Pravastatin

Pravastatin is a hydrophilic statin characterized by particularly few interactions with other medications. It is NOT metabolized via the cytochrome P450 system, which makes it ideal for patients who take many other medications.

Pravastatin was known under the brand names Pravastatin® and Pravasin® and is now widely available as a generic. In the large WOSCOPS and CARE trials, pravastatin demonstrated the efficacy of statin therapy in both primary and secondary prevention.

Compared with atorvastatin and rosuvastatin, its LDL-lowering effect is more moderate, which makes pravastatin an option for mildly to moderately elevated cholesterol.

Pravastatin inhibits cholesterol synthesis:

Mechanism of action:

• Directly active substance (not a prodrug)
• Inhibits HMG-CoA reductase
• Reduces hepatic cholesterol biosynthesis
• Compensatory upregulation of LDL receptors

Lipid-lowering effect:

• LDL cholesterol: reduction of 20–35%
• Triglycerides: reduction of 10–15%
• HDL cholesterol: increase of 3–8%

Special features:

• Hydrophilic: low uptake into non-hepatic tissues
• NO CYP3A4 metabolism → hardly any interactions with CYP inhibitors
• No problem with grapefruit juice
• Not metabolized via the cytochrome P450 system

Onset of action: LDL reduction measurable after 1–2 weeks. Maximum effect after 4 weeks.

Pravastatin is suitable for:

• Adults with hypercholesterolemia
• Primary prevention in case of increased cardiovascular risk
• Secondary prevention after a heart attack
• Patients taking many concomitant medications

Particularly recommended for:

• Polypharmacy (many medications taken at the same time)
• If muscle problems occurred with lipophilic statins
• Organ transplantation (interaction with ciclosporin manageable)
• Mild to moderate cholesterol elevation

Not suitable:

• Pregnancy and breastfeeding
• Active liver disease
• If a strong LDL reduction (> 35%) is required

Starting dose:

• 10–20 mg once daily

Usual dose:

• 20–40 mg once daily

Maximum dose:

• 40 mg daily

Available strengths:

• 10 mg, 20 mg, 40 mg tablets

LDL reduction by dose:

• 10 mg: approx. 20–25%
• 20 mg: approx. 25–30%
• 40 mg: approx. 30–35%

Dose adjustment:

• Renal impairment: starting dose 10 mg in moderate or severe renal impairment
• Hepatic impairment: contraindicated in active disease
• With ciclosporin: start with 20 mg pravastatin, increase up to 40 mg only with caution

How to take:

• Once daily, preferably in the evening (cholesterol synthesis is highest at night)
• Regardless of meals
• Swallow the tablet with water

Important notes:

• Regular laboratory monitoring (liver function tests, lipid profile) after 4–12 weeks
• If you have muscle pain or dark urine: inform your doctor
• No problem with grapefruit juice (unlike simvastatin/atorvastatin)
• Alcohol in moderation

If you miss a dose: Take it if it is not yet too late in the day. Otherwise, take the next regular dose.

Pravastatin must not be taken in case of:

• Active liver disease or unexplained elevation of transaminases
• Pregnancy and breastfeeding
• Hypersensitivity to pravastatin

Caution in case of:

• Renal impairment (dose adjustment)
• Hypothyroidism
• History of muscle disorders
• High alcohol consumption
• Concomitant therapy with fibrates

Pregnancy: Contraindicated. Reliable contraception required.

Common (1–10%):

• Headache
• Gastrointestinal complaints (nausea, diarrhea, flatulence)
• Muscle pain
• Fatigue

Uncommon (0.1–1%):

• Dizziness
• Sleep disturbances
• Skin rash
• Visual disturbances

Rare:

• Myopathy, rhabdomyolysis
• Hepatitis
• Peripheral neuropathy
• Pancreatitis

General: The hydrophilic nature of pravastatin reduces uptake into muscle cells, which theoretically leads to fewer muscle problems.

Key advantage: Pravastatin is NOT metabolized via CYP3A4 or CYP2C9 → hardly any interactions with CYP inhibitors.

Caution with:

• Ciclosporin: start pravastatin at 20 mg, increase up to 40 mg only with caution (increased levels)
• Fibrates (gemfibrozil): increased risk of myopathy
• Fusidic acid: temporarily pause the statin
• Colchicine: increased risk of myopathy
• Macrolide antibiotics (e.g. erythromycin, clarithromycin): increased risk of myopathy

No relevant interaction with:

• Grapefruit juice
• CYP3A4 inhibitors (itraconazole, verapamil, etc.)
• Amiodarone
• Diltiazem

Note: Pravastatin has the most favorable interaction profile of all statins and is therefore particularly suitable for patients who take many other medications.