atorvastatin

REMS

Adjunctive management of primary hypercholesterolemia and mixed dyslipidemia.
Primary prevention of coronary heart disease (myocardial infarction, stroke, angina, and coronary revascularization) in asymptomatic patients with increased total and low-density lipoprotein cholesterol (LDL-C) and decreased high-density lipoprotein cholesterol (HDL-C).

Action ⬆ ⬇

Inhibits 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, an enzyme that is responsible for catalyzing an early step in the synthesis of cholesterol.

Therapeutic effects:

Lowering of total and LDL-C and triglycerides. Slightly increases HDL-C.
Reduces the risk of MI and stroke sequelae.
Slows the progression of coronary atherosclerosis with resultant decrease in coronary heart disease-related events.

Pharmacokinetics ⬆ ⬇

Absorption: 14% absorbed following oral administration.

Distribution: Extensively distributed to tissues.

Protein Binding: ≥98%.

Metabolism/Excretion: Extensively metabolized by the liver, most during first pass; excreted in bile and feces. <2% excreted unchanged by the kidneys. 2 metabolites have lipid-lowering activity.

Half-Life: 14 hr (lipid-lowering activity due to atorvastatin and its metabolites—20–30 hr).

Time/Action Profile ⬆ ⬇

(cholesterol-lowering effect)

ROUTE	ONSET	PEAK	DURATION
PO	unknown	unknown	20–30 hr‡

‡Following discontinuation.

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Hypersensitivity;
Active liver disease or unexplained persistent elevations in AST and ALT;
Lactation: Lactation.

Use Cautiously in:

History of liver disease;
Alcoholism;
Uncontrolled hypothyroidism or renal impairment (↑ risk of myopathy);
Rep: Women of reproductive potential;
OB: Use statin therapy during pregnancy only if potential maternal benefit justifies potential fetal risk (if needed, consider using a more water-soluble agent [pravastatin or rosuvastatin] that is less likely to cross the placenta);
Pedi: Children 10 yr (safety and effectiveness not established);
Geri: risk of myopathy in older adults.

Adv. Reactions/Side Effects ⬆ ⬇

CV: chest pain, peripheral edema

Derm: rash, pruritus

EENT: rhinitis

Endo: hyperglycemia

GI: abdominal cramps, constipation, diarrhea, flatus, heartburn, altered taste, drug-induced hepatitis, dyspepsia, ↑liver enzymes, nausea, pancreatitis

GU: erectile dysfunction

MS: arthralgia, arthritis, immune-mediated necrotizing myopathy (IMNM), myopathy, myositis, RHABDOMYOLYSIS

Neuro: amnesia, confusion, dizziness, headache, insomnia, memory loss, weakness

Resp: bronchitis

Misc: HYPERSENSITIVITY REACTIONS (INCLUDING ANAPHYLAXIS AND ANGIOEDEMA)

Interactions ⬆ ⬇

Drug-drug:

Metabolized by the hepatic CYP3A4 enzyme system.
Cholesterol-lowering effect may be additive with bile acid sequestrants (cholestyramine, colestipol).
Bioavailability may be ↓ by bile acid sequestrants.
↑risk of myopathy with concurrent use of clarithromycin, colchicine, cyclosporine, darunavir/ritonavir, elbasvir/grazoprevir, erythromycin, fosamprenavir, fosamprenavir/ritonavir, gemfibrozil, glecaprevir/pibrentasvir, itraconazole, ledipasvir/sofosbuvir, letermovir, lopinavir/ritonavir, nelfinavir, niacin (>1 g/day), or tipranavir/ritonavir; concurrent use with cyclosporine, gemfibrozil, glecaprevir/pibrentasvir, or tipranavir/ritonavir should be avoided; use lowest dose with lopinavir/ritonavir; use ↓ doses with clarithromycin, darunavir/ritonavir, elbasvir/grazoprevir, fosamprenavir, fosamprenavir/ritonavir, itraconazole, letermovir, or nelfinavir.
May slightly ↑ serum digoxin levels.
May ↑ levels of oral contraceptives.
May ↑ effects of warfarin.

Grapefruit juice↑ levels and risk of rhabdomyolysis.

Route/Dosage ⬆ ⬇

PO (Adults ): 10–20 mg once daily initially; (may start with 40 mg/day if LDL-C needs to be ↓ by >45%); may be ↑ every 2–4 wk up to 80 mg/day; Concurrent use of nelfinavir: Dose should not exceed 40 mg/day; Concurrent use of clarithromycin, itraconazole, letermovir, darunavir/ritonavir, fosamprenavir, fosamprenavir/ritonavir, or elbasvir/grazoprevir: Dose should not exceed 20 mg/day.
PO (Children 10–17 yr): 10 mg/day initially, may be ↑ every 4 wk up to 20 mg/day; Concurrent use of nelfinavir: Dose should not exceed 40 mg/day; Concurrent use of clarithromycin, itraconazole, darunavir/ritonavir, fosamprenavir, fosamprenavir/ritonavir therapy, or elbasvir/grazoprevir: Dose should not exceed 20 mg/day.

Availability ⬆ ⬇

(Generic available)

Tablets: 10 mg; 20 mg; 40 mg; 80 mg
Oral suspensionorange flavor: 20 mg/5 mL
In combination with: amlodipine (Caduet); see Appendix [not included in this PDA edition].

Assessment ⬆ ⬇

Obtain a diet history, especially with regard to fat consumption.

Lab Test Considerations:

Evaluate serum cholesterol and triglyceride levels before initiating, after 2–4 wk of therapy, and periodically thereafter.
- Monitor liver function tests prior to initiation of therapy and as clinically indicated. If symptoms of serious liver injury, hyperbilirubinemia, or jaundice occur, discontinue atorvastatin and do not restart. May also cause ↑ alkaline phosphatase and bilirubin levels.
- If patient develops muscle tenderness during therapy, monitor CK levels. If CK levels are >10 times the upper limit of normal or myopathy occurs, discontinue therapy. Monitor for signs and symptoms of IMNM (proximal muscle weakness and ↑ CK), persisting despite discontinuation of statin therapy. Perform muscle biopsy to diagnose; shows necrotizing myopathy without significant inflammation. IMNM can recur with use of same or different statin. Treat with immunosuppressive agents.

Implementation ⬆ ⬇

Do not confuse Lipitor with Zyrtec. Do not confuse atorvastatin with atomoxetine.
PO: May be administered without regard to food.
- Use a calibrated oral syringe or other oral dosing device scored using metric units of measurements to ensure accurate dose. Administer once daily at any time of day, only on an empty stomach (1 hr before or 2 hr after a meal).
- Avoid grapefruit and grapefruit juice during therapy; may increase risk of toxicity.

Patient/Family Teaching ⬆ ⬇

Instruct patient to take medication as directed. If a dose is missed, do not take the missed dose and take next scheduled dose. Do not double up on missed doses. Advise patient to avoid drinking more than one quart of grapefruit juice per day during therapy. Medication helps control but does not cure elevated serum cholesterol levels.
Advise patient that this medication should be used in conjunction with diet restrictions (fat, cholesterol, carbohydrates, alcohol), exercise, and cessation of smoking.
Instruct patient to notify health care professional if unexplained muscle pain, tenderness, or weakness, especially if accompanied by fever or malaise, or signs and symptoms of liver injury (fatigue, anorexia, right upper abdominal discomfort, dark urine, jaundice) occur.
Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care professional before taking any new medications.
Advise patient to notify health care professional of medication regimen prior to treatment or surgery.
Rep: Instruct females of reproductive potential to use effective contraception during therapy, to notify health care professional promptly if pregnancy is planned or suspected, and to avoid breastfeeding during therapy. Use statin therapy during pregnancy only if potential maternal benefit justifies potential fetal risk (if needed, consider using a more water-soluble agent [pravastatin or rosuvastatin] that is less likely to cross the placenta).
Emphasize the importance of follow-up exams to determine effectiveness and to monitor for side effects.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇