Pravastatin. 10 mg. 30 tablets
Pravastatin. 10 mg. 30 tablets
4 . CLINICAL DATA
Treatment with pravastatin was conducted in the absence of an adequate therapeutic response of the administered diet and exercise.
Pravastatin is shown in :
• to lower elevated levels of total and LDL cholesterol in patients with primary hypercholesterolemia .
Progression of atherosclerotic disease and clinical cardiac sydovi incidents:
• delay of progression of atherosclerosis ;
• Reduce the incidence of clinical cardiovascular events sydovi .
Prevention of coronary events .
• Reduce the need for myocardial revascularization ;
• Improving survival by reducing syrdechno cardiovascular mortality.
• Reduce the risk of recurrent myocardial infarction and the need for myocardial revascularization procedures .
4.2 . The dosage and method of administration
Pravastatin is used in compliance with the mandatory diet with restriction of saturated -fat and cholesterol when response to diet and other nonpharmacological measures has not been adequate.
Pravastatin is administered orally once a day, preferably at bedtime . The starting dose is 10 mg per day, it can be increased if necessary gradually over 4 week intervals to 40 mg daily maximum . The therapeutic dose is adjusted for each patient individually , depending on therapeutic response and tolerability to the drug. Not recommended its adoption during the meal .
Therapeutic efficacy and safety of pravastatin has not been studied in children and is therefore not recommended for use with them.
No evidence of increased sensitivity to the drug and changes in pharmacokinetic parameters in patients aged > 65 years , so it is not necessary to specifically reduce the dosage for them.
Patients with renal insufficiency:
In patients with mild or moderate renal impairment requiring treatment be carried out with a low dosage and monitoring of renal function.
In severe renal impairment / creatinine clearance <30 ml / min / need treatment with pravastatin should be evaluated carefully.
4.3 . Contraindications
Hypersensitivity to one of the components of the tablet - drug or excipients , active liver disease or persistent elevations of liver function tests ;
Pregnancy and lactation .
4.4 . Special warnings and special precautions for use
• It is recommended that treatment with pravastatin in patients with homozygous familial hypercholesterolemia , as its effectiveness in them is weak due to lack of functional LDL - receptor ;
• Careful assessment and monitoring of liver function is required in patients with a history of significant alcohol consumption, at elevations of hepatic transaminases during treatment with pravastatin or in the presence of abnormal liver tests before initiation of treatment with the drug ;
• During treatment with pravastatin patients need to be monitored for the development of muscle pain, muscle weakness , increased activity kreatinikinaza , especially in the case of concomitant treatment with cyclosporine for patients with renal transplantation.
4.5 . drug Interactions
• No clinically relevant interactions with pravastatin drugs such as diuretics, ACE - inhibitors, calcium channel blockers , nitrates .
• Pravastatin is not metabolised by the cytochrome P450 system , so do not expect adverse clinically significant drug interactions at this level .
• Diltiazem , a relatively weak inhibitor of the cytochrome P450 does not cause changes in the pharmacokinetics of pravastatin paramateri when co-administered .
• Co-administration with cimetidine did not observe significant changes in the AUC of pravastatin .
• Concomitant administration with itraconazole , erythromycin or clarithromycin , the mean AUC and Cmax of pravastatin increase. Itraconazole , and macrolides are known inhibitors of cytochrome P450 ZA4 and transport of P-glycoprotein and is therefore not recommended to be administered with pravastatin .
• Concomitant administration of pravastatin with fibrates , nicotinic acid / niacin / cyclosporine and other HMG CoA - reductase inhibitors have an increased risk of myopathy and rhabdomyolysis.
- The mean Cmax, AUC, tl / 2 ( of pravastatin significantly increased in cardiac transplant patients who are treated with cyclosporine , and therefore not recommended to be administered .
• In patients with renal transplantation are at risk of increased average AUC24H of pravastatin when co-administered with cyclosporine .
• The excretion in urine of pravastatin and its binding to plasma proteins can be significantly reduced under the effect of gemfibrozil and therefore should be avoided concomitant administered .
• Nicotinic acid , aspirin, antacids / applied 1 hour prior to pravastatin / cimetidine or probucol did not significantly affect the bioavailability of pravastatin and do not expect significant changes in the therapeutic effect when co-administered with it.
o Administration of pravastatin 1 hour before or 4 hours after cholestyramine and 1 hour before colestipol in the diet did not induce significant changes in bioavailability or therapeutic effects of pravastatin .
• Not detectable clinically meaningful improvements in the therapeutic effectiveness of pravastatin when co-administered with propranolol .
• Administration of pravastatin and digoxin in healthy volunteers repeatedly not showing change in pharmacokinetic parameters in either one of the drugs .
• Despite the observed increases in AUC and C max of pravastatin by warfarin and other oral anticoagulants, concomitant administration leads to significant changes in the anticoagulant activity of the latter.
4.6 . Pregnancy and lactation
Administration of pravastatin, such as agent lowering the level of cholesterol during pregnancy may lead to abnormalities in the developing fetus . The products of cholesterol biosynthesis imat_vazhno important for fetal development and the use of inhibitors of cholesterol synthesis during pregnancy is associated with a risk of harm to the fetus . Not recommended adoption of pravastatin during lactation as it is excreted in small amounts in breast milk and may adversely affect the infant.
4.7 . EFFECTS ON THE ABILITY TO DRIVE AND USE MACHINES
No evidence of adverse effect on the mental and ??????????????????????????? of pravastatin .
4.7 . SIDE EFFECTS
Distributed system - the body - the class side effects may be: from the central nervous system / 0410 /
May occur with prolonged paresthesia / over 2 years / using pravstatin ; disturbances in the function of major cranial nerve / abnormal taste , abnormal ekstraokularni movements, facial paresis / , headache , tremor , vertigo
Psychiatric / 0500 /
Deterioration of memory processes , anxiety , insomnia, depression.
Musculoskeletal / 0200 /
In rare cases possible myalgia , arthralgia, rhabdomyolysis. Body as a Whole / General Reactions -1810 /
In rare cases possible hypersensitivity reactions : anaphylaxis, angioedema syndrome similar to lupus erythematosus , rheumatic polymyalgia , dermatomyositis , vasculitis , purpura , thrombocytopenia , eosinophilia, arthritis , arthralgia , urticaria, asthenia , photosensitivity , dyspnea, epidermal necrolysis, erythema multiforme, Stevens-Johnson syndrome , fatigue, like symptoms " flu ."
By Cardiovascular / 1010 /
Very rarely - pain in the chest.
Gastro - intestinal tract / 0600 /
More common effects are: nausea , vomiting , abdominal pain, constipation , diarrhea , flatulence, anorexia , rarely - pancreatitis , hepatitis, exacerbation of chronic hepatitis , jaundice, fatty liver , rarely - cirrhosis, fulminant hepatic necrosis. Transient increases in plasma levels of transaminases are possible in rare cases.
Haematological disorders / 1210,1220,1230 /
In rare cases, these violations are possible in white , red blood cells and clotting : transient asymptomatic eosinophilia, leucopenia, anemia and thrombocytopenia.
RESPIRATORY / 1100 /
In rare cases like symptoms " cold " , rhinitis, cough.
Skin and appendages / 0100 /
More often - skin rash , pruritus , rarely - alopecia , discoloration and drying of the skin and mucous membranes, damage to hair and nails.
Impairment of reproductive functions / 1420 /
Rarely - suppression of libido , erectile dysfunction, gynecomastia.
Sensory disturbances / 0433 / Progression of cataracts, ophthalmoplegia .
4.8 . OVERDOSE
In adopting a very high dose pravastatin were not observed clinical signs of toxicity or laboratory abnormalities . Treatment of overdosage is symptomatic , using generally accepted measures for the rapid elimination of unabsorbed drug and by maintaining a vital functions of the patient.
5 . Pharmacological
ATC code S10AA03
Serum lipid -lowering drugs
Cholesterol-lowering drugs and triglitsiredite
Inhibitors of HMG CoA - reductase
5.1. Pharmacodynamic properties
Pravastatin place its lipid-lowering effect in two ways: first - klyucheviya reversible inhibition of enzyme in cholesterol synthesis - HMG CoA reductase inhibitors. As a result of this action is blocking the conversion of HMG CoA to mevalonic acid and reduced intracellular cholesterol.
Compared with other statins - inhibitors of HMG CoA - reductase action on the enzyme of pravastatin is predominantly in the liver / 95% / , than in other locations - spleen , testis , kidney, adrenal . Pravastatin has structural similarity with a portion of HMG CoA , namely , D -hydroxy- D -methylglutaryl . By decreasing the intracellular reserves of cholesterol , stimulate the synthesis of pravastatin PRM - receptors in the cell membranes and thereby enhances receptor-mediated catabolism and clearance of circulating atherogenic Hall. - PRM. The second - pravastatin inhibits LDL - cholesterol levels by inhibiting synthesis of VLDL in holasterol lipoprotein , very low density , which is the precursor of LDL - cholesterol ..
Pravastatin administered in doses of 40 mg for 7 days, induces a decrease in plasma cholesterol levels by 20% , the Hall . - LDL by 23% and triglycerides of the total - 31% saotvetno.Pravastatin leads to a decrease in the levels of ApoB 12% of short-term and up to 30 % - on the continued application.
Along with the lowering of cholesterol and triglycerides act pravastatin has a positive effect on the endothelial dysfunction resulting in slowing the progression of atherosclerosis.
5.2 . pharmacokinetics
Rapidly absorbed after oral administration in a single dose in the form of sodium salt. Approximately 34% of the dose is absorbed with an absolute bioavailability of the drug is relatively low - 17%. Suffered greatly first pass effect.
Peak plasma concentrations occur between 0.6 to 1.6 hours. When administered at doses of 10 , 20, 40 mg, plasma concentrations were respectively 9,1; 26,5; 45,8 g / L
Food and Cholestyramine decreased systemic bioavailability of pravastatin when co-administered .
The volume of distribution in the re -administration of pravastatin is approximately 0,46 L / kg.S plasma protein binds Approximately 50%. Mainly distributed in hepatocytes , in minor quantities are excreted in breast milk, and in minimal amounts cross the blood -brain barrier.
Metabolized primarily in the liver and the main metabolite is 3 ( -hydroxy isomeric compound. Pharmacological activity is very weak and is 1/2 to 1/ 10 of that of pravastatin . Maximum plasma concentrations of the metabolite was observed between 0.9 - 1.3 hours . half-life of pravastatin ranges from 1.3 to 2.6 hours, and of its main metabolite, is 0.8 to 1.3 hours.
Excretion of pravastatin in two main roads - kidney and gall . Approximately 70 % of an oral dose is excreted in the bile and feces and 20% - in the urine within 96 chas.Tezi two routes of excretion of pravastatin create an opportunity for compensatory mechanisms alteranativna excretion in cases of hepatic or renal impairment.
In patients with renal and hepatic impairment no significant deviations in the main pharmacokinetic parameters : Cmax; AUC; t 1/2
5.3 . Preclinical safety data
Pravastatin refers to non-toxic substances. The median lethal dose / LD50 / test in mice upon oral administration of pravastatin exceed 1 g / kg teglo.Provedenite tests teratogenicity and embryotoxicity showed no abnormalities in the processes of fertilization and development of the offspring in the treatment of experimental animals with pravastatin at doses significantly above the therapeutic - 20 , 50, 200 and 1000 mg / kg body weight of the rat and 50 mg / kg weight of the rabbit.
In in vitro studies using standard microbiological tests have not found any mutagenic potential in pravastatin .
In tests on rats with long - 2 years of use of high doses of pravastatin 10, 30, 100 mg / kg body weight was detected in a high percentage of liver malignancies and lymphomas in the groups with the higher doses of the drug.
6 . PHARMACEUTICAL PARTICULARS
6.1. List of excipients and their amounts in mg / tablet
Pravastatin tab. 10 mg
Lactose monohydrate 60,0
Cellulose microcrystalline 100,0
Magnesium oxide 5,0
Magnesium stearate 2,0 Pravastatin tab. 20 mg
Lactose monohydrate 110,0
Cellulose microcrystalline 177,0
Magnesium oxide 6,0
Magnesium stearate 3,0
6.2 . Incompatibilities
He is known
6.3. Expiration date
2 / two / years
6.4 . Special precautions for storage
Keep dry and protected from direct sunlight locations at temperatures not exceeding 25 ° C.
6.5. Packaging Data
Tablets containing 10 mg or 20 mg Pravastatin each are packed in blisters PVDC / aluminum foil , 3 blisters in a cardboard box.