Atorvastatin Calcium
Atorvastatin Calcium Prescribing Information
Atorvastatin calcium tablets are indicated:
• To reduce the risk of:
o Myocardial infarction (MI), stroke, revascularization procedures, and angina in adults with
multiple risk factors for coronary heart disease (CHD) but without clinically evident CHD
o MI and stroke in adults with type 2 diabetes mellitus with multiple risk factors for CHD but without clinically evident CHD
o Non-fatal MI, fatal and non-fatal stroke, revascularization procedures, hospitalization for
congestive heart failure, and angina in adults with clinically evident CHD
• As an adjunct to diet to reduce low-density lipoprotein cholesterol (LDL-C) in:
o Adults with primary hyperlipidemia.
o Adults and pediatric patients aged 10 years and older with heterozygous familial hypercholesterolemia (HeFH).
• As an adjunct to other LDL-C-lowering therapies, or alone if such treatments are unavailable, to reduce LDL-C in adults and pediatric patients aged 10 years and older with homozygous familial hypercholesterolemia (HoFH).
• As an adjunct to diet for the treatment of adults with:
o Primary dysbetalipoproteinemia
o Hypertriglyceridemia
• Take orally once daily with or without food (
• Take atorvastatin calcium tablets orally once daily at any time of the day, with or without food.
• Assess LDL-C when clinically appropriate, as early as 4 weeks after initiating atorvastatin calcium tablets, and adjust the dosage if necessary.
• If a dose is missed, advise patients not to take the missed dose and resume with the next scheduled dose.
• Assess LDL-C when clinically appropriate, as early as 4 weeks after initiating atorvastatin calcium tablets, and adjust dosage if necessary (
• Take atorvastatin calcium tablets orally once daily at any time of the day, with or without food.
• Assess LDL-C when clinically appropriate, as early as 4 weeks after initiating atorvastatin calcium tablets, and adjust the dosage if necessary.
• If a dose is missed, advise patients not to take the missed dose and resume with the next scheduled dose.
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The recommended starting dosage of atorvastatin calcium tablets are 10 mg to 20 mg once daily. The dosage range is 10 mg to 80 mg once daily. Patients who require reduction in LDL-C greater than 45% may be started at 40 mg once daily.
o Recommended starting dosage is 10 or 20 mg once daily; dosage range is 10 mg to 80 mg once daily.
o Patients requiring LDL-C reduction >45% may start at 40 mg once daily.
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The recommended starting dosage of atorvastatin calcium tablets are 10 mg once daily. The dosage range is 10 mg to 20 mg once daily.
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The recommended starting dosage of atorvastatin calcium tablets are 10 mg to 20 mg once daily. The dosage range is 10 mg to 80 mg once daily.
• See full prescribing information for atorvastatin calcium tablets dosage modifications due to drug interactions (
Concomitant use of atorvastatin calcium tablets with the following drugs requires dosage modification of atorvastatin calcium tablets
• In patients taking saquinavir plus ritonavir, darunavir plus ritonavir, fosamprenavir, fosamprenavir plus ritonavir, elbasvir plus grazoprevir or letermovir, do not exceed atorvastatin calcium tablets 20 mg once daily.
• In patients taking nelfinavir, do not exceed atorvastatin calcium tablets 40 mg once daily.
• In patients taking clarithromycin or itraconazole, do not exceed atorvastatin calcium tablets 20 mg once daily.
For additional recommendations regarding concomitant use of atorvastatin calcium tablets with other anti-viral medications, azole antifungals or macrolide antibiotics,
Atorvastatin Calcium Tablets, USP:
• 10 mg of atorvastatin: white to off-white, oval, biconvex film coated tablets debossed with '10' on one side and 'A 53' on other side
• 20 mg of atorvastatin: white to off-white, oval, biconvex film coated tablets debossed with '20' on one side and 'A 54' on other side
• 40 mg of atorvastatin: white to off-white, oval, biconvex film coated tablets debossed with '40' on one side and 'A 55' on other side
• 80 mg of atorvastatin: white to off-white, oval, biconvex film coated tablets debossed with '80' on one side and 'A 56' on other side
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Discontinue atorvastatin calcium when pregnancy is recognized. Alternatively, consider the ongoing therapeutic needs of the individual patient. Atorvastatin calcium decreases synthesis of cholesterol and possibly other biologically active substances derived from cholesterol; therefore, atorvastatin calcium may cause fetal harm when administered to pregnant patients based on the mechanism of action
Available data from case series and prospective and retrospective observational cohort studies over decades of use with statins in pregnant women have not identified a drug-associated risk of major congenital malformations. Published data from prospective and retrospective observational cohort studies with atorvastatin calcium use in pregnant women are insufficient to determine if there is a drug-associated risk of miscarriage
The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.
A Medicaid cohort linkage study of 1,152 statin-exposed pregnant women compared to 886,996 controls did not find a significant teratogenic effect from maternal use of statins in the first trimester of pregnancy, after adjusting for potential confounders – including maternal age, diabetes mellitus, hypertension, obesity, and alcohol and tobacco use – using propensity score-based methods. The relative risk of congenital malformations between the group with statin use and the group with no statin use in the first trimester was 1.07 (95% confidence interval 0.85 to 1.37) after controlling for confounders, particularly pre-existing diabetes mellitus. There were also no statistically significant increases in any of the organ-specific malformations assessed after accounting for confounders. In the majority of pregnancies, statin treatment was initiated prior to pregnancy and was discontinued at some point in the first trimester when pregnancy was identified. Study limitations include reliance on physician coding to define the presence of a malformation, lack of control for certain confounders such as body mass index, use of prescription dispensing as verification for the use of a statin, and lack of information on non-live births.
In a study in pregnant rats administered 20, 100, or 225 mg/kg/day from gestation day 7 through to lactation day 20 (weaning), there was decreased survival at birth, postnatal day 4, weaning, and post-weaning in pups of mothers dosed with 225 mg/kg/day, a dose at which maternal toxicity was observed. Pup body weight was decreased through postnatal day 21 at 100 mg/kg/day, and through postnatal day 91 at 225 mg/kg/day. Pup development was delayed (rotorod performance at 100 mg/kg/day and acoustic startle at 225 mg/kg/day; pinnae detachment and eye-opening at 225 mg/kg/day). These doses correspond to 6 times (100 mg/kg) and 22 times (225 mg/kg) the human exposure at the MRHD, based on AUC.
Atorvastatin crosses the rat placenta and reaches a level in fetal liver equivalent to that of maternal plasma.
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There is no information about the presence of atorvastatin in human milk, the effects of the drug on the breastfed infant or the effects of the drug on milk production. However, it has been shown that another drug in this class passes into human milk. Studies in rats have shown that atorvastatin and/or its metabolites are present in the breast milk of lactating rats. When a drug is present in animal milk, it is likely that the drug will be present in human milk
Because of the potential for serious adverse reactions in a breastfed infant, based on the mechanism of action, advise patients that breastfeeding is not recommended during treatment with atorvastatin calcium
Following a single oral administration of 10 mg/kg of radioactive atorvastatin to lactating rats, the concentration of total radioactivity was determined. Atorvastatin and/or its metabolites were measured in the breast milk and pup plasma at a 2:1 ratio (milk:plasma).
• Acute liver failure or decompensated cirrhosis
Increases in serum transaminases have been reported with use of atorvastatin calcium
Patients who consume substantial quantities of alcohol and/or have a history of liver disease may be at increased risk for hepatic injury
Consider liver enzyme testing before atorvastatin calcium initiation and when clinically indicated thereafter. Atorvastatin calcium is contraindicated in patients with acute liver failure or decompensated cirrhosis
• Hypersensitivity to atorvastatin or any excipients in atorvastatin calcium. Hypersensitivity reactions, including anaphylaxis, angioneurotic edema, erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis, have been reported
The following adverse reactions have been identified during post-approval use of atorvastatin calcium. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
There have been rare reports of immune-mediated necrotizing myopathy associated with statin use.
There have been rare reports of cognitive impairment (e.g., memory loss, forgetfulness, amnesia, memory impairment, confusion) associated with the use of all statins. Cognitive impairment was generally nonserious, and reversible upon statin discontinuation, with variable times to symptom onset (1 day to years) and symptom resolution (median of 3 weeks). There have been rare reports of new-onset or exacerbation of myasthenia gravis, including ocular myasthenia, and reports of recurrence when the same or a different statin was administered.
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Concomitant use of atorvastatin calcium tablets with the following drugs requires dosage modification of atorvastatin calcium tablets
• In patients taking saquinavir plus ritonavir, darunavir plus ritonavir, fosamprenavir, fosamprenavir plus ritonavir, elbasvir plus grazoprevir or letermovir, do not exceed atorvastatin calcium tablets 20 mg once daily.
• In patients taking nelfinavir, do not exceed atorvastatin calcium tablets 40 mg once daily.
• In patients taking clarithromycin or itraconazole, do not exceed atorvastatin calcium tablets 20 mg once daily.
For additional recommendations regarding concomitant use of atorvastatin calcium tablets with other anti-viral medications, azole antifungals or macrolide antibiotics,
Atorvastatin calcium may cause myopathy (muscle pain, tenderness, or weakness associated with elevated creatine kinase [CK]) and rhabdomyolysis. Acute kidney injury secondary to myoglobinuria and rare fatalities have occurred as a result of rhabdomyolysis in patients treated with statins, including atorvastatin calcium.
Risk factors for myopathy include age 65 years or greater, uncontrolled hypothyroidism, renal impairment, concomitant use with certain other drugs (including other lipid-lowering therapies), and higher atorvastatin calcium dosage
Atorvastatin calcium exposure may be increased by drug interactions due to inhibition of cytochrome P450 enzyme 3A4 (CYP3A4) and/or transporters (e.g., breast cancer resistant protein [BCRP], organic anion-transporting polypeptide [OATP1B1/OATP1B3] and P-glycoprotein [P-gp]), resulting in an increased risk of myopathy and rhabdomyolysis. Concomitant use of cyclosporine, gemfibrozil, tipranavir plus ritonavir, or glecaprevir plus pibrentasvir with atorvastatin calcium is not recommended. Atorvastatin calcium dosage modifications are recommended for patients taking certain anti-viral, azole antifungals, or macrolide antibiotic medications
Concomitant intake of large quantities, more than 1.2 liters daily, of grapefruit juice is not recommended in patients taking atorvastatin calcium
Discontinue atorvastatin calcium if markedly elevated CK levels occur or if myopathy is either diagnosed or suspected. Muscle symptoms and CK elevations may resolve if atorvastatin calcium is discontinued. Temporarily discontinue atorvastatin calcium in patients experiencing an acute or serious condition at high risk of developing renal failure secondary to rhabdomyolysis (e.g., sepsis; shock; severe hypovolemia; major surgery; trauma; severe metabolic, endocrine, or electrolyte disorders; or uncontrolled epilepsy).
Inform patients of the risk of myopathy and rhabdomyolysis when starting or increasing the atorvastatin calcium dosage. Instruct patients to promptly report any unexplained muscle pain, tenderness or weakness, particularly if accompanied by malaise or fever.
Atorvastatin calcium is a substrate of CYP3A4 and transporters (e.g., OATP1B1/1B3, P-gp, or BCRP). Atorvastatin calcium plasma levels can be significantly increased with concomitant administration of inhibitors of CYP3A4 and transporters. Table 2 includes a list of drugs that may increase exposure to atorvastatin calcium and may increase the risk of myopathy and rhabdomyolysis when used concomitantly and instructions for preventing or managing them
Cyclosporine or Gemfibrozil | |
Clinical Impact: | Atorvastatin plasma levels were significantly increased with concomitant administration of atorvastatin calcium and cyclosporine, an inhibitor of CYP3A4 and OATP1B1 [see Clinical Pharmacology (12.3)]. Gemfibrozil may cause myopathy when given alone. The risk of myopathy and rhabdomyolysis is increased with concomitant use of cyclosporine or gemfibrozil with atorvastatin calcium. |
Intervention: | Concomitant use of cyclosporine or gemfibrozil with atorvastatin calcium is not recommended. |
Anti-Viral Medications | |
Clinical Impact: | Atorvastatin plasma levels were significantly increased with concomitant administration of atorvastatin calcium with many anti-viral medications, which are inhibitors of CYP3A4 and/or transporters (e.g., BCRP, OATP1B1/1B3, P-gp, MRP2, and/or OAT2) [see Clinical Pharmacology (12.3)]. Cases of myopathy and rhabdomyolysis have been reported with concomitant use of ledipasvir plus sofosbuvir with atorvastatin calcium. |
Intervention: |
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Examples: | Tipranavir plus ritonavir, glecaprevir plus pibrentasvir, lopinavir plus ritonavir, simeprevir, saquinavir plus ritonavir, darunavir plus ritonavir, fosamprenavir, fosamprenavir plus ritonavir, elbasvir plus grazoprevir, letermovir, nelfinavir, and ledipasvir plus sofosbuvir. |
Select Azole Antifungals or Macrolide Antibiotics | |
Clinical Impact: | Atorvastatin plasma levels were significantly increased with concomitant administration of atorvastatin calcium with select azole antifungals or macrolide antibiotics, due to inhibition of CYP3A4 and/or transporters [see Clinical Pharmacology (12.3)]. |
Intervention: | In patients taking clarithromycin or itraconazole, do not exceed atorvastatin calcium 20 mg [see Dosage and Administration (2.5)]. Consider the risk/benefit of concomitant use of other azole antifungals or macrolide antibiotics with atorvastatin calcium. Monitor all patients for signs and symptoms of myopathy particularly during initiation of therapy and during upward dose titration of either drug. |
Examples: | Erythromycin, clarithromycin, itraconazole, ketoconazole, posaconazole, and voriconazole. |
Niacin | |
Clinical Impact: | Cases of myopathy and rhabdomyolysis have been observed with concomitant use of lipid modifying dosages of niacin (≥1 gram/day niacin) with atorvastatin calcium. |
Intervention: | Consider if the benefit of using lipid modifying dosages of niacin concomitantly with atorvastatin calcium outweighs the increased risk of myopathy and rhabdomyolysis. If concomitant use is decided, monitor patients for signs and symptoms of myopathy particularly during initiation of therapy and during upward dose titration of either drug. |
Fibrates (other than Gemfibrozil) | |
Clinical Impact: | Fibrates may cause myopathy when given alone. The risk of myopathy and rhabdomyolysis is increased with concomitant use of fibrates with atorvastatin calcium. |
Intervention: | Consider if the benefit of using fibrates concomitantly with atorvastatin calcium outweighs the increased risk of myopathy and rhabdomyolysis. If concomitant use is decided, monitor patients for signs and symptoms of myopathy particularly during initiation of therapy and during upward dose titration of either drug. |
Colchicine | |
Clinical Impact: | Cases of myopathy and rhabdomyolysis have been reported with concomitant use of colchicine with atorvastatin calcium. |
Intervention: | Consider the risk/benefit of concomitant use of colchicine with atorvastatin calcium. If concomitant use is decided, monitor patients for signs and symptoms of myopathy particularly during initiation of therapy and during upward dose titration of either drug. |
Grapefruit Juice | |
Clinical Impact: | Grapefruit juice consumption, especially excessive consumption, more than 1.2 liters/daily, can raise the plasma levels of atorvastatin and may increase the risk of myopathy and rhabdomyolysis. |
Intervention: | Avoid intake of large quantities of grapefruit juice, more than 1.2 liters daily, when taking atorvastatin calcium. |
Of the total number of atorvastatin calcium-treated patients in clinical trials, 15,813 (40%) were ≥65 years old and 2,800 (7%) were ≥75 years old. No overall differences in safety or effectiveness were observed between these patients and younger patients.
Advanced age (≥65 years) is a risk factor for atorvastatin calcium-associated myopathy and rhabdomyolysis. Dose selection for an elderly patient should be cautious, recognizing the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy and the higher risk of myopathy. Monitor geriatric patients receiving atorvastatin calcium for the increased risk of myopathy
Renal impairment is a risk factor for myopathy and rhabdomyolysis. Monitor all patients with renal impairment for development of myopathy. Renal impairment does not affect the plasma concentrations of atorvastatin calcium, therefore there is no dosage adjustment in patients with renal impairment
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There have been rare reports of immune-mediated necrotizing myopathy (IMNM), an autoimmune myopathy, associated with statin use, including reports of recurrence when the same or a different statin was administered. IMNM is characterized by proximal muscle weakness and elevated serum creatine kinase that persists despite discontinuation of statin treatment; positive anti-HMG CoA reductase antibody; muscle biopsy showing necrotizing myopathy; and improvement with immunosuppressive agents. Additional neuromuscular and serologic testing may be necessary. Treatment with immunosuppressive agents may be required. Discontinue atorvastatin calcium if IMNM is suspected.
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Increases in serum transaminases have been reported with use of atorvastatin calcium
Patients who consume substantial quantities of alcohol and/or have a history of liver disease may be at increased risk for hepatic injury
Consider liver enzyme testing before atorvastatin calcium initiation and when clinically indicated thereafter. Atorvastatin calcium is contraindicated in patients with acute liver failure or decompensated cirrhosis