Pravachol (Pravastatin)
 Only available by prescription.
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Pravachol (Pravastatin)
Description:
Indications and Clinical Use
Therapy with lipid-altering agents should be considered a component of multiple risk factor intervention in those individuals at increased risk for atherosclerotic vascular disease due to dyslipidemia. PRAVACHOL (pravastatin sodium) should be used in addition to a diet restricted in saturated fat and cholesterol when the response to diet and other non-pharmacological measures alone has been inadequate (see National Cholesterol Education Program (NCEP) Guidelines in Table 1).
Hypercholesterolemia
PRAVACHOL is indicated as an adjunct to diet (at least an equivalent of the Adult Treatment Panel III [ATP III TLC diet]) for the reduction of elevated Total and Low Density Lipoprotein Cholesterol (LDL-C) levels in patients with primary hypercholesterolemia (Types IIa and IIb), when the response to diet and other non-pharmacologic measures alone has been inadequate.
Prior to initiating therapy with PRAVACHOL, secondary causes for hypercholesterolemia, such as obesity, poorly controlled diabetes mellitus, hypothyroidism, nephrotic syndrome, dysproteinemias, obstructive liver disease, other drug therapy or alcoholism, should be excluded and it should be determined that patients for whom treatment with PRAVACHOL is being considered have an elevated LDL-C level as the cause for an elevated total serum cholesterol. A lipid profile should be performed to measure Total Cholesterol, High Density Lipoprotein Cholesterol (HDL-C) and Triglycerides (TG).
For patients with total triglycerides less than 4.52 mmol/L (400 mg/dL), LDL-C can be estimated using the following equation: LDL-C (mmol/L)=Total Cholesterol−[(0.37×triglycerides)+HDL-C]
LDL-C (mg/dL)=Total Cholesterol−[(0.16×triglycerides)+HDL-C]
When total triglyceride levels exceed 4.52 mmol/L (400 mg/dL), this equation is less accurate and LDL-C concentrations should be determined by ultracentrifugation.
Pravachol (Pravastatin) Manufacturer:
Bristol-Myers Squibb
Pravachol (Pravastatin) Side Effects:
Primary Prevention of Coronary Events
In hypercholesterolemic patients without clinically evident coronary heart disease, PRAVACHOL is indicated to:
Reduce the risk of myocardial infarction;
Reduce the risk for undergoing myocardial revascularization procedures;
Reduce the risk of total mortality by reducing cardiovascular deaths.
In the West of Scotland Study (WOS), the effect of PRAVACHOL treatment on fatal and nonfatal coronary heart disease (CHD) was assessed in 6 595 patients (aged 45 to 64 years) without a previous myocardial infarction, but with elevated LDL-C levels between 4-6.7 mmol/L (156-254 mg/dL). The patients were followed for a median of 4.8 years.
PRAVACHOL significantly reduced the rate of first coronary events (either CHD death or nonfatal MI) by 31% (248 events in the placebo group [CHD death=44, non-fatal MI=204] vs 174 events in the PRAVACHOL group [CHD death=31, non-fatal MI=143], p=0.0001). The effect of these cumulative cardiovascular event rates was evident after 6 months of treatment. The risk reduction with PRAVACHOL was similar and significant throughout the entire range of baseline LDL cholesterol levels. This reduction was also similar and significant across the age range studied with a 40% risk reduction for patients younger than 55 years and a 27% risk reduction for patients 55 years and older.
PRAVACHOL also significantly decreased the risk for undergoing myocardial revascularization procedures (coronary artery bypass graft surgery by 37% [80 vs 51 patients, p=0.009] and coronary angiography by 31% [128 vs 90, p=0.007]). Cardiovascular deaths were decreased by 32% (73 vs 50, p=0.03), and there was no increase in deaths from non-cardiovascular causes.
The West of Scotland Study excluded female patients, elderly subjects and most patients with familial hypercholesterolemia (FH). Consequently it has not been established to what extent the findings of the WOS study can be extrapolated to these subpopulations of hypercholesterolemic patients.
In patients with heterozygous FH, optimal reduction in total and LDL cholesterol necessitates a combination drug therapy in the majority of patients. (For homozygous FH see Warnings and Precautions, Homozygous Familial Hypercholesterolemia.)
Because information on familial combined hyperlipidemic (FCH) patients is not available from the WOS study, the effect of PRAVACHOL in this subgroup of high risk dyslipidemic patients could not be assessed.
Secondary Prevention of Cardiovascular Events
In patients with total cholesterol in the normal to moderately elevated range who have clinically evident coronary heart disease, PRAVACHOL is indicated to:
Reduce the risk of total mortality
Reduce the risk of death due to coronary heart disease
Reduce the risk of myocardial infarction
Reduce the risk of undergoing myocardial revascularization procedures
Reduce the risk of stroke and transient ischemic attack (TIA)
Reduce total hospitalization
In the Long-Term Intervention with Pravastatin in Ischemic Disease (LIPID) study, the effect of PRAVACHOL 40 mg daily was assessed in 9014 men and women with normal to elevated serum cholesterol levels (baseline Total-C=155-271 mg/dL [4.0-7.0 mmol/L]; median Total- C=218 mg/dL [5.66 mmol/L]; median LDL-C=150 mg/dL [3.88 mmol/L]), and who had experienced either a myocardial infarction or had been hospitalized for unstable angina pectoris in the preceding 3-36 months.
Treatment with PRAVACHOL significantly reduced the risk for CHD death by 24% (p=0.0004). The risk for coronary events (either CHD death or nonfatal MI) was significantly reduced by 24% (p<0.0001) in the PRAVACHOL treated patients. The risk for fatal or nonfatal myocardial infarction was reduced by 29% (p<0.0001). PRAVACHOL reduced both the risk for total mortality by 23% (p<0.0001) and cardiovascular mortality by 25% (p<0.0001). The risk for undergoing myocardial revascularization procedures (coronary artery bypass grafting or percutaneous transluminal coronary angioplasty) was significantly reduced by 20% (p<0.0001) in the PRAVACHOL treated patients. PRAVACHOL also significantly reduced the risk for stroke by 19% (p=0.0477). Treatment with PRAVACHOL significantly reduced the number of days of hospitalization per 100 person-years of follow-up by 15% (p<0.001). The effect of PRAVACHOL on reducing CHD events was consistent regardless of age, gender, or diabetic status.
In the Cholesterol and Recurrent Events (CARE) study the effect of PRAVACHOL 40 mg daily on coronary heart disease death and nonfatal MI was assessed in 4159 men and women with normal serum cholesterol levels (baseline mean Total-C=209 mg/dL [5.4 mmol/L]), and who had experienced a myocardial infarction in the preceding 3-20 months. Treatment with PRAVACHOL significantly reduced the rate of a recurrent coronary event (either CHD death or nonfatal MI) by 24% (274 patients with events [13.3%] in the placebo group vs. 212 patients [10.4%] in the PRAVACHOL group, p=0.003). The reduction in risk for this combined endpoint was significant for both men and women; in women, the reduction in risk was 43% (p=0.033). The risk of undergoing revascularization procedures (coronary artery bypass grafting or percutaneous transluminal coronary angioplasty) was significantly reduced by 27% (p<0.001) in the PRAVACHOL treated patients (391 [19.6%] vs 294 [14.2%] patients). PRAVACHOL also significantly reduced the risk for stroke by 32% (p=0.032), and stroke or transient ischemic attack (TIA) combined by 26% (124 [6.3%] vs 93 [4.7%] patients, p=0.025).
PRAVACHOL was also found to reduce the rate of progression of atherosclerosis in patients with coronary heart disease as part of a treatment strategy to lower Total and LDL-cholesterol to target levels. In two trials including this type of patients{*Pravastatin Limitation of Atherosclerosis in the Coronary/Carotid Arteries (PLAC I and II)} (i.e. in a secondary prevention intervention), PRAVACHOL monotherapy was shown to reduce the rate of progression of atherosclerosis as evaluated by quantitative angiography and B-mode ultrasound. This effect may be associated with an improvement in the coronary endpoints (fatal or non fatal myocardial infarction). In these trials, however, no effect was observed in all cause mortality.
Pediatrics (<16 years of age)
Only limited experience with the use of statins in children is available. There is no experience to date with the use of PRAVACHOL in such patients. Treatment in these patients is not recommended at this time.
Geriatrics (≥65 years of age)
Pharmacokinetic evaluation of pravastatin in patients over the age of 65 years indicates an increased AUC. As a precautionary measure, the lowest dose should be administered initially in these patients.
Contraindications
Patients who are hypersensitive to this drug or to any ingredient in the formulation.
Active liver disease or unexplained persistent elevations of serum transaminases (see Warnings and Precautions).
In Pregnant and Nursing Women
Cholesterol and other products of cholesterol biosynthesis are essential components for fetal development (including synthesis of steroids and cell membranes). Since HMG-CoA reductase inhibitors such as PRAVACHOL (pravastatin sodium) decrease cholesterol synthesis and possibly the synthesis of other biologically active substances derived from cholesterol, they may cause fetal harm when administered to pregnant women. PRAVACHOL should be administered to women of childbearing age only when such patients are highly unlikely to conceive and have been informed of the possible harm. If the patient becomes pregnant while taking PRAVACHOL, the drug should be discontinued immediately and the patient apprised of the potential harm to the fetus. Atherosclerosis being a chronic process, discontinuation of lipid metabolism regulating drugs during pregnancy should have little impact on the outcome of longterm therapy of primary hypercholesterolemia (see Warnings and Precautions, Pregnant Women, Nursing Women).
Warnings and Precautions
Muscle Effects
Elevations of creatinine phosphokinase levels (CK [MM fraction]), have been reported with the use of HMG-CoA reductase inhibitors, including PRAVACHOL.
Effects on skeletal muscle such as myalgia, myopathy and, rarely, rhabdomyolysis have been reported in patients treated with PRAVACHOL.
Muscle weakness and rhabdomyolysis have been reported in patients receiving other HMG-CoA reductase inhibitors concomitantly with itraconozole and cyclosporine.
The benefits and risks of using HMG-CoA reductase inhibitors concomitantly with immunosuppressive drugs, fibrates, erythromycin, systemic azole derivative antifungal agents or lipid-lowering doses of niacin should be carefully considered.
Rare cases of rhabdomyolysis with acute renal failure secondary to myoglobinuria, have been reported with PRAVACHOL and with other HMG-CoA reductase inhibitors.
Myopathy, defined as muscle pain or muscle weakness in conjunction with increases in creatine phosphokinase (CK) values to greater than ten times the upper limit of normal, should be considered in any patient with diffuse myalgias, muscle tenderness or weakness, and/or marked elevation of CK. Patients should be advised to report promptly any unexplained muscle pain, tenderness or weakness, particularly if associated with malaise or fever. Patients who develop any signs or symptoms suggestive of myopathy should have their CK levels measured. PRAVACHOL therapy should be discontinued if markedly elevated CK levels are measured or myopathy is diagnosed or suspected.
As with other statins, the risk of myopathy including rhabdomyolysis may be substantially increased by concomitant immunosuppressive therapy including cyclosporines, and by concomitant therapy with gemfibrozil, erythromycin or niacin (see Warnings and Precautions).
Myopathy has not been observed in clinical trials involving small numbers of patients who were treated with PRAVACHOL together with immunosupressants, fibric acid derivatives or niacin.
The use of fibrates alone is occasionally associated with myopathy. In a limited size clinical trial of combined therapy with pravastatin (40 mg/day) and gemfibrozil (1200 mg/day), myopathy was not reported, although a trend towards CK elevations and musculoskeletal symptoms was seen. The combined use of pravastatin and fibrates should generally be avoided.
No information is available on the combined therapy of pravastatin with erythromycin.
Pre-disposing Factors for Myopathy/Rhabdomyolysis: PRAVACHOL, as with other HMG-CoA reductase inhibitors, should be prescribed with caution in patients with pre-disposing factors for myopathy/rhabdomyolysis. Such factors include: personal or family history of hereditary muscular disorders; previous history of muscle toxicity with another HMG-CoA reductase inhibitor; concomitant use of a fibrate or niacin; hypothyroidism; alcohol abuse; excessive physical exercise; age >70 years; renal impairment; hepatic impairment; diabetes with hepatic fatty change; surgery and trauma; frailty; situation where an increase in plasma levels of active ingredient may occur.
PRAVACHOL therapy should be temporarily withheld or discontinued in any patient with an acute serious condition suggestive of myopathy or predisposing to the development of rhabdomyolysis (e.g. sepsis, hypotension, major surgery, trauma, severe metabolic endocrine and electrolyte disorders, or uncontrolled seizures).
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| Product Code:1729 |
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