Treatment of primary hypercholesterolemia or mixed dyslipidemia, as a diet-supporting treatment, when the response to diet and other non-pharmacological treatments (eg physical exercise, weight loss) is insufficient. Decrease of mortality and morbidity for cardiovascular diseases in patients with moderate or severe hypercholesterolaemia and with a high risk of the first cardiovascular event as a dietary supportive treatment. Decrease in mortality and morbidity of cardiovascular disease in patients with a history of myocardial infarction or unstable angina, and with normal or elevated cholesterol, as adjunctive therapy to correct other risk factors. Reduction of hyperlipidemia occurring after transplants in patients receiving immunosuppressive treatment after parenchymal transplantation.
Composition:
1 tabl contains 20 mg or 40 mg of pravastatin sodium. The preparation contains lactose.
Action:
Pravastatin is an inhibitor competing with 3-hydroxy-3-methylglutarylcoenzyme A (HMG-CoA) reductase, an enzyme catalyzing the early stage of cholesterol biosynthesis, and in two ways lipid-lowering. First, as a reversible and specific inhibitor competing with HMG-CoA reductase, it does little to reduce the synthesis of intracellular cholesterol. This leads to an increase in the number of LDL-cholesterol receptors on the surface of cells and increases the catabolism and clearance of circulating LDL-cholesterol. Second, pravastatin inhibits the production of LDL-cholesterol by inhibiting the synthesis of VLDL-cholesterol, the precursor of LDL-cholesterol in the liver. Both in healthy people and in hypercholesterolemic patients, the preparation reduces the following lipid parameters: total cholesterol, LDL-cholesterol, apolipoprotein B, VLDL-cholesterol and triglycerides, and increases HDL-cholesterol and apolipoprotein A. After oral administration, the drug quickly absorbs from the tract. Maximum plasma concentrations are reached after 1-1.5 hours after administration. On average, 34% of the oral dose is absorbed and the total bioavailability is 17%. 66% of the dose is the first-pass effect of the liver, which is the main site of action of the drug. researchin vitro showed that pravastatin is transported to the interior of hepatocytes, and uptake by other cells is much smaller. The drug is about 50% bound to plasma proteins. After oral administration, 20% of the dose is excreted in the urine and 70% in the faeces. T0,5 in plasma is 1.5-2 hours.
Contraindications:
Hypersensitivity to the active substance or to any of the excipients. Active liver disease, including unexplained persistent elevations of serum transaminases 3 times the upper limit of the values considered normal. Pregnancy and lactation.
Precautions:
The efficacy of pravastatin in patients with homozygous familial hypercholesterolaemia has not been evaluated; this treatment is not suitable when hypercholesterolemia is caused by an increased level of HDL-cholesterol. Caution should be exercised in patients with elevated liver aminotransferases and therapy should be discontinued if alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels exceed 3 times the upper limit of normal and persistent values. Caution should be exercised in patients with a history of liver disease or alcohol abusers. Caution should be exercised when administering the preparation to patients with factors predisposing to muscle adverse reactions: renal failure, hypothyroidism, muscular toxicity after administration of statins or fibrates in history, with hereditary muscular diseases in the patient or his family or those who abuse alcohol. In such cases, CK activity should be determined before starting treatment. The determination of CK activity should also be considered before starting treatment in people over 70 years of age, in particular in the presence of other predisposing factors.If the CK activity is significantly elevated from the initial value (more than 5 times the upper limit of the values considered normal), treatment should not be started and the results should be re-marked after 5-7 days. The initial value of CK activity can be used as a reference in case of a subsequent increase during statin treatment. Patients who develop unexplained muscular symptoms such as pain or tenderness, muscle weakness or muscle cramps during statin treatment should consider the occurrence of myopathy. In such cases, creatine kinase (CK) activity should be determined. Temporary statin therapy should be temporarily suspended when the CK activity exceeds the upper limit of the values considered normal or when there are strong clinical symptoms more than 5 times. In order to confirm the results, the CK activity should be re-determined after about 5-7 days. The results should be interpreted in the context of other potential factors that may have caused temporary muscle damage, such as intense physical exercise or muscle injury. If the CK activity is significantly elevated (more than 5 times the upper limit of values considered normal), statin treatment should be discontinued. Discontinuation of treatment should also be considered if there is a strong muscle symptom, even if the CK increase is less than or equal to the 5-fold upper limit of what is considered normal. If the symptoms resolve and CK activity returns to normal, re-treatment with statins may be considered using the lowest doses under strict control. Re-treatment with statins is not recommended if you have suspected hereditary muscle disease. Co-administration of pravastatin with fibrates is not recommended due to the increased risk of muscle disorders. Caution should be used with statins simultaneously with nicotinic acid. An increased incidence of myopathy has been reported in patients taking statins concurrently with cytochrome P450 inhibitors. Statin treatment should be discontinued if suspected interstitial lung disease. Caution for use in patients at high risk of diabetes (patients with fasting Glucose from 5.6 to 6.9 mmol / l, BMI> 30 kg / m2, with increased triglycerides, with hypertension should be subjected to clinical and biochemical control). Pravastatin is not recommended for use in children under 8 years due to inadequate safety and efficacy data. Pre-pubertal children should be carefully evaluated for the benefit / risk ratio before starting treatment. The preparation contains lactose - it should not be used in patients with rare hereditary galactose intolerance, Lapp lactase deficiency or malabsorption of glucose-galactose.
Pregnancy and lactation:
The preparation is contraindicated during pregnancy and breastfeeding and in women planning pregnancy.
Side effects:
Uncommon: dizziness, headache, sleep disturbances, insomnia, blurred vision (including blurred vision and double vision), indigestion, heartburn, abdominal pain, nausea, vomiting, constipation, diarrhea, bloating, increase in serum transaminases, pruritus, rash, urticaria, abnormalities of the scalp and hair (including baldness), musculoskeletal pain including joint pain, muscle cramps, muscle weakness and elevated CK levels, urinary disorders (including urinary pain, frequent urination) urine, urination at night), sexual dysfunction, fatigue. Very rare: peripheral polyneuropathy (especially after long-term use), paraesthesia, hypersensitivity reactions (anaphylaxis, angioedema, symptoms similar to systemic lupus erythematosus), pancreatitis, jaundice, hepatitis, fulminant hepatic necrosis, decay of striated muscles (which may be accompanied by acute renal failure secondary to myoglobinuria), myopathy, myositis or polymyositis. Isolated cases of tendon disorders, sometimes complicated by tendon rupture. Side effects characteristic of statins: nightmares, memory loss, depression, isolated cases of interstitial lung disease (more information during long-term use), diabetes (in people at increased risk).
Dosage:
Orally. Adults.hypercholesterolemiaThe recommended dose is 10-40 mg once a day.Response to treatment is visible in the first week of treatment, and the full effect occurs within 4 weeks, therefore, periodic lipid testing should be performed and the dose adjusted accordingly. The maximum daily dose is 40 mg.Prevention of diseases of the cardiovascular system: initial and maintenance dose is 40 mg per day.Dosing after transplantsthe recommended starting dose for organ transplant recipients receiving immunosuppressive therapy is 20 mg / day; depending on changes in lipid parameters, the dose can be increased under strict medical supervision up to a maximum of 40 mg per day. In patients with moderate or severe renal or hepatic failure, the initial dose is 10 mg / day and the dose should be adjusted depending on the lipid parameters. No dose adjustment is necessary in elderly patients unless there are risk factors for muscle side effects. When using a preparation with bile acid binding resins (eg cholestyramine or cholestipol), it should be used for 1 hour before or at least 4 h after resin administration. In patients receiving cyclosporine with or without immunosuppressive medicinal products, treatment should be started at 20 mg daily, with caution and gradually increasing to 40 mg.Children and adolescents (aged 8 to 18 years) with heterozygous familial hypercholesterolemia: 10 - 20 mg once daily in patients 8 to 13 years of age, as no more than 20 mg doses were tested in this population, and 10 - 40 mg daily for patients between 14 and 18 years of age. The drug is used once a day, preferably in the evening, regardless of the meal.
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