Asto-Chol

Uses

Asto-Chol is an HMG-CoA reductase inhibitor used to lower lipid levels and to reduce the risk of cardiovascular events, including myocardial infarction and stroke.

Asto-Chol is indicated for primary prevention of coronary events hypercholesterolemic patients without clinical evidence of coronary heart disease. Its use includes the reduction of risk on myocardial infarction, undergoing myocardial revascularization procedures and cardiovascular mortality.

As well, pravastatin can be used as a secondary prevention agent for cardiovascular events in patients with clinically evident coronary heart disease. This indication includes the reduction of risk of total mortality by reducing coronary death, myocardial infarction, undergoing myocardial revascularization procedures, stroke, and stroke/transient ischemic attack as well as to slow the progression of coronary atherosclerosis.

The term cardiovascular events correspond to all the incidents that can produce damage to the heart muscle including the interruption of blood flow.

As adjunctive therapy to diet, pravastatin is used in:

• Patients with primary hypercholesterolemia and mixed dyslipidemias including hyperlipidemia type IIa and IIb.
• Patients with elevated serum triglycerides including type IV hyperlipidemia.
• Patients with heterozygous familial hypercholesterolemia in patients over 8 years of age with low-density lipoprotein (LDL) cholesterol higher than 190 mg/dl after diet modifications or LDL levels higher than 160 mg/dl and familial history of premature cardiovascular diseases or at least two cardiovascular risk factors.

In patients that do not respond adequately to diet, pravastatin is used to treat patients with primary dysbetalipoproteinemia (type III hyperlipidemia).

Dyslipidemia is defined as an elevation of plasma cholesterol, triglycerides or both as well as to the presence of low levels of high-density lipoprotein. This condition represents an increased risk for the development of atherosclerosis.

Asto-Chol is also used to associated treatment for these conditions: Acute Coronary Events, Cardiovascular Outcomes, Coronary Artery Atherosclerosis, Coronary Death, Death, Dysbetalipoproteinemia, Heterozygous Familial Hypercholesterolemia, High Cholesterol, Hyperlipidemias, Mixed Dyslipidemias, Myocardial Infarction, Myocardial Revascularization, Secondary prevention cardiovascular event, Stroke, Transient Ischemic Attack, Elevation of serum triglyceride levels

How Asto-Chol works

Asto-Chol is a specific inhibitor of the hepatic HMG-CoA reductase in humans. The inhibition of this enzyme produces a reduction in cholesterol biosynthesis as HMG-CoA reductase activity is an early-limiting step in cholesterol biosynthesis.

The inhibitory mechanism of action produces a reduction in cholesterol synthesis which in order has been observed to increase the number of LDL receptors on cell surfaces and an enhancement in receptor-mediated metabolism of LDL and clearance.

On the other hand, pravastatin-driven inhibition of LDL production inhibits hepatic synthesis of VLDL as the LDL is the precursor for these molecules.

Toxicity

The reported oral LD50 of pravastatin in mice is of 8939 mg/kg. There haven't been significant overdosage reports however, in the case of overdosage, symptomatic treatment is recommended along with laboratory monitoring and supportive measures.

In carcinogenic studies, high dose administration of pravastatin has been reported to increase the incidence of hepatocellular carcinomas in males and lung carcinomas in females. There is no evidence relating the administration of pravastatin with mutagenicity in different assays not to produce effects in fertility or reproductive potential.

Food Interaction

• Take with or without food. Lipid lowering effects are similar in the fasting and fed state.

Asto-Chol Alcohol interaction

[Moderate]

Concomitant use of statin medication with substantial quantities of alcohol may increase the risk of hepatic injury.

Transient increases in serum transaminases have been reported with statin use and while these increases generally resolve or improve with continued therapy or a brief interruption in therapy, there have been rare postmarketing reports of fatal and non-fatal hepatic failure in patients taking statins.

Patients who consume substantial quantities of alcohol and/or have a history of liver disease may be at increased risk for hepatic injury.

Active liver disease or unexplained transaminase elevations are contraindications to statin use.

Patients should be counseled to avoid substantial quantities of alcohol in combination with statin medications and clinicians should be aware of the increased risk for hepatotoxicity in these patients.

Asto-Chol Drug Interaction

Unknown: aspirin, aspirin, ubiquinone, duloxetine, apixaban, omega-3 polyunsaturated fatty acids, insulin glargine, furosemide, pregabalin, metoprolol, metoprolol, esomeprazole, clopidogrel, levothyroxine, acetaminophen, cyanocobalamin, ascorbic acid, cholecalciferol, alprazolam, cetirizine

Asto-Chol Disease Interaction

Major: liver disease, rhabdomyolysis, renal dysfunctionModerate: cognitive impairment, diabetes, renal disease

Volume of Distribution

The reported steady-state volume of distribution of pravastatin is reported to be of 0.5 L/kg. This pharmacokinetic parameter in children was found to range from 31-37 ml/kg.

Elimination Route

Asto-Chol is absorbed 60-90 min after oral administration and it presents a low bioavailability of 17%. This low bioavailability can be presented due to the polar nature of pravastatin which produces a high range of first-pass metabolism and incomplete absorption.

Asto-Chol is rapidly absorbed from the upper part of the small intestine via proton-coupled carrier-mediated transport to be later taken up in the livery by the sodium-independent bile acid transporter. The reported time to reach the peak serum concentration in the range of 30-55 mcg/L is of 1-1.5 hours with an AUC ranging from 60-90 mcg.h/L.

Half Life

The reported elimination half-life of pravastatin is reported to be of 1.8 hours.

Clearance

The reported clearance rate of pravastatin ranges from 6.3-13.5 ml.min/kg in adults while in children it has been reported to be of 4-11 L/min.

Elimination Route

From the administered dose of pravastatin, about 70% is eliminated in the feces while about 20% is obtained in the urine.

When pravastatin is administered intravenously, approximately 47% of the administered dose is eliminated via the urine with 53% of the dose eliminated either via biotransformation of biliary.

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