Pravastatin Sodium

1. Health Canada Product Monograph — Pravastatin Sodium

• Used with dietary changes to lower elevated total and LDL cholesterol in patients with primary hypercholesterolemia when diet and other non-drug measures alone have not been enough.
• Used in patients with high cholesterol who do not yet have known coronary heart disease, to reduce the risk of heart attack, the need for procedures to restore blood flow to the heart, and death from cardiovascular causes.
• Used in patients with established coronary heart disease to reduce the risk of death, heart attack, stroke, revascularization procedures, and hospitalization, and to slow progression of atherosclerosis.

Contraindicated in pregnancy. Confirm pregnancy status and discuss alternative therapy with the prescriber before dispensing.

• Pravastatin is contraindicated during pregnancy, because cholesterol and related compounds made in the body are essential for normal fetal development, and blocking their production could cause fetal harm.
• It should only be given to women of childbearing potential who are very unlikely to become pregnant and who have been informed of the possible risk; if pregnancy occurs while taking pravastatin, the drug should be stopped right away and the patient counselled about the potential risk to the fetus.

• Only a very small amount of pravastatin passes into breast milk, but because of the possibility of adverse effects in a nursing infant, breastfeeding should be discontinued or the medication stopped while nursing.

• Older adults (65 years and older) tend to have higher blood levels of pravastatin, so the lowest effective dose should be used initially.
• Elderly patients may be more prone to muscle-related side effects such as myopathy, so they should be monitored closely, particularly if other risk factors for muscle toxicity are present.

• Pravastatin has not been studied in children under 16 years of age, and Health Canada has not authorized its use in this population.

• The usual starting dose is 20 mg once daily at bedtime; patients needing a larger reduction in LDL cholesterol may start at 40 mg once daily, and doses up to 80 mg once daily are reserved for those who do not reach their treatment goal on lower doses.
• Pravastatin may be taken without regard to meals.
• Patients with significant liver or kidney impairment should start at a lower dose of 10 mg daily.
• Patients on cyclosporine should start at a reduced dose and be titrated upward cautiously, as this combination substantially raises pravastatin blood levels.
• Combining pravastatin with a bile acid-binding resin, such as cholestyramine or colestipol, requires spacing the doses at least one hour before or four hours after the resin to avoid reduced absorption.

• Nausea or vomiting.
• Diarrhea, abdominal pain, or constipation.
• Flatulence or heartburn.
• Headache or dizziness.
• Fatigue.
• Muscle aches (myalgia) or general musculoskeletal pain.
• Skin rash.
• Cold- or flu-like symptoms, including cough and rhinitis.

Serious side effects require immediate discussion with the prescriber or emergency care.

• Muscle pain, tenderness, or weakness may signal myopathy or, rarely, rhabdomyolysis (severe muscle breakdown), which can lead to kidney injury.
• Marked, persistent increases in liver enzymes can occur, and rare cases of serious liver injury, including liver failure and jaundice, have been reported.
• A rare autoimmune muscle disease (immune-mediated necrotizing myopathy) has been reported, causing muscle weakness that can persist even after stopping the statin.
• Severe allergic-type reactions, including angioedema and anaphylaxis, have been reported.
• Rare serious skin reactions, including Stevens-Johnson syndrome, toxic epidermal necrolysis, and erythema multiforme, have been reported.
• Blood disorders such as hemolytic anemia and low platelet counts have been reported rarely.
• Increases in blood sugar and HbA1c levels have been reported, which may unmask or worsen diabetes in susceptible patients.
• Interstitial lung disease has rarely been reported with long-term statin therapy, presenting as shortness of breath, dry cough, and fatigue.
• Statins may rarely trigger or worsen myasthenia gravis or ocular myasthenia.
• Seek immediate medical attention for unexplained muscle pain or weakness with fever or dark urine, yellowing of the skin or eyes, signs of a severe allergic reaction, or new muscle weakness affecting the eyes or breathing.

• Use with caution in patients who consume substantial amounts of alcohol or who have a history of liver disease.
• Use with caution in patients with risk factors for myopathy, such as advanced age over 65, renal impairment, uncontrolled hypothyroidism, or a personal or family history of muscle disorders.
• Use with caution when combined with fibrates, niacin, cyclosporine, or macrolide antibiotics, as the risk of muscle toxicity is increased.
• Use with caution in frail patients or those with conditions such as sepsis, hypotension, major surgery, trauma, or uncontrolled seizures, since these can predispose to rhabdomyolysis.
• Pravastatin should be temporarily stopped in patients with an acute serious illness that increases the risk of kidney injury from muscle breakdown.

• Known hypersensitivity to pravastatin or to any ingredient in the formulation.
• Active liver disease or unexplained, persistent elevations of liver transaminases exceeding three times the upper limit of normal.
• Pregnancy.

• Cyclosporine can markedly increase pravastatin blood levels, so a lower starting dose and cautious titration are needed when the two are combined.
• Combining pravastatin with fibrates, such as gemfibrozil or fenofibrate, or with lipid-lowering doses of niacin increases the risk of myopathy and rhabdomyolysis, so this combination should generally be avoided or used only with careful monitoring.
• Macrolide antibiotics such as erythromycin may increase statin exposure and the risk of muscle-related side effects.
• Bile acid-binding resins such as cholestyramine or colestipol reduce pravastatin absorption if taken at the same time, so doses should be separated by several hours.
• Coadministration with digoxin has been associated with increased digoxin levels with other HMG-CoA reductase inhibitors, so patients on digoxin should be monitored closely.
• Drugs that inhibit the cytochrome P450 3A4 pathway are less of a concern with pravastatin than with some other statins, since pravastatin is not extensively metabolized by this enzyme, but caution is still advised with drugs known to increase the risk of myopathy.
• Antacids may reduce, and cimetidine may modestly increase, pravastatin absorption, though neither interaction is considered clinically significant.

• Pravastatin may be taken with or without food, as the therapeutic effect on cholesterol reduction is similar either way.

• Usually taken once daily at bedtime, since cholesterol synthesis in the liver is greatest overnight, though it may be taken at other consistent times if needed.

• Store at room temperature (15 to 30 degrees C), protected from moisture and light, and keep out of reach and sight of children.

• Pravastatin is a statin used along with diet to lower cholesterol and reduce the risk of heart attack, stroke, and other cardiovascular problems.
• It is usually taken once daily at bedtime, with or without food, at a dose your prescriber sets based on your cholesterol levels and health history.
• Common effects include mild stomach upset, headache, muscle aches, and fatigue.
• Contact your doctor's office right away for unexplained muscle pain, tenderness, or weakness (especially with fever or dark urine), yellowing of the skin or eyes, or signs of a severe allergic reaction.
• Do not take pravastatin if you are or could become pregnant, and tell your doctor immediately if you become pregnant while taking it, since it may harm the developing baby.
• Store tablets at room temperature away from moisture and light, and let your pharmacist know about all other medications, especially fibrates, niacin, or cyclosporine.