No

Antilipemic Agent (HMG-CoA Reductase Inhibitor)

Adjunct to dietary therapy to decrease elevated serum total and LDL cholesterol concentrations in primary hypercholesterolemia; primary prevention of coronary artery disease (patients without symptomatic disease with average to moderately elevated total and LDL cholesterol and below average HDL cholesterol)

X

Hypersensitivity to lovastatin or any component; active liver disease; unexplained persistent elevations of serum transaminases; pregnancy

Liver function must be monitored by periodic laboratory assessment. Rhabdomyolysis with acute renal failure has occurred. Risk is increased with concurrent use of clarithromycin, danazol, diltiazem, fluvoxamine, indinavir, nefazodone, nelfinavir, ritonavir, verapamil, troleandomycin, cyclosporine, fibric acid derivatives, erythromycin, niacin, or azole antifungals. Weigh the risk versus benefit when combining any of these drugs with lovastatin. Temporarily discontinue in any patient experiencing an acute or serious condition predisposing to renal failure secondary to rhabdomyolysis. Use with caution in patients who consume large amounts of alcohol or have a history of liver disease.

>10%: Neuromuscular and skeletal: Increased CPK (>2x normal) (11%)

1% to 10%:

Central nervous system: Headache (2.1% to 3.2%), dizziness (0.5% to 1.2%)

Dermatologic: Rash (0.8% to 1.3%)

Gastrointestinal: Abdominal pain (2.0% to 2.5%), constipation (2.0% to 3.5%), diarrhea (2.2% to 2.6%), dyspepsia (1.0% to 1.6%), flatulence (3.7% to 4.5%), nausea (1.9% to 2.5%)

Neuromuscular & skeletal: Myalgia (1.8% to 3.0%), weakness (1.2% to 1.7%), muscle cramps (0.6% to 1.1%)

Ocular: Blurred vision (0.8% to 1.3%)

<1% (Limited to important or life-threatening symptoms): Chest pain, acid regurgitation, xerostomia, vomiting, leg pain, arthralgia, insomnia, paresthesia, alopecia, pruritus, eye irritation

Additional class-related events or case reports (not necessarily reported with lovastatin therapy): Myopathy, increased CPK (>10x normal), rhabdomyolysis, renal failure (secondary to rhabdomyolysis), alteration in taste, impaired extraocular muscle movement, facial paresis, tremor, memory loss, vertigo, paresthesia, peripheral neuropathy, peripheral nerve palsy, anxiety, depression, psychic disturbance, hypersensitivity reaction, angioedema, anaphylaxis, systemic lupus erythematosus-like syndrome, polymyalgia rheumatica, dermatomyositis, vasculitis, purpura, thrombocytopenia, leukopenia, hemolytic anemia, positive ANA, increased ESR, eosinophilia, arthritis, urticaria, photosensitivity, fever, chills, flushing, malaise, dyspnea, rash, toxic epidermal necrolysis, erythema multiforme, Stevens-Johnson syndrome, pancreatitis, hepatitis, cholestatic jaundice, fatty liver, cirrhosis, fulminant hepatic necrosis, hepatoma, anorexia, vomiting, alopecia, pruritus, nodules, skin discoloration, dryness of skin/mucous membranes, nail changes, gynecomastia, decreased libido, erectile dysfunction, impotence, cataracts, ophthalmoplegia, elevated transaminases, increased alkaline phosphatase, increased GGT, hyperbilirubinemia, thyroid dysfunction

Very few adverse events; treatment is symptomatic

CYP3A3/4 substrate

Cholestyramine reduces absorption of several HMG-CoA reductase inhibitors. Separate administration times by at least 4 hours.

Cholestyramine and colestipol (bile acid sequestrants): Cholesterol-lowering effects are additive.

Clofibrate and fenofibrate may increase the risk of myopathy and rhabdomyolysis.

Gemfibrozil: Increased risk of myopathy and rhabdomyolysis.

Grapefruit juice may inhibit metabolism of lovastatin via CYP3A3/4; avoid high dietary intakes of grapefruit juice.

Isradipine may decrease lovastatin blood levels.

Niacin may increase risk of myopathy and rhabdomyolysis.

Warfarin effect (hypoprothrombinemic response) may be increased; monitor INR closely when lovastatin is initiated or discontinued.

Lovastatin acts by competitively inhibiting 3-hydroxyl-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, the enzyme that catalyzes the rate-limiting step in cholesterol biosynthesis

Onset of effect: 3 days of therapy required for LDL cholesterol concentration reductions

Absorption: Oral: 30%

Protein binding: 95%

Half-life: 1.1-1.7 hours

Time to peak serum concentration: Oral: 2-4 hours

Elimination: ~80% to 85% of dose excreted in feces and 10% in urine following liver hydrolysis

Adults: Oral: Initial: 20 mg with evening meal, then adjust at 4-week intervals; maximum dose: 80 mg/day; before initiation of therapy, patients should be placed on a standard cholesterol-lowering diet for 3-6 months and the diet should be continued during drug therapy

Before initiation of therapy, patients should be placed on a standard cholesterol-lowering diet for 3-6 months and the diet should be continued during drug therapy.

Plasma triglycerides, cholesterol, and liver function tests

liver transaminases (S), altered thyroid function tests

HMG-CoA reductase inhibitors are effective in secondary prevention of cardiovascular events in patients with hyperlipidemia. In these situations, the target of therapy is a reduction in LDL cholesterol to <100 mg/dL. HMG-CoA reductase inhibitors have also been shown to be effective in primary prevention of coronary artery disease in individuals without established cardiovascular disease but who have multiple risk factors. Selection of lipid-lowering therapy should be based on the patient's lipid profile, concomitant disease states, and the cost of therapy. The benefits of lipid-lowering are also compelling in women and in the elderly. Important side effects relate to elevated liver enzymes and rhabdomyolysis. LFTs need to be monitored at specified intervals.

May cause dizziness

None reported

No information available to require special precautions

No effects or complications reported

Take with evening meal (highest rate of cholesterol synthesis occurs from midnight to morning). If sleep disturbances occur, take earlier in the day. Do not change dosage without consulting prescriber. Maintain diet and exercise program as identified by prescriber. Have periodic ophthalmic exams while taking lovastatin (check for cataracts). You may experience mild GI disturbances (eg, gas, diarrhea, constipation); inform prescriber if these are severe or if you experience severe muscle pain, weakness, or tenderness. Pregnancy/breast-feeding precautions: Inform prescriber if you are pregnant. Do not get pregnant 1 month during or for 1 month following therapy. Consult prescriber for instruction on appropriate contraceptive measures. This drug may cause severe fetal defects. Do not breast-feed.

Urge patient to adhere to cholesterol-lowering diet

Tablet: 10 mg, 20 mg, 40 mg

"HMG-CoA Reductase Inhibitors for Hypercholesterolemia," N Engl J Med, 1988, 319(18):1222-3.

Huchzermeyer H and Munzenmaier R, "Lovastatin-Induced Acute Cholestatic Hepatitis," Dtsch Med Wochenschr, 1995, 120(8):252-6.

Kogan AD and Orenstein S, "Lovastatin-Induced Acute Rhabdomyolysis," Postgrad Med J, 1990, 66(774):294-6.

"Summary of the Second Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel II)," JAMA, 1993, 269(23):3015-23.

The Lovastatin Study Group II, "Therapeutic Response to Lovastatin (Mevinolin) in Nonfamilial Hypercholesterolemia: A Multicenter Study," JAMA, 1986, 256(20):2829-34.