Gravastin
Gravastin Uses, Dosage, Side Effects, Food Interaction and all others data.
Gravastin is the 6-alpha-hydroxy acid form of mevastatin. Gravastin was firstly approved in 1991 becoming the second available statin in the United States. It was the first statin administered as the active form and not as a prodrug. This drug was developed by Sankyo Co. Ltd.; however, the first approved pravastatin product was developed by Bristol Myers Squibb and FDA approved in 1991.
Gravastin is made through a fermentation process in which mevastatin is first obtained. The manufacturing process is followed by the hydrolysis of the lactone group and the biological hydroxylation with Streptomyces carbophilus to introduce the allylic 6-alcohol group.
The action of pravastatin on the 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase produces an increase in the expression of hepatic LDL receptors which in order decreases the plasma levels of LDL cholesterol.
| Trade Name | Gravastin |
| Availability | Prescription only |
| Generic | Pravastatin |
| Pravastatin Other Names | Pravastatin, Pravastatin acid, Pravastatina, Pravastatine, Pravastatinum |
| Related Drugs | Nexletol, Nexlizet, Zetia, Praluent, Repatha, aspirin, atorvastatin, clopidogrel, simvastatin, rosuvastatin |
| Weight | 10mg |
| Type | Caplet |
| Formula | C23H36O7 |
| Weight | Average: 424.5277 Monoisotopic: 424.246103506 |
| Protein binding | Due its polarity, pravastatin binding to plasma proteins is very limited and the bound form represents only about 43-48% of the administered dose. However, the activity of p-glycoprotein in luminal apical cells and OATP1B1 produce significant changes to pravastatin distribution and elimination. |
| Groups | Approved |
| Therapeutic Class | |
| Manufacturer | Graha Farma |
| Available Country | Indonesia |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Gravastin is an HMG-CoA reductase inhibitor used to lower lipid levels and to reduce the risk of cardiovascular events, including myocardial infarction and stroke.
Gravastin 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.
Gravastin 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 Gravastin works
Gravastin 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.
Gravastin 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.
Gravastin 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
Gravastin 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
Gravastin 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.
Gravastin 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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FAQ
What is Gravastin used for?
Gravastin is a statin medication, used for preventing cardiovascular disease in those at high risk and treating abnormal lipids. It should be used together with diet changes, exercise, and weight loss. It's used to lower cholesterol if you've been diagnosed with high blood cholesterol. It's also taken to prevent heart disease, including heart attacks and strokes.
How safe is Gravastin?
Gravastin seems to be a very safe medicine. It's unusual to have any side effects. Do not take Gravastin if you are pregnant, trying to get pregnant or breastfeeding. Take Gravastin even if you feel well, as you will still be getting the benefits.
How does Gravastin work?
Gravastin works by slowing the production of cholesterol in the body to decrease the amount of cholesterol that may build up on the walls of the arteries and block blood flow to the heart, brain, and other parts of the body.
What are the common side effects of Gravastin?
Common side effects of Gravastin are include:
- a common cold.
- indigestion.
- constipation.
- dizziness.
- a skin rash.
- headache.
- nausea.
- heartburn.
Is Gravastin safe during pregnancy?
Do not take Gravastin if you are pregnant, trying to get pregnant or breastfeeding. This Gravastin should only be used in women of childbearing potential who are highly unlikely to conceive and have been informed of the potential hazards.
Is Gravastin safe during breastfeeding?
Levels of Gravastin in milk are low, but no relevant published information exists with its use during breastfeeding. The consensus opinion is that women taking a statin should not breastfeed because of a concern with disruption of infant lipid metabolism.
Can I drink alcohol with Gravastin?
Yes, you can drink alcohol while taking Gravastin. However, drinking a lot of alcohol may increase the chances of you getting muscle and liver side effects.
Can I drive after taking Gravastin?
Yes, you can drive or cycle while taking Gravastin.
Can I take Gravastin on an empty stomach?
Gravastin doesn't upset the stomach, so you can take it with or without food.
Does Gravastin have to be taken with food?
This Gravastin may be taken with or without food.
How much Gravastin can I take in a day?
Adults,At first, 40 milligrams (mg) once a day. Your doctor may adjust your dose if needed. Children 14 to 18 years of age 40 mg once a day. Children 8 to 13 years of age 20 mg once a day.
How long does Gravastin take to work?
Peak levels of Gravastin are seen within one to one and a half hours following administration; however, it may take one to two weeks of regular dosing before improvements in your cholesterol levels are seen, and up to four weeks before the maximal cholesterol-lowering effects of Gravastin are apparent.
What is the half life of Gravastin?
The mean elimination half-life of Gravastin was 1.6 hours (range, 0.85-4.2 hours).
Can I take Gravastin for a long time?
Gravastin oral tablet is used for long-term treatment. It comes with risks if you don't take it as prescribed. If you stop taking the drug suddenly or don't take it at all: Your Gravastin levels may not be controlled. This puts you at higher risk of heart disease, heart attack, or stroke.
How long can I take Gravastin?
Usually, treatment with a statin such as Gravastin is for life. The benefits will only continue for as long as you take it.
Can I stop taking Gravastin suddenly?
Don't suddenly stop taking your prescribed medication without talking to your doctor. If you have side effects from the drug, your doctor might adjust your dosage or recommend a different statin.
Who should not take Gravastin?
You should not take Gravastin if you have active liver disease, or if you are pregnant or breastfeeding. Tell your doctor about all your current medicines and any you start or stop using. Many drugs can interact, and some drugs should not be used together.
What happens if I miss a dose?
Take the medicine as soon as you can, but skip the missed dose if it is almost time for your next dose. Do not take two doses at one time.
What happen if I take too much Gravastin?
If you take too much: You could have dangerous levels of the drug in your body. Symptoms of an overdose of this drug can include: severe pain in the abdomen (stomach area) vomiting.
What happen If I stop taking Gravastin?
Don't suddenly stop taking your prescribed medication without talking to your doctor. If you have side effects from the drug, your doctor might adjust your dosage or recommend a different statin.
Can Gravastin affects my heart ?
Lipid Lowering by Gravastin Increases Parasympathetic Modulation of Heart Rate | Circulation.
Can Gravastin affect my kidneys?
This trial found that taking 20 mg Gravastin for 2 years had no significant effect on kidney function or urinary protein excretion in patients with ADPKD.
Is Gravastin bad for my liver?
You may wonder about the cholesterol medications known as statins and whether they can hurt your liver. While atorvastatin, simvastatin, lovastatin, and pravastatin can frequently affect liver function blood tests, they do not tend to cause concerning liver damage.
Will Gravastin affect my fertility?
There's no firm evidence to suggest that taking Gravastin will reduce fertility in either men or women. However, speak to a pharmacist or your doctor before taking it if you're trying to get pregnant.
