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).

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.

Drug-Food:

Grapefruit juice↑ levels and risk of rhabdomyolysis.

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].

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.

US Brand Names ⬆ ⬇

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.

Classifications ⬆ ⬇

Therapeutic Classification: lipid-lowering agents

Pharmacologic Classification: hmg coa reductase inhibitors

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.

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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Indications ⬇