Livazo 4 mg pills No.30

Livazo (LIVAZO) Instructions for use

Composition

active ingredient : Calcium Pivastatin;

1 film coated tablet contains 1.045 mg of calcium of piacavastatin, equivalent to 1 mg of pivastatin, or

1 film coated tablet contains 2.09 mg of calcium of piacavastatin, equivalent to 2 mg of pivastatin, or

1 film coated tablet contains 4.18 mg of calcium of piacavastatin, equivalent to 4 mg of pivastatin;

auxiliary substances: lactose, hydroxypropyl cellulose low substituted, gipermellose, magnesium aluminum silicate, magnesium stearate, titanium dioxide (E 171), triethyl citrate, silicon dioxide, colloidal.

Dosage form

Tablets coated with a film coat.

Pharmacological group

Hypilipidemic means. HMG CoA reductase inhibitors. Code АТС С10А А08.

Indications

To reduce elevated total cholesterol (CHO) and low density lipoprotein cholesterol (LDL cholesterol) in adult patients with primary hypercholesterolemia, including heterozygous familial hypercholesterolemia and combined (mixed) dyslipidemia, when the response to diet and other non-drug therapy is insufficient.

Contraindications

• Hypersensitivity to pivastatin or to any of the excipients or other statins;
• severe hepatic failure, liver disease in the active phase, or persistent elevation of serum transaminases of unknown etiology (more than 3 times higher than the upper limit of the norm [VMN])
• the value of clearance of creatinine (QC) more than 5 times exceeds the upper limit of the norm;
• myopathy;
• concomitant therapy with cyclosporine.

Method of administration and dose

For oral use only, the tablet should be swallowed whole.

Livadia can be taken at any time of the day, regardless of meals. It is desirable for the patient to take the pills at the same time each day. Statin therapy, as a rule, is more effective in the evening through the daily rhythm of lipid metabolism. Patients should be on a low cholesterol diet before treatment is started. It is important that patients continue to adhere to the diet during treatment.

Adults	The initial dose is 1 mg once a day. Dose correction should be done at intervals of 4 weeks or more.Doses should be selected individually, in accordance with the level of LDL cholesterol, the treatment regimen and the patient's condition. Most patients need a dose of 2 mg. The maximum daily dose is 4 mg.
Older patients	There is no need for dose correction.
Patients with impaired kidney function	The initial dose is 1 mg once a day. Dose correction should be done at intervals of 4 weeks or more.Doses should be selected individually, in accordance with the level of LDL cholesterol, the treatment regimen and the patient's condition. In case of impaired renal function, no light dose correction is required, however, Pivastatin should be used with caution. A dose of 4 mg with mild and moderate renal impairment should only be used ONLY with careful monitoring of renal function after gradual titration of the dose. For patients with severe renal insufficiency, a dose of 4 mg is not recommended.
Patients with mild to moderate hepatic impairment	A dose of 4 mg is not recommended for patients with mild to moderate hepatic impairment. The maximum daily dose of 2 mg can be used with careful monitoring of the liver function.

Adverse reactions

Adverse reactions and their frequency observed with the use of Livazo at recommended doses in controlled clinical trials and in the post-marketing period, as indicated below, according to the classes of system organs. The frequency is determined as follows:

very common (≥ 1/10);
often (≥ 1/100, <1/10);
rare (≥ 1/1 000, <1/100);
single (1/10 000, <1/1 000)
rare (<1 / 10,000) and frequency is unknown.
From the side of the blood and lymphatic system

Rare: Anemia.

Disturbance of metabolism, metabolism

Uncommon: anorexia.

mental disorders

Rare insomnia.

neurological disorders

Frequent: headache.

Rare: dizziness, dysgeusia, drowsiness.

From the side of the vision organs

Single: reduced visual acuity.

On the part of the hearing and vestibular apparatus

Rare ringing in the ears.

Gastrointestinal disorders

Often: constipation, diarrhea, dyspepsia, nausea.

Rare: abdominal pain, dry mouth, vomiting.

Lonely: glucosinidia, acute pancreatitis.

Disorders of the digestive system

Uncommon: increased transaminase activity (AsAT, AlAT).

Single: cholestatic jaundice, deviations from the norm of indicators of liver function, liver disease.

From the skin and subcutaneous tissue

Rare: Itching, rash.

Lonely: urticaria, erythema.

On the part of the musculoskeletal system, connective tissue and bones

Frequent: myalgia, arthralgia.

Rare: muscle spasms.

Single: myopathy, rhabdomyolysis.

Frequency not known: immuno-mediated necrotic myopathy (see section "Peculiarities of use".

From the urinary system

Rare: pollakiuria.

general disorders

Rare: asthenia, malaise, fatigue, peripheral edema.

An increase in the level of CFC in the blood> 3 times the upper limit of the norm (VMN) was noted in 49 out of 2,800 (1.8%) patients receiving Livazo during controlled clinical trials. The level was ³ 10 times higher than the BMD and was accompanied by symptoms of the muscles (myalgia, myopathy and, rarely, rhabdomyolysis) were isolated.

Post marketing experience

The vast majority of patients in the study received 1 mg or 2 mg of pivastatin, not 4 mg. In 10.4% of patients, unwanted events were noted and 7.4% of patients refused treatment because of the development of adverse events. The myalgia rate was 1.08%. Most of the unwanted phenomena were easy. The incidence of adverse events was higher for 2 years in patients with drug allergies (20.4%) or liver or kidney disease (13.5%) in history.

During post-marketing surveillance, there were two reports of rhabdomyolysis, requiring hospitalization (0.01% of patients).

In addition, there are spontaneous postmarketing reports of skeletal muscle effects, including myalgia and myopathy, in patients who received Livasot at all recommended doses. There were also reports of the development of rhabdomyolysis, accompanied by and without acute renal failure, including lethal rhabdomyolysis.

Overdose

Overdosage may increase the symptoms of adverse reactions. There is no special therapy in case of overdose.Treatment should be symptomatic and supportive therapy should be performed if necessary. The liver function and the KFK level should be monitored. Hemodialysis is ineffective. There is no antidote.

Use during pregnancy and breastfeeding

Livasis is contraindicated during pregnancy and breastfeeding. Women of reproductive age should use appropriate contraceptive measures during the treatment of Livas. Since cholesterol and other cholesterol biosynthesis products are important for fetal development, the potential risk of inhibition of HMG CoA reductase outweighs the benefits of treatment during pregnancy. Animal studies indicate reproductive toxicity, but no teratogenic potential. If a patient plans to become pregnant, treatment should be stopped at least one month before conception. If pregnancy occurs during the use of Livazo, treatment should be stopped immediately.

Livasis is contraindicated during breastfeeding. Pitavalastine is excreted in breast milk in animals. It is not known whether a human breast milk product is excreted. If you need to use pivastatin, you must refrain from breastfeeding.

Where are you

The drug is not used in pediatric practice.

Application features

Impact on the muscles

As with other HMG-CoA reductase inhibitors (statins), there is a likelihood of developing myalgia, myopathy and rarely rhabdomyolysis. Patients should be advised to report any muscle discomfort. Levels of KFK (CK) in any patient should be determined, reporting pain, sensitivity or weakness in the muscles, especially if they are accompanied by anemia or fever.

The CFC should not be determined after vigorous exercise or in the presence of any other cause of increased KK, which can make confusion in interpreting the result. At elevated concentrations of KK (> 5 times the upper limit of the norm), the confirmatory test must be carried out within 5-7 days.

Very rare cases of immunosuppressed necrotic myopathy (IONM) have been reported during or after treatment with certain statins. IONM is clinically characterized by persistent weakness of the proximal muscles and an increase in the serum of blood of the level of KFK, which persists despite the discontinuation of treatment with statins.

Before treatment

As with other statins, Liviaz should be prescribed with caution to patients with a tendency to develop rhabdomyolysis.The level of KFK should be determined to establish the starting level in the following situations:

1. kidney failure
2. hypothyroidism
3. personal or family history of hereditary muscular disorders;
4. muscular toxicity when using fibrates or other statin in the history
5. liver disease or alcohol abuse in history
6. elderly patients (aged 70) with other definite risk factors for the development of rhabdomyolysis

In such situations, clinical monitoring is recommended, and the relationship between the potential risk and the expected benefit from treatment should be assessed.

During the treatment

Patients are advised to report pain, weakness or cramps in the muscles immediately after they occur. The levels of KFK (CK) should be determined and treatment should be discontinued when the CPC level is increased by more than 5 times the upper limit of the normal range. Consideration should be given to discontinuing treatment if the muscle symptoms are severe, even if the level of KFK is not more than 5 times the upper limit of the norm. If the symptoms disappear and the KFK level returns to normal, then the issue of resuming treatment of Livasot at a dose of 1 mg and with careful monitoring may be considered.

Influence on the liver

As with other statins, Liviaz should be used with caution in patients with a history of liver disease or those who regularly consume excessive amounts of alcohol. Prior to treatment with Livazo, and periodically during the course of treatment, liver function tests should be monitored. Lavazo therapy should be discontinued in patients with stable elevation of serum transaminases (ALT and AST), which exceeds 3 times the BMI.

Influence on the kidneys

Liposuction should be administered with caution to patients with moderate to severe renal insufficiency. The dose should be increased only with careful monitoring of renal function after gradual titration of the dose. A dose of 4 mg is not recommended for patients with severe renal insufficiency.

Interstitial diseases of the lungs

Interstitial lung disease has been reported with some statins, especially with long-term therapy. Symptoms may include shortness of breath, unproductive cough and a deterioration in the general health (fatigue, body weight loss, and fever).In the event of suspicion of developing an interstitial lung disease in a patient, statin therapy should be discontinued.

Other effects

Temporary suspension of Livas therapy is recommended for treatment with erythromycin, other macrolide antibiotics or fusidic acid. Liposuction should be administered with caution to patients taking medications leading to the development of myopathy (eg, fibrates or niacin).

Lactose

Tablets contain lactose. Patients with rare hereditary problems of galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption should not take this medication.

Ability to influence the speed of reaction when driving motor vehicles or other mechanisms

Considering the possibility of dizziness and drowsiness during the treatment of Livazo, one must refrain from driving the car and working with the mechanisms.

Interaction with other drugs and other types of interactions

Pitavalastine is actively transported to hepatocytes in several ways (including the polypeptide that transports organic anions, OATP) that can be involved in some of the following interactions.

Ciclosporin: Simultaneous administration of a single dose of cyclosporin with Livazo in equilibrium resulted in a 4.6-fold increase in AUC of piumustatin. Livia is contraindicated in patients who receive cyclosporine.

Erythromycin: Concomitant use with Livazo resulted in a 2.8-fold increase in AUC of pitavastatin. A temporary suspension of Livas cure is recommended during treatment with erythromycin or other macrolide antibiotics.

Gemfibrozil and other fibrates: the use of monotherapy with fibers is sometimes associated with the development of myopathy. Simultaneous use of fibrates with statins was associated with an increased risk of myopathy and rhabdomyolysis. Levazo should be administered with caution at the same time as the fibers. During pharmacokinetic studies, the concomitant use of lavazo with gemfibrozil has resulted in a 1.4 fold increase in AUC of pivastatin and a 1.2 fold increase in phenofibrate AUC.

Niacin: Studies of the interaction of the drug Livaso and niacin have not been conducted. Monotherapy with niacin was associated with the development of myopathy and rhabdomyolysis. Thus, Liviaz should be administered with caution at the same time as niacin.

Fusidic acid has been reported with serious muscle problems, such as rhabdomyolysis, due to the interaction between fusidic acid and statins. During the treatment of fusidic acid, a temporary suspension of Livas cure is recommended.

Rifampicin: the concomitant use of Livazo resulted in a 1.3-fold increase in AUC of pivastatin due to decreased absorption of the liver.

Protease inhibitors: the concomitant administration of Livazo may result in minor changes in AUC of piacavastatin.

Ezetimib and its metabolite glucuronide inhibit the absorption of cholesterol from food and bile. Simultaneous administration with Livazo does not affect the level of ezetimib or its metabolite glucuronide in plasma, and ezetimib does not affect the concentration of piacavastatin in plasma.

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

Digoxin, a well-known P-gp substrate, does not interact with Livazo. At the same time, no significant change was observed in the concentration of pivastatin or digoxin.

Warfarin: the equilibrium pharmacokinetic and pharmacodynamic properties (INR and PT) of warfarin in healthy volunteers did not depend on the simultaneous application of Livazo 4 mg per day. However, as with other statins in patients receiving warfarin, prothrombin time or the international normalization ratio (EMF) should be monitored when Livaso is included in the treatment regimen.

Pharmacological properties

Pharmacodynamics.

Pitavalastin is competitive inhibition of HMG CoA reductase, limiting the rate of action of the enzyme in cholesterol biosynthesis, and inhibits the synthesis of cholesterol in the liver. As a result, the expression of LDL receptors in the liver increases, contributing to the capture of circulating LDL from the blood, reduction of total cholesterol (CH) and LDL cholesterol (CHL-LDL) in the blood. Its sustained inhibition of hepatic cholesterol synthesis reduces the secretion of LP in the bloodstream, lowering levels of triglycerides in plasma (TG).

Livazo reduces elevated levels of LDL cholesterol, total cholesterol and triglycerides, and increases cholesterol levels of high density lipoprotein (CHL-HDL). The drug reduces Apo-B and leads to a variable increase in Aro-Al (see Table below).

Dose-response in patients with primary hypercholesterolemia (corrected mean change in percentage from baseline for 12 weeks)

Dose	N	LDL cholesterol	OXS *	X-HDL	tg	Apo-B	Apo-Al
placebo	51	4.0	1.3	2.5	2.1	0.3	3.2
1 mg	52	33.3	22.8	9.4	14.8	24.1	8.5
2 mg	49	38.2	26.1	9.0	17.4	30.4	5.6
4 mg	50	46.5	32.5	8.3	21.2	36.1	4.7

* uncorrected

Pharmacokinetics.

Suction: Pivastatin is rapidly absorbed from the upper gastrointestinal tract, and peak plasma concentrations are reached within one hour after ingestion. Suction does not depend on food intake. The drug, in its unchanged form, passes enterhepatic circulation and is well absorbed from the small intestine and pelvic gut. The bioavailability of pivastatin is 51%.

The distribution of pivastatin is more than 99% bound to proteins in human plasma, mainly albumin and alpha 1-acid glycoprotein, and the average volume of distribution is approximately 133 liters.Pytavastatyn actively transportyruetsya in hepatotsytы, place action and metabolism, with many pechenochnыmy carrier in volume including OATP1B1 and OATP1B3. Plasma AUC javljaetsja variable prymerno with 4 bands kratnыm Between High society and low values. Studies in SLCO1B1 (gene kodyruyuschyy OATP1B1) pozvoljajut Suppose something of the given gene polymorphism Can obъyasnyt Bolshoi fluctuations in AUC. Pytavastatyn not javljaetsja substrate for p-glycoprotein.

Pytavastatyn metabolism in neyzmenennom video javljaetsja preobladayuschey chastyu drug in plasma. Primary metabolite - neaktyvnыy lactone, kotoryya formyruetsya through konъyuhat hlyukuronyda pytavastatynu эfyrnoho type UDP hlyukuronozyltransferazoyu (UGT1A3 and 2B7). Studies in vitro with 13 Using chelovecheskoho isoforms of cytochrome P450 (CYP) pokazыvayut, something pytavastatynu metabolism with pomoshchju CYP javljaetsja mynymalnыm; CYP2C9 (and in smaller degrees CYP2CS) otvechaet for metabolism pytavastatynu for neznachytelnыm metabolites.

Withdrawal: pytavastatyn in neyzmenennom video quickly vыvodytsya IZ liver in zhelch, but podverhaetsya enterohepatic retsyrkulyatsyy, something to bring Duration ego action. I pytavastatynu vыvodytsya 5% with urine. Period poluvыvedenyya kolebletsya from 5.7 hour (one dose) to 8.9 hour (ravnovesnoe STATUS), and obviously middle heometrycheskoe oral sostavljaet ride height 43.4 l / h after odnokratnoy dozы.

Effect of food: Maximum Concentration pytavastatynu snyzhalas in plasma by 43% when s Application pyschey with the High Content fats, but AUC ostavalas neyzmennoy.

Osobыe group patsyentov

Pozhylыe patsyentы: AUC pytavastatynu 1.3 times in pozhylыh Above patsyentov in age from 65 years. This is not vlyyalo on Security and Efficiency Lyvazo pozhylыm patsyentam.

Gender: AUC pytavastatynu uvelychena 1.6 times in women. This is not vlyyalo on Security and Efficiency Application Lyvazo women.

Race: no otmechalos nykakoy raznytsы Between pharmacokinetic profiles pytavastatynu zdorovыh dobrovoltsev monholoydnoy and evropeoydnoy races.

Children: pharmacokinetic data at pedyatrycheskoy populyatsyy not.

Renal failure: for patsyentov with renal insufficiency and an average degree patsyentov on hemodialysis importance AUC uvelychyvalos 1.8 times and 1.7 times, respectively.

It should Lyvazo with caution assign patsyentam with renal insufficiency an average or severe degree. Increase dozы It should be held at tschatelnom Only Monitoring kidney function gradually after tytrovanyya dozы. Patsyentam with severe renal insufficiency is not recommended Degrees Apply a dose of 4 mg.

Pechenochnaya failure: the patsyentov with mild (class A classification by Child-Pyu) hepatic insufficiency AUC bыla Above 1.6 times, than in zdorovыh dobrovoltsev and in patsyentov with hepatic insufficiency an average degree (class B classification for Child-P "th ) AUC bыla 3.9 times higher. Restrictions dozы recommended patsyentam with hepatic insufficiency mild and an average degree. Lyvazo patsyentam contraindicated with severe hepatic insufficiency.

Basic physical and chemical properties

Round white pills pokrыtыe obolochkoy, with One storony kotorыh vыtesnenы bukvы "CC", and with Different storony - "1" (for Lyvazo 1 mg) or "2" (for Lyvazo 2mg) or "4" (for Lyvazo 4 mg).

Shelf life

4 years

Storage conditions

For protection of light from hranyt in blister packaging. Hranyt at temperatures Above 25 ° C

Packaging

For dozyrovanyya 1 mg to 7, 14 or 15 tablets belыh, pokrыtыh PVDC, PVC / AL blister; 1 or 2 blister packs in kartonnoy.

For dozyrovanyya 2 mg for 7, 14, 15 or 20 tablets belыh, pokrыtыh PVDC, PVC / AL blister; 1, 2 or 5 blysterov in kartonnoy pack.

For dozyrovanyya 4 mg for 7, 14 or 15 tablets belыh, pokrыtыh PVDC, PVC / AL blister; 1 or 2 blister packs in kartonnoy.

Vacation category

By recipe