Vogdia

Yellow, oblong, biconvex tablet with engraved 40 on one side and plain on the other.
Each tablet contains Pravastatin sodium 40 mg.

Pharmacology: Pharmacodynamics: Pravastatin sodium is a competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, which is the rate-limiting enzyme involved in de novo cholesterol synthesis. This reduction in cholesterol leads to an increased LDL-receptors, improved receptor-mediated catabolism and clearance of circulating LDL. It also blocks the production of LDL by inhibiting the synthesis of its precursor, very low density lipoprotein (VLDL), in the liver. In addition to the ability of HMG-CoA reductase inhibition, Pravastatin sodium also possess pleiotropic properties including improved endothelial function, reduced inflammation at the site of the coronary plaque, inhibition of platelet aggregation, and anticoagulant effects.
Pharmacokinetics: Absorption: Pravastatin sodium is rapidly absorbed. The average absorption is 34% of the administered dose, with bioavailability of 17%. Time to peak concentration is in the range of 1 to 1.5 hours.
Distribution: Protein binding is approximately 50%. The volume of distribution is 0.46 L/kg.
Metabolism: Pravastatin sodium undergoes extensive first-pass metabolism by the liver. The primary metabolite of Pravastatin sodium is the 3-alpha-hydroxy-iso-Pravastatin (2.5% to 10% activity of parent drug).
Excretion: Plasma elimination half-life in adults is 77 hours (including all metabolites), approximately 2 to 3 hours (Pravastatin sodium), approximately 1.5 hours (3-alpha-hydroxy-iso-Pravastatin). About 70% of an oral dose of Pravastatin sodium is excreted in the feces, and about 20% is excreted in the urine.

Hypercholesterolaemia: Treatment of primary hypercholesterolaemia or mixed dyslipidaemia, as an adjunct to diet, when response to diet and other non-pharmacological treatments (eg. exercise, weight reduction) is inadequate.
Primary prevention: Reduction of cardiovascular mortality and morbidity in patients with moderate or severe hypercholesterolaemia and at high risk of a first cardiovascular event, as an adjunct to diet.
Secondary prevention: Reduction of cardiovascular mortality and morbidity (myocardial infarction, revascularization, ischemic stroke and transient ischemic attack) in patients with a history of myocardial infarction or unstable angina pectoris and with either normal or increased cholesterol levels, as an adjunct to correction of other risk factors.
Post-transplantation: Reduction of post-transplantation hyperlipidaemia in patients receiving immunosuppressive therapy following solid-organ transplantation.

Doses should be individualized according to the baseline low-density lipoprotein (LDL)-cholesterol levels, the recommended goal of therapy, and patient response. Adjustments should be made at intervals of 4 weeks or more. Doses may need adjusted based on concomitant medications. Pravastatin sodium tablets are administered orally once daily preferably in the evening with or without food.
Hypercholesterolemia: The recommended dose range is 10-40 mg once daily. The therapeutic response is seen within a week and the full effect of a given dose occurs within four weeks, therefore periodic lipid determinations should be performed and the dosage adjusted accordingly. The maximum daily dose is 40 mg.
Cardiovascular prevention: In all preventive morbidity and mortality trials, the only studied starting and maintenance dose was 40 mg daily.
Dosage after transplantation: Following organ transplantation a starting dose of 20 mg per day is recommended in patients receiving immunosuppressive therapy (see Interactions). Depending on the response of the lipid parameter, the dose may be adjusted up to 40 mg under close medical supervision.
Special population: Children: The documentation on efficacy and safety in patients less than 18 years old is limited, therefore, the use of Pravastatin sodium is not recommended in these patients.
Elderly patients: There is no dose adjustment necessary in these patients unless there are predisposing risk factors.
Renal or hepatic impairment: a starting dose of 10 mg a day is recommended in patients with moderate or severe renal impairment or significant hepatic impairment. The dosage should be adjusted according to the response of lipid parameters and under medical supervision.
Concomitant therapy: The lipid lowing effects of Pravastatin sodium on total cholesterol and LDL-cholesterol are enhanced when combined with a bile acid binding resin (eg. cholestyramine, colestipol). Pravastatin sodium tablets should be given either one hour before or at least four hours after the resin.
For patients taking cyclosporine with or without other immunosuppressive medicinal products, treatment should begin with 20 mg of pravastatin once daily and titration to 40 mg should be performed with caution.

There has been limited experience with overdosage of Pravastatin sodium. There is no specific treatment for Pravastatin sodium overdose. Treatment is symptomatic and supportive. Severe toxicity is not expected after an overdose.

Hypersensitivity to Pravastatin sodium or any component of the formulation (lactose, microcrystalline cellulose, corn starch, magnesium oxide, croscarmellose, crospovidone, povidone, yellow iron oxide, colloidal silicon dioxide, magnesium stearate).
Active liver disease including unexplained persistent elevations of serum transaminases.
Pregnancy and breastfeeding.

Based on the notification of the Ministry of Public Health: Do not use the drug in pregnant and breast-feeding women.
Do not use the drug in patients with liver disease.
If there is myalgia at calf, back or whole body, stop taking drug and consult physician.
Liver function tests should be performed before taking drug, 6 and 12 weeks after taking drug. For patients who routinely use the drug, liver function tests should be performed every 6 months or as recommended by a physician. If the transaminase level is greater than three times of upper normal limit, stop taking drug and consult physician.
Use with caution with digoxin, warfarin because the level of these drugs in blood may be high and become dangerous.
The risk of myopathy or rhabdomyolysis will increase when administer the drug with other following drugs, eg. azole antifungals such as ketoconazole, itraconazole, macrolides such as erythromycin, clarithromycin; HIV protease inhibitors such as indinavir, ritonavir, nelfinavir, saquinavir; verapamil, diltiazem, gemfibrozil, nicotinic acid, cyclosporine, amiodarone.
The risk of rhabdomyolysis will increase under the following conditions, eg. use at high dose, the elderly; patients with hepatic or renal insufficiency, alcoholism, patients with hypothyroidism.
Caution should be exercised when taking this drug with colchicine especially in the elderly or patients with renal insufficiency because there is a risk of myopathy or rhabdomyolysis.
The use of this drug may increase the risk of increasing in blood sugar level.

Endocrine and metabolic: Reduced cholesterol synthesis as a result of therapy could theoretically lead to reduced adrenal or gonadal steroid hormone production. Patients with signs/symptoms of endocrine dysfunction should be evaluated as clinically indicated. Use caution with concomitant medications (eg. spironolactone, cimetidine, ketoconazole) that may reduce steroid hormone levels/activity.
Hepatic: Liver function abnormalities have been reported. Use caution in patients who have a recent (less than 6 months) history of hepatic disease, signs of suspected hepatic disease (unexplained aminotransferase elevations, jaundice), or are heavy users of alcohol. Liver enzyme tests should be obtained at baseline and as clinically indicated, routine periodic monitoring of liver enzymes is not necessary. Hepatic failure, some cases fatal, has been reported. Prompt interruption of therapy may be required.
Musculoskeletal: Rhabdomyolysis with acute renal failure secondary to myoglobinuria has been reported. Patients should be monitored closely. This risk is dose-related and is increased with concurrent use of erythromycin, cyclosporine, fibric acid derivatives (eg. gemfibrozil), or niacin (doses ≥1 g/day). Temporarily withhold therapy in patients experiencing conditions predisposing to the development of renal failure secondary to rhabdomyolysis (eg. sepsis, hypotension, major surgery, trauma, uncontrolled epilepsy, severe metabolic, endocrine, or electrolyte disorders). Discontinue therapy in any patient in which CPK levels are markedly elevated (>10 times ULN) or if myopathy is suspected/diagnosed. Use caution in patients with inadequately treated hypothyroidism and those taking other drugs associated with myopathy (eg. colchicine). These patients are predisposed to myopathy. Patients should be instructed to report unexplained muscle pain, tenderness, weakness, or brown urine. Immune-mediated necrotizing myopathy (IMNM), an autoimmune mediated myopathy, has been rarely reported. Discontinue use if suspected. Supportive therapy may be required.
Neurologic: Use caution in patients with preexisting amyotrophic lateral sclerosis (ALS). Rate of ALS functional decline may increase with statin therapy.
Renal: Acute or serious conditions that predispose patients to the development of renal failure secondary to rhabdomyolysis (eg. sepsis, hypotension, major surgery, trauma, severe metabolic, endocrine or electrolyte disorders, or uncontrolled epilepsy). Dosage interruption is required.

Pregnancy: Pravastatin sodium is contraindicated in pregnant females or those who may become pregnant. Pravastatin sodium was found to cross the placenta. Cholesterol biosynthesis may be important in fetal development. Serum cholesterol and triglycerides increase normally during pregnancy. The discontinuation of lipid lowering medications temporarily during pregnancy is not expected to have significant impact on the long term outcomes of primary hypercholesterolemia treatment. Pravastatin sodium should be discontinued immediately if an unplanned pregnancy occurs during treatment. Adequate contraception is recommended if an HMG-CoA reductase inhibitor is required in females of reproductive potential. Females planning a pregnancy should discontinue the HMG-CoA reductase inhibitor 1 to 2 months prior to attempting to conceive.
Breastfeeding: Use of Pravastatin sodium in breastfeeding women is contraindicated. A small amount of Pravastatin sodium is present in breast milk.

Common: Dermatologic: Rash (1.2% to 7.2%).
Gastrointestinal: Diarrhea (4.7% to 8.5%), Nausea and vomiting (4% to 10.5%).
Musculoskeletal: Musculoskeletal pain (3.9% to 24.9%).
Neurologic: Headache (3.5% to 7.5%).
Respiratory: Cough (1.2% to 8.2%), Rhinitis (1.2% to 7%), Upper respiratory infection (4.1% to 21.2%).
Serious: Endocrine metabolic: Diabetes mellitus.
Gastrointestinal: Pancreatitis.
Hepatic: Increased liver enzymes (up to 1.2%).
Musculoskeletal: Autoimmune necrotizing myopathy, Statin-associated (Rare), Disorder of muscle (Less than 0.1%), Rhabdomyolysis, Rupture of tendon.

Pravastatin sodium is not significantly metabolised by the cytochrome P450 enzyme system, although caution has been advised when such combinations are used.
Anticoagulants: No change in warfarin activity has been seen in patients given both warfarin and Pravastatin sodium. An epidemiological study in patients stabilised on warfarin found that risk of hospitalisation from gastrointestinal bleeding was not raised when Pravastatin sodium was added to therapy.
Antidepressants: Increased creatine kinase concentrations occurred in a patient given Pravastatin sodium with nefazodone. A study in healthy subjects found that St. John's wort had no effect on Pravastatin sodium.
Antifungals: Pravastatin sodium is not significantly metabolised by the cytochrome P450 enzyme system. Effect of itraconazole and ketoconazole, which are inhibitors of CYP3A4, on Pravastatin sodium appears to be minimal.
Antivirals: HIV-protease inhibitors are inhibitors of the cytochrome P450 isoenzyme CYP3A4 and may affect the metabolism of statins. The plasma concentration of Pravastatin sodium was reduced with ritonavir-boosted saquinavir. Efavirenz is an inducer of CYP3A4 and a study in healthy subjects found that it could reduce plasma concentrations of Pravastatin sodium, although it is not metabolised by CYP3A4.
Colchicine: Use with caution. Colchicine increases the risk of rhabdomyolysis when given with Pravastatin sodium.
Fruit juices: Grapefruit juice inhibits the cytochrome P450 isoenzyme CYP3A4. Pravastatin sodium, which is not significantly metabolised by CYP3A4, does not appear to be affected.
Fusidic acid: Concurrent use of fusidic acid and Pravastatin sodium may result in increased exposure of fusidic acid and/or Pravastatin sodium. The risk of myopathy including rhabdomyolysis may be increased. If the treatment with systemic fusidic acid is necessary, Pravastatin sodium should be discontinued.
Immunosuppressants: The mechanism of the interaction may be additive toxicity, since both Pravastatin sodium and cyclosporine are known to cause myopathy, but effects on plasma concentrations may also be involved. Pharmacokinetic studies have shown that cyclosporine increases the plasma concentrations of Pravastatin sodium. Clinical and biochemical monitoring of patients receiving this combination is recommended.
Lipid regulating drugs: Myopathy and myositis are recognised adverse effects of both statins and fibric acid derivatives, including fibrates and gemfibrozil, and the risk is increased if they are given together. Studies have shown increased plasma concentrations of Pravastatin sodium when given with gemfibrozil.
Concurrent use of cholestyramine or colestipol and Pravastatin sodium may result in reduced effectiveness of Pravastatin sodium. There was no clinically significant decrease in bioavailability or therapeutic effect when Pravastatin sodium was administered one hour before or four hours after cholestyramine or one hour before colestipol.

Store below 30°C.

Dyslipidaemic Agents

C10AA03 - pravastatin ; Belongs to the class of HMG CoA reductase inhibitors. Used in the treatment of hyperlipidemia.

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