Livazo

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

The drug reduces the increased values of LDL cholesterol in patients, and also triglycerides along with total cholesterol. Also, the drug increases the values of HDL cholesterol. In addition, when using medicinal tablets, there is a decrease in Apo-B values, as well as a variable increase in Apo-Al levels. [1]

Indications Livazo

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

It is prescribed for adults with primary hypercholesterolemia (also in the case of a familial form of the disease that has a heterozygous nature, and in addition with combined  dyslipidemia ), in situations where the effect of non-drug treatment and diet is insufficient.

Release form

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

Pharmacodynamics

Pitavastatin competitively slows down the action of HMG-CoA reductase, reducing the rate of enzyme activity during cholesterol biosynthesis, and also slows down intrahepatic cholesterol binding. This leads to an increase in the expression of the endings of LDL within the liver, due to which the capture of circulating LDL elements from the blood is carried out, and in addition, a decrease in the level of total cholesterol, as well as LDL cholesterol inside the blood.

With a steady slowing down of intrahepatic cholesterol binding, the release of LDL inside the blood is weakened - by lowering the plasma triglyceride values. [2]

Pharmacokinetics

Absorption.

Pitavastatin is absorbed at high speed through the upper gastrointestinal tract; the Cmax index inside the blood plasma is noted after 60 minutes from the moment of oral administration. Absorption does not change with food consumption. [3]

The unchanged element is involved in enterohepatic circulation, after which it is absorbed inside the ileum with the small intestine. Bioavailability indicators of pitavastatin are 51%.

Distribution processes.

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

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

Plasma AUC varies with approximately 4-fold range between minimum and maximum marks. Testing using SLCO1B1 (the gene that encodes OATP1B1) concludes that the polymorphism of this gene can explain the marked fluctuation in the AUC level.

Exchange processes.

Unchanged pitavastatin is the main element of the drug inside the blood plasma. Its main metabolic component is the inactive lactone, formed from the pivastatin glucuronide conjugate of the UDP ester form using glucuronosyltransferase.

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

Excretion.

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

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

The Cmax values of pitavastatin within the blood plasma decreased by 43% when administered with a meal containing a high level of fat; the AUC indicator did not change.

Dosing and administration

The medication is used internally - the tablet is swallowed whole. You can use the medicine without reference to food intake, at any time of the day (but it is recommended to take it at the same time). Statins are usually more effective when used in the evening due to the circadian rhythm of lipid metabolism. Before starting therapy, the patient should be transferred to a diet with reduced intake of cholesterol. In addition, you need to adhere to such a diet during therapy.

The drug should first be used in a daily portion of 1 mg, 1 time. It is necessary to change the dosage at least 1 month apart. Portions are selected personally, taking into account the values of LDL cholesterol, the patient's condition and the used treatment regimen. For most patients, a dosage of 2 mg is suitable. A maximum of 4 mg is allowed per day.

Persons with renal dysfunction.

In the case of mild renal dysfunction, there is no need to change the dosage, but the use of pitavastatin should be done very carefully.

In the case of mild to moderate stages of impairment, a 4 mg serving is consumed exclusively under the condition of constant monitoring of renal activity and after gradual titration of the portion.

People with severe kidney failure should not take a dosage of 4 mg.

Individuals with hepatic dysfunction.

For moderate or mild lesions, a dosage of 4 mg is not prescribed. A maximum of 2 mg is allowed per day, with the condition of careful observation of hepatic function.

• Application for children

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

Use Livazo during pregnancy

It is forbidden to use Livazo with HB or pregnancy. Patients of childbearing age need to use reliable contraception during therapy. Since cholesterol and other products of its biosynthesis are very important in fetal development, the possible risk of slowing down the action of HMG CoA reductase still outweighs the expected benefits of therapy during pregnancy. Animal tests have shown reproductive toxicity, but have not identified teratogenic potential.

When planning conception, therapy should be stopped at least 1 month before conception occurs. In case of pregnancy when using drugs, treatment is immediately canceled.

Livazo should not be used while breastfeeding. In animals, secretion of pitavastatin with mother's milk was noted. There is no information as to whether the drug can be secreted in human breast milk. If the patient needs to take pitavastatin, breastfeeding should be avoided.

Contraindications

Among the contraindications:

• severe intolerance to pitavastatin or auxiliary components or other statins;
• failure of liver function in a severe stage;
• hepatic diseases in the active phase or a steady increase in serum transaminase levels of an unexplained nature (more than three times the maximum limit of the norm);
• QC indicators exceeding the highest limits of the norm by more than five times;
• myopathy;
• use in combination with cyclosporine.

Side effects Livazo

The main side symptoms:

• lesions associated with the blood system and lymph: sometimes anemia appears;
• problems with metabolic and metabolic processes: sometimes anorexia occurs;
• mental disorders: sometimes insomnia develops;
• disorders of the NS function: headaches are often observed. Sometimes - dysgeusia, hypesthesia, drowsiness and dizziness;
• visual impairment: a single weakening of visual acuity is noted;
• problems with the work of the vestibular apparatus and auditory organs: sometimes there is ear ringing;
• disturbances in the gastrointestinal tract: dyspepsia, diarrhea, constipation and nausea are often noted. Sometimes vomiting, abdominal pain and xerostomia develop. Occasionally there is discomfort in the gastrointestinal tract. The active phase of pancreatitis or glossodynia is observed singly;
• disorders of the hepatobiliary system: sometimes the values of transaminases (ALT with AST) increase. Hepatic pathologies, cholestatic jaundice and changes in the normal values of hepatic function are rarely observed;
• lesions of subcutaneous tissues and epidermis: sometimes rashes or itching occur. Erythema or urticaria appears singly;
• problems with the function of connective tissues, ODA and bones: arthralgia or myalgia often develops. Muscle spasms are sometimes noted. Rhabdomyolysis or myopathy appears occasionally. Perhaps the development of a necrotic form of myopathy, which has an immune-mediated character;
• violations of urinary activity: 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 actions are performed, as well as, if necessary, supportive procedures are performed. It is necessary to monitor the work of the liver and CPK indicators. The medicine has no antidote. The hemodialysis procedure will be ineffective.

Interactions with other drugs

Cyclosporine.

The introduction of the 1st portion of cyclosporine (at equilibrium values) together with the medication caused a 4.6-fold increase in the AUC of pitavastatin. It was not possible to determine how cyclosporine in the equilibrium value affects the equilibrium level of Livazo. Do not use the medicine if you are taking cyclosporine.

Erythromycin.

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

Gemfibrozil and other fibrates.

In the case of monotherapy using fibrates, myopathy sometimes occurs. In the case of a combination of fibrates and statins, the risk of developing rhabdomyolysis and myopathy increases. The medication must be very carefully combined with fibrates.

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

Niacin.

Interaction testing with niacin has not been performed. With monotherapy with the introduction of niacin, the development of rhabdomyolysis and myopathy occurred. Because of this, the medication must be used carefully with niacin.

Fusidic acid.

In the case of the combined administration of statins and systemic fusidic acid, the likelihood of myopathy, which also includes rhabdomyolysis, increases. At the moment, it has not been possible to determine the mechanism for the development of this effect.

There is information about the development of rhabdomyolysis (in some cases, fatal) when using this combination. If you need to use fusidic acid, you must abandon the introduction of Livazo at the time of its use.

Rifampicin.

Administration with medication caused a 1.3-fold increase in the AUC values of pitavastatin - due to the weakening of intrahepatic absorption.

Protease inhibitors.

The combination with medication can lead to slight changes in the AUC level of pitavastatin.

Warfarin.

As with the introduction of other statins, in persons using warfarin, it is necessary to monitor PTT or INR if Livazo is included in the treatment regimen.

Storage conditions

Livazo must be stored in a place closed from the penetration of sunlight. Temperature level - no more than 25 ° С.

Shelf life

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

Analogs

An analogue of the drug is Pitavastatin.

Reviews

Livazo gets positive reviews for the most part. 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 occasionally - because pitavastatin is a statin of the 4th (last) generation, the safest for the human body.