Pravastatin Sodium

• Hyperlipidemia:
  Treatment of elevated total cholesterol, LDL cholesterol, and triglycerides, and to increase HDL cholesterol in patients with primary hypercholesterolemia (heterozygous familial and nonfamilial).
• Mixed dyslipidemia:
  To reduce elevated cholesterol and triglycerides in mixed dyslipidemia.
• Prevention of cardiovascular disease:
• Primary prevention of coronary heart disease (CHD) in patients with multiple risk factors (e.g., age, smoking, hypertension, low HDL cholesterol, family history).
• Secondary prevention to reduce risk of myocardial infarction, stroke, and coronary revascularization in patients with established CHD or atherosclerotic vascular disease.
• Homozygous familial hypercholesterolemia:
  Adjunct to other lipid-lowering treatments including LDL apheresis.
• Off-label uses:
  Occasionally used in other atherosclerotic cardiovascular diseases and certain inflammatory conditions due to pleiotropic effects.

• Adults:
• Initial dose: 10–20 mg orally once daily, typically in the evening.
• Maintenance dose: 20–40 mg once daily; maximum dose Pravastatin 40 mg/day (some guidelines permit up to 80 mg, but caution advised).
• Dose adjustments based on LDL cholesterol response and tolerance.
• Elderly:
  Use standard dosing; monitor for adverse effects.
• Pediatrics (≥8 years):
  Approved for familial hypercholesterolemia; usual dose Pravastatin 10–20 mg once daily.
• Renal impairment:
  Use caution; start at lower doses in severe impairment.
• Hepatic impairment:
  Contraindicated in active liver disease or unexplained persistent elevations of serum transaminases.
• Administration:
  Oral tablets, with or without food. Evening administration preferred for optimal LDL reduction.

Pravastatin sodium is a selective, competitive inhibitor of HMG-CoA reductase, the rate-limiting enzyme in cholesterol biosynthesis in the liver. By inhibiting this enzyme, pravastatin decreases the synthesis of mevalonate, a cholesterol precursor, leading to upregulation of hepatic LDL receptors. This increases clearance of LDL cholesterol from the bloodstream, thereby lowering plasma LDL cholesterol levels and total cholesterol. Pravastatin also modestly lowers triglycerides and raises HDL cholesterol, contributing to its overall lipid-lowering effect.

• Absorption:
  Approximately 34% bioavailability after oral administration.
• Distribution:
  Volume of distribution approximately 0.72 L/kg; low plasma protein binding (~50%).
• Metabolism:
  Minimally metabolized by the liver; not significantly dependent on CYP450 enzymes (minor metabolism via CYP3A4 and CYP2C9).
• Elimination:
  Primarily excreted unchanged in urine (~20%) and bile.
• Half-life:
  Approximately 1.8 hours.
• Onset of action:
  Significant LDL cholesterol reduction seen within 1–2 weeks; maximal effect typically by 4–6 weeks.

• Pregnancy: Category X. Statins are contraindicated during pregnancy due to potential teratogenicity and cholesterol synthesis interference vital for fetal development.
• Lactation:
  Unknown if excreted in human milk; statins are generally not recommended during breastfeeding.

• Lipid-lowering agent
• HMG-CoA reductase inhibitor (Statin class)

• Known hypersensitivity to pravastatin or any component of the formulation.
• Active liver disease or unexplained persistent elevation of hepatic transaminases.
• Pregnancy and lactation.
• Severe hepatic impairment.

• Monitor liver function tests before and during therapy.
• Risk of myopathy and rhabdomyolysis, especially when combined with certain drugs (e.g., fibrates, niacin, CYP inhibitors).
• Use with caution in patients with renal impairment.
• Caution in elderly patients due to increased risk of adverse effects.
• Discontinue therapy if significant liver enzyme elevations or muscle symptoms occur.
• Educate patients to report unexplained muscle pain, tenderness, or weakness.

• Common:
  Headache, abdominal pain, nausea, myalgia.
• Serious but rare:
  Myopathy, rhabdomyolysis, elevated liver enzymes, hypersensitivity reactions (rash, pruritus).
• Others:
  Fatigue, dizziness, increased blood glucose.

• Increased risk of myopathy with fibrates, niacin, cyclosporine, macrolide antibiotics, azole antifungals, and protease inhibitors.
• Minimal CYP450 interaction compared to other statins; lower potential for drug interactions.
• Avoid concomitant use with strong CYP3A4 inhibitors that may increase statin levels.
• Grapefruit juice has minimal effect on pravastatin compared to other statins.

• Current guidelines recommend pravastatin as an effective option for primary and secondary prevention of cardiovascular disease with a favorable safety profile.
• Emphasis on individualized risk assessment and target LDL cholesterol levels.
• Monitoring recommendations for muscle symptoms and liver enzymes reinforced.

• Store at 20°C to 25°C (68°F to 77°F).
• Protect from moisture and light.
• Keep tablets in original container tightly closed.
• Do not freeze.