No

Antilipemic Agent (HMG-CoA Reductase Inhibitor)

Adjunct to diet for the reduction of elevated total and LDL cholesterol, apolipoprotein B, and triglyceride levels in patients with hypercholesterolemia (Type IIA, IIB, and IIC); adjunctive therapy to diet for treatment of elevated serum triglyceride levels (Type IV); treatment of primary dysbetalipoproteinemia (Type III) in patients who do not respond adequately to diet; to increase HDL cholesterol in patients with primary hypercholesterolemia and mixed dyslipidemia. Also may be used in hypercholesterolemic patients without clinically evident heart disease to reduce the risk of myocardial infarction, to reduce the risk for revascularization, and reduce the risk of death due to cardiovascular causes

X

Hypersensitivity to atorvastatin 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 atorvastatin. Discontinue in any patient experiencing an acute or serious condition predisposing to renal failure secondary to rhabdomyolysis.

>10%: Central nervous system: Headache (2.5% to 16.7%)

2% to 10%:

Central nervous system: Weakness (0% to 3.8%), insomnia, dizziness

Cardiovascular: Chest pain, peripheral edema

Dermatologic: Rash (1.1% to 3.9%)

Gastrointestinal: Abdominal pain (0% to 3.8%), constipation (0% to 2.5%), diarrhea (0% to 3.85), dyspepsia (1.3% to 2.85), flatulence (1.1% to 2.8%), nausea

Genitourinary: Urinary tract infection

Neuromuscular & skeletal: Arthralgia (0% to 5.1%), myalgia (0% to 5.6%), back pain (0% to 3.8%), arthritis

Miscellaneous: Infection (2% to 10%), flu-like syndrome (0% to 3.2%), allergic reaction (0% to 2.8%)

Respiratory: Sinusitis (0% to 6.4%), pharyngitis (0% to 2.5%), bronchitis, rhinitis

<2% (Limited to important or life-threatening symptoms): Pneumonia, dyspnea, epistaxis, face edema, fever, photosensitivity, malaise, edema, gastroenteritis, elevated transaminases, colitis, vomiting, gastritis, xerostomia, rectal hemorrhage, esophagitis, eructation, glossitis, stomatitis, anorexia, increased appetite, biliary pain, chelitis, duodenal ulcer, dysphagia, enteritis, melena, gingival hemorrhage, tenesmus, hepatitis, pancreatitis, cholestatic jaundice, paresthesia, somnolence, abnormal dreams, decreased libido, emotional lability, incoordination, peripheral neuropathy, torticollis, facial paralysis, hyperkinesia, depression, hypesthesia, hypertonia, leg cramps, bursitis, myasthenia, myositis, tendinous contracture, pruritus, alopecia, dry skin, urticaria, acne, eczema, seborrhea, skin ulcer, cystitis, hematuria, impotence, dysuria, nocturia, epididymitis, fibrocystic breast disease, vaginal hemorrhage, nephritis, abnormal urination, amblyopia, tinnitus, deafness, glaucoma, taste loss, taste perversion, palpitation, vasodilation, syncope, migraine, postural hypotension, phlebitis, arrhythmia, angina, hypertension, hyperglycemia, gout, weight gain, hypoglycemia, ecchymosis, anemia, lymphadenopathy, thrombocytopenia, petechiae, pharyngitis, rhinitis, myopathy

Postmarketing reports have included anaphylaxis, angioneurotic edema, bullous rashes, erythema multiforme, toxic epidermal necrolysis, Stevens-Johnson syndrome, and rhabdomyolysis.

Additional class-related events or case reports (not necessarily reported with atorvastatin 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, 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

Few symptoms of overdose anticipated

Treatment is supportive

CYP3A3/4 enzyme 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.

Niacin may increase the risk of myopathy and rhabdomyolysis.

Inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, the rate limiting enzyme in cholesterol synthesis (reduces the production of mevalonic acid from HMG-CoA); this then results in a compensatory increase in the expression of LDL receptors on hepatocyte membranes and a stimulation of LDL catabolism

Onset of effect: Maximal reduction in plasma cholesterol and triglycerides in 2 weeks; initial changes in 3-5 days

Absorption: Rapid

Protein binding: 98%

Metabolism: Undergoes enterohepatic recycling; not a prodrug; metabolized to active ortho- and parahydroxylated derivates and an inactive beta-oxidation product

Half-life: 14 hours (parent)

Time to peak serum concentration: 1-2 hours (maximal reduction in plasma cholesterol and triglycerides in 2 weeks)

Elimination: 2% excreted as unchanged drug in the urine

Adults: Oral: Initial: 10 mg once daily, titrate up to 80 mg/day if needed

Dosing adjustment in hepatic impairment: Do not use in active liver disease.

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.

Lipid levels after 2-4 weeks; LFTs, CPK

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. Among the HMG-CoA reductase inhibitors, atorvastatin produces the greatest reduction in LDL cholesterol at therapeutic doses. Important side effects relate to elevated liver enzymes and rhabdomyolysis. LFTs need to be monitored at specified intervals.

Rare reports of euphoria

None reported

No information available to require special precautions

No effects or complications reported

May take with meals at any time of day. Maintain adequate hydration (2-3 L/day of fluids unless instructed to restrict fluid intake). You will need laboratory evaluation during therapy. May cause headache (mild analgesic may help); diarrhea (yogurt or buttermilk may help); euphoria, giddiness, confusion (use caution when driving or engaging in tasks that require alertness until response to medication is known). Report unresolved diarrhea, excessive or acute muscle cramping or weakness, changes in mood or memory, yellowing of skin or eyes, easy bruising or bleeding, and unusual fatigue. Pregnancy/breast-feeding precautions: Inform prescriber if you are pregnant. Do not get pregnant or engage in sexual activity during therapy and for 1 month following therapy unless using barrier contraceptive measures. This drug can cause severe fetal defects. Do not donate blood for same period of time. Do not breast-feed.

Tablet: 10 mg, 20 mg, 40 mg

Gibson DM, Bron NJ, Richens A, et al, "Effect of Age and Gender on Pharmacokinetics of Atorvastatin in Humans," J Clin Pharmacol, 1996, 36(3):242-6.

"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.