Dosing and uses of Lipitor (atorvastatin)
Adult dosage forms and strengths
tablet
- 10mg
- 20mg
- 40mg
- 80mg
Hyperlipidemia
Primary hypercholesterolemia and mixed dyslipidemia
- Indicated as an adjunct to diet for treatment of elevated total-C, Apo B, and TG levels and to increase HDL-C in patients with primary hypercholesterolemia (heterozygous familial and nonfamilial) and mixed dyslipidemia (Fredrickson type IIa and IIb)
- 10-20 mg PO qDay initially
- Starting dose in patients requiring larger LDL-C reduction (ie, >45%): 40 mg PO qDay
- Maintenance: 10-80 mg PO qDay
- After initiation and/or upon dose titration, check lipid levels after 2-4 weeks and adjust dose accordingly
Hypertriglyceridemia
- Adjunct to diet for elevated TG levels (Fredrickson type IV)
- 10 mg PO qDay initially
- Maintenance: 10-80 mg PO qDay maintenance
- After initiation and/or upon dose titration, check lipid levels after 2-4 weeks and adjust dose accordingly
Primary dysbetalipoproteinemia
- Dysbetalipoproteinemia (Fredrickson type III) in patient with inadequate response to diet
- Maintenance: 10-80 mg PO qDay
- After initiation and/or upon dose titration, check lipid levels after 2-4 weeks and adjust dose accordingly
Homozygous familial hypercholesterolemia
- Reduction of total-C and LDL-C in HoFH as an adjunct to other lip-lowering treatments (eg, LDL apheresis) or if such treatments are unavailable
- 10-80 mg PO qDay
Cardiovascular Disease Prevention
10-80 mg PO qDay
Indications
- Reduction of risk of stroke and heart attack in type 2 diabetes patients without evidence of heart disease but with other CV risk factors
- Reduction of risk of stroke, heart attack, and revascularization procedures in patients without evidence of coronary heart disease (CHD) but with multiple risk factors other than diabetes (eg, smoking, HTN, low HDL-C, family history of early CHD)
- Patients with CHD, to reduce risks of MI, stroke, revascularization procedures, hospitalization for CHF, and angina
Dosage considerations
Coadministration with other drugs
- Bile acid sequestrant: Administer atorvastatin/ezetimibe ≥2 hr before or ≥4 hr after administering bile acid sequestrant
- Cyclosporine, tipranavir plus ritonavir, telaprevir, gemfibrozil: Avoid coadministration with atorvastatin (increased risk of rhabdomyolysis)
- Lopinavir plus ritonavir: Use lowest dose of atorvastatin necessary
- Clarithromycin, itraconazole, saquinavir plus ritonavir, darunavir plus ritonavir, fosamprenavir: Do not exceed atorvastatin dose of 20 mg/day
- Nelfinavir, boceprevir: Do not exceed atorvastatin dose of 40 mg/day
Overdose management
- Generally considered safe in acute overdose, although not formally studied
- Adverse drug reactions from overdose may include peripheral neuropathy, diarrhea, increased K+, myopathy, rhabdomyolysis, acute renal failure, elevated LFTs, eye lens opacities
- Treatment is supportive
Pediatric dosage forms and strengths
tablet
- 10mg
- 20mg
- 40mg
- 80mg
Heterozygous Familial Hypercholesterolemia
Indicated as an adjunct to diet to reduce total-C, LDL-C, and apo B levels in boys and postmenarchal girls aged 10-17 years with HeFH who have an inadequate response to diet alone (ie, LDL-C remains ≥190 mg/dL or LDL-C remains ≥160 mg/dL and there is positive family history or early CV disease or 2 or more other CVD risk factors present)
<10 years: Safety and efficacy not established
≥10 years: Initially, 10 mg PO qDay; titrate at 4-week intervals; not to exceed 20 mg PO qDay
Homozygous Familial Hypercholesterolemia (Off-label)
<10 years: Safety and efficacy not established
≥10 years: 10-40 mg PO qDay
Lipitor (atorvastatin) adverse (side) effects
>10%
Diarrhea (5-14%)
Nasopharyngitis (4-13%)
Arthralgia (4-12%)
1-10%
Insomnia (1-5%)
Urinary tract infection (4-8%)
Nausea (4-7%)
Dyspepsia (3-6%)
Increased transaminases (2-3%)
Muscle spasms (2-5%)
Musculoskeletal pain (2-5%)
Myalgia (3-8%)
Limb pain (3-8%)
Pharyngolaryngeal pain (1-4%)
Frequency not defined
Angina
Syncope
Dyspnea
Myopathy
Anaphylaxis
Stevens-Johnson syndrome
Myositis
Warnings
Contraindications
Hypersensitivity to atorvastatin
Active liver disease or unexplained transaminase elevation
Pregnancy, lactation
Cautions
Nonserious and reversible cognitive side effects may occur
Increased blood sugar and glycosylated hemoglobin (HbA1c) levels reported with statin intake
Use with caution in the elderly; risk of myopathy
Heavy alcohol use, renal failure, history of liver disease
Fatal and nonfatal hepatic failure reported (rare)
Risk of rhabdomyolysis
Risk of myopathy: Increased by coadministration with fibrates, niacin, cyclosporine, macrolides, telaprevir, boceprevir, combinations of HIV protease inhibitors (eg, saquinavir plus ritonavir, lopinavir plus ritonavir, tipranavir plus ritonavir, darunavir plus ritonavir, fosamprenavir, and fosamprenavir plus ritonavir), or azole antifungals
Withhold or discontinue treatment in any patient developing myopathy, renal failure, or transaminase levels >3x ULn
Temporary therapy discontinuation recommended for patients with acute surgical or medical conditions, elective major surgery, or serious condition suggestive of a myopathy or risk factor predisposing to development of renal failure secondary to rhabdomyolysis
Rare reports of immune-mediated necrotizing myopathy (IMNM), characterized by increased serum creatine kinase that persists despite discontinuation of statin
Use caution in hepatic impairment, recent stroke
CYP3A4 substrate; avoid grapefruit products and caution with other CYP3A4 inhibitors
Secondary causes of hyperlipidemia should be ruled out before initiating therapy
Pregnancy and lactation
Pregnancy category: X
Lactation: Because of the potential for adverse reactions in nursing infants, women taking this drug should not breastfeed; contraindicated in nursing mothers.
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Lipitor (atorvastatin)
Mechanism of action
HMG-CoA reductase inhibitor; inhibits rate-limiting step in cholesterol biosynthesis by competitively inhibiting HMG-CoA reductase
Absorption
Bioavailability: 14% (parent drug)
Onset: 3-5 days
Duration: 48-72 hr
Peak serum time: 1-2 hr
Maximum effect: 2 weeks
Distribution
Protein bound: 98%
Vd: 381 L
Metabolism
Via hepatic P450 enzyme CYP3A4
Metabolites: Ortho- and parahydroxylated derivatives and beta-oxidation product (inactive)
Elimination
Half-life: 14 hr
Dialyzable: No (HD)
Excretion: Mainly via bile; urine (2%)
Pharmacogenomics
SLCO1B1 (OATP1B1) CC genotype significantly increases AUCs of parent drug and metabolites compared with the CT or TT genotypes
This polymorphism is proposed to reduce transport into the liver, the main site of statin metabolism and elimination
SLCO1B1 polymorphism is thought to have a lesser effect on the more hydrophilic statins (eg, rosuvastatin, fluvastatin) compared with those that are more lipophilic (eg, atorvastatin, simvastatin)
Other genetic polymorphisms of elimination (eg, CYP450, P-glycoprotein) for each individual drug must also be considered, to explain variability for statin clearance among patients that exhibit SCLO1B1 polymorphism
SLCO1B1 CC genotype is most common in Caucasians and Asians (15%)
Risk of myopathy is 2.6- to 4.3-fold higher if the C allele is present and 16.9-fold higher in CC homozygotes than in TT homozygotes
Genetic testing laboratories
- Optivia Biotechnology, Inc (https://optiviabio.com)
