Lovastatin

Pronunciation

Pronunciation: LOW-vuh-STAT-in
Class: HMG-CoA reductase inhibitor

Trade Names

Altoprev
- Tablets, extended-release 10 mg
- Tablets, extended-release 20 mg
- Tablets, extended-release 40 mg
- Tablets, extended-release 60 mg

Mevacor
- Tablets 10 mg
- Tablets 20 mg
- Tablets 40 mg

Apo-Lovastatin (Canada)
CO Lovastatin (Canada)
Gen-Lovastatin (Canada)
Nu-Lovastatin (Canada)
PMS-Lovastatin (Canada)
RAN-Lovastatin (Canada)
ratio-Lovastatin (Canada)
Sandoz Lovastatin (Canada)

Pharmacology

Increases rate at which body removes cholesterol from blood and reduces production of cholesterol in body by inhibiting enzyme that catalyzes early rate-limiting step in cholesterol synthesis; increases HDL; reduces LDL, VLDL, and triglycerides.

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Pharmacokinetics

Absorption

About 35% absorbed. T max is 2 to 4 h.

Distribution

More than 95% protein bound (highly selective for the liver; achieved substantially higher concentrations than nontarget tissue). Crosses the blood-brain and placental barriers.

Metabolism

Major metabolites are beta-hydroxyacid and 6′-hydroxy derivative. Undergoes extensive first-pass metabolism (CYP 3A4). Less than 5% of an oral dose reaches general circulation.

Elimination

10% excreted in urine; 83% excreted in feces.

Special Populations

Renal Function Impairment

For Ccr less than 30 mL/min, use doses over 20 mg/day with caution because of increased plasma concentration.

Indications and Usage

To reduce elevated cholesterol and LDL cholesterol levels in patients with primary hypercholesterolemia (types IIa and IIb [immediate-release only]); to slow progression of coronary atherosclerosis in patients with coronary heart disease; to reduce risk of MI, unstable angina, and coronary revascularization procedures; as an adjunct to diet to reduce total and LDL cholesterol and apolipoprotein B levels in adolescent boys and girls (who are at least 1 yr postmenarche) 10 to 17 yr with heterozygous familial hypercholesterolemia (immediate-release only). As an adjunct to diet for reduction of elevated total and LDL cholesterol, apolipoprotein B, and triglycerides and to increase HDL cholesterol in patients with primary hypercholesterolemia (heterozygous familial and nonfamilial) and mixed dyslipidemia (Fredrickson types IIa and IIb) when response to diet restricted in saturated fat and cholesterol and to nonpharmacological measures alone has been inadequate (extended-release only).

Contraindications

Active liver disease or unexplained persistent elevations of LFTs; pregnancy; lactation.

Dosage and Administration

Adults Immediate-release

PO 10 to 80 mg/day in a single dose with evening meal or 2 divided doses.

Extended-release

PO 10 to 60 mg/day as a single dose in the evening at bedtime. Individualize dose according to recommended goal of therapy. For patients requiring a small reduction in cholesterol level, a starting dose of 10 mg may be considered.

Heterozygous Familial Hypercholesterolemia
Adolescents (10 to 17 yr) Immediate-release

PO 10 to 40 mg/day (max, 40 mg/day).

General Advice

Administer with meals. If given as a single dose, administer with evening meal.

Storage/Stability

Store at room temperature (at or below 86°F) in tightly closed, light-resistant container.

Drug Interactions

Azole antifungal agents (eg, itraconazole), cyclosporine, danazol, gemfibrozil, grapefruit juice, macrolide antibiotics (eg, erythromycin), niacin, verapamil

Severe myopathy or rhabdomyolysis may occur with coadministration.

Isradipine

May increase the clearance of lovastatin and its metabolites by increasing hepatic blood flow.

Warfarin

Enhanced anticoagulant effect.

Laboratory Test Interactions

None well documented.

Adverse Reactions

CNS

Headache; dizziness; paresthesia; insomnia.

Dermatologic

Rash; pruritus.

EENT

Blurred vision; dysfunction of certain cranial nerves (including alteration of taste, impairment of extraocular movement, facial paresis).

GI

Nausea; vomiting; diarrhea; abdominal pain; constipation; flatulence; heartburn; dyspepsia; pancreatitis.

Hepatic

Hepatitis; cholestatic jaundice; fatty change in liver; cirrhosis; fulminant hepatic necrosis; hepatoma.

Miscellaneous

Myalgia; muscle cramps; myopathy; rhabdomyolysis with increased CPK; arthralgias; hypersensitivity syndrome (eg, anaphylaxis, angioedema, lupus erythematosus–like syndrome, polymyalgia rheumatica, vasculitis, purpura, thrombocytopenia, leukopenia, hemolytic anemia, arthritis, arthralgia, urticaria, fever, chills, dyspnea, toxic epidermal necrolysis, erythema multiforme).

Precautions

Monitor

LFTs

Ensure that LFTs are performed every 4 to 6 wk during first 3 mo of therapy, every 6 to 8 wk during next 18 mo, and every 6 mo thereafter.


Pregnancy

Category X .

Lactation

Undetermined.

Children

Safety and efficacy not established in children younger than 18 yr of age.

Hepatic Function

Use with caution in patients who consume substantial quantities of alcohol or those with liver disease. Marked, persistent increases in serum transaminases have occurred during therapy.

Adults older than 70 yr of age

The AUC of lovastatin is increased.

Ophthalmologic effects

There was a high prevalence of baseline lenticular opacities during the early trials of lovastatin.

Skeletal muscle effects

Rhabdomyolysis with renal dysfunction secondary to myoglobinuria has been reported, mostly in those taking lovastatin concomitantly with cyclosporine, erythromycin, gemfibrozil, or nicotinic acid. Immunosuppressants may increase active lovastatin metabolites, which are associated with myopathy, myalgia, and muscle weakness associated with markedly increased CPK levels.

Overdosage

Symptoms

No specific symptoms with overdose of up to 6 g.

Patient Information

  • Caution patient that this medication must not be taken during pregnancy or when pregnancy is possible. Advise patient to use reliable form of birth control while taking this drug.
  • Advise patient to take medication with evening meal if possible.
  • Explain importance of adhering to low-cholesterol, low-fat diet during treatment. Suggest consultation with nutritionist as needed.
  • Instruct patient to report the following symptoms to health care provider: unexplained muscle pain, tenderness, or weakness, especially if accompanied by fever or malaise.
  • Caution patient to avoid or decrease alcohol intake.
  • Advise patient not to take any additional medications or supplementation without approval by health care provider.
  • Emphasize importance of returning for follow-up LFTs and blood cholesterol tests as instructed.
  • Explain that this treatment must be continued over years.

Copyright © 2009 Wolters Kluwer Health.

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