Fluvastatin

Approved (adults)

• Primary hypercholesterolemia or mixed dyslipidemia (Fredrickson IIa/IIb): To reduce LDL-C, total-C, ApoB, and TG and to raise HDL-C as an adjunct to diet.
• Cardiovascular risk reduction in established atherosclerotic CVD: To reduce the risk of major coronary events in appropriate patients (e.g., post-PCI/known CHD) when statin therapy is indicated.

Approved (pediatrics)

• Heterozygous familial hypercholesterolemia (HeFH), ages 10–16 years: As an adjunct to diet when LDL-C remains elevated.

Clinically accepted off-label

• Primary prevention in adults meeting guideline thresholds for moderate-intensity statin therapy based on ASCVD risk.
• Post-transplant dyslipidemia (careful dosing with cyclosporine).
• Diabetes or CKD with dyslipidemia when a moderate-intensity statin is indicated and drug–drug interaction profile favors fluvastatin.

Formulations

• Immediate-release (IR) capsules: 20 mg, 40 mg.
• Extended-release (ER) tablet (Lescol XL®): 80 mg once daily.

Adults

• Typical starting dose (IR): 40 mg once daily in the evening; may titrate to 40 mg twice daily.
• ER: 80 mg once daily at any time (consistency preferred).
• Dose range: 20–80 mg/day. Reassess lipids 4–12 weeks after initiation or dose change, then every 3–12 months.

Pediatrics (HeFH, 10–16 yrs)

• Start 20 mg once daily; may titrate to 40 mg once daily (some regions allow up to 80 mg/day; use specialist guidance). Evening dosing preferred for IR. Safety not established <10 years.

Elderly

• No routine adjustment; start conservatively and titrate by response and tolerability.

Renal impairment

• Mild–moderate: No adjustment usually needed.
• Severe (eGFR <30 mL/min/1.73 m²): Consider 20 mg once daily initially and titrate cautiously; monitor for myopathy.

Hepatic impairment

• Active liver disease or unexplained persistent transaminase elevations: Contraindicated.
• If prior liver disease, use only if benefits outweigh risks with close LFT monitoring.

Administration tips

• With or without food.
• If using cholestyramine/other bile-acid sequestrants, give fluvastatin ≥4 hours after the resin.
• Swallow ER tablets whole (do not crush/split).

Duration

• Chronic, long-term therapy to maintain lipid goals and risk reduction.

Fluvastatin is a competitive inhibitor of HMG-CoA reductase, the rate-limiting enzyme converting HMG-CoA to mevalonate in hepatic cholesterol biosynthesis. Inhibition lowers intrahepatic cholesterol, upregulates LDL receptors on hepatocytes, and increases clearance of circulating LDL and VLDL remnants. Net effects are reductions in LDL-C (≈25–35% with 80 mg ER), total-C, ApoB, TG, and a modest rise in HDL-C. Downstream pleiotropic effects (e.g., improved endothelial function, reduced inflammation) may contribute to ASCVD risk reduction.

• Absorption: Rapid; Tmax ~0.5–1.5 h (IR), ~3 h (ER). Food may delay but not reduce overall exposure.
• Bioavailability: Absolute ~24% (extensive first-pass extraction).
• Distribution: Highly protein bound (>98%), large hepatic extraction; primary site of action is liver.
• Metabolism: Extensive hepatic CYP2C9 (major); minor via CYP2C8/3A4. Multiple inactive metabolites.
• Elimination half-life: ~2–3 h (effective LDL-C lowering persists with daily dosing).
• Excretion: Predominantly biliary/fecal; ≲6% urinary.
• Steady state: Within a few days; lipid effects assessed after 4–12 weeks.

• Pregnancy: FDA removed the absolute contraindication to statins (2021). However, discontinue fluvastatin when pregnancy is recognized in most patients; consider continuation only in very high-risk situations (e.g., homozygous FH with prior events) after specialist consultation. No adequate human data; potential fetal risk from interference with cholesterol synthesis.
• Lactation: Statins may pass into breast milk; breastfeeding is not recommended during fluvastatin therapy. Consider temporary interruption of the statin or alternative feeding if therapy is essential.
• Contraception: Advise effective contraception for patients who may become pregnant.

• Primary class: Antilipemic agent (statin).
• Subclass / intensity: Moderate-intensity at ER 80 mg qd or IR 40 mg bid (expected LDL-C reduction ~30–49%); lower-intensity at 20–40 mg qd.

• Hypersensitivity to fluvastatin or any excipient.
• Active liver disease or unexplained persistent elevations of serum transaminases.
• Concomitant use situations leading to uncontrolled severe myopathy (e.g., re-challenge after statin-induced immune-mediated necrotizing myopathy).

• Myopathy/Rhabdomyolysis: Risk increased with higher doses, advanced age, hypothyroidism, renal impairment, or interacting drugs (e.g., cyclosporine). Educate on muscle pain/weakness; check CK if symptomatic; stop if marked elevation or rhabdomyolysis suspected.
• Hepatic effects: Statins can raise ALT/AST; obtain baseline LFTs and repeat if clinically indicated (e.g., symptoms). Discontinue if persistent >3× ULN or hepatitis symptoms.
• Glycemic effects: Small increases in HbA1c/fasting glucose; benefits generally outweigh risks.
• Immune-mediated necrotizing myopathy (rare): Progressive proximal weakness, high CK persisting after discontinuation; manage with immunosuppression.
• Renal failure secondary to rhabdomyolysis: Prompt recognition and treatment required.
• Alcohol/liver disease: Use cautiously; avoid heavy alcohol intake.
• Thyroid disorders: Correct hypothyroidism before initiation to reduce myopathy risk.

Monitoring

• Lipids: 4–12 weeks after start or dose change, then q3–12 months.
• LFTs: Baseline, then as clinically indicated.
• CK: When muscle symptoms occur or high risk.
• Diabetes risk: Periodic glucose/HbA1c in at-risk patients.

Common (≥1%):

• Musculoskeletal: Myalgia, arthralgia, back pain.
• GI: Dyspepsia, nausea, abdominal pain, diarrhea.
• Neurologic: Headache, dizziness, fatigue, insomnia.
• Liver enzymes: Mild, asymptomatic ALT/AST elevations.

Serious / rare:

• Myopathy/rhabdomyolysis (dose/drug-interaction related; may occur weeks–months after start or uptitration).
• Immune-mediated necrotizing myopathy.
• Hepatitis, cholestatic jaundice, marked transaminase elevations.
• Hypersensitivity reactions (rash, pruritus, angioedema).
• Cognitive effects (memory issues—usually reversible on discontinuation).
• New-onset diabetes (small absolute risk).

Timing/dose-dependence: Muscle and hepatic events are dose-dependent and more likely with interacting drugs and comorbidities; many non-serious AEs occur within the first 2–8 weeks.

CYP/Transport

• CYP2C9 inhibitors ↑ fluvastatin exposure: Fluconazole, amiodarone, fluvoxamine—consider dose reduction/monitor for myopathy.
• CYP inducers ↓ levels: Rifampin, carbamazepine—may reduce efficacy.

Immunosuppressants

• Cyclosporine: Marked ↑ exposure—limit fluvastatin to 20 mg/day and monitor closely.

Fibrates & Niacin

• Gemfibrozil (avoid) and other fibrates/niacin: ↑ risk of myopathy—use only if benefits outweigh risks with vigilant monitoring.

Warfarin and other anticoagulants

• Potential ↑ INR; check INR when starting/changing fluvastatin.

Colchicine

• Additive myotoxicity risk—monitor for muscle symptoms.

Bile-acid sequestrants

• ↓ Absorption of fluvastatin; administer ≥4 hours after cholestyramine/colesevelam/colestipol.

Macrolides/azoles

• Less interaction than with CYP3A4-dependent statins but monitor if potent inhibitors are used concomitantly.

Food/alcohol

• No major food restrictions; avoid excessive alcohol (hepatic risk).
• Grapefruit juice: Minimal effect relative to other statins (CYP3A4 minor pathway), but heavy intake is best avoided.

• FDA (2021): Removal of blanket pregnancy contraindication for statins; most pregnant patients should stop therapy, but continuation may be considered in very high-risk cases after risk–benefit assessment.
• ACC/AHA lipid guidelines: Classify fluvastatin 40 mg bid or ER 80 mg qd as moderate-intensity statin therapy (expected LDL-C reduction 30–49%). Use for primary/secondary prevention based on ASCVD risk, age, LDL-C level, and comorbidities.
• Ongoing emphasis on shared decision-making, target ≥30% LDL-C reduction for moderate-intensity goals, and periodic safety monitoring.

• Temperature: Store at 20–25°C (68–77°F); excursions to 15–30°C permitted.
• Protection: Keep tightly closed, protect from moisture and light.
• Handling: ER tablets—do not crush, split, or chew.
• Dispensing: Keep in original container when feasible; observe expiry dates.