Livaso

Livazo belongs to the subgroup of lipid-lowering drugs; it is a substance that slows down the activity of HMG CoA reductase.

The drug reduces elevated LDL cholesterol levels in patients, as well as triglycerides and total cholesterol. The drug also increases HDL cholesterol levels. In addition, when taking medicinal tablets, there is a decrease in Apo-B levels, as well as a variable increase in Apo-Al levels. [ 1 ]

Indications Livaso

It is used to reduce elevated levels of total cholesterol, as well as LDL cholesterol values.

It is prescribed to adults with primary hypercholesterolemia (also in the case of a familial form of the disease, which is heterozygous, and also in case of combineddyslipidemia ), in situations where the effect of non-drug treatment and diet is insufficient.

Release form

The release of the therapeutic substance is realized in tablet form – with a volume of 1 or 4 mg – 7, 14 or 15 pieces inside a blister pack; 1-2 packs inside a box. It is also produced in tablets with a volume of 2 mg – 7, 14, 15 or 20 pieces inside a cell plate; inside a pack – 1, 2 or 5 such plates.

Pharmacodynamics

Pitavastatin competitively inhibits the action of HMG-CoA reductase, reducing the rate of enzyme activity in cholesterol biosynthesis, and also inhibits intrahepatic cholesterol binding. This leads to an increase in the expression of LDL endings inside the liver, due to which the capture of circulating LDL elements from the blood occurs, and in addition, the level of TC, as well as LDL-C in the blood, decreases.

With a sustained slowdown in intrahepatic cholesterol binding, there is a weakening of LDL secretion into the blood – by lowering plasma triglyceride levels. [ 2 ]

Pharmacokinetics

Absorption.

Pitavastatin is rapidly absorbed from the upper gastrointestinal tract; peak plasma concentrations are reached within 60 minutes of oral administration. Absorption is not affected by food.[ 3 ]

The unchanged element participates in enterohepatic circulation, after which it is absorbed inside the ileum with the small intestine. The bioavailability of pitavastatin is 51%.

Distribution processes.

The drug is synthesized with protein at a level of over 99%; the majority is bound to albumin, as well as acidic α1-glycoprotein. The average distribution volume is about 133 l.

The substance actively moves into hepatocytes, where it acts and participates in metabolic processes with the help of many intrahepatic carriers, including OATP1B1 with OATP1B3.

Plasma AUC levels vary with an approximately 4-fold range between minimum and maximum values. Testing using SLCO1B1 (the gene that encodes OATP1B1) suggests that polymorphisms in this gene may explain the marked variation in AUC levels.

Exchange processes.

Unchanged pitavastatin is the major constituent of the drug in plasma. Its major metabolic component is an inactive lactone formed from the pivastatin conjugate glucuronide of the UDP ester form by glucuronosyltransferase.

In vitro tests using 13 isoforms of the hemoprotein P450 (CYP) revealed that the metabolism of pitavastatin with the participation of CYP is very weak; the metabolism of the drug with some metabolic elements occurs with the help of CYP2C9 (and also, less actively, CYP2CS).

Excretion.

Unchanged pitavastatin is excreted into bile from the liver at high speed, but it also participates in enterohepatic recirculation, which increases the duration of its activity.

Less than 5% of the drug is excreted in urine. The half-life varies in the range of 5.7-8.9 hours (the first value is determined when administering the 1st portion, and the second - at equilibrium values). The average clearance rate when using a 1-fold portion is 43.4 l/hour.

Plasma Cmax values of pitavastatin were decreased by 43% when administered with a high-fat meal; AUC was not changed.

Dosing and administration

The medication is taken orally - the tablet is swallowed whole. The medication can be taken without reference to food intake, at any time of the day (but it is recommended to take it at the same time). The use of statins is usually more effective if they are taken in the evening - due to the daily rhythm of lipid metabolism. Before starting therapy, the patient should be transferred to a diet with reduced cholesterol intake. In addition, it is necessary to adhere to such a diet during the therapy.

The drug should be used initially in a daily dose of 1 mg, once. The dosage should be changed at least every 1 month. The doses are selected individually, taking into account the LDL-C values, the patient's condition and the treatment regimen used. Most patients are treated with a dosage of 2 mg. A maximum of 4 mg is allowed per day.

Persons with renal dysfunction.

In case of mild renal dysfunction, no dosage adjustment is necessary, but pitavastatin should be used with extreme caution.

In mild to moderate stages of the disorder, a 4 mg dose is used only under the condition of constant monitoring of renal function and after gradual titration of the dose.

People with severe renal impairment are prohibited from taking a dosage of 4 mg.

Persons with liver dysfunction.

In case of moderate or mild lesions, a dosage of 4 mg is not prescribed. A maximum of 2 mg per day is allowed, subject to careful monitoring of liver function.

• Application for children

There is no information on how safe and effective it is to use Livazo in pediatrics (under 18 years of age).

Use Livaso during pregnancy

Livazo should not be used during breastfeeding or pregnancy. Patients of childbearing age should use reliable contraception during therapy. Since cholesterol and other products of its biosynthesis are very important for fetal development, the possible risk of slowing the action of HMG-CoA reductase still outweighs the expected benefit of therapy during pregnancy. Animal tests have shown reproductive toxicity, but have not determined teratogenic potential.

When planning conception, at least 1 month before conception, therapy should be stopped. If pregnancy occurs while using the drug, treatment should be stopped immediately.

Livazo should not be used during breastfeeding. Pitavastatin has been secreted in animal milk. There is no information on whether the drug can be secreted in human milk. If a patient needs to take pitavastatin, breastfeeding should be discontinued.

Contraindications

Among the contraindications:

• severe intolerance to pitavastatin or excipients or other statins;
• severe liver failure;
• liver disease in the active phase or a persistent increase in serum transaminase levels of unknown origin (more than three times the maximum normal limit);
• QC values exceeding the highest normal limits by more than five times;
• myopathy;
• use in combination with cyclosporine.

Side effects Livaso

Main side effects:

• lesions associated with the blood and lymphatic system: sometimes anemia appears;
• problems with metabolic and exchange processes: sometimes anorexia occurs;
• mental disorders: sometimes insomnia develops;
• disorders of the nervous system function: headaches are often observed. Sometimes – dysgeusia, hypoesthesia, drowsiness and dizziness;
• visual impairment: occasional weakening of visual acuity is observed;
• problems with the functioning of the vestibular apparatus and auditory organs: sometimes tinnitus is noted;
• gastrointestinal disorders: dyspepsia, diarrhea, constipation and nausea are often observed. Sometimes vomiting, abdominal pain and xerostomia develop. Occasionally, discomfort in the gastrointestinal tract appears. An active phase of pancreatitis or glossodynia is observed sporadically;
• disorders of the hepatobiliary system: sometimes the values of transaminases (ALT with AST) increase. Liver pathologies, cholestatic jaundice and changes in normal values of liver function are observed sporadically;
• lesions of subcutaneous tissues and epidermis: sometimes rashes or itching occur. Erythema or urticaria appear occasionally;
• problems with the function of connective tissues, musculoskeletal system and bones: arthralgia or myalgia often develops. Muscle spasms are sometimes observed. Rhabdomyolysis or myopathy appears occasionally. The development of a necrotic form of myopathy, which is immune-mediated, is possible;
• urinary disorders: pollakiuria is sometimes observed;
• systemic lesions: sometimes there is malaise, asthenia, increased fatigue or peripheral edema.

Overdose

In case of poisoning, potentiation of side effects may occur.

There is no specific therapy; symptomatic measures are taken, and supportive measures are given if needed. Liver function and CPK levels should be monitored. The drug has no antidote. Hemodialysis will be ineffective.

Interactions with other drugs

Cyclosporine.

Co-administration of cyclosporine (at steady state) with the drug resulted in a 4.6-fold increase in pitavastatin AUC. The effect of steady state cyclosporine on steady state Livazo could not be determined. The drug should not be used with cyclosporine.

Erythromycin.

The use of the above substance caused a 2.8-fold increase in the AUC level of the drug. During the period of administration of erythromycin or other macrolides, therapy with the drug should be suspended.

Gemfibrozil and other fibrates.

In case of monotherapy with fibrates, myopathy sometimes occurs. In case of combination of fibrates and statins, the risk of rhabdomyolysis and myopathy increases. The drug should be combined with fibrates very carefully.

In pharmacokinetic testing, administration of the drug with gemfibrozil caused a 1.4-fold increase in pitavastatin AUC values; while the AUC of fenofibrate increased by 1.2-fold.

Niacin.

No interaction testing of the drug with niacin has been performed. Rhabdomyolysis and myopathy have occurred with niacin monotherapy. Therefore, the drug should be used with caution with niacin.

Fusidic acid.

In case of combined administration of statins and systemic fusidic acid, the probability of myopathy, including rhabdomyolysis, increases. At present, it has not been possible to determine the mechanism of development of this effect.

There is information about the development of rhabdomyolysis (in some cases - with a fatal outcome) when using such a combination. If it is necessary to use fusidic acid, it is necessary to stop administering Livazo during its use.

Rifampicin.

Administration with the drug resulted in a 1.3-fold increase in pitavastatin AUC values due to decreased intrahepatic absorption.

Protease inhibitors.

Combination with the drug may lead to slight changes in the AUC level of pitavastatin.

Warfarin.

As with other statins, patients using warfarin should have their PT or INR monitored if Livazo is included in the treatment regimen.

Storage conditions

Livazo must be stored in a place protected from sunlight. Temperature level – no more than 25°C.

Shelf life

Livazo is allowed to be used within a 5-year period from the date of sale of the pharmaceutical substance.

Analogues

The analogue of the drug is Pitavastatin.

Reviews

Livazo receives mostly positive reviews. In the case of using a standard dosage (2 mg), a stable positive effect developed after 1.5 months. In the case of strict adherence to medical instructions, negative manifestations developed only sporadically - because pitavastatin is a 4th (last) generation statin, the safest for the human body.