pravastatin sodium
Pravachol

Available forms
Available by prescription only
Tablets: 10 mg, 20 mg, 40 mg, 80 mg

Indications and dosages
 Primary and secondary prevention of coronary events; hyperlipidemia. Adults: Initially, 40 mg P.O. once daily at the same time each day, with or without food. Adjust dosage q 4 weeks based on patient tolerance and response. Maximum daily dose is 80 mg.
≡ Dosage adjustment. For patients with renal or hepatic dysfunction, start with 10 mg P.O. daily. For patients taking immunosuppressants concomitantly, pravastatin therapy should begin with 10 mg P.O. at bedtime and adjustment to higher doses should be done with caution. Most patients treated with this combination received a maximum dose of 20 mg/day.

Pharmacodynamics
Antilipemic action: Inhibits the enzyme 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase. This hepatic enzyme is an early (and rate limiting) step in the synthetic pathway of cholesterol.

Pharmacokinetics
Absorption: Rapidly absorbed. Average oral absorption is 34%; absolute bioavailability of 17%. Food reduces bioavailability, but same drug effects if drug is taken with or 1 hour before meals.
Distribution: Plasma levels proportional to dose, but don’t necessarily correlate perfectly with lipid-lowering effects. About 50% bound to plasma proteins. Undergoes extensive first-pass extraction, possibly because of active transport system into hepatocytes.
Metabolism: Metabolized by liver. At least six metabolites identified; some active.
Excretion: Excreted by liver and kidneys.

Contraindications and precautions
Contraindicated in patients hypersensitive to drug; in those with active liver disease or conditions that cause unexplained, persistent elevations of serum transaminase levels; in pregnant and breast-feeding women; and in women of childbearing age unless there is no risk of pregnancy.
  Use cautiously in patients who consume large quantities of alcohol or have history of liver disease.

Interactions
Drug-drug. Cholestyramine, colestipol: Decreases plasma levels of pravastatin. Administer pravastatin 1 hour before or 4 hours after these drugs.
Cimetidine, ketoconazole, spironolactone: Increases risk of endocrine dysfunction. No intervention appears needed; take complete drug history in patients who develop endocrine dysfunction.
Erythromycin, fibric acid derivatives (clofibrate, gemfibrozil), high doses of niacin (1 g or more nicotinic acid daily), immunosuppressants (such as cyclosporine): Increases risk of rhabdomyolysis. Monitor patient closely if drugs must be given together.
Gemfibrozil: Decreases protein-binding and urinary clearance of pravastatin. Avoid use together.
Hepatotoxic drugs: Increases risk of hepatotoxicity. Use together cautiously.
Drug-herb. Red yeast rice: Contains components similar to those of statin drugs, increasing the risk of adverse events or toxicity. Discourage use together.
Drug-lifestyle. Chronic alcohol abuse: Increases risk of hepatotoxicity. Monitor patient closely and discourage alcohol use.
Sun exposure: Causes photosensitivity reaction. Advise patient to take precautions.

Adverse reactions
CNS: headache, dizziness, fatigue.
CV: chest pain.
EENT: rhinitis.
GI: vomiting, diarrhea, heartburn, abdominal pain, constipation, flatulence, nausea.
GU: renal failure secondary to myoglobinuria, urinary abnormality.
Musculoskeletal: myositis, myopathy, localized muscle pain, myalgia, rhabdomyolysis.
Respiratory: cough.
Skin: rash, photosensitivity.
Other: flu-like symptoms, flu syndrome, common cold.

Effects on lab test results
• May increase ALT, AST, CK, alkaline phosphatase, and bilirubin levels.
• May alter thyroid function test values.

Overdose and treatment
No information available.
 Treat symptomatically.

Special considerations
• Stop drug temporarily in patients with an acute condition that suggests a developing myopathy and in patients with risk factors that may predispose them to development of renal failure secondary to rhabdomyolysis (including severe acute infection; severe endocrine, metabolic, or electrolyte disorders; hypotension; major surgery; or uncontrolled seizures).
• Watch for signs of myositis. Rarely, myopathy and marked elevations of CK level, possibly leading to rhabdomyolysis and renal failure secondary to myoglobinuria, have occurred.
• Initiate drug therapy only after diet and other nonpharmacologic therapies have proved ineffective. Patients should continue a cholesterol-lowering diet during therapy.
• Give drug in evening, preferably at bedtime. Drug may be given without regard to meals.
• Dosage adjustments should be made about every 4 weeks. May reduce dosage if cholesterol levels fall below target range.
Breast-feeding patients
• Drug appears in breast milk. Women shouldn’t breast-feed while taking drug.
Pediatric patients
• Safety and efficacy in children younger than age 18 haven’t been established.
Geriatric patients
• Maximum effectiveness is usually evident with daily doses of 20 mg or less.

Patient education
• Teach patient appropriate dietary management (restricting total fat and cholesterol intake), weight control, and exercise. Explain importance of these interventions in controlling serum lipids.
• Because of drug’s possible impact on liver function, advise patient to restrict alcohol intake.
• Tell patient to call if he experiences adverse reactions, particularly muscle aches and pains.
• Inform patient to take drug at bedtime.
• Tell patient to avoid excessive exposure to sunlight because of photosensitivity reactions.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use