Fluvastatin

Fluvastatin is a synthetic statin that is broken down via several metabolic pathways and only to a small extent via CYP3A4. It is used to treat hypercholesterolemia and for secondary prevention after coronary angioplasty (cardiac catheterization procedure).

Fluvastatin was known under the brand name Locol® (as an extended-release tablet: Locol® XL) and is now available as a generic (e.g., Fluvastatin-ratiopharm®). The LIPS study (Lescol Intervention Prevention Study) showed a particular benefit after percutaneous coronary intervention (PCI).

It is one of the less potent statins and is used mainly for mild to moderate cholesterol elevation or as a statin with a favorable interaction profile.

Fluvastatin inhibits cholesterol biosynthesis:

Mechanism of action:

• Inhibits HMG-CoA reductase
• Fully synthetic statin (indole derivative)
• Reduces hepatic cholesterol production
• Compensatory upregulation of LDL receptors

Lipid-lowering effect:

• LDL cholesterol: reduction of 20–35% (dose-dependent)
• Triglycerides: reduction of 10–15%
• HDL cholesterol: increase of 3–8%

Special features:

• Metabolized via CYP2C9 (not CYP3A4!) → different interactions than simvastatin/atorvastatin
• High selectivity for liver cells
• Rapid uptake into the liver (high first-pass effect)
• Extended-release form (XL) enables constant drug levels

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

Fluvastatin is suitable for:

• Adults with hypercholesterolemia
• Secondary prevention after coronary angioplasty (PTCA/PCI)
• Mixed dyslipidemia
• Patients who have to take CYP3A4 inhibitors

Particularly recommended for:

• After a cardiac catheterization procedure (LIPS study)
• When other statins are not possible due to CYP3A4 interactions
• Mild to moderate cholesterol elevation

Not suitable:

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

Capsules:

• 20–40 mg once daily in the evening

Extended-release tablets (XL):

• 80 mg once daily (can be taken at any time of day)

Available strengths:

• 20 mg, 40 mg capsules
• 80 mg extended-release tablets (XL)

LDL reduction by dose:

• 20 mg: approx. 20–25%
• 40 mg: approx. 25–30%
• 80 mg (XL): approx. 33–35%

Dose adjustment:

• Mild to moderate renal impairment: no adjustment needed
• Hepatic impairment: contraindicated in active disease

Capsules (20/40 mg):

• Take once daily in the evening (short half-life)
• Regardless of meals
• Swallow the capsule whole with water

Extended-release tablets (80 mg XL):

• Once daily, at any time of day
• Do not split, chew, or crush the tablet
• Regardless of meals

Important information:

• Laboratory check after 4–12 weeks (liver function tests, lipids)
• Report muscle pain to your doctor
• No problem with grapefruit juice (not a CYP3A4 substrate)

If you miss a dose: Take it at the next regular time. Do not take a double dose.

Fluvastatin must not be taken in cases of:

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

Caution in cases of:

• Renal impairment
• Hypothyroidism
• History of muscle disorders
• High alcohol consumption
• Concomitant use of fibrates
• CYP2C9 inhibitors (fluconazole)

Pregnancy: Contraindicated. Reliable contraception required.

Common (1–10%):

• Sleep disturbances
• Headache
• Gastrointestinal complaints (dyspepsia, abdominal pain, nausea)
• Muscle pain
• Elevated liver enzymes

Uncommon (0.1–1%):

• Fatigue
• Dizziness
• Skin rash
• Paresthesia

Rare:

• Myopathy, rhabdomyolysis
• Hepatitis
• Vasculitis
• Hypersensitivity reactions

General: Fluvastatin is considered a well-tolerated statin. The rate of myopathy is comparable to that of other statins at therapeutic doses.

Metabolism via CYP2C9 (not CYP3A4!): This means different interactions than with simvastatin or atorvastatin.

Caution with:

• Fluconazole (CYP2C9 inhibitor → increased fluvastatin levels)
• Fibrates (gemfibrozil) → risk of myopathy
• Phenytoin → mutual changes in levels
• Warfarin → INR monitoring (fluvastatin mildly inhibits CYP2C9)
• Cyclosporine → increased levels of both substances
• Colchicine → risk of myopathy

No relevant interaction with:

• Grapefruit juice (not a CYP3A4 substrate)
• Erythromycin, clarithromycin
• Itraconazole, ketoconazole
• Verapamil, diltiazem, amiodarone

Advantage: Most CYP3A4-dependent interactions that are problematic with simvastatin and atorvastatin do not apply to fluvastatin.