Pravastatin Sodium - Indication, Dosage, Precautions, Side Effects, and Pharmacological Aspects

Drug Overview:

Pravastatin sodium is taken along with a nutritious diet to increase good cholesterol (HDL: high-density lipoproteins) and decrease bad cholesterol and fats (such as low-density lipoproteins and triglycerides) in the blood. It is a member of the class of medications known as statins. It functions by reducing the quantity of cholesterol the liver produces. Along with adopting a healthy lifestyle (such as a low-cholesterol or low-fat diet), this medication may perform better if an individual exercises, loses weight (if overweight), and stops smoking.

In February 2000, the American Food and Drug Administration (US FDA) authorized the country's first sales of Pravastatin sodium.

Drug Group: Statins are a group of lipid-lowering substances that lower cholesterol production, including Pravastatin sodium. The enzyme HMG-CoA (3-hydroxy-3-methylglutaryl coenzyme A) reductase, which catalyzes the initial rate-limiting step in cholesterol production (HMG Co A to melvonate), is competitively inhibited by these drugs.

Available Doses and Dosage Forms:

The drug is available in 10 mg (milligrams), 20 mg, 40 mg, and 80 mg. It is available in the form of tablets meant for oral consumption.

For Patients:

What Is Hyperlipidemia?

Hyperlipidemia, also known as dyslipidemia or high cholesterol, is characterized by an excessive amount of lipids (fats) in the blood. Atherosclerosis, a condition where cholesterol and fat accumulate along artery walls, reduces blood flow, and, as a result, the oxygen supply to numerous internal organs, including the heart and brain, will be compromised. By reducing cholesterol and fat levels in the blood, Pravastatin sodium can successfully lessen the risk of developing heart disease, angina, strokes, and heart attacks. This is supported by scientific research.

How Does Pravastatin Sodium Work?

Pravastatin is a member of the class of drugs known as HMG-CoA reductase inhibitors, or statins. Its mode of action is to slow down the body's manufacture of cholesterol. This decrease in cholesterol synthesis reduces the danger of clogged blood flow to key organs, including the heart, brain, and other physiological areas, by preventing cholesterol accumulation along artery walls. The accumulation of cholesterol and fats along arterial walls, known as atherosclerosis, can lead to diminished blood circulation and reduced oxygen supply to essential organs. By effectively lowering cholesterol and lipid levels in the bloodstream, Pravastatin sodium has demonstrated its ability to serve as a preventative measure against conditions like heart disease, angina (manifesting as chest pain), strokes (hindered blood flow to brain cells), and heart attacks (collapsed cardiac blood flow).

What Are the Things to Inform the Doctor Before Taking the Drug?

• Inform the doctor and chemist about any vitamins, nutritional supplements, herbal items, and prescription and over-the-counter medicines the patient intends to take.

• The patient should mention certain drugs like antacids, antifungals, Cimetidine, Clarithromycin, Colchicine, Cyclosporine, Digoxin, Diltiazem, Erythromycin, and other drugs that decrease cholesterol, including Gemfibrozil, Fenofibrate, and Niacin, Ritonavir, Darunavir, Spironolactone, Verapamil, and Warfarin, to their doctors. The dose of these drugs may need to be changed, or the patient may need to be closely watched for any negative effects. Pravastatin sodium can interact with drugs not on this list, so it is crucial to tell the doctor about the current medications to receive safe and effective care.

• If patients have allergies, especially to Pravastatin sodium, other drugs, or any ingredients in Pravastatin sodium pills, they should tell their doctor and pharmacist. To be sure they understand the medication's composition, they can also ask their chemist for a list of its constituents.

• If a patient has a history of liver illness, they should let their doctor know. Even if the patient does not suspect liver disease, the doctor will perform the required laboratory tests to evaluate the liver's functionality. The doctor would advise against taking Pravastatin sodium if the patient has liver disease or if the test findings show a chance of developing liver disease.

• If a person drinks more than two alcoholic beverages per day, is 65 years of age or older, has a history of liver illness, or has ever had seizures, low blood pressure, muscular pain, or weakness due to thyroid or renal disease, they should speak with their doctor. These particulars are necessary for the doctor to be thoroughly aware of the patient's medical history and present state of health.

• When using Pravastatin sodium, it is suggested not to get pregnant. It is advised to discuss appropriate birth control choices with the doctor while undergoing therapy. Pravastatin sodium must be stopped, and a doctor must be contacted immediately if pregnancy develops while taking the medication.

• It is suggested not to breastfeed while using Pravastatin sodium. This safety measure is in place to protect the health of the person taking the medicine and the breastfeeding infant.

How Is Pravastatin Sodium Administered?

• Oral ingestion of Pravastatin sodium tablets is the recommended method of administration. It can be taken with or without meals and is typically taken once a day. Sticking to a regular daily routine of taking Pravastatin sodium is the best action. It is crucial to follow the directions listed on the prescription label, and any questions should be answered by talking to a doctor or chemist. Pravastatin sodium should be used exactly as directed; it is not recommended to change the dosage by increasing it, reducing it, or taking it more frequently than recommended.

• Pravastatin sodium should be used at least one hour before or four hours after using certain cholesterol-lowering medicines, such as bile acid-binding resins like Colestipol or Cholestyramine if the patient is also taking these medications. This care is essential to avoid any potential interactions between these products and Pravastatin sodium that can prevent the latter's full absorption.

• The doctor may start pravastatin sodium at a low dosage that may be gradually increased, with a frequency of no more than once every four weeks. Even if there is no discomfort, the person should continue to take Pravastatin sodium as prescribed. Pravastatin sodium discontinuation without a doctor's prescription is discouraged and should be avoided.

What Are the Side Effects of Pravastatin Sodium?

If the individual experiences any side effects from Pravastatin sodium, they should promptly inform their doctor if these symptoms are persistent, bothersome, or intensify in severity.

• Loss of memory.

• Heartburn.

• Confusion.

• Headache.

The doctors should be contacted immediately for any of the severe side effects mentioned below:

• Yellowing of the eyes and skin.

• Dark-colored urine.

• Nausea.

• Tiredness.

• Weakness of the muscles.

• Pain and tenderness in the muscles.

• Rashes and itching.

• Hoarseness of the voice.

• Appetite loss.

• Symptoms that are similar to flu.

• Difficulty swallowing and eating.

• Pain in the stomach (right side).

Dietary Considerations: The person has to maintain a low-fat, low-cholesterol diet. It is essential to carefully adhere to any nutritional and exercise recommendations from their doctor or dietician. This proactive approach will support their treatment plan's efficacy and wellness objectives.

Missed Dose: If a dosage is forgotten, the person should take it as soon as they remember. It is advised to forgo the missed dosage and resume the regular dosing schedule if the following dose is almost due. To make up for a missed dosage, it is not recommended to double the dose; therefore, refrain from doing so. The success and safety of the medicine depend on consistent adherence to the recommended dose schedule.

Overdose: In the event of overdosing, the nearest healthcare center’s doctor in charge should be consulted immediately.

Storage: The drug should be kept in its original container, well closed, and out of the reach of children. It should not be kept in the bathroom and should instead be maintained at room temperature. Following these storage recommendations ensures that the drug is stable and safe.

For Doctors:

Indication: Utilization of lipid-altering medicines should be just one component of a larger approach involving several risk factor therapies for those with hypercholesterolemia and a markedly elevated risk for atherosclerotic vascular disease. Drug therapy becomes a vital supplementary strategy when dietary changes, such as limiting saturated fat and cholesterol and other nonpharmacologic treatments, have failed to provide the desired results.

1. Cardiovascular Disease Prevention

Pravastatin Sodium Is Advised for Use in Hypercholesterolemia Individuals Without Clinically Noticeable Coronary Heart Disease (CHD) to:

• To lower the chance of myocardial infarction (MI).

• To lessen the danger of myocardial revascularization treatments.

• To decrease the likelihood of cardiovascular death while maintaining the same rate of non-cardiovascular death.

2. Pravastatin Sodium Is Advised for People With Clinically Indicated CHD To:

• Decrease the risk of coronary death to lower the overall mortality risk.

• Decrease the chance of myocardial infarction (MI).

• Lessen the danger of myocardial revascularization treatments.

• Lessening the chance of having a stroke or a TIA (transient ischemic attack).

• Slows the development of coronary atherosclerosis.

3. Hyperlipidemia:

• Pravastatin sodium is used in patients with primary hypercholesterolemia and mixed dyslipidemia as an adjunct to diet to lower elevated total cholesterol (Total-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein B (ApoB), and triglyceride (TG) levels and to increase high-density lipoprotein cholesterol (HDL-C).

• It supplements the diet for treating individuals with high blood TG levels.

• It is used to treat individuals with primary dysbetalipoproteinemia (Fredrickson Type III) who do not improve with diet.

Dose: Available as 10 mg, 20 mg, 40 mg, and 80 mg tablets for oral consumption (taken orally).

Dosing Considerations: It is advised that the patient be put on a typical cholesterol-lowering diet before starting Pravastatin sodium therapy. This diet plan should be continuously followed for the duration of the Pravastatin sodium medication.

1. For Adults: The recommended initial dosage is 40 milligrams (mg) once daily. If the required cholesterol levels are not reached with the recommended first dosage of 40 mg once a day, an increase to 80 mg once a day is indicated. A starting dosage of 10 mg per day is suggested for people with significant renal impairment. Pravastatin sodium is administered orally and may be taken once a day, regardless of food timing.

2. For Pediatric Population:

• Age Ranging From 8 to 13 Years - For youngsters aged eight to 13, a dosage of 20 mg once a day is advised. No research has been done on doses higher than 20 mg in this patient population.

• Age Ranging From 14 to 18 Years - For teenagers 14 to 18 years old, a beginning dosage of 40 mg once a day is advised. This patient population has not been investigated at doses higher than 40 mg.

3. For Patients on Cyclosporine Therapy: Pravastatin sodium treatment should start with a dose of 10 mg once a day at bedtime in patients who are also on immunosuppressive medications like Cyclosporine, and titration to higher dosages should be done carefully. The average dosage of Pravastatin sodium used in this combination is 20 mg daily.

What Are the Pharmacological Aspects of Pravastatin Sodium?

1. Physical Properties of the Drug:

• Drug Group - Statins.

• Appearance - White to off-white, odorless, fine, or crystalline powder.

• Chemical Name - 1-Naphthalene-heptanoic acid, 1,2,6,7,8,8ahexahydro-β,δ,6-trihydroxy-2-methyl-8-(2-methyl-1-oxobutoxy)-, monosodium salt, [1S­[1α(βS*,δS*),2α,6α,8β(R*),8aα]].

• Empirical Formula - C23H35NaO7.

• Molecular Weight - 446.52.

• Solubility - Soluble in methanol and water. Almost insoluble in acetone, acetonitrile, chloroform, and ether, and just slightly soluble in isopropanol.

• Components of the Drug - Microcrystalline cellulose, lactose, magnesium stearate, magnesium oxide, and croscarmellose sodium.

2. Mechanism of Action:

• Pravastatin sodium lowers LDL via interacting with two different mechanisms.

• It works by inhibiting HMG-CoA reductase in the main route. Pravastatin sodium interferes with the HMG-CoA reductase enzyme's ability to do its function by acting as a reversible competitive inhibitor. The conversion of HMG-CoA to mevalonate, a critical step in the production of cholesterol, is controlled by this enzymatic activity, which predominately takes place inside the liver.

• Pravastatin sodium simultaneously prevents the production of very low-density lipoproteins (VLDL), which are the building blocks of low-density lipoproteins (LDL).

• These activities have the effect of increasing the number of cellular LDL receptors. As a result, this enhancement improves the absorption of LDL from the circulation, simplifying its elimination.

• A decrease in LDL and circulating cholesterol levels follows as a result of these individual effects.

• Other typical results include a small decrease in triglycerides and a simultaneous increase in high-density lipoproteins (HDL).

3. Pharmacokinetics:

• Absorption: Pravastatin sodium is taken orally to deliver it in its active form. According to clinical investigations in humans, pravastatin sodium generally reaches its peak plasma concentrations one to two hours after oral administration. According to calculations based on the urine recovery of the entire radiolabeled medication, Pravastatin sodium has an average absorption rate of around 34 percent when taken orally, transforming to an absolute bioavailability of about 17 percent. The presence of food in the digestive tract might result in a decrease in systemic bioavailability. However, the medication's lipid-lowering effects are the same whether taken together with or eaten an hour before meals.

• Distribution: About 50 percent of the medication in circulation has been linked to plasma proteins.

• Metabolism: 3 alpha-hydroxy Pravastatin sodium is the primary active metabolite of Pravastatin sodium. The parent drug's cholesterol-lowering properties are carried over into this metabolite.In the liver, Pravastatin sodium goes through a large amount of first-pass metabolism before being partly transformed into its active form.

• Excretion: About 20 percent of an oral radiolabeled dosage delivered is excreted through the urinary system, and roughly 70 percent is removed through the feces. In healthy individuals, renal excretion accounts for about 47 percent of the total body clearance of radiolabeled Pravastatin sodium; non-renal routes, such as biliary excretion and biotransformation clear the other 53 percent.

Clinical Studies:

Individuals with familial and nonfamilial polygenic hypercholesterolemia, as well as those with diabetes mellitus, have shown that Pravastatin sodium is beneficial in decreasing cholesterol levels. Pravastatin sodium can lower LDL cholesterol by 15 to 40 percent and total cholesterol by 15 to 30 percent when taken daily in doses between 10 and 40 mg. Additionally, it causes a two to 20 percent increase in high-density lipoprotein cholesterol and simultaneously lowers triglyceride levels. Pravastatin sodium is typically well tolerated since clinical trials have generally shown few adverse side effects. Pravastatin sodium yields comparable reductions in LDL cholesterol and increases in HDL cholesterol compared to Lovastatin, possibly with a reduced incidence of side effects.

What Are the Contraindications of Pravastatin Sodium?

• Hypersensitivity.

• Pregnancy.

• Lactation.

• Liver disease.

• Disorders of the skeletal muscles.

Warnings and Precautions:

1. Skeletal Muscles:

• Pravastatin sodium may cause myalgia, rhabdomyolysis, myopathy, and increased creatine phosphokinase levels (CPK). If there is a considerable increase in CPK levels or the patient has myopathy confirmed or suspected, Pravastatin sodium medication must be stopped immediately.

• Pravastatin sodium usage should also be temporarily stopped for individuals suffering from rhabdomyolysis or who are dealing with an acute or serious medical condition that raises the risk of renal failure brought on by rhabdomyolysis. Serious metabolic or endocrine problems, trauma, sepsis, hypotension, severe surgery, electrolyte imbalances, or uncontrolled epilepsy are a few examples of such circumstances.

• When statins are used with drugs like Erythromycin, Cyclosporine, Niacin, or fibrates, the risk of myopathy increases, although the danger of myopathy is occasionally associated with using Fibrates alone, using them in combination with Pravastatin sodium demands careful consideration.

• Given the possible hazards connected with this combination, it is wise to weigh the potential benefits of further lipid level modifications with the combined use of Pravastatin sodium and Fibrates.

2. Liver: Anomalies in liver function have been connected to statin use. Doing liver function tests before starting treatment and whenever necessary is advised. Medication should be stopped immediately for serious liver damage, high bilirubin levels, or jaundice. Resuming Pravastatin sodium is not advised if no other cause has been found.

3. Endocrinal Functions:

• Statins prevent the synthesis of new cholesterol, reducing the blood's cholesterol level. This method could affect steroid hormones in the gonads or adrenal glands. However, the results of clinical trials conducted for Pravastatin sodium in post-menopausal women and men yielded conflicting results regarding the drug's possible impact on steroid hormone levels at rest.

• More patient research must determine how statins affect spermatogenesis and fertility.

• Pravastatin sodium-treated patients with clinical signs of endocrine disruption must undergo the proper testing.

• Additionally, care should be taken when administering a statin or other cholesterol-lowering medication to patients simultaneously taking medications (such as Cimetidine, Ketoconazole, or Spironolactone) that may reduce the production or action of steroid hormones.

What Are the Drug Interactions of Pravastatin Sodium?

1. Cyclosporine - When Cyclosporine is administered concurrently, the risk of myopathy and rhabdomyolysis increases. Pravastatin sodium dosage for concurrent Cyclosporine usage should be limited to 20 mg once daily.

2. Clarithromycin - When Clarithromycin is administered concurrently, the risk of myopathy and rhabdomyolysis increases. Pravastatin sodium should not be used with Clarithromycin in doses greater than 40 mg once a day.

3. Gemfibrozil - Concomitant administration of Pravastatin sodium with Gemfibrozil should be avoided due to an increased risk of myopathy or rhabdomyolysis when HMG-CoA reductase inhibitors are used.

4. Niacin - When Pravastatin sodium is used with Niacin, the risk of adverse effects on the skeletal muscle may be increased. In this situation, a Pravastatin sodium dose reduction should be considered.

5. Colchicine - When Colchicine is administered concurrently with Pravastatin sodium, the risk of myopathy and rhabdomyolysis increases.

6. Other Fibrates - As concurrent use of other fibrates is known to enhance the risk of myopathy during therapy with HMG-CoA reductase inhibitors, Pravastatin sodium should be taken cautiously.

Specific Considerations:

• Pregnancy - It is unknown whether taking Pravastatin sodium while pregnant is safe. There are no comprehensive and controlled studies that include pregnant women, even though there are examples of unintended Pravastatin sodium exposure during pregnancy that do not show any adverse clinical effects. As a result, it is unclear how Pravastatin sodium may affect fetal health or a woman's capacity to become pregnant. When the benefits surpass any possible dangers to the fetus, Pravastatin sodium use during pregnancy should be considered. Patients in these situations must be fully educated about the risks before making a choice.

• Lactation - Care should be taken since Pravastatin sodium is excreted in small amounts in human breast milk. Breastfeeding is not advised for mothers who are taking Pravastatin sodium due to the possibility of serious adverse effects on nursing babies.

• Pediatric Population - The pediatric population has yet to be studied for 40 mg and above doses. It is advised that pregnant children and young women on Pravastatin sodium get in-depth counseling on the best methods of contraception. No studies have been done on double-blind, placebo-controlled Pravastatin sodium trials with kids under the age of eight. According to research studies on children aged eight to 18, the most common and major adverse effects reported were headaches and influenza.

• Geriatric Population - Pravastatin sodium has a similar beneficial effect on older people as it does on younger people. This includes a reduction in cardiovascular events and changes to lipid profiles. Adverse events occurring in the elderly were similar to those seen in the general population. Pravastatin sodium should be given to seniors with caution and moderation since advanced age (65 years or more) is a known risk factor for myopathy.

• Homozygous Familial Hypercholesterolemia - In individuals with rare homozygous familial hypercholesterolemia, Pravastatin sodium has not been studied. Statins are less effective in this patient population since they do not have functioning LDL receptors.