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Tuesday, July 29, 2025

Pravastatin


Generic Name: Pravastatin
Brand Names: Pravachol (US), Selektine, Lipostat (UK), among others


Drug Class: Lipid-lowering agent; Statin (HMG-CoA reductase inhibitor)
Pharmaceutical Category: Cardiovascular agent; Antihyperlipidemic
Formulations: Oral tablets (10 mg, 20 mg, 40 mg, 80 mg)
Route of Administration: Oral

1. Pharmacological Classification

Pravastatin is a statin, a class of drugs known as HMG-CoA reductase inhibitors. Statins are first-line agents for reducing elevated cholesterol levels, especially low-density lipoprotein cholesterol (LDL-C), and are well-established in the prevention of atherosclerotic cardiovascular disease (ASCVD). Among the statins, pravastatin is hydrophilic and less hepatoselective, which affects its pharmacokinetic and safety profile.

2. Mechanism of Action

Pravastatin competitively inhibits 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, the rate-limiting enzyme in the hepatic cholesterol biosynthesis pathway.

This inhibition results in:

  • Reduced intrahepatic cholesterol synthesis

  • Upregulation of hepatic LDL receptors

  • Enhanced clearance of circulating LDL-C

  • Mild increase in HDL-C

  • Modest decrease in triglycerides

Unlike lipophilic statins (e.g., simvastatin, atorvastatin), pravastatin is more hepatoselective and less likely to cross the blood–brain barrier, which may reduce risk of CNS side effects.

3. Therapeutic Indications

A. Hyperlipidemia and Dyslipidemia

  • Primary hypercholesterolemia (heterozygous familial or nonfamilial)

  • Mixed dyslipidemia (types IIa and IIb)

B. Cardiovascular Disease Risk Reduction

  • Primary prevention in individuals with risk factors (e.g., hypertension, diabetes, smoking, family history)

  • Secondary prevention of cardiovascular events in patients with:

    • Prior myocardial infarction (MI)

    • History of stroke or TIA

    • Documented coronary artery disease

    • Peripheral arterial disease

C. Post-Transplant Hyperlipidemia (off-label)

  • Often used due to lower potential for drug–drug interactions compared to other statins

4. Dosage and Administration

Initial Dose (Adults)

  • 10–40 mg once daily in the evening or bedtime (when cholesterol synthesis peaks)

  • Can be taken with or without food

Titration

  • Adjust dose at 4-week intervals based on LDL-C goals

  • Max dose: 80 mg once daily (for high-risk patients, under close monitoring)

Children (8–18 years)

  • Initiate at 10–20 mg once daily (based on age and response)

  • Used in familial hypercholesterolemia

5. Pharmacokinetics

  • Absorption: ~34% (oral bioavailability); food slightly delays but does not reduce total absorption

  • Peak plasma level: 1–1.5 hours post-dose

  • Distribution: Highly hydrophilic; minimal CNS penetration

  • Protein Binding: ~50%

  • Metabolism: Not significantly metabolized by CYP450 enzymes (unlike other statins), mainly via sulfation

  • Excretion: Primarily via bile and urine (~20%)

  • Half-life: ~1.8 hours (longer duration of action due to hepatic effects)

6. Contraindications

  • Active liver disease, including unexplained persistent elevations in liver enzymes

  • Pregnancy and breastfeeding (Category X under old classification)

  • Hypersensitivity to pravastatin or any formulation excipients

7. Warnings and Precautions

Liver Function

  • Risk of transaminase elevations (ALT/AST)

  • Rare reports of fatal and nonfatal hepatic failure

  • Baseline liver function tests (LFTs) recommended, with periodic monitoring during therapy

Skeletal Muscle Effects

  • Myopathy, rhabdomyolysis, and creatine kinase (CK) elevation can occur

  • Risk increases with:

    • Advanced age (>65)

    • High-dose pravastatin

    • Renal impairment

    • Use with other myotoxic agents (e.g., fibrates, niacin)

Endocrine Effects

  • May modestly reduce testosterone or affect glycemic control

  • Slight increase in HbA1c and risk of new-onset diabetes in susceptible individuals

Renal Impairment

  • Dosage adjustment may be needed for severe renal dysfunction

8. Adverse Effects

Common (≥1%)

  • Headache

  • Nausea

  • Muscle pain or cramps (myalgia)

  • Abdominal pain

  • Fatigue

  • Rash

  • Upper respiratory infections

Less Common (0.1–1%)

  • Insomnia

  • Dizziness

  • Elevated liver enzymes

  • Dyspepsia

  • Diarrhea

  • Arthralgia

Rare (<0.1%)

  • Rhabdomyolysis (life-threatening)

  • Myositis

  • Pancreatitis

  • Hepatitis

  • Hypersensitivity reactions (e.g., angioedema)

9. Drug Interactions

Pravastatin is not metabolized by CYP3A4, which reduces its potential for drug–drug interactions compared to simvastatin or atorvastatin. Still, caution is warranted with certain agents:

a. Fibrates (e.g., gemfibrozil)

  • ↑ Risk of myopathy/rhabdomyolysis

  • Avoid unless benefit outweighs risk

b. Niacin (≥1 g/day)

  • Additive myotoxic risk

c. Cyclosporine

  • Increases pravastatin plasma levels; dose adjustment required

d. Colestyramine/Colestipol

  • May reduce pravastatin absorption; give pravastatin 1 hour before or 4 hours after resin

e. Macrolides (e.g., erythromycin, clarithromycin) and azole antifungals

  • Minor interaction, still monitor for muscle toxicity

f. Warfarin

  • May enhance anticoagulant effect; monitor INR after initiation or dose adjustment

g. Digoxin

  • Slight increase in serum levels; monitor if clinically warranted

10. Pregnancy and Lactation

Pregnancy

  • Contraindicated: Statins reduce cholesterol synthesis, essential for fetal development.

  • Risk of fetal malformation, miscarriage, and low birth weight.

  • Discontinue immediately if pregnancy is detected.

Lactation

  • Excreted in human milk; not recommended during breastfeeding due to potential risk to the infant.

11. Monitoring Parameters

  • Lipid profile (baseline, at 4–12 weeks after initiation or dose changes, then annually)

  • Liver enzymes (ALT/AST) before starting, then as clinically indicated

  • CK levels if unexplained muscle pain, tenderness, or weakness arises

  • Renal function in older adults or patients with kidney disease

  • HbA1c or fasting glucose in diabetic or prediabetic patients

12. Formulations and Brand Availability

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

  • Global Brands:

    • Pravachol (Pfizer)

    • Lipostat (UK)

    • Selektine, Cholstat, Prareduct

    • Available in generic formulations globally

13. Comparative Notes and Clinical Pearls

  • Pravastatin is preferred in:

    • Patients on multiple drugs (e.g., transplant recipients) due to low CYP interaction

    • Patients with history of statin-associated muscle symptoms (SAMS); better tolerated than simvastatin or atorvastatin

    • Elderly or frail individuals needing low-to-moderate intensity therapy

  • Less potent than atorvastatin or rosuvastatin on LDL-C reduction:

    • Pravastatin 40 mg = ~30% LDL-C reduction

    • Not suitable for very high-intensity statin therapy requirements

  • Shown to reduce all-cause mortality and cardiovascular events in major clinical trials (e.g., WOSCOPS, LIPID)



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