Livazo Tab n / a film about 1mg 28 pc

Description

Composition
Active substance:
Per tablet:
calcium pitavastatin 1 mg to 1,045 mg; 2 mg to 2,090 mg; 4 mg-4,180 mg (equivalent Pitavastatin): 1 mg to 1,000 mg; 2 mg to 2,000 mg; 4 mg to 4,000 mg.
Excipients:
Per tablet:
Lactose monohydrate, low substituted giproloza, hypromellose, magnesium aluminometasilicate, magnesium stearate, Opadry white, hypromellose, titanium dioxide, triethyl citrate, colloidal silicon dioxide.
Description:
Round, biconvex tablets, film-coated white. A cross section of the core of white color. On one side of the tablet – engraving “KS”, on the other – engraving “1”, “2” or “4”, according to the dosage.
Product form:
Tablets, film-coated 1 mg, 2 mg and 4 mg.
For the 1 mg dosage: 7, 14, 15 tablets in AL / PVC blister of the blister 1 or 2 together with instructions for use in a cardboard box.
For dosage of 2 mg: 7, 10, 14, 15, 20 tablets in AL / PVC blister, 1, 2, 3 or 5 blisters together with instructions for use in a cardboard box.
For the dosage of 4 mg: 7, 10, 14, 15 tablets in AL / PVC blister, 1, 2, 3 blisters with instruction for use in a cardboard box.
Contraindications
• Increased sensitivity to Pitavastatin auxiliary components of the drug and other inhibitors of HMG-CoA reductase inhibitors (statins). • Severe hepatic insufficiency (more than 9 points on the Child-Pugh) or Class C according to the classification of Child-Pugh, liver disease in its active phase, including a persistent increase in “liver” in serum transaminases (more than 3 times compared with the upper limit of normal (ULN)). • Lactose intolerance, lactase deficiency or glucose-galactose malabsorption. • Myopathy. • Simultaneous administration of cyclosporine. • Pregnancy, lactation, lack of adequate contraception in women of childbearing age. • Age 18 years (effectiveness and safety have been established).
Carefully:
When there is a risk of myopathy / rhabdomyolysis – renal failure, hypothyroidism, personal or family history of hereditary muscular disease and the previous history of muscle toxicity with other inhibitors
HMG-CoA reductase inhibitor or a fibrate, a history of liver disease or alcohol abuse, age over 70 years.
Dosage
1 mg
Indications
Primary hypercholesterolemia including geterozigotnuyusemeynuyu hypercholesterolemia (type IIa hyperlipidemia Fredrickson classification) or mixed hypercholesterolemia (type IIb hyperlipidemia classification
Fredrickson), hypertriglyceridemia (hyperlipidemia type IV classification
Fredrickson) as an adjunct to diet when diet and other non-pharmacological treatments (eg exercise, weight loss) are not sufficient.
Interaction with other drugs
Pitavastatin actively transported into hepatocytes numerous human hepatic transporters (including organic anions transport polypeptide [OATP]), which may be included in some of the following interactions.
Cyclosporin: simultaneous reception of a single dose of cyclosporine with Pitavastatin at equilibrium leads to a 4.6-fold increase in AUC pitavastatin. 10
Effect of cyclosporin in equilibrium equilibrium condition Pitavastatin unknown. Livazo drug is contraindicated in patients treated with cyclosporine.
Erythromycin: simultaneous reception of erythromycin with Pitavastatin leads to 2,8-fold increase in AUC pitavastatin. It recommended temporary discontinuation of pitavastatin during treatment with erythromycin or other macrolide antibiotics.
Gemfibrozil and other fibrates: In rare cases, the fibrate monotherapy was associated with the development of myopathy. The simultaneous use of fibrates with statins associated with increased incidence of rhabdomyolysis and myopathy. Caution must be exercised while the use of pitavastatin with fibrates. In studies of the pharmacokinetics of the simultaneous use of pitavastatin with gemfibrozil resulted in an increase in AUC 1,4kratnomu pitavastatin and fenofibrate AUC increased 1.2 times.
Nicotinic acid (a lipid-lowering doses): study of the interaction in the treatment of Pitavastatin and nicotinic acid in the lipid-lowering doses (more than 1 g / day) was conducted. Use of nicotinic acid in monotherapy was associated with the development of myopathy and rhabdomyolysis. Therefore, while the use of nicotinic acid in a lipid-lowering doses (more than 1 g / day) Livazo drug should be used with caution.
Fusidic acid: were reported severe muscle disorders such as rhabdomyolysis, which are attributed to the interaction between fusidic acid and statins. During treatment with fusidic acid is recommended to suspend the application of Livazo.
Rifampicin: co-administration with Pitavastatin resulted in 1.3-fold increase in AUC due Pitavastatin reduce accumulation in the liver.
HIV protease inhibitors: co-administration with Pitavastatin led to minor changes in pitavastatin AUC.
Ezetimibe and its glucuronide metabolite inhibit the uptake of dietary and biliary cholesterol. The simultaneous use of pitavastatin no effect on plasma concentrations of ezetimibe or its glucuronide metabolite and ezetimibe had no effect on plasma concentrations of pitavastatin. Inhibitors of CYP3A4 isoenzyme: interaction studies with itraconazole and grapefruit juice, known inhibitors of CYP3A4 isoenzyme, showed no clinically significant effect on the plasma concentrations of pitavastatin.
Digoxin known substrate of P-glycoprotein (Pgp), does not interact with Pitavastatin. In a joint application no significant changes in pitavastatin or digoxin concentrations in plasma.
Warfarin: equilibrium state pharmacokinetics and pharmacodynamics (INR [International Normalized Ratio] and MF [prothrombin time]) in healthy volunteers warfarin did not change in the combined use with Pitavastatin warfarin in a dose of 4 mg daily. However, as the use of other statins, patients receiving warfarin, adding to the pitavastatin treatment should be monitored px and INR.
Overdose
Specific treatment of overdose is not.
Necessary to symptomatic therapy, to monitor the activity of CPK and liver function. Hemodialysis is ineffective.
pharmachologic effect
Pharmacological group:
Lipid-lowering drugs – HMG-CoA reductase inhibitor.
Pharmacodynamics:
Pitavastatin – competitive inhibitor of HMG-CoA (3-hydroxy-3-metilglyutarilkoenzim
A) reductase, the enzyme catalyzing the initial step of the synthesis of cholesterol – the formation of mevalonic acid from HMG-CoA. Since the conversion of HMG-CoA into mevalonic acid is the initial step of the synthesis of cholesterol, the use of pitavastatin does not cause accumulation in the body is potentially toxic sterols. HMG-CoA is readily metabolized to acetyl-CoA, which is involved in the synthesis of many processes in the body. The efficiency Livazo drug in reducing the concentration of total cholesterol (TC) in the blood plasma, low density lipoprotein cholesterol (LDL), cholesterol, very low density lipoproteins (VLDL), triglycerides (TG) and apolipoprotein B (Apo-B), and also increase (HDL-C), high density lipoprotein cholesterol and apolipoprotein A1 (Apo-A1)
When treating primary hypercholesterolemia and combined (mixed) dyslipidemia, for administration of therapeutic doses, pitavastatin significantly reduced the concentration of LDL cholesterol, total cholesterol, HDL-cholesterol not, TG and Apo-B and increased cholesterol concentration 2
HDL and Apo-A1. Reduces the ratio of total cholesterol / HDL cholesterol and Apo-B / Apo-A1. In applying Livazo 2 mg LDL reduction was achieved at a concentration of 38-39%, and 44-45% – in applying a dose of 4 mg. In most cases, the assignment of 2 mg dose, achieved a target LDL-C by treatment recommendations
European Atherosclerosis Society (EAS).
When treating older patients with primary hypercholesterolemia and mixed dyslipidemia (65 years) in the appointment Livazo dose of 1 mg, 2 mg or 4 mg of LDL cholesterol values ​​were reduced by 31%, 39.0% and 44.3%, respectively, the target level established by the EAS, was achieved in 90% of patients.
When treating patients with primary hypercholesterolemia or mixed dyslipidemia in combination with 2 or more factors of cardiovascular risk, mixed dyslipidemia or in combination with type 2 diabetes, approximately 80% of patients reached the set EAS targets for LDL-C. cholesterol levels
LDL in these groups of patients was reduced by 44% and 41% respectively.
For long-term reception Livazo target value set EAS, it maintained stable by continuously lowering the concentration of LDL cholesterol (-30.5%) and the concentration of HDL cholesterol consistently grew large with an increased concentration
HDL-C in patients with initially lower values ​​of this parameter (
Atherosclerosis:
In the treatment of patients undergoing percutaneous coronary intervention for acute coronary syndrome under control intravascular ultrasound appointment pitavastatin 4 mg for 8-12 months led to a reduction in coronary plaque volume by approximately 17% and was accompanied by a reversal of the remodeling of the vascular wall (from 113.0 to 105.4 mm 3).
The beneficial effects on mortality and morbidity are not currently evaluated.
Diabetes mellitus: 3
Patients with hyperlipidemia, and impaired glucose tolerance in the appointment
Livazo at doses of 1 mg / day or 2 mg / day in addition to recommendations for lifestyle changes, new-onset diabetes occurs less frequently than in patients who were not receiving lipid-lowering therapy: 39.9% versus 45.7% for the period 2.8 years, the hazard ratio was 0.82.
Meta-analysis of the safety of pitavastatin in relation to diabetes risk showed a neutral effect of the drug Livazo against the risk of new cases of diabetes compared with other statin therapy.
Pharmacokinetics:
Suction:
Pitavastatin is rapidly absorbed in the upper gastrointestinal tract (GIT), maximum concentration (Cmax) in plasma is achieved within 1 hour after taking the drug. Food intake does not affect absorption. Cmax pitavastatin plasma is reduced by 43% when co-administered with oily food, but the area under the curve “concentration-time» (AUC) remains unchanged.
Unchanged drug undergoes enterohepatic recycling and well absorbed from the jejunum and ileum. Pitavastatin absolute bioavailability is 51%.
Distribution:
More than 99% of Pitavastatin binds to plasma proteins, mainly albumin and alpha-1 acid glycoprotein. The average distribution volume is 133 liters.
Pitavastatin actively penetrates into the hepatocytes with the help of transport proteins
OATR1V1 and OATR1V3. AUC varies between 4-fold increase from a minimum to a maximum value. Pitavastatin is not a substrate for P-glycoprotein.
Metabolism:
The plasma is contained mainly unchanged pitavastatin. The major metabolite is an inactive lactone, which is formed of pitavastatin glucuronide conjugate ether type with UDP-glucuronosyltransferase (UGT1A3 and 2V7). cytochrome
P450 influences the metabolism of pitavastatin is minimal. Isozyme CYP2C9 (and to a lesser extent CYP2C8 isozyme) involved in the metabolism of Pitavastatin to secondary metabolites.
Excretion: pitavastatin in unmodified form is rapidly cleared from the liver in the bile, but undergoes enterohepatic recycling, ensuring its long-lasting effect. Less than 5% of Pitavastatin excreted by the kidneys. Plasma half-life ranges from 5.7 hours (single dose) to 8.9 hours (in an equilibrium state), the average clearance is 43.4 l / h after a single oral administration.
Pharmacokinetics in different patient groups:
Elderly patients: when evaluating the pharmacokinetics of pitavastatin in elderly patients over 65 years of pitavastatin AUC was 1.3 times higher. This does not affect the efficacy or safety.
Hepatic impairment: in patients with mild hepatic impairment (Class A classification Child-Pugh) AUC was 1.6 times higher than in healthy volunteers, while in patients with moderate hepatic impairment (class B classification Chayld- Pugh) AUC was 3.9 times higher. When expressed human liver use of pitavastatin contraindicated.
Renal impairment: Patients with moderate renal failure and hemodialysis, there was an increase in AUC of 1.8 times and 1.7 times, respectively.
Sex differences: Marked increase in AUC in women compared to men is 1.6 times in healthy volunteers study, which does not affect the efficacy and safety of the drug Livazo.
Race: the results of pharmacokinetic analysis of data obtained in healthy volunteers of different race (Japanese and caucasian population), factors such as age and gender did not affect the pharmacokinetics of pitavastatin.
Pregnancy and breast-feeding
Pregnancy:
Use of the drug is contraindicated in pregnancy Livazo. Women of childbearing age in the treatment Livazo should use reliable methods of contraception. Since cholesterol and other products of cholesterol biosynthesis are needed for the development of the fetus, the potential risk of inhibition of HMG-CoA reductase inhibitors outweigh the benefits of treatment with the drug during pregnancy. Animal studies have shown that pitavastatin has reproductive toxicity, but no teratogenic potential. If the patient is planning pregnancy should stop 6
treatment for at least one month prior to conception. If pregnancy occurs during use Livazo, treatment should be discontinued immediately.
Breastfeeding:
Use of the drug Livazo during breast-feeding is contraindicated.
Pitavastatin is excreted in the milk of lactating rats. Data on the allocation of pitavastatin in breast milk are not available. If necessary, use Livazo during lactation breastfeeding should be discontinued.
Conditions of supply of pharmacies
Prescription.
side effects
In controlled clinical trials, when receiving the recommended doses of less than 4% of patients receiving drug treatment Livazo was excluded from the study due to adverse reactions. The most common was myalgia.
Depending on the frequency of occurrence of adverse reactions are the following according to the World Health Organization classification: very common: 10, often from 1/100 to
From the side of hematopoiesis:
Uncommon: anemia
From a metabolism:
Uncommon: anorexia
Mental disorders:
Often insomnia
From the nervous system:
Common: headache
Uncommon: dizziness, taste disturbance, drowsiness
From the senses:
Uncommon: tinnitus
Rare: blurred vision
For the skin:
Uncommon: pruritus, rash
Rare: urticaria, erythema
On the part of the musculoskeletal system:
Common: myalgia, arthralgia
Uncommon: muscle spasms
Frequency not known: immune-mediated necrotizing myopathy
From the urinary system:
Uncommon: pollakiuria
From the digestive system:
Common: constipation, diarrhea, dyspepsia, nausea,
Uncommon: abdominal pain, dryness of the oral mucosa, vomiting
Rare: glossodiniya, acute pancreatitis, cholestatic jaundice
Laboratory findings:
Uncommon: povyshenieaktivnosti “liver” transaminase, aspartate aminotransferase (AST), alanine aminotransferase (ALT), increased activity of creatine phosphokinase (CPK).
In clinical studies, after receiving Livazo observed increase in activity
CK 3 times above ULN 49 patients 2,800 (1.8%). Levels exceeding ULN is 10 times or more with concomitant muscle symptoms were rare, and only observed in one patient out of 2406 patients receiving 4 mg Livazo (0.04%) in the clinical trial program.
Other:
Uncommon: asthenia, malaise, fatigue, peripheral edema
Post-Marketing Experience applications:
It was carried out a two-year prospective study of post-marketing surveillance of 20,000 patients in Japan. The vast majority of these patients received pitavastatin in a dose of 1 or 2 mg, 4 mg but not. In 10.4% of patients were recorded adverse reactions for which a causal relationship can not be excluded with Pitavastatin, and 7.4% of patients discontinued treatment due to adverse reactions. The frequency of occurrence was 1.08% myalgia. Most adverse reactions were mild. Over 2 years the incidence of adverse events was higher in patients with a history of drug allergy (20.4%) or liver or kidney disease (13.5%).
Adverse reactions and their frequency of occurrence, observed in post-marketing surveillance study, a prospective, but not in the international controlled clinical trials, with application of the drug at the recommended doses are given below.
Of the liver and biliary tract:
Rare: abnormal liver function, liver disease
On the part of the musculoskeletal system:
Rare: myopathy, rhabdomyolysis
The post-marketing surveillance study, there were two reports of rhabdomyolysis, in which patients required hospitalization (0.01% of the patients).
In addition, there are spontaneous reports of side effects with the musculoskeletal system, including myalgia and myopathy in patients treated
Ливазо во всех рекомендуемых дозах. Были также получены сообщения о рабдомиолизе с острой почечной недостаточностью и без нее, в том числе, о рабдомиолизе с летальным исходом.
Были также получены спонтанные сообщения о следующих нежелательных реакциях (частота основана на случаях, наблюдаемых в пострегистрационных исследованиях):
From the nervous system:
Нечасто: гипестезия
From the digestive system:
Редко: дискомфорт в животе
Нежелательные явления при применении других статинов: – нарушение сна, включая кошмарные сновидения; – амнезия; – сексуальная дисфункция; – depression; – интерстициальное заболевание легких; – сахарный диабет: частота возникновения зависит от наличия или отсутствия факторов риска (концентрация глюкозы в крови натощак 5,6 ммоль/л, индекс массы тела >30 кг/м2, повышенная концентрация ТГ, артериальная гипертензия в анамнезе); – повышение гликозилированного гемоглобина.
special instructions
Воздействие на мышечную ткань:
Как и при применении других ингибиторов ГМГ-КоА редуктазы (статинов), существует вероятность развития миалгии, миопатии и, в редких случаях, рабдомиолиза. Следует предупредить пациентов о необходимости сообщать о любых мышечных симптомах.
Активность КФК следует определять у любого пациента, сообщающего о мышечной боли, болезненности мышц при пальпации или слабости, особенно если это сопровождаются недомоганием или лихорадкой.
Активность КФК не следует определять после физических нагрузок или при наличии каких-либо других возможных причин повышения КФК, которые могут исказить результат. При повышении активности КФК (в 5 раз выше ВГН), в течение 5-7 дней следует выполнить контрольный анализ.
Отмечены очень редкие случаи иммуноопосредованной некротизирующей миопатии (ИОНМ) во время лечения или при прекращении приема статинов. ИОНМ клинически проявляется в виде стойкой слабости проксимальных мышц и повышения активности
КФК в сыворотке крови, которые сохраняются несмотря на отмену статинов.
До лечения:
Как и все статины, Ливазо следует с осторожностью назначать пациентам, имеющим предрасполагающие факторы развития рабдомиолиза. Следует определить активность
КФК для установления контрольного исходного значения в следующих случаях: • почечная недостаточность, • гипотиреоз, • личный или семейный анамнез наследственных мышечных заболеваний, • предшествующий анамнез мышечной токсичности при лечении фибратами или другими статинами, • наличие в анамнезе заболеваний печени или злоупотребления алкоголем, • пациентам старше 70 лет с другими предрасполагающими факторами риска развития рабдомиолиза.
В таких случаях рекомендован клинический мониторинг, и риск лечения следует рассматривать в зависимости от возможной пользы. Лечение Ливазо нельзя начинать, если активность КФК в 5 раз превышает ВГН.
Во время лечения:
Следует рекомендовать пациенту немедленно сообщать врачу о мышечной боли, слабости или судорогах. Следует определить активность КФК, и лечение прекратить, если активность КФК повышена (в 5 раз выше ВГН). Следует рассмотреть вопрос о прекращении лечения при возникновении тяжелых мышечных симптомов, даже если активность КФК не превышает ВГН в 5 раз. При разрешении симптомов и возвращении активности КФК к норме, может быть рассмотрен вопрос о повторном назначении Ливазо в дозе 1 мг при соблюдении тщательного контроля.
Воздействие на печень:
Как и все статины, Ливазо следует с осторожностью назначать пациентам, имеющим в анамнезе заболевания печени, или пациентам, регулярно употребляющим избыточное количество алкоголя. Перед началом лечения Ливазо и затем периодически во время лечения следует проводить функциональные печеночные пробы. Пациентам со стойким повышением активности «печеночных» трансаминаз (АЛТ и АСТ), превышающим ВГН в 3 раза, следует прекратить лечение Ливазо.
Воздействие на почки:
Ливазо следует с осторожностью назначать пациентам с почечной недостаточностью умеренной или тяжелой степени. Повышать дозу следует только при тщательном контроле. Доза 4 мг не рекомендована пациентам с тяжелой почечной недостаточностью.
Сахарный диабет:
Некоторые данные свидетельствуют о том, что статины, как класс, приводят к увеличению уровней глюкозы в крови, повышая риск развития сахарного диабета в будущем, а у некоторых пациентов с высоким риском развития сахарного диабета могут привести к уровню гипергликемии, при котором становится показанным формальное лечение сахарного диабета. Тем не менее, эта опасность перевешивается снижением сосудистого риска при лечении статинами, и поэтому не должна являться причиной для прекращения лечения статинами. За пациентами, имеющими риск развития гипергликемии (концентрация глюкозы натощак от 5,6 до 6,9 ммоль/л, индекс массы тела (ИМТ)> 30 кг/ м2, повышенную концентрацию ТГ, артериальную гипертензию), необходим клинический и биохимический контроль в соответствии с национальными рекомендациями. Вместе с тем, по результатам как постмаркетинговых наблюдений для оценки безопасности, так и проспективных исследований не было выявлено никаких подтверждённых сигналов о риске сахарного диабета при применении питавастатина.
Интерстициальные заболевания легких:
Редкие случаи интерстициальных заболеваний легких регистрировали при применении некоторых статинов, особенно при длительной терапии.
Наблюдаемые клинические признаки включают одышку, непродуктивный кашель и ухудшение общего состояния здоровья (повышенная утомляемость, потеря массы тела и лихорадка). При подозрении на развитие интерстициального заболевания легких терапию статинами следует прекратить.
Effects on ability to drive vehicles, mechanisms:
Необходимо соблюдать осторожность при управлении транспортными средствами или выполнении другой работы, требующей повышенного внимания, поскольку возможно развитие таких нежелательных реакций как головокружение и сонливость.
Storage conditions
Store in a dark place at a temperature not higher than 25 ° C. Keep out of the reach of children.
Dosing and Administration
Внутрь, таблетки необходимо проглатывать целиком.
Предпочтителен прием таблетки в одно и то же время суток, лучше вечером, в соответствии с циркадным ритмом липидного обмена. До начала и в процессе лечения пациенты должны придерживаться гипохолестеринемической диеты.
Начальная доза препарата 1 мг в сутки однократно. При необходимости дозу препарата увеличивают с интервалами не менее 4 недель до 2 мг в сутки. Дозу следует подбирать индивидуально в соответствии с концентрациями ХС ЛПНП, целью лечения и ответом пациента на лечение. Большинству пациентов требуется доза 2 мг. Максимальная суточная доза – 4 мг.
Пациенты с легкими и умеренными нарушениями функции печени: рекомендована максимальная суточная доза 2 мг.
Пациенты с нарушением функции почек: при нарушении функции почек легкой степени тяжести (желательно объективно оценить данную степень с отражением клиренса креатинина или скорости клубочковой фильтрации), препарат Ливазо следует применять с осторожностью. Данные по применению максимальной суточной дозы препарата 4 мг при нарушениях функции почек любой степени тяжести ограничены, поэтому назначать максимальную суточную дозу 4 мг необходимо только при тщательном контроле функции почек после постепенного повышения дозы. Не рекомендуется пациентам с тяжелыми нарушениями функции почек назначать максимальную суточную дозу в 4 мг; рекомендуется рассмотреть ограничение максимальной суточной дозы до 2 мг при тяжелой почечной недостаточности.
Пациенты пожилого возраста: коррекция дозы не требуется.
Information
Appearance may differ from that depicted in the picture. There are contraindications. You need to read the manual or consult with a specialist