.

Pharmacological properties

Pharmacodynamics.

Pitavastatin competitively inhibits HMG-CoA reductase, the rate-limiting enzyme in cholesterol biosynthesis, and inhibits cholesterol synthesis in the liver. As a result, the expression of LDL receptors in the liver is increased, contributing to the capture of circulating LDL from the blood, reducing total cholesterol (C) and LDL-cholesterol (LDL-C) in the blood. Its sustained inhibition of hepatic cholesterol synthesis reduces the secretion of LDL into the blood, reducing plasma triglyceride (TG) levels.

Livazo reduces elevated LDL-C, total cholesterol, and triglycerides and increases high-density lipoprotein (HDL-C) cholesterol. The drug reduces Apo-B and leads to a variable increase in Apo-A1 (see table below).

Dose-response in patients with primary hypercholesterolemia (adjusted mean percent change from baseline over 12 weeks)

*unadjusted

Clinical efficacy

In controlled clinical trials involving a total of 1687 patients with primary hypercholesterolemia and mixed dyslipidemia, Livazo consistently reduced LDL-C, total cholesterol (TC), non-HDL-C, triglycerides (TG), and apolipoprotein-B, and increased HDL-C and apolipoprotein-A1. The TG/HDL and apo-B/apo-A1 ratios were reduced. Livazo at a dose of 2 mg reduced LDL-C by 38-39%, and at a dose of 4 mg – by 44-45%. The majority of patients taking 2 mg of Livazo achieved the “target” LDL-C (according to the recommendations of the European Society for the Study of Atherosclerosis (ESATA) < 3 mmol/L.

In controlled clinical trials in 942 patients ≥ 65 years of age with primary hypercholesterolemia and mixed dyslipidemia (mean baseline LDL-C approximately 4.2 mmol/L) who received Livazo at doses of 1 mg, 2 mg, or 4 mg, LDL-C was reduced by 31%, 39%, and 44.3%, respectively, and approximately 90% of patients in the Livazo group achieved the ETVA-recommended target value for this parameter. More than 80% of patients took concomitant medications, but the incidence of adverse reactions was similar in all treatment groups, and less than 5% of patients withdrew from the study due to adverse reactions. The safety and efficacy results were similar in patients in different age subgroups (65-69, 70-74, and ≥ 75 years).

In controlled clinical trials involving 761 patients with primary hypercholesterolemia or mixed dyslipidemia, with two or more cardiovascular risk factors (mean baseline LDL-C level of about 4.1 mmol/L), or mixed dyslipidemia with type 2 diabetes (mean baseline LDL-C level of about 3.6 mmol/L), about 80% of patients in the Livazo group achieved the target LDL-C value according to the ETVA recommendations (3 or 2.5 mmol/L, depending on the degree of risk). In the patient groups, the LDL-C value was reduced by 44% and 41%, respectively.

In addition to the 2-year observational study (LIVES-01), 6582 hypercholesterolemic patients treated with pitavastatin (1, 2 or 4 mg) continued treatment for an additional 3 years (total of 5 years of treatment). During this 5-year study, the reduction in LDL-C (-30.5%) was maintained from 3 months and throughout the study, HDL-C increased by 1.7% at 3 months to 5.7% at 5 years, with patients with lower baseline HDL-C (<40 mg/dL) increasing to a greater extent, with serum levels increasing by 11.9% at 3 months and 28.9% at 5 years.

Atherosclerosis

The JAPAN-ACS trial compared the effects of 8-12 months of treatment with pitavastatin (4 mg) or atorvastatin (20 mg) on coronary atherosclerotic plaque volume in 251 patients undergoing percutaneous coronary angioplasty for acute coronary syndrome, as assessed by intravascular ultrasound. This trial demonstrated a reduction in plaque volume of approximately 17% for both regimens. Both pitavastatin and atorvastatin were shown to be effective. In both cases, plaque regression was associated with negative vascular remodeling (from 113.0 to 105.4 mm3). In this trial, there was no significant correlation between LDL-C reduction and plaque regression, in contrast to the results obtained in placebo-controlled trials.

Positive effects on mortality and morbidity have not yet been evaluated.

Diabetes mellitus

In an open-label, prospective, controlled trial of 1,269 Japanese patients with impaired glucose tolerance who were randomized to Livazo (1 mg or 2 mg daily) for quality of life improvement and a control group not receiving Livazo, 45.7% of the control group developed diabetes mellitus over 2.8 years compared with 39.9% of the Livazo group.

A meta-analysis of 4815 non-diabetic patients enrolled in randomized, double-blind, controlled trials of at least 12 weeks duration showed that Livazo did not affect the risk of developing primary diabetes mellitus (diabetes mellitus developed in 0.98% of patients in the control group and 0.50% of patients in the Livazo group). 6.5% of patients in the control group were treated with placebo, the remaining patients received statins including atorvastatin, pravastatin, and simvastatin.

Children

In a double-blind, randomized, multicenter, placebo-controlled study NK-104-4.01EU, 106 patients, children and adolescents ≥ 6 years and < 17 years of age (48 male and 58 female), at high risk for hyperlipidemia (plasma LDL-C ≥ 160 mg/dL (4.1 mmol/L) or LDL-C ≥ 130 mg/dL (3.4 mmol/L) with additional risk factors), received pitavastatin 1 mg, 2 mg, 4 mg, or placebo daily for 12 weeks. Most patients had a diagnosis of heterozygous familial hypercholesterolemia at baseline, approximately 41% of patients were between 6 and 10 years of age, and approximately 20%, 9%, 12%, and 9% were Tanner stages II, III, IV, and V, respectively. The mean LDL-C was reduced by 23.5%, 30.1%, and 39.3% after taking pitavastatin at doses of 1, 2, and 4 mg, respectively, compared with 1.0% in the placebo group.

In a 52-week open-label extension and safety study, NK-104-4.02EU (total number of patients: 113, including 87 patients from the 12-week placebo-controlled study, 55 male, 58 female), children and adolescents ≥ 6 years of age and < 17 years of age at high risk for hyperlipidemia received pitavastatin for 52 weeks. All patients started pitavastatin at a dose of 1 mg/day with the option to increase the dose to 2 mg and 4 mg to achieve an optimal treatment goal of LDL-C < 110 mg/dL (2.8 mmol/L), based on LDL-C levels at weeks 4 and 8 of treatment. Approximately 37% of patients enrolled in the study were 6–10 years of age and approximately 22%, 11%, 12%, and 13% were Tanner stages II, III, IV, and V, respectively. The majority of patients (n = 103) were titrated to 4 mg/day of pitavastatin. The mean LDL-C decreased by 37.8% at 52 weeks of treatment. Overall, 47 patients (42.0%) achieved the AHA-recommended LDL-C target of <130 mg/dL, and 23 patients (20.5%) achieved the AHA-recommended LDL-C target of <110 mg/dL at 52 weeks of treatment. LDL-C values at the end of week 52 were reduced by 40.2% in patients aged ≥ 6 to < 10 years (n = 42), by 36.7% in patients aged ≥ 10 to < 16 years (n = 61), and by 34.5% in patients aged 16 to 17 years (n = 9). Patient gender did not influence response to treatment. In addition, mean total cholesterol was reduced by 29.5% and mean serum TG was reduced by 7.6% at the end point of week 52 of treatment.

The Paediatric Committee of the European Medicines Agency has waived the obligation to provide the results of studies on the use in children under 6 years of age and the treatment of children of any age with homozygous familial hypercholesterolemia.

HIV-infected patients

The INTREPID study enrolled a total of 252 HIV-infected patients with dyslipidemia (126 patients in each group) who, after a 4-week run-in period and diet, were randomized to receive either pitavastatin 4 mg once daily or pravastatin 40 mg once daily for 52 weeks. The primary efficacy endpoint was assessed at week 12.

Fasting serum LDL-C decreased by 31% and 30% in the pitavastatin group and by 21% and 20% in the pravastatin group at 12 and 52 weeks, respectively (mean treatment difference was -9.8%, P < 0.0001 at week 12 and -8.4%, P = 0.0007 at week 52). There was a statistically significant difference in the change from baseline in the mean of secondary efficacy parameters, such as total cholesterol, non-HDL-C, and apolipoprotein B, at weeks 12 and 52, with greater reductions in the pitavastatin group than in the pravastatin group, respectively, for each parameter. No new safety signals or adverse reactions were observed with pitavastatin 4 mg. At week 52, virologic failure (defined as HIV-1 RNA viral load > 200 copies/mL and > 0.3-log increase from baseline) was reported in 4 patients (3.2%) in the pitavastatin group and 6 patients (4.8%) in the pravastatin group, with no statistically significant differences between treatments.

Pharmacokinetics.

Absorption: Pitavastatin is rapidly absorbed from the upper gastrointestinal tract, with peak plasma concentrations occurring within 1 hour after oral administration. Absorption is independent of food intake. The drug undergoes enterohepatic circulation unchanged and is well absorbed from the small intestine and ileum. The absolute bioavailability of pitavastatin is 51%.

Distribution: Pitavastatin is more than 99% bound to human plasma proteins, primarily albumin and alpha-1-acid glycoprotein, and the mean volume of distribution is approximately 133 L. Pitavastatin is actively transported into hepatocytes, the site of action and metabolism, by multiple hepatic transporters, including OATP1B1 and OATP1B3. Plasma AUC is variable with an approximately 4-fold range between peak and trough values. Studies with SLCO1B1 (the gene encoding OATP1B1) suggest that polymorphisms in this gene may explain the large variation in AUC. Pitavastatin is not a substrate for p-glycoprotein.

Metabolism: Unchanged pitavastatin is the predominant component of the drug in plasma. The major metabolite is an inactive lactone, which is formed via the glucuronide conjugate of pitavastatin ester type by UDP glucuronosyltransferases (UGT1A3 and 2B7). In vitro studies using 13 human cytochrome P450 (CYP) isoforms indicate that pitavastatin is minimally metabolized by CYP; CYP2C9 (and to a lesser extent CYP2C8) is responsible for the metabolism of pitavastatin to minor metabolites.

Elimination: Pitavastatin is rapidly excreted unchanged in the bile from the liver, but undergoes enterohepatic recirculation, which determines its duration of action. Less than 5% of pitavastatin is excreted in the urine. The plasma half-life ranges from 5.7 hours (single dose) to 8.9 hours (steady state), and the apparent geometric mean oral clearance is 43.4 L/hour after a single dose.

Food effect: The maximum plasma concentration of pitavastatin was decreased by 43% when administered with a high-fat meal, but the AUC remained unchanged.

Special patient groups

Elderly patients: The AUC of pitavastatin is 1.3 times higher in elderly patients aged 65 years and older. This did not affect the safety and efficacy of Livazo in elderly patients.

Gender: The AUC of pitavastatin was increased 1.6-fold in women. This did not affect the safety and efficacy of Livazo in women.

Race: No difference was observed between the pharmacokinetic profiles of pitavastatin in healthy volunteers of Mongoloid and Caucasian races.

Children: There are limited pharmacokinetic interaction studies in children and adolescents. In the NK-104-4.01EU study, a dose-dependent effect on 1-hour plasma concentrations of pitavastatin was observed in randomised controlled trials. The 1-hour plasma concentrations were also found to be (inversely) related to body weight and may be higher in children than in adults.

Renal impairment: For patients with moderate renal impairment and patients on hemodialysis, AUC values increased 1.8-fold and 1.7-fold, respectively.

Hepatic impairment: In patients with mild (Child-Pugh Class A) hepatic impairment, the AUC was 1.6-fold higher than in healthy volunteers, and in patients with moderate (Child-Pugh Class B) hepatic impairment, the AUC was 3.9-fold higher. Dose limitation is recommended in patients with mild to moderate hepatic impairment. Livazo is contraindicated in patients with severe hepatic impairment.

Indication

To reduce elevated total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) in adult patients, adolescents and children over 6 years of age with primary hypercholesterolemia, including heterozygous familial hypercholesterolemia and combined (mixed) dyslipidemia, when the response to diet and other non-drug therapy is inadequate.

Contraindication

Known hypersensitivity to pitavastatin or to any of the excipients or other statins;

severe hepatic insufficiency, active liver disease, or persistent elevation of serum transaminases of unknown etiology (more than 3 times the upper limit of normal [ULN]);

myopathy;

concomitant therapy with cyclosporine;

pregnancy, breastfeeding (see section "Use during pregnancy or breastfeeding").

Interaction with other medicinal products and other types of interactions

Pitavastatin is actively transported into hepatocytes by several pathways (including organic anion transporting polypeptide, OATP), which may be involved in some of the interactions listed below.

Cyclosporine: Coadministration of a single dose of cyclosporine with Livazo at steady state resulted in a 4.6-fold increase in pitavastatin AUC. The effect of steady state cyclosporine on the steady state of Livazo is unknown. Livazo is contraindicated in patients receiving cyclosporine.

Erythromycin: Co-administration with Livazo resulted in a 2.8-fold increase in pitavastatin AUC. Temporary interruption of Livazo treatment is recommended during treatment with erythromycin or other macrolide antibiotics.

Gemfibrozil and other fibrates: The use of fibrates alone has occasionally been associated with myopathy. Concomitant use of fibrates with statins has been associated with an increased risk of myopathy and rhabdomyolysis. Livazo should be administered with caution with fibrates. In pharmacokinetic studies, co-administration of Livazo with gemfibrozil resulted in a 1.4-fold increase in the AUC of pitavastatin and a 1.2-fold increase in the AUC of fenofibrate.

Niacin: Interaction studies between Livazo and niacin have not been conducted. Niacin monotherapy has been associated with myopathy and rhabdomyolysis. Therefore, Livazo should be administered with caution when co-administered with niacin.

Fusidic acid: The risk of myopathy, including rhabdomyolysis, is increased when systemic fusidic acid is administered concomitantly with statins. The mechanism of this interaction (pharmacodynamic or pharmacokinetic, or both) is currently unknown. There have been reports of rhabdomyolysis (including fatalities) in patients receiving this combination. If fusidic acid is considered necessary, Livazo treatment should be discontinued for the duration of fusidic acid treatment (see section 4.4).

Glecaprevir and pibrentasvir: Concomitant use of glecaprevir/pibrentasvir and an HMG-CoA reductase inhibitor may increase the plasma concentration of the latter. The use of Livazo with glecaprevir/pibrentasvir has not been studied, but the same interaction is likely. It is recommended to use Livazo tablets at a dosage of 1 mg at the beginning of treatment with glecaprevir/pibrentasvir; clinical monitoring of the condition of patients receiving this combination is necessary.

Rifampicin: Co-administration with Livazo resulted in a 1.3-fold increase in pitavastatin AUC due to decreased hepatic absorption.

Protease inhibitors and non-nucleoside reverse transcriptase inhibitors: Co-administration of lopinavir/ritonavir, darunavir/ritonavir, atazanavir or efavirenz with Livazo may result in minor changes in the AUC of pitavastatin.

Ezetimibe and its glucuronide metabolite inhibit the absorption of cholesterol from food and bile. Co-administration with Livazo does not affect the plasma concentrations of ezetimibe or its glucuronide metabolite, and ezetimibe does not affect the plasma concentrations of pitavastatin.

CYP3A4 inhibitors: Interaction studies with itraconazole and grapefruit juice, known CYP3A4 inhibitors, did not reveal a clinically significant effect on pitavastatin plasma concentrations.

Digoxin, a known P-gp substrate, does not interact with Livazo. No significant change in pitavastatin or digoxin concentrations was observed when co-administered.

Warfarin: The steady-state pharmacokinetic and pharmacodynamic properties (INR and PT) of warfarin in healthy volunteers were not affected by the concomitant use of Livazo 4 mg/day. However, as with other statins, prothrombin time or international normalized ratio (INR) should be monitored in patients receiving warfarin when Livazo is added to the regimen.

Children

Interactions with other drugs have only been studied in adults. The extent of interactions in pediatric patients is unknown.

Application features

As with other HMG-CoA reductase inhibitors (statins), myalgia, myopathy, and, rarely, rhabdomyolysis may occur. Patients should be advised to report any muscle discomfort. Creatine kinase (CK) levels should be measured in any patient who reports muscle pain, tenderness, or weakness, especially if accompanied by malaise or fever.

Creatine kinase should not be measured after vigorous exercise or in the presence of any other cause of elevated CK that may confound interpretation of the result. For elevated CK concentrations (> 5 times the ULN), a confirmatory test should be performed within 5–7 days.

Very rare cases of immune-mediated necrotizing myopathy (IMNM) have been reported during or after treatment with some statins. IMMNM is clinically characterized by persistent proximal muscle weakness and elevated serum creatine kinase levels that persist despite discontinuation of statin treatment.

Livazo should not be used concomitantly with systemic fusidic acid or within 7 days of stopping fusidic acid treatment. Patients for whom systemic fusidic acid is essential should discontinue statin treatment for the duration of fusidic acid treatment. There have been reports of rhabdomyolysis (including fatal cases) in patients receiving the combination of fusidic acid and statins (see section 4.5). All patients should be advised to seek medical advice immediately if they experience any symptoms of muscle weakness, muscle pain or tenderness.

Statin therapy may be resumed 7 days after the last dose of fusidic acid. In exceptional cases where a patient requires prolonged systemic fusidic acid treatment, e.g. for the treatment of severe infections, the need for concomitant use of Livazo and fusidic acid should be considered on a case-by-case basis and the patient should be closely monitored.

Before starting treatment

As with other statins, Livazo should be used with caution in patients with a predisposition to rhabdomyolysis. Creatinine kinase levels should be measured to establish baseline levels in the following situations:

renal failure;

hypothyroidism;

personal or family history of hereditary muscle disorders;

history of muscle toxicity while taking a fibrate or other statin;

liver disease or history of alcohol abuse;

Elderly patients (70 years and older) with other specific risk factors for developing rhabdomyolysis.

In such situations, clinical monitoring is recommended, and the potential risk/benefit ratio of treatment should be assessed. It is not recommended to initiate treatment with Livazo if creatinine clearance (CC) is more than 5 times the upper limit of normal.

During treatment

Patients are advised to report muscle pain, weakness or cramps as soon as they occur. Creatine kinase (CK) levels should be measured and treatment should be discontinued if CK levels increase to more than 5 times the upper limit of normal. Discontinuation of treatment should be considered if muscle symptoms are severe, even if CK levels are not more than 5 times the upper limit of normal. If symptoms resolve and CK levels return to normal, resumption of Livazo treatment at a dose of 1 mg and close monitoring may be considered.

Effect on the liver

As with other statins, Livazo should be used with caution in patients with a history of liver disease or in those who regularly consume excessive amounts of alcohol. Liver function tests should be performed before initiating treatment with Livazo and periodically during treatment. Livazo should be discontinued in patients with persistent elevations of serum transaminases (ALT and AST) greater than 3 times the upper limit of normal.

Effects on the kidneys

Livazo should be administered with caution to patients with moderate or severe renal impairment. Dose increases should only be made with careful monitoring of renal function after gradual dose titration. The 4 mg dose is not recommended for patients with severe renal impairment.

There is some evidence that statins as a class of drugs increase blood glucose levels and in some patients at increased risk of developing diabetes, they may cause hyperglycemia, which will require appropriate treatment. However, this risk should not be a reason to discontinue statin treatment, given the greater therapeutic effect of statins on reducing the risk of developing cardiovascular disease. In patients at increased risk of developing hyperglycemia (fasting glucose level 5.6 to 6.9 mmol/l, body mass index > 30 kg/m2, elevated blood triglycerides, arterial hypertension), clinical and biochemical parameters should be monitored according to national guidelines. However, there is no confirmed fact of the risk of developing diabetes with the use of pitavastatin from post-marketing observational safety studies or prospective studies (see section "Pharmacological properties").

Interstitial lung diseases

Interstitial lung disease has been reported with some statins, especially with long-term therapy. Symptoms may include shortness of breath, nonproductive cough, and worsening of general health (fatigue, weight loss, and fever). If a patient is suspected of developing interstitial lung disease, statin therapy should be discontinued.

Children

There are limited data on the long-term effects on development and sexual maturation in pediatric patients aged 6 years and older taking Livazo. Female adolescents should be advised of appropriate contraceptive measures during treatment with Livazo.

Other effects

Temporary interruption of Livazo therapy is recommended during treatment with erythromycin, other macrolide antibiotics, or fusidic acid. Livazo should be administered with caution to patients taking drugs known to cause myopathy (e.g. fibrates or niacin).

In isolated cases, statins have been reported to re-induce or exacerbate pre-existing myasthenia gravis or ocular myasthenia. If symptoms worsen, Livazo treatment should be discontinued. Relapses have been reported with re-administration of the same or a different statin.

Lactose

The tablets contain lactose. Patients with rare hereditary forms of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

Use during pregnancy or breastfeeding

Pregnancy. Livazo is contraindicated during pregnancy (see section 4.3). Women of childbearing potential should use appropriate contraceptive measures during treatment with Livazo. Since cholesterol and other products of cholesterol biosynthesis are essential for fetal development, the potential risk of inhibition of HMG-CoA reductase outweighs the benefits of treatment during pregnancy. Animal studies have shown reproductive toxicity but no teratogenic potential. If the patient is planning to become pregnant, treatment should be discontinued at least one month before conception. If pregnancy occurs during treatment with Livazo, treatment should be discontinued immediately.

Breastfeeding. Livazo is contraindicated during breast-feeding (see section 4.3). Pitavastatin is excreted in animal milk. It is not known whether the drug is excreted in human milk.

Fertility: No data available at this time.

Ability to influence reaction speed when driving vehicles or other mechanisms

Given the possibility of dizziness and drowsiness during treatment with Livazo, it is necessary to refrain from driving vehicles and working with other mechanisms.

Method of administration and doses

Doses.

Patients should be on a cholesterol-lowering diet before starting treatment. It is important that patients continue to follow this diet during treatment.

The usual starting dose is 1 mg once daily. Dose adjustments should be made at intervals of 4 weeks or more. Dosage should be individualized based on LDL-C levels, treatment regimen, and patient condition. The maximum daily dose is 4 mg.

Elderly patients.

There is no need for dose adjustment in patients over 70 years of age.

Patients with renal impairment.

No dose adjustment is necessary in patients with mild renal impairment, but pitavastatin should be used with caution. Data on the use of the 4 mg dose in patients with mild to severe renal impairment are limited. Therefore, the 4 mg dose in mild to moderate renal impairment should ONLY be used with careful monitoring of renal function after gradual dose titration.

The 4 mg dose is not recommended for patients with severe renal impairment.

Patients with mild to moderate hepatic impairment.

The 4 mg dose is not recommended in patients with mild to moderate hepatic impairment. A maximum daily dose of 2 mg may be used with careful monitoring of liver function.

Children

Treatment of children aged 6 years and older and adolescents should be carried out only under the supervision of a physician experienced in the treatment of hyperlipidemia, with constant monitoring of the patient's condition. For children aged 6 years and older and adolescents with heterozygous familial hypercholesterolemia, the usual starting dose is 1 mg once daily. Dose adjustments should be made at intervals of 4 weeks or more. Doses should be individualized, based on LDL-C levels, treatment regimen, and patient condition. For children aged 6 to 9 years, the maximum daily dose is 2 mg. For children aged 10 years and older, the maximum daily dose is 4 mg (see sections 4.8, 5.1, and 5.2).

Children under 6 years old.

The efficacy and safety of Livazo in children under 6 years of age have not been studied.

Method of application.

For oral use only, the tablet should be swallowed whole. Livazo tablets can be taken with or without food. It is recommended that the patient take the tablets at the same time each day. Statin therapy is generally more effective when administered in the evening, given the circadian rhythm of lipid metabolism.

If a child or adolescent cannot swallow the tablet whole, if necessary, the tablet can be dissolved in a glass of water, which should be drunk immediately.

To ensure a full dose, another volume of water should be used to rinse the glass and drunk immediately. The tablets should not be dissolved in acidic fruit juices or milk.

Children

Children from 6 years old.

Treatment of children aged 6 years and older with Livazo should only be carried out under the supervision of a physician experienced in the treatment of hyperlipidemia, with constant monitoring of the patient's condition.

Children under 6 years old.

The efficacy and safety of Livazo in children under 6 years of age have not been studied.

Overdose

In case of overdose, symptoms of adverse reactions may be aggravated. There is no specific therapy for overdose. Treatment should be symptomatic, and supportive therapy should be administered if necessary. Liver function and CK levels should be monitored. Hemodialysis is ineffective. There is no antidote.

Side effects

In pooled controlled clinical trials, less than 4% of patients receiving Livazo at recommended doses were withdrawn due to adverse reactions. The most frequently documented adverse reaction following pitavastatin administration in controlled clinical trials was myalgia.

Adverse reactions and their frequencies observed with Livazo at recommended doses in controlled clinical trials and in the post-marketing period are listed below by system organ class. The frequencies are defined as follows:

very common (≥ 1/10);

common (≥ 1/100, < 1/10);

uncommon (≥ 1/1000, < 1/100);

rare (≥1/10,000, <1/1,000);

rare (less than < 1/10,000) and frequency unknown.

Blood and lymphatic system disorders

Uncommon: anemia.

Metabolic disorders, metabolism

Uncommon: anorexia.

Mental disorders

Uncommon: insomnia.

From the nervous system

Common: headache.

Uncommon: dizziness, dysgeusia, drowsiness, hypoesthesia.

Frequency unknown: myasthenia gravis.

From the organs of vision

Rare: decreased visual acuity.

Frequency unknown: ocular myasthenia.

From the side of the organs of hearing and vestibular apparatus

Uncommon: ringing in the ears.

Gastrointestinal disorders

Common: constipation, diarrhea, dyspepsia, nausea.

Uncommon: abdominal pain, dry mouth, vomiting.

Uncommon: glossodynia, acute pancreatitis.

Rare: gastrointestinal discomfort.

Hepatobiliary system

Uncommon: increased transaminase activity (aspartate aminotransferase, alanine aminotransferase).

Rare: cholestatic jaundice, abnormal liver function tests, liver disease.

Skin and subcutaneous tissue disorders

Uncommon: itching, rash.

Rare: urticaria, erythema.

Frequency unknown: angioedema.

Musculoskeletal, connective tissue and bone disorders

Common: myalgia, arthralgia.

Uncommon: muscle spasms.

Rare: myopathy, rhabdomyolysis.

Frequency unknown: lupus-like syndrome, immune-mediated necrotizing myopathy (see section "Special warnings and precautions for use").

From the urinary system

Uncommon: pollakiuria.

From the reproductive system and mammary glands:

Uncommon: gynecomastia.

General disorders

Uncommon: asthenia, malaise, fatigue, peripheral oedema.

Blood creatine kinase elevations > 3 times the upper limit of normal (ULN) were observed in 49 of 2800 (1.8%) patients treated with Livazo in controlled clinical trials. Levels ≥ 10 times the ULN associated with muscle symptoms (myalgia, myopathy, and, rarely, rhabdomyolysis) were rare.

Children

The clinical safety database contains safety information for 142 pediatric patients who received pitavastatin, of whom 87 patients were 6 to 11 years of age and 55 patients were 12 to 17 years of age. Overall, 91 patients received pitavastatin for one year, 12 patients received pitavastatin for 2.5 years, and 2 patients