Fluvastatin Sodium - Indications, Contraindications, and Side Effects

Overview

Fluvastatin sodium is used to treat mixed dyslipidemia (imbalance of lipids) and hypercholesterolemia (high cholesterol) to reduce the total cholesterol levels in the blood. This treatment reduces low-density lipoprotein and triglycerides and increases high-density lipoprotein. When Fluvastatin sodium is combined with a low-fat diet, regular exercises, and weight-loss programs, it may decrease the risk of stroke and heart attacks in people with cardiac diseases or those with a risk of developing heart diseases. Fluvastatin sodium was approved by the United States Food and Drug Administration (USFDA) on August 5th,1999.

How Does Fluvastatin Sodium Work?

Fluvastatin sodium belongs to a class of medications known as statins or HMG-CoA reductase inhibitors and is important in limiting cholesterol synthesis in the liver. Fluvastatin sodium binds to the enzyme’s active site and creates competition with HMG-CoA thus reducing the production of mevalonate, the next molecule that eventually produces cholesterol. The lowering of cholesterol stimulates the breakdown of low-density lipoprotein (LDL) and increases the expression of LDL receptors. This in turn, reduces the cholesterol accumulation on the walls of arteries and prevents heart diseases.

Indications of Fluvastatin Sodium

• Fluvastatin sodium is used along with a healthy diet in patients with mixed dyslipidemia and primary hypercholesterolemia to reduce the levels of total cholesterol, triglycerides (TG), Low-Density Lipoprotein Cholesterol (LDL-C), and Apolipoprotein B (Apo B), and also increase High-Density Lipoprotein Cholesterol (HDL-C).

• This drug is also indicated for the same conditions in adolescent boys and girls between 10 to 16 years of age, at least one-year post-menarche, and with heterozygous familial hypercholesterolemia and family history or risk of premature cardiovascular diseases.

• Fluvastatin sodium is also used in patients with congenital heart disease (cardiac disorder present at birth) to slow the progression of coronary atherosclerosis (thickening of the arteries) or to decrease the risk of coronary revascularization procedures.

Contraindications of Fluvastatin Sodium

Fluvastatin sodium is contraindicated in the following conditions:

• Allergy or hypersensitivity to the drug or its ingredients.

• In pregnant women and lactating mothers.

• Patients with active liver diseases or individuals with persistent elevations in serum transaminase levels.

Available Doses and Dose Forms

• The recommended dose range of Fluvastatin sodium is 20 to 80 mg/day (milligrams per day). It is available in 20 mg and 40 mg capsules and 80 mg extended-release tablets. The drug is taken as a single dose, with or without food.

• As the maximum effect of the given dose is observed within four weeks, a lipid profile is done, after which the drug's duration and dosage are adjusted along with the patient’s response to the treatment.

• For patients requiring a reduction of LDL-C of less than 25 percent, the starting dose of Fluvastatin sodium is 20 mg. For patients requiring a reduction of LDL-C of more than 25 percent, the starting dose is one 40 mg capsule in the evening, one 80 mg extended-release tablet to be taken as a single dose any time of the day or in divided doses of 40 mg capsules twice daily.

Warnings and Precautions

• Fluvastatin sodium can cause rhabdomyolysis with acute renal failure, which may be secondary to myoglobinuria. Therefore, it must be prescribed with caution in individuals who are above 65 years old or prone to myopathy, such as patients with renal impairment and untreated hypothyroidism. The treatment with Fluvastatin sodium must be discontinued in cases of elevated creatine phosphokinase (CPK) levels or if myopathy is suspected or diagnosed.

• Treatment with Fluvastatin sodium can cause an increase in aspartate aminotransferase (AST) or alanine transaminase (ALT); however, it may be transient and improve on continued treatment or a short interruption in therapy. If serious liver injury or clinical symptoms of jaundice or hyperbilirubinemia (accumulation of bilirubin in the blood) are observed, the treatment must be interrupted.

• Treatment with Fluvastatin sodium can raise fasting serum glucose levels and hemoglobin A1c (HbA1c). Therefore, patients with endocrine dysfunction must be previously evaluated, and caution is necessary during the treatment.

• Animal studies have reported that Fluvastatin sodium may cause CNS effects such as ataxia, ptosis, and loss of righting reflux. Hence, patients must be frequently monitored during the treatment.

Adverse Effects of Fluvastatin Sodium

Serious side effects of Fluvastatin sodium include:

• Nausea.

• Fever.

• Muscle pain and weakness.

• Abdominal pain.

• Difficulty swallowing or breathing.

• Swelling of face, eyes, tongue, throat, hands, and feet.

• Extreme tiredness or lack of energy.

• Dark-colored urine.

• Unusual bruising or bleeding.

• Yellowish discoloration of eyes and skin.

• Loss of appetite.

• Rash.

Some common side effects of Fluvastatin sodium include:

• Headache.

• Cough.

• Forgetfulness.

• Confusion.

• Difficulty falling asleep.

• Heartburn.

• Sinus pain.

For Patients

What Is Hypercholesterolemia?

Hypercholesterolemia is a condition in which there is a high level of cholesterol in the blood, which can lead to an increased risk of stroke and other cardiac diseases. A person is diagnosed with hypercholesterolemia when the low-density lipoprotein (LDL) level is more than 190 mg/dL (milligrams per deciliter), or above 160 mg/dL along with a major risk factor, or higher than 130 mg/dL along with two other risk factors. The risk factors of hypercholesterolemia include:

• A family history of premature heart disease.

• High blood pressure.

• Age.

• Diabetes (increased blood glucose levels).

• Low levels of high-density lipoprotein (HDL).

Hypercholesterolemia can be managed by decreasing LDL levels which can be achieved by regular medications, a healthy diet, lowering stress, physical exercises, proper blood pressure and blood sugar control, and avoiding smoking and alcohol consumption.

What Is Fluvastatin Sodium?

Fluvastatin sodium is a prescription medicine recommended along with a proper diet to reduce high cholesterol and triglyceride levels (fats) in the blood. This medicine also helps prevent medical conditions such as atherosclerosis (thickening of arteries), blood vessel disorders, and other cardiac problems. It belongs to a group of medicines called statins, which lower the amount of fatty substances or bad cholesterol and increase the levels of good cholesterol.

How Effective Is Fluvastatin Sodium?

Various studies evaluating the effectiveness of Fluvastatin sodium have demonstrated that the recommended dose of 10 mg to 80 mg (milligrams) per day reduces LDL cholesterol levels by 15 to 33 percent. It also showed reduced triglyceride levels and a significant increase in HDL levels. Fluvastatin sodium extended-release tablets reduced the LDL cholesterol levels by 30 to 50 percent. However, according to research, Atorvastatin is better at lowering cholesterol than other statins, including Fluvastatin, Simvastatin, and Lovastatin.

How Should Fluvastatin Sodium Be Taken?

Fluvastatin sodium capsules or tablets must be taken once or twice a day orally with or without food, around the same time every day, or as prescribed by the doctor. The tablets must be swallowed whole, not chewed, split, or crushed. The doctor begins the treatment with the lowest dose, followed by a gradual increase, but not more than once every four weeks. Patients must take the capsules even if they feel well and should not stop the treatment without the doctor’s consent.

What Are the Side Effects of Fluvastatin Sodium?

Side effects of Fluvastatin sodium include:

• Fever.

• Headache.

• Cough.

• Muscle pain.

• Tiredness.

• Stomach pain.

• Rash.

• Itching.

• Difficulty swallowing or breathing.

• Dark-colored urine.

• Unusual bleeding.

• Loss of appetite.

• Confusion.

What Must the Patient Inform the Doctor Before Taking Fluvastatin Sodium?

• Before starting the treatment, patients must tell the doctor if they are allergic to Fluvastatin sodium, its components, or any other medications.

• Female patients must not become pregnant while taking Fluvastatin sodium, as it may harm the fetus; hence, suitable and efficient birth control methods must be followed. Patients must notify the doctor immediately if they become pregnant or suspect pregnancy during treatment.

• Breastfeeding is not recommended while taking Fluvastatin sodium, as the drug can pass into breast milk. Therefore, the drug must be discontinued temporarily while breastfeeding. However, if the patient is at risk for cardiovascular diseases, treatment can be continued, but alternatives to breast milk, such as infant formula, must be considered.

• Patients must inform the doctor if they have diseases of the liver, kidney, thyroid, muscle disorders, seizures, low blood pressure, diabetes, or any other medical conditions before starting treatment with Fluvastatin sodium.

• Patients must inform the doctor if they drink more than two alcoholic beverages in a day, as they can increase the risk of side effects.

• Patients must inform the doctor that they are taking Fluvastatin sodium before any surgical procedure or dental treatment.

• Patients must inform the healthcare provider if they are taking Erythromycin, Diclofenac, Ketoconazole, Phenytoin, Fenofibrate, Rifampin, or any other medications, vitamins, nutritional supplements, or over-the-counter (OTC) medicines before starting the treatment with Fluvastatin sodium.

What Are the Precautionary Measures to Be Followed While Taking Fluvastatin Sodium?

• The dose of Fluvastatin sodium must not be altered, or the medicine must not be discontinued without the doctor’s consultation.

• The doctor will recommend specific blood tests to check the cholesterol levels during the treatment based on which the dose is modified.

• A low-fat diet must be followed during the treatment with Fluvastatin sodium.

• Some patients may develop liver issues or muscle problems such as weakness and pain or may feel more tired than usual. The healthcare provider must be consulted during such situations.

• Side effects are usually mild and may resolve independently; however, a doctor must be consulted immediately if the patients experience any severe side effects.

Dietary Considerations

A low-fat or low-cholesterol diet is recommended during the treatment with Fluvastatin sodium. Patients can also refer to the National Cholesterol Education Program (NCEP) for dietary information.

Missed Dose

If the patient forgets a dose of Fluvastatin sodium, the missed dose must be taken as soon as remembered. If it has been more than 12 hours since the last dose, or if it is time for the next dose, the dose can be skipped and the regular dose schedule can be followed. However, a double dose must not be taken to compensate for the missed dose.

Overdose

In case of an overdose of Fluvastatin sodium or any serious side effects such as breathing difficulty or seizures (sudden, abnormal electrical activity in the brain), a healthcare professional must be contacted immediately.

Storage

Fluvastatin sodium must be stored in its original packaging at 25 degrees Celsius (59 to 86 degrees Fahrenheit), away from sunlight and moisture.

For Doctors

Pharmacological Aspects of Fluvastatin Sodium

Mechanism of Action

Fluvastatin is an HMG-CoA reductase inhibitor responsible for converting HMG-CoA to mevalonate, a precursor of cholesterol. It acts by selectively and competitively inhibiting cholesterol biosynthesis, thus decreasing cholesterol levels in hepatic cells. This further stimulates the production of LDL receptors, thus increasing the uptake of LDL particles. These biochemical processes finally cause a reduction in the plasma cholesterol concentration.

Pharmacodynamics

Fluvastatin sodium is the first synthetically manufactured HMG-CoA reductase inhibitor and antilipemic drug that lowers the LDL and triglycerides in mixed dyslipidemia and primary hypercholesterolemia. It slows the progression of atherosclerosis in patients with congenital heart disease and further lowers the risk of coronary revascularization procedures. Compared to other statins, Fluvastatin sodium has a shorter half-life, extensive protein binding, no active metabolites, and minimum Cerebrospinal Fluid (CSF) penetration.

Pharmacokinetics

• Absorption: After an oral administration of Fluvastatin sodium, the peak concentration (C max) is achieved in less than one hour. The bioavailability of the drug is around 24 percent following an administration of a 10 mg dose.

• Distribution: 98 percent of Fluvastatin sodium is bound to plasma proteins, and the mean volume of distribution is approximately 0.35 L/kg (liters per kilogram).

• Metabolism: Fluvastatin sodium gets metabolized in the liver via hydroxylation and beta-oxidation.

• Excretion: After an oral administration, about 90 percent of Fluvastatin sodium is excreted in feces, and around five percent of the oral dose is recovered in urine. The half-life of the drug is approximately three hours.

Drug Interactions

Some of the drugs that interact with Fluvastatin sodium include:

• Fluconazole.

• Posaconazole.

• Cyclosporine.

• Phenytoin.

• Warfarin.

• Niacin.

• Daptomycin.

• Fenofibrate.

• Primidone.

• Mifepristone.

Clinical Studies

• Twelve placebo-controlled studies were conducted in patients with mixed dyslipidemia and primary hypercholesterolemia. 1621 patients were administered Fluvastatin sodium in daily doses of 20 mg, 40 mg, and 80 mg for six weeks. Results were evaluated after 24 weeks of treatment, demonstrating a significant reduction in plasma LDL-C, TG, TC, and ApoB and an increase in HDL-C. The most common adverse events leading to discontinuation were elevated transaminase, pain in the upper abdomen, dyspepsia, fatigue, and diarrhea.

• Clinical studies were conducted in pediatric and adolescent patients with primary hypercholesterolemia or a family history of premature ischemic heart disease. Treatment was started with 20 mg Fluvastatin sodium capsules and gradually increased every six weeks to 40 mg and then 80 mg daily. The results demonstrated a significant decrease in LDL-C and TC.

• A double-blind, randomized, multicentre placebo-controlled study was performed involving 1677 patients with coronary heart disease who have undergone the procedure of Percutaneous Coronary Intervention (PCI) with a risk of recurrent cardiac events. 40 mg of Fluvastatin was administered twice a day, and the median duration of administration was 3.9 years. The results showed a significant reduction (22 percent) in the risk of recurrence of cardiac events.

Nonclinical Toxicology

No evidence of mutagenicity was reported in animal studies involving in vitro tests. Dose levels of 0.6, 2, and 6 mg/kg/day (milligram/kilogram/day) of Fluvastatin sodium did not affect fertility or reproductive potential in female rats. The carcinogenic potential of Fluvastatin sodium was observed during animal studies, including squamous papilloma and carcinoma of the forestomach in rats at dose levels of six, nine, and 18 to 24 mg/kg/day. Still, no hepatic carcinoma or hepatic adenomas were reported.

Specific Considerations

• Fluvastatin sodium is contraindicated in pregnant women, females of reproductive potential, and lactating mothers.

• The safety and efficacy of Fluvastatin sodium are established in pediatric patients aged nine to 16 years.

• Treatment with Fluvastatin sodium in patients above 65 showed no significant changes compared to younger patients. However, the drug must be prescribed with caution in elderly people.

• Fluvastatin sodium is not recommended in patients with liver and severe kidney impairment, and dose modifications may not be required in patients with mild to moderate renal dysfunction.