PRA-va-sta-tin

Therapeutic Classification: lipid-lowering agents

Pharmacologic Classification: hmg coa reductase inhibitors (statins)

• Adjunctive management of primary hypercholesterolemia and mixed dyslipidemias.
• Primary prevention of coronary heart disease (myocardial infarction, coronary revascularization, cardiovascular mortality) in asymptomatic patients with increased total and low-density lipoprotein cholesterol (LDL-C) and decreased high-density lipoprotein cholesterol (HDL-C).
• Secondary prevention of MI, coronary revascularization, stroke, and overall mortality in patients with clinically evident coronary heart disease.

• Inhibits 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, an enzyme responsible for catalyzing an early step in the synthesis of cholesterol.

• Lowering of total cholesterol and LDL-C and triglycerides. Slightly increases HDL-C.
• Slows the progression of coronary atherosclerosis with resultant decrease in coronary heart disease-related events.

Absorption: Poorly and variably absorbed following oral administration.

Distribution: Unknown.

Metabolism/Excretion: Extensively metabolized by the liver, most during first pass; excreted in bile and feces. 20% excreted unchanged by the kidneys.

Half-life: 1.3–2.7 hr.

(cholesterol-lowering effect)

Contraindicated in:

• Hypersensitivity
• Active liver disease or unexplained persistent ↑ in AST and ALT
• Lactation: Lactation.

Use Cautiously in:

• History of liver disease
• Alcoholism
• Renal impairment
• Women of reproductive potential
• OB: Use statin therapy during pregnancy only if potential maternal benefit justifies potential fetal risk (if needed, consider using a more water-soluble agent [pravastatin or rosuvastatin] that is less likely to cross the placenta)
• Pedi: Children <8 yr (safety and effectiveness not established).

CV: chest pain, peripheral edema.

Derm: rash, pruritus.

EENT: rhinitis.

Endo: hyperglycemia.

GI: abdominal cramps, constipation, diarrhea, flatus, heartburn, altered taste, drug-induced hepatitis, dyspepsia, ↑ liver enzymes, nausea, pancreatitis.

GU: erectile dysfunction.

MS: arthralgia, arthritis, immune-mediated necrotizing myopathy, myalgia, myositis, RHABDOMYOLYSIS.

Neuro: amnesia, confusion, dizziness, headache, insomnia, memory loss, weakness.

Resp: bronchitis.
Misc: hypersensitivity reactions.

Drug-Drug:

• Bioavailability may be ↓ by bile acid sequestrants; administer pravastatin 1 hr before or 4 hr after bile acid sequestrants.
• Risk of myopathy is ↑ by concurrentcyclosporine, fibrates, colchicine, erythromycin, clarithromycin, azithromycin, or large doses of niacin; concurrent use with gemfibrozil should be avoided; consider lower dose of pravastatin with niacin.
• May ↑ effects of warfarin.
• Levels may be significantly ↑ by azole antifungals ; temporarily discontinue HMG-CoA reductase inhibitor, effect is less than with other statins.
• Ritonavir may ↓ levels and effectiveness.

• PO (Adults): 40 mg once daily at bedtime; may be ↑ after 4 wk, if needed to 80 mg once daily at bedtime); Concurrent cyclosporine therapy: Initiate therapy with 10 mg once daily at bedtime; may be ↑ after 4 wk, if needed, to 20 mg once daily at bedtime (max dose = 20 mg/day); Concurrent clarithromycin therapy: Dose should not exceed 40 mg/day.
• PO (Children 14–18 yr): 40 mg once daily (max dose = 40 mg/day).
• PO (Children 8–13 yr): 20 mg once daily (max dose = 20 mg/day).

(Generic available)

• Tablets: 10 mg; 20 mg; 40 mg; 80 mg;

• Obtain a diet history, especially with regard to fat consumption.

• Evaluate serum cholesterol and triglyceride levels before initiating, after 4–6 wk of therapy, and periodically thereafter.
  • Monitor liver function tests prior to initiation of therapy and as clinically indicated. If symptoms of serious liver injury, hyperbilirubinemia, or jaundice occur, discontinue pravastatin and do not restart. May also cause ↑ alkaline phosphatase and bilirubin levels.
  • If patient develops muscle tenderness during therapy, monitor CK levels. If CK levels are markedly ↑ or myopathy occurs, discontinue therapy.

• PO: Administer once daily in the evening. May be administered without regard to food.
  • Avoid grapefruit and grapefruit juice during therapy; may increase risk of toxicity.
  • If administered in conjunction with bile acid sequestrants (cholestyramine, colestipol), administer 1 hr before or 4 hr after bile acid sequestrant.

• Instruct patient to take medication as directed, not to skip doses or double up on missed doses. Advise patient to avoid drinking more that 200 mL/day of grapefruit juice during therapy. Medication helps control but does not cure elevated serum cholesterol levels.
• Advise patient that this medication should be used in conjunction with diet restrictions (fat, cholesterol, carbohydrates, alcohol), exercise, and cessation of smoking.
• Instruct patient to notify health care professional if unexplained muscle pain, tenderness, or weakness occurs, especially if accompanied by fever or malaise.
• Advise patient to wear sunscreen and protective clothing to prevent photosensitivity reactions (rare).
• Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications.
• Advise patient to notify health care professional of medication regimen prior to treatment or surgery.
• Instruct females of reproductive potential to use effective contraception during therapy, to notify health care professional promptly if pregnancy is planned or suspected and to avoid breastfeeding during therapy. Use statin therapy during pregnancy only if potential maternal benefit justifies potential fetal risk (if needed, consider using a more water-soluble agent [pravastatin or rosuvastatin] that is less likely to cross the placenta).
• Emphasize the importance of follow-up exams to determine effectiveness and to monitor for side effects.

• Decrease in total cholesterol and LDL-C levels.
  • Increase in HDL-C levels.
  • Decrease in triglyceride levels.
• Slowing of the progression of coronary artery disease.

Pravachol