ATORVASTATIN CALCIUM
These highlights do not include all the information needed to use ATORVASTATIN CALCIUM TABLETS safely and effectively. See full prescribing information for ATORVASTATIN CALCIUM TABLETS. ATORVASTATIN CALCIUM tablets, for oral use Initial U.S. Approval: 1996
5b94b6f4-6f64-4551-abcb-8e845fb13813
HUMAN PRESCRIPTION DRUG LABEL
Aug 20, 2025
Quallent Pharmaceuticals Health LLC
DUNS: 815564528
Products 4
Detailed information about drug products covered under this FDA approval, including NDC codes, dosage forms, ingredients, and administration routes.
ATORVASTATIN CALCIUM
Product Details
FDA regulatory identification and product classification information
FDA Identifiers
Product Classification
Product Specifications
INGREDIENTS (13)
ATORVASTATIN CALCIUM
Product Details
FDA regulatory identification and product classification information
FDA Identifiers
Product Classification
Product Specifications
INGREDIENTS (13)
ATORVASTATIN CALCIUM
Product Details
FDA regulatory identification and product classification information
FDA Identifiers
Product Classification
Product Specifications
INGREDIENTS (13)
ATORVASTATIN CALCIUM
Product Details
FDA regulatory identification and product classification information
FDA Identifiers
Product Classification
Product Specifications
INGREDIENTS (13)
Drug Labeling Information
PACKAGE LABEL.PRINCIPAL DISPLAY PANEL
PACKAGE LABEL.PRINCIPAL DISPLAY PANEL
Atorvastatin calcium tablets 10 mg-1000s container label
Atorvastatin calcium tablets 20 mg-1000s container label
Atorvastatin calcium tablets 40 mg-1000s container label
Atorvastatin calcium tablets 80 mg-1000s container label
INDICATIONS & USAGE SECTION
1 INDICATIONS AND USAGE
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
Atorvastatin calcium tablets are an HMG-CoA reductase inhibitor (statin)
indicated ( 1):
• 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 (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 to reduce LDL-C in adults
and pediatric patients aged 10 years and older with homozygous familial
hypercholesterolemia.
• As an adjunct to diet for the treatment of adults with:
o Primary dysbetalipoproteinemia.
o Hypertriglyceridemia.
CONTRAINDICATIONS SECTION
4 CONTRAINDICATIONS
• Acute liver failure or decompensated cirrhosis [see Warnings and Precautions ( 5.3)]
• 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 [see Adverse Reactions ( 6.2)].
• Acute liver failure or decompensated cirrhosis ( 4).
• Hypersensitivity to atorvastatin or any excipient in atorvastatin calcium (
4).
WARNINGS AND PRECAUTIONS SECTION
5 WARNINGS AND PRECAUTIONS
5.1 Myopathy and Rhabdomyolysis
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
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 [see Drug Interactions ( 7.1) and Use in Specific Populations ( 8.5, 8.6)].
Steps to Prevent or Reduce the Risk of Myopathy and Rhabdomyolysis
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 [see Dosage and Administration ( 2.5)] .
Cases of myopathy/rhabdomyolysis have been reported with atorvastatin co-
administered with lipid modifying doses (>1 gram/day) of niacin, fibrates,
colchicine, and ledipasvir plus sofosbuvir [see Adverse Reactions ( 6.1)] .
Consider if the benefit of use of these products outweighs the increased risk
of myopathy and rhabdomyolysis [see Drug Interactions ( 7.1)].
Concomitant intake of large quantities, more than 1.2 liters daily, of
grapefruit juice is not recommended in patients taking atorvastatin calcium
[see Drug Interactions ( 7.1)].
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.
5.2 Immune-Mediated Necrotizing Myopathy
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.
5.3 Hepatic Dysfunction
Increases in serum transaminases have been reported with use of atorvastatin
calcium [see Adverse Reactions ( 6.1)] . In most cases, these changes appeared
soon after initiation, were transient, were not accompanied by symptoms, and
resolved or improved on continued therapy or after a brief interruption in
therapy. Persistent increases to more than three times the ULN in serum
transaminases have occurred in approximately 0.7% of patients receiving
atorvastatin calcium in clinical trials. There have been rare postmarketing
reports of fatal and non-fatal hepatic failure in patients taking statins,
including 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 [see Use in Specific Populations ( 8.7)].
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 [see Contraindications ( 4)] . If serious hepatic injury with clinical symptoms
and/or hyperbilirubinemia or jaundice occurs, promptly discontinue
atorvastatin calcium.
5.4 Increases in HbA1c and Fasting Serum Glucose Levels
Increases in HbA1c and fasting serum glucose levels have been reported with statins, including atorvastatin calcium. Optimize lifestyle measures, including regular exercise, maintaining a healthy body weight, and making healthy food choices.
5.5 Increased Risk of Hemorrhagic Stroke in Patients on atorvastatin
calcium 80 mg with Recent Hemorrhagic Stroke
In a post-hoc analysis of the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial where 2,365 adult patients, without CHD who had a stroke or TIA within the preceding 6 months, were treated with atorvastatin calcium 80 mg, a higher incidence of hemorrhagic stroke was seen in the atorvastatin calcium 80 mg group compared to placebo (55, 2.3% atorvastatin calcium vs. 33, 1.4% placebo; HR: 1.68, 95% CI: 1.09, 2.59; p=0.0168). The incidence of fatal hemorrhagic stroke was similar across treatment groups (17 vs. 18 for the atorvastatin and placebo groups, respectively). The incidence of non-fatal hemorrhagic stroke was significantly higher in the atorvastatin calcium group (38, 1.6%) as compared to the placebo group (16, 0.7%). Some baseline characteristics, including hemorrhagic and lacunar stroke on study entry, were associated with a higher incidence of hemorrhagic stroke in the atorvastatin calcium group [see Adverse Reactions ( 6.1)] . Consider the risk/benefit of use of atorvastatin calcium 80 mg in patients with recent hemorrhagic stroke.
• Myopathy and Rhabdomyolysis:Risk factors include age 65 years or greater,
uncontrolled hypothyroidism, renal impairment, concomitant use with certain
other drugs, and higher atorvastatin calcium dosage. Discontinue atorvastatin
calcium if markedly elevated CK levels occur or myopathy is diagnosed or
suspected. Temporarily discontinue atorvastatin calcium in patients
experiencing an acute or serious condition at high risk of developing renal
failure secondary to rhabdomyolysis. Inform patients of the risk of myopathy
and rhabdomyolysis when starting or increasing atorvastatin calcium dosage.
Instruct patients to promptly report unexplained muscle pain, tenderness, or
weakness, particularly if accompanied by malaise or fever ( 2.5, 5.1, 7.1,
8.5, 8.6).
• Immune-Mediated Necrotizing Myopathy (IMNM):Rare reports of IMNM, an
autoimmune myopathy, have been reported with statin use. Discontinue
atorvastatin calcium if IMNM is suspected ( 5.2).
• Hepatic Dysfunction:Increases in serum transaminases have occurred, some
persistent. Rare reports of fatal and non-fatal hepatic failure have occurred.
Consider testing liver enzymes before initiating therapy and as clinically
indicated thereafter. If serious hepatic injury with clinical symptoms and/or
hyperbilirubinemia or jaundice occurs, promptly discontinue atorvastatin
calcium ( 5.3).
ADVERSE REACTIONS SECTION
6 ADVERSE REACTIONS
The following important adverse reactions are described below and elsewhere in
the labeling:
• Myopathy and Rhabdomyolysis [see Warnings and Precautions ( 5.1)]
• Immune-Mediated Necrotizing Myopathy [see Warnings and Precautions ( 5.2)]
• Hepatic Dysfunction [see Warnings and Precautions ( 5.3)]
• Increases in HbA1c and Fasting Serum Glucose Levels [see Warnings and Precautions ( 5.4)]
6.1 Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, the adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
In the atorvastatin calcium placebo-controlled clinical trial database of 16,066 patients (8755 atorvastatin calcium vs. 7,311 placebo; age range 10 to 93 years, 39% female, 91% White, 3% Black or African American, 2% Asian, 4% other) with a median treatment duration of 53 weeks, the most common adverse reactions in patients treated with atorvastatin calcium that led to treatment discontinuation and occurred at a rate greater than placebo were: myalgia (0.7%), diarrhea (0.5%), nausea (0.4%), alanine aminotransferase increase (0.4%), and hepatic enzyme increase (0.4%).
Table 1 summarizes adverse reactions reported in ≥ 2% and at a rate greater than placebo in patients treated with atorvastatin calcium (n=8,755), from seventeen placebo-controlled trials.
Table 1: Adverse Reactions Occurring in**≥ 2% in Patients Atorvastatin Calcium -Treated with any Dose and Greater than Placebo**
|
Adverse Reaction |
% Placebo N=7,311 |
% 10 mg N=3,908 |
% 20 mg N=188 |
% 40 mg N=604 |
% 80 mg N=4,055 |
% Any dose N=8,755 |
|
Nasopharyngitis |
8.2 |
12.9 |
5.3 |
7.0 |
4.2 |
8.3 |
|
Arthralgia |
6.5 |
8.9 |
11.7 |
10.6 |
4.3 |
6.9 |
|
Diarrhea |
6.3 |
7.3 |
6.4 |
14.1 |
5.2 |
6.8 |
|
Pain in extremity |
5.9 |
8.5 |
3.7 |
9.3 |
3.1 |
6.0 |
|
Urinary tract infection |
5.6 |
6.9 |
6.4 |
8.0 |
4.1 |
5.7 |
|
Dyspepsia |
4.3 |
5.9 |
3.2 |
6.0 |
3.3 |
4.7 |
|
Nausea |
3.5 |
3.7 |
3.7 |
7.1 |
3.8 |
4.0 |
|
Musculoskeletal pain |
3.6 |
5.2 |
3.2 |
5.1 |
2.3 |
3.8 |
|
Muscle spasms |
3.0 |
4.6 |
4.8 |
5.1 |
2.4 |
3.6 |
|
Myalgia |
3.1 |
3.6 |
5.9 |
8.4 |
2.7 |
3.5 |
|
Insomnia |
2.9 |
2.8 |
1.1 |
5.3 |
2.8 |
3.0 |
|
Pharyngolaryngeal pain |
2.1 |
3.9 |
1.6 |
2.8 |
0.7 |
2.3 |
Other adverse reactions reported in placebo-controlled trials include:
Body as a Whole:malaise, pyrexia
Digestive System:abdominal discomfort, eructation, flatulence, hepatitis, cholestasis
Musculoskeletal System:musculoskeletal pain, muscle fatigue, neck pain, joint swelling
Metabolic and Nutritional System:transaminases increase, liver function test abnormal, blood alkaline phosphatase increase, creatine phosphokinase increase, hyperglycemia
Nervous System:nightmare
Respiratory System:epistaxis
Skin and Appendages:urticaria
Special Senses:vision blurred, tinnitus
Urogenital System:white blood cells urine positive
Elevations in Liver Enzyme Tests
Persistent elevations in serum transaminases, defined as more than 3 times the ULN and occurring on 2 or more occasions, occurred in 0.7% of patients who received atorvastatin calcium in clinical trials. The incidence of these abnormalities was 0.2%, 0.2%, 0.6%, and 2.3% for 10, 20, 40, and 80 mg, respectively.
One patient in clinical trials developed jaundice. Increases in liver enzyme tests in other patients were not associated with jaundice or other clinical signs or symptoms. Upon dose reduction, drug interruption, or discontinuation, transaminase levels returned to or near pretreatment levels without sequelae. Eighteen of 30 patients with persistent liver enzyme elevations continued treatment with a reduced dose of atorvastatin calcium.
Treating to New Targets Study (TNT)
In TNT, [see Clinical Studies (14.1)]10,001 patients (age range 29 to 78 years, 19% female; 94% White, 3% Black or African American, 1% Asian, 2% other) with clinically evident CHD were treated with atorvastatin calcium 10 mg daily (n=5006) or atorvastatin calcium 80 mg daily (n=4995). In the high- dose atorvastatin calcium group, there were more patients with serious adverse reactions (1.8%) and discontinuations due to adverse reactions (9.9%) as compared to the low-dose group (1.4%; 8.1%, respectively) during a median follow-up of 4.9 years. Persistent transaminase elevations (≥3 x ULN twice within 4 to 10 days) occurred in 1.3% of individuals with atorvastatin calcium 80 mg and in 0.2% of individuals with atorvastatin calcium 10 mg. Elevations of CK (≥ 10 x ULN) were higher in the high-dose atorvastatin calcium group (0.3%) compared to the low-dose atorvastatin calcium group (0.1%).
Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL)
In SPARCL, 4,731 patients (age range 21 to 92 years, 40% female; 93% White, 3%
Black or African American, 1% Asian, 3% other) without clinically evident CHD
but with a stroke or transient ischemic attack (TIA) within the previous 6
months were treated with atorvastatin calcium 80 mg (n=2365) or placebo
(n=2366) for a median follow-up of 4.9 years. There was a higher incidence of
persistent hepatic transaminase elevations (≥ 3 x ULN twice within 4 to 10
days) in the atorvastatin calcium group (0.9%) compared to placebo (0.1%).
Elevations of CK (>10 x ULN) were rare, but were higher in the atorvastatin
calcium group (0.1%) compared to placebo (0.0%). Diabetes was reported as an
adverse reaction in 6.1% of subjects in the atorvastatin calcium group and
3.8% of subjects in the placebo group.
In a post-hoc analysis, atorvastatin calcium 80 mg reduced the incidence of ischemic stroke (9.2% vs. 11.6%) and increased the incidence of hemorrhagic stroke (2.3% vs. 1.4%) compared to placebo. The incidence of fatal hemorrhagic stroke was similar between groups (17 atorvastatin calcium vs. 18 placebo). The incidence of non-fatal hemorrhagic strokes was significantly greater in the atorvastatin calcium group (38 non-fatal hemorrhagic strokes) as compared to the placebo group (16 non-fatal hemorrhagic strokes). Patients who entered the trial with a hemorrhagic stroke appeared to be at increased risk for hemorrhagic stroke (16% atorvastatin calcium vs. 4% placebo).
Adverse Reactions from Clinical Studies of Atorvastatin Calcium in Pediatric
Patients with HeFH
In a 26-week controlled study in pediatric patients with HeFH (ages 10 years
to 17 years) (n=140, 31% female; 92% White, 1.6% Black or African American,
1.6% Asian, 4.8% other), the safety and tolerability profile of atorvastatin
calcium 10 to 20 mg daily, as an adjunct to diet to reduce total cholesterol,
LDL-C, and apo B levels, was generally similar to that of placebo [see Use in Specific Populations ( 8.4) and Clinical Studies (14.6)].
6.2 Postmarketing Experience
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.
Gastrointestinal Disorders:pancreatitis
General Disorders:fatigue
Hepatobiliary Disorders:fatal and non-fatal hepatic failure
Immune System Disorders:anaphylaxis
Injury:tendon rupture
Musculoskeletal and Connective Tissue Disorders:rhabdomyolysis, myositis.
There have been rare reports of immune-mediated necrotizing myopathy
associated with statin use.
Nervous System Disorders:dizziness, peripheral neuropathy.
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.
Psychiatric Disorders:depression
Respiratory Disorders:interstitial lung disease
Skin and Subcutaneous Tissue Disorders:angioneurotic edema, bullous rashes
(including erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal
necrolysis)
Most common adverse reactions (incidence ≥5%) are nasopharyngitis, arthralgia,
diarrhea, pain in extremity, and urinary tract infection ( 6.1).
To report SUSPECTED ADVERSE REACTIONS, contact
QuallentPharmaceuticals Health LLC at 1-877-605-7243****or FDA at
1-800-FDA-1088 or www.fda.gov/medwatch.
DRUG INTERACTIONS SECTION
7 DRUG INTERACTIONS
7.1 Drug Interactions that may Increase the Risk of Myopathy and
Rhabdomyolysis with atorvastatin calcium
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 [see Warnings and Precautions ( 5.1) and Clinical Pharmacology ( 12.3)].
****Table 2: Drug Interactions that may Increase the Risk of Myopathy and Rhabdomyolysis with Atorvastatin Calcium
|
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: |
|
|
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. |
7.2 Drug Interactions that may Decrease Exposure to atorvastatin calcium
Table 3 presents drug interactions that may decrease exposure to atorvastatin
calcium and instructions for preventing or managing them.
Table 3: Drug Interactions that may Decrease Exposure to Atorvastatin
Calcium
|
Rifampin | |
|
Clinical Impact: |
Concomitant administration of atorvastatin calcium with rifampin, an inducer of cytochrome P450 3A4 and inhibitor of OATP1B1, can lead to variable reductions in plasma concentrations of atorvastatin. Due to the dual interaction mechanism of rifampin, delayed administration of atorvastatin calcium after administration of rifampin has been associated with a significant reduction in atorvastatin plasma concentrations. |
|
Intervention: |
Administer atorvastatin calcium and rifampin simultaneously. |
7.3 Atorvastatin calcium Effects on Other Drugs
Table 4 presents atorvastatin calcium’s effect on other drugs and instructions
for preventing or managing them.
Table 4: Atorvastatin Calcium Effects on Other Drugs
|
Oral Contraceptives | |
|
Clinical Impact: |
Co-administration of atorvastatin calcium and an oral contraceptive increased plasma concentrations of norethindrone and ethinyl estradiol [see Clinical Pharmacology ( 12.3)]. |
|
Intervention: |
Consider this when selecting an oral contraceptive for patients taking atorvastatin calcium. |
|
Digoxin | |
|
Clinical Impact: |
When multiple doses of atorvastatin calcium and digoxin were co-administered, steady state plasma digoxin concentrations increased [see Clinical Pharmacology ( 12.3)]. |
|
Intervention: |
Monitor patients taking digoxin appropriately. |
• See full prescribing information for details regarding concomitant use of
atorvastatin calcium with other drugs or grapefruit juice that increase the
risk of myopathy and rhabdomyolysis ( 2.5, 7.1).
• Rifampin:May reduce atorvastatin plasma concentrations. Administer
simultaneously with atorvastatin calcium ( 7.2).
• Oral Contraceptives:May increase plasma levels of norethindrone and ethinyl
estradiol; consider this effect when selecting an oral contraceptive ( 7.3).
• Digoxin:May increase digoxin plasma levels; monitor patients appropriately (
7.3).
SPL UNCLASSIFIED SECTION
Patient Information
|
Atorvastatin Calcium Tablets USP, for oral use |
|
What are atorvastatin calcium tablets? |
|
Do not take atorvastatin calcium tablets if you: |
|
Before you take atorvastatin calcium tablets, tell your healthcare provider
about all of your medical conditions, including if you: |
|
How should I take atorvastatin calcium tablets? |
|
What should I avoid while taking atorvastatin calcium tablets? |
|
What are the possible side effects of atorvastatin calcium tablets? Your chances of getting muscle problems are higher if you: The most common side effects of atorvastatin calcium tablets include: Talk to your healthcare provider or pharmacist if you have side effects that
bother you or that will not go away. |
|
How do I store atorvastatin calcium tablets? |
|
General information about the safe and effective use of atorvastatin calcium
tablets. |
|
What are the ingredients in atorvastatin calcium tablets? Manufactured for: By: Annora Pharma Pvt. Ltd. |
This Patient Package Information has been approved by the U.S. Food and Drug Administration
Revised: 07/2025
CLINICAL STUDIES SECTION
14 CLINICAL STUDIES
Prevention of Cardiovascular Disease
In the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT), the effect of
atorvastatin calcium on fatal and non-fatal coronary heart disease was
assessed in 10,305 patients with hypertension, 40 to 80 years of age (mean of
63 years; 19% female; 95% White, 3% Black or African American, 1% South Asian,
1% other), without a previous myocardial infarction and with total cholesterol
(TC) levels ≤251 mg/dL. Additionally, all patients had at least 3 of the
following cardiovascular risk factors: male gender (81%), age >55 years (85%),
smoking (33%), diabetes (24%), history of CHD in a first-degree relative
(26%), TC:HDL >6 (14%), peripheral vascular disease (5%), left ventricular
hypertrophy (14%), prior cerebrovascular event (10%), specific ECG abnormality
(14%), proteinuria/albuminuria (62%). In this double-blind, placebo-controlled
trial, patients were treated with anti-hypertensive therapy (goal BP <140/90
mm Hg for patients without diabetes; <130/80 mm Hg for patients with diabetes)
and allocated to either atorvastatin calcium 10 mg daily (n=5,168) or placebo
(n=5,137), using a covariate adaptive method which took into account the
distribution of nine baseline characteristics of patients already enrolled and
minimized the imbalance of those characteristics across the groups. Patients
were followed for a median duration of 3.3 years.
The effect of 10 mg/day of atorvastatin calcium on lipid levels was similar to that seen in previous clinical trials.
Atorvastatin calcium significantly reduced the rate of coronary events [either fatal coronary heart disease (46 events in the placebo group vs. 40 events in the atorvastatin calcium group) or non-fatal MI (108 events in the placebo group vs. 60 events in the atorvastatin calcium group)] with a relative risk reduction of 36% [(based on incidences of 1.9% for atorvastatin calcium vs. 3.0% for placebo), p=0.0005 (see Figure 1)]. The risk reduction was consistent regardless of age, smoking status, obesity, or presence of renal dysfunction. The effect of atorvastatin calcium was seen regardless of baseline LDL levels.
Figure 1: Effect of Atorvastatin Calcium 10 mg/day on Cumulative Incidence of Non-Fatal Myocardial Infarction or Coronary Heart Disease Death (in ASCOT- LLA)
Atorvastatin calcium also significantly decreased the relative risk for revascularization procedures by 42% (incidences of 1.4% for atorvastatin calcium and 2.5% for placebo). Although the reduction of fatal and non-fatal strokes did not reach a pre-defined significance level (p=0.01), a favorable trend was observed with a 26% relative risk reduction (incidences of 1.7% for atorvastatin calcium and 2.3% for placebo). There was no significant difference between the treatment groups for death due to cardiovascular causes (p=0.51) or noncardiovascular causes (p=0.17).
In the Collaborative Atorvastatin Diabetes Study (CARDS), the effect of atorvastatin calcium on cardiovascular disease (CVD) endpoints was assessed in 2,838 subjects (94% White, 2% Black or African American, 2% South Asian, 1% other; 68% male), ages 40 to 75 with type 2 diabetes based on WHO criteria, without prior history of cardiovascular disease and with LDL ≤160 mg/dL and triglycerides (TG) ≤600 mg/dL. In addition to diabetes, subjects had 1 or more of the following risk factors: current smoking (23%), hypertension (80%), retinopathy (30%), or microalbuminuria (9%) or macroalbuminuria (3%). No subjects on hemodialysis were enrolled in the trial. In this multicenter, placebo-controlled, double-blind clinical trial, subjects were randomly allocated to either atorvastatin calcium 10 mg daily (1429) or placebo (1411) in a 1:1 ratio and were followed for a median duration of 3.9 years. The primary endpoint was the occurrence of any of the major cardiovascular events: myocardial infarction, acute CHD death, unstable angina, coronary revascularization, or stroke. The primary analysis was the time to first occurrence of the primary endpoint.
Baseline characteristics of subjects were: mean age of 62 years, mean HbA1c 7.7%; median LDL-C 120 mg/dL; median TC 207 mg/dL; median TG 151 mg/dL; median HDL-C 52 mg/dL.
The effect of atorvastatin calcium 10 mg/day on lipid levels was similar to that seen in previous clinical trials.
Atorvastatin calcium significantly reduced the rate of major cardiovascular events (primary endpoint events) (83 events in the atorvastatin calcium group vs. 127 events in the placebo group) with a relative risk reduction of 37%, HR 0.63, 95% CI (0.48, 0.83) (p=0.001) (see Figure 2). An effect of atorvastatin calcium was seen regardless of age, sex, or baseline lipid levels.
Atorvastatin calcium significantly reduced the risk of stroke by 48% (21 events in the atorvastatin calcium group vs. 39 events in the placebo group), HR 0.52, 95% CI (0.31, 0.89) (p=0.016) and reduced the risk of MI by 42% (38 events in the atorvastatin calcium group vs. 64 events in the placebo group), HR 0.58, 95.1% CI (0.39, 0.86) (p=0.007). There was no significant difference between the treatment groups for angina, revascularization procedures, and acute CHD death.
There were 61 deaths in the atorvastatin calcium group vs. 82 deaths in the placebo group (HR 0.73, p=0.059).
Figure 2: Effect of Atorvastatin Calcium 10 mg/day on Time to Occurrence of Major Cardiovascular Event (myocardial infarction, acute CHD death, unstable angina, coronary revascularization, or stroke) in CARDS
In the Treating to New Targets Study (TNT), the effect of atorvastatin calcium 80 mg/day vs. atorvastatin calcium 10 mg/day on the reduction in cardiovascular events was assessed in 10,001 subjects (94% White, 81% male, 38% ≥65 years) with clinically evident coronary heart disease who had achieved a target LDL-C level <130 mg/dL after completing an 8-week, open-label, run-in period with atorvastatin calcium 10 mg/day. Subjects were randomly assigned to either 10 mg/day or 80 mg/day of atorvastatin calcium and followed for a median duration of 4.9 years. The primary endpoint was the time-to-first occurrence of any of the following major cardiovascular events (MCVE): death due to CHD, non-fatal myocardial infarction, resuscitated cardiac arrest, and fatal and non-fatal stroke. The mean LDL-C, TC, TG, non-HDL, and HDL cholesterol levels at 12 weeks were 73, 145, 128, 98, and 47 mg/dL during treatment with 80 mg of atorvastatin calcium and 99, 177, 152, 129, and 48 mg/dL during treatment with 10 mg of atorvastatin calcium.
Treatment with atorvastatin calcium 80 mg/day significantly reduced the rate of MCVE (434 events in the 80 mg/day group vs. 548 events in the 10 mg/day group) with a relative risk reduction of 22%, HR 0.78, 95% CI (0.69, 0.89), p=0.0002 (see Figure 3 and Table 7). The overall risk reduction was consistent regardless of age (<65, ≥65) or sex.
****Figure 3: Effect of Atorvastatin Calcium 80 mg/day vs. 10 mg/day on Time to Occurrence of Major Cardiovascular Events (TNT)
Table 7: Overview of Efficacy Results in TNT
|
Endpoint |
Atorvastatin****10 mg (N=5,006) |
Atorvastatin****80 mg (N=4,995) |
HRa**(95%CI)** | ||
|
PRIMARY ENDPOINT |
n |
(%) |
n |
(%) | |
|
First major cardiovascular endpoint |
548 |
(10.9) |
434 |
(8.7) |
0.78 (0.69, 0.89) |
|
Components of the Primary Endpoint | |||||
|
CHD death |
127 |
(2.5) |
101 |
(2.0) |
0.80 (0.61, 1.03) |
|
Non-fatal, non-procedure related MI |
308 |
(6.2) |
243 |
(4.9) |
0.78 (0.66, 0.93) |
|
Resuscitated cardiac arrest |
26 |
(0.5) |
25 |
(0.5) |
0.96 (0.56, 1.67) |
|
Stroke (fatal and non-fatal) |
155 |
(3.1) |
117 |
(2.3) |
0.75 (0.59, 0.96) |
|
SECONDARY ENDPOINTS* | |||||
|
First CHF with hospitalization |
164 |
(3.3) |
122 |
(2.4) |
0.74 (0.59, 0.94) |
|
First PVD endpoint |
282 |
(5.6) |
275 |
(5.5) |
0.97 (0.83, 1.15) |
|
First CABG or other coronary revascularization procedure b |
904 |
(18.1) |
667 |
(13.4) |
0.72 (0.65, 0.80) |
|
First documented angina endpoint b |
615 |
(12.3) |
545 |
(10.9) |
0.88 (0.79, 0.99) |
|
All-cause mortality |
282 |
(5.6) |
284 |
(5.7) |
1.01 (0.85, 1.19) |
|
Components of All-Cause Mortality | |||||
|
Cardiovascular death |
155 |
(3.1) |
126 |
(2.5) |
0.81 (0.64, 1.03) |
|
Noncardiovascular death |
127 |
(2.5) |
158 |
(3.2) |
1.25 (0.99, 1.57) |
|
Cancer death |
75 |
(1.5) |
85 |
(1.7) |
1.13 (0.83, 1.55) |
|
Other non-CV death |
43 |
(0.9) |
58 |
(1.2) |
1.35 (0.91, 2.00) |
|
Suicide, homicide, and other traumatic non-CV death |
9 |
(0.2) |
15 |
(0.3) |
1.67 (0.73, 3.82) |
*Secondary endpoints not included in primary endpoint
HR=hazard ratio; CHD=coronary heart disease; CI=confidence interval;
MI=myocardial infarction;
CHF=congestive heart failure; CV=cardiovascular; PVD=peripheral vascular
disease; CABG=coronary artery bypass graft
Confidence intervals for the Secondary Endpoints were not adjusted for
multiple comparisons
aAtorvastatin 80 mg: atorvastatin 10 mg
bComponent of other secondary endpoints
Of the events that comprised the primary efficacy endpoint, treatment with atorvastatin calcium 80 mg/day significantly reduced the rate of non-fatal, non-procedure related MI and fatal and non-fatal stroke, but not CHD death or resuscitated cardiac arrest (Table 7). Of the predefined secondary endpoints, treatment with atorvastatin calcium 80 mg/day significantly reduced the rate of coronary revascularization, angina, and hospitalization for heart failure, but not peripheral vascular disease. The reduction in the rate of CHF with hospitalization was only observed in the 8% of patients with a prior history of CHF.
There was no significant difference between the treatment groups for all-cause mortality (Table 7). The proportions of subjects who experienced cardiovascular death, including the components of CHD death and fatal stroke, were numerically smaller in the atorvastatin calcium 80 mg group than in the atorvastatin calcium 10 mg treatment group. The proportions of subjects who experienced noncardiovascular death were numerically larger in the atorvastatin calcium 80 mg group than in the atorvastatin calcium 10 mg treatment group.
Primary Hyperlipidemia in Adults
Atorvastatin calcium reduces total-C, LDL-C, apo B, and TG, and increases
HDL-C in patients with hyperlipidemia (heterozygous familial and nonfamilial)
and mixed dyslipidemia. Therapeutic response is seen within 2 weeks, and
maximum response is usually achieved within 4 weeks and maintained during
chronic therapy.
In two multicenter, placebo-controlled, dose-response trials in patients with hyperlipidemia, atorvastatin calcium given as a single dose over 6 weeks, significantly reduced total-C, LDL-C, apo B, and TG. (Pooled results are provided in Table 8.)
**Table 8: Dose Response in Patients with Primary Hyperlipidemia (Adjusted Mean % Change From Baseline)**a
|
Dose |
N |
TC |
LDL-C |
Apo B |
TG |
HDL-C |
|
Placebo |
21 |
4 |
4 |
3 |
10 |
-3 |
|
10 |
22 |
-29 |
-39 |
-32 |
-19 |
6 |
|
20 |
20 |
-33 |
-43 |
-35 |
-26 |
9 |
|
40 |
21 |
-37 |
-50 |
-42 |
-29 |
6 |
|
80 |
23 |
-45 |
-60 |
-50 |
-37 |
5 |
aResults are pooled from 2 dose-response trials.
In three multicenter, double-blind trials in patients with hyperlipidemia,
atorvastatin calcium was compared to other statins. After randomization,
patients were treated for 16 weeks with either atorvastatin calcium 10 mg per
day or a fixed dose of the comparative agent (Table 9).
****Table 9: Mean Percentage Change From Baseline at Endpoint (Double- Blind, Randomized, Active-Controlled Trials)
|
Treatment |
N |
Total-C |
LDL-C |
Apo B |
TG |
HDL-C |
|
Trial 1 | ||||||
|
Atorvastatin 10 mg |
707 |
-27 a |
-36 a |
-28 a |
-17 a |
+7 |
|
Lovastatin 20 mg |
191 |
-19 |
-27 |
-20 |
-6 |
+7 |
|
95% CI for Diff 1 |
-9.2, -6.5 |
-10.7, -7.1 |
-10.0, -6.5 |
-15.2, -7.1 |
-1.7, 2.0 | |
|
Trial 2 | ||||||
|
Atorvastatin 10 mg |
222 |
-25 b |
-35 b |
-27 b |
-17 b |
+6 |
|
Pravastatin 20 mg |
77 |
-17 |
-23 |
-17 |
-9 |
+8 |
|
95% CI for Diff 1 |
-10.8, -6.1 |
-14.5, -8.2 |
-13.4, -7.4 |
-14.1, -0.7 |
-4.9, 1.6 | |
|
Trial 3 | ||||||
|
Atorvastatin 10 mg |
132 |
-29 c |
-37 c |
-34 c |
-23 c |
+7 |
|
Simvastatin 10 mg |
45 |
-24 |
-30 |
-30 |
-15 |
+7 |
|
95% CI for Diff 1 |
-8.7, -2.7 |
-10.1, -2.6 |
-8.0, -1.1 |
-15.1, -0.7 |
-4.3, 3.9 |
1A negative value for the 95% CI for the difference between treatments favors
atorvastatin calcium for all except HDL-C, for which a positive value favors
atorvastatin calcium. If the range does not include 0, this indicates a
statistically significant difference.
aSignificantly different from lovastatin, ANCOVA, p ≤0.05
bSignificantly different from pravastatin, ANCOVA, p ≤0.05
cSignificantly different from simvastatin, ANCOVA, p ≤0.05
Table 9 does not contain data comparing the effects of atorvastatin calcium 10
mg and higher dosages of lovastatin, pravastatin, and simvastatin. The drugs
compared in the trials summarized in the table are not necessarily
exchangeable.
Hypertriglyceridemia in Adults
The response to atorvastatin calcium in 64 patients with isolated
hypertriglyceridemia treated across several clinical trials is shown in the
table below (Table 10). For the atorvastatin calcium-treated patients, median
(min, max) baseline TG level was 565 (267 to 1502).
Table 10: Combined Patients with Isolated Elevated TG: Median (min, max) Percentage Change From Baseline
|
Placebo (N=12) |
Atorvastatin |
Atorvastatin |
Atorvastatin | |
|
TG |
-12.4 (-36.6, 82.7) |
-41.0 (-76.2, 49.4) |
-38.7 (-62.7, 29.5) |
-51.8 (-82.8, 41.3) |
|
Total-C |
-2.3 (-15.5, 24.4) |
-28.2 (-44.9, -6.8) |
-34.9 (-49.6, -15.2) |
-44.4 (-63.5, -3.8) |
|
LDL-C |
3.6 (-31.3, 31.6) |
-26.5 (-57.7, 9.8) |
-30.4 (-53.9, 0.3) |
-40.5 (-60.6, -13.8) |
|
HDL-C |
3.8 (-18.6, 13.4) |
13.8 (-9.7, 61.5) |
11.0 (-3.2, 25.2) |
7.5 (-10.8, 37.2) |
|
non-HDL-C |
-2.8 (-17.6, 30.0) |
-33.0 (-52.1, -13.3) |
-42.7 (-53.7, -17.4) |
-51.5 (-72.9, -4.3) |
Dysbetalipoproteinemia in Adults
The results of an open-label crossover trial of 16 patients (genotypes: 14 apo
E2/E2 and 2 apo E3/E2) with dysbetalipoproteinemia are shown in the table
below (Table 11).
****Table 11: Open-Label Crossover Trial of 16 Patients with Dysbetalipoproteinemia
|
Median % Change (min, max) | |||
|
Median (min, max) at Baseline (mg/dL) |
Atorvastatin 10 mg |
Atorvastatin 80 mg | |
|
Total-C |
442 (225, 1320) |
-37 (-85, 17) |
-58 (-90, -31) |
|
TG |
678 (273, 5990) |
-39 (-92, -8) |
-53 (-95, -30) |
|
IDL-C + VLDL-C |
215 (111, 613) |
-32 (-76, 9) |
-63 (-90, -8) |
|
non-HDL-C |
411 (218, 1272) |
-43 (-87, -19) |
-64 (-92, -36) |
HoFHin Adults and Pediatric Patients
In a trial without a concurrent control group, 29 patients (mean age of 22 years, median age of 24 years, 31% <18 years) with HoFH received maximum daily doses of 20 to 80 mg of atorvastatin calcium. The mean LDL-C reduction in this trial was 18%. Twenty-five patients with a reduction in LDL-C had a mean response of 20% (range of 7% to 53%, median of 24%); the remaining 4 patients had 7% to 24% increases in LDL-C. Five of the 29 patients had absent LDL- receptor function. Of these, 2 patients also had a portacaval shunt and had no significant reduction in LDL-C. The remaining 3 receptor-negative patients had a mean LDL-C reduction of 22%.
HeFH in Pediatric Patients
In a double-blind, placebo-controlled trial followed by an open-label phase,
187 males and post-menarchal females 10 years to 17 years of age (mean age
14.1 years; 31% female; 92% White, 1.6% Black or African American, 1.6% Asian,
4.8% other) with heterozygous familial hypercholesterolemia (HeFH) or severe
hypercholesterolemia, were randomized to atorvastatin calcium (n=140) or
placebo (n=47) for 26 weeks and then all received atorvastatin calcium for 26
weeks. Inclusion in the trial required 1) a baseline LDL-C level ≥190 mg/dL or
2) a baseline LDL-C level ≥160 mg/dL and positive family history of FH or
documented premature cardiovascular disease in a first or second-degree
relative. The mean baseline LDL-C value was 219 mg/dL (range: 139 to 385
mg/dL) in the atorvastatin calcium group compared to 230 mg/dL (range: 160 to
325 mg/dL) in the placebo group. The dosage of atorvastatin calcium (once
daily) was 10 mg for the first 4 weeks and uptitrated to 20 mg if the LDL-C
level was >130 mg/dL. The number of atorvastatin calcium -treated patients who
required uptitration to 20 mg after Week 4 during the double-blind phase was
78 (56%).
Atorvastatin calcium significantly decreased plasma levels of total-C, LDL-C, TG, and apolipoprotein B during the 26-week double-blind phase (see Table 12).
Table 12: Lipid-altering Effects of Atorvastatin Calcium in Adolescent Males and Females with Heterozygous Familial Hypercholesterolemia or Severe Hypercholesterolemia (Mean Percentage Change From Baseline at Endpoint in Intention-to-Treat Population)
|
DOSAGE |
N |
Total-C |
LDL-C |
HDL-C |
TG |
Apolipoprotein B |
|
Placebo |
47 |
-1.5 |
-0.4 |
-1.9 |
1.0 |
0.7 |
|
Atorvastatin Calcium |
140 |
-31.4 |
-39.6 |
2.8 |
-12.0 |
-34.01 |
The mean achieved LDL-C value was 130.7 mg/dL (range: 70.0 to 242.0 mg/dL) in the atorvastatin calcium group compared to 228.5 mg/dL (range: 152.0 to 385.0 mg/dL) in the placebo group during the 26-week double-blind phase.
Atorvastatin was also studied in a three year open-label, uncontrolled trial that included 163 patients with HeFH who were 10 years to 15 years old (82 males and 81 females). All patients had a clinical diagnosis of HeFH confirmed by genetic analysis (if not already confirmed by family history). Approximately 98% were White, and less than 1% were Black, African American or Asian. Mean LDL-C at baseline was 232 mg/dL. The starting atorvastatin dosage was 10 mg once daily and doses were adjusted to achieve a target of <130 mg/dL LDL-C. The reductions in LDL-C from baseline were generally consistent across age groups within the trial as well as with previous clinical trials in both adult and pediatric placebo-controlled trials.
SPL PATIENT PACKAGE INSERT SECTION
Patient Information
|
Atorvastatin Calcium Tablets USP, for oral use |
|
What are atorvastatin calcium tablets? |
|
Do not take atorvastatin calcium tablets if you: |
|
Before you take atorvastatin calcium tablets, tell your healthcare provider
about all of your medical conditions, including if you: Ask your healthcare provider or pharmacist for a list of medicines if you are not sure. Know all the medicines you take. Keep a list of them to show your healthcare provider and pharmacist when you get a new medicine. |
|
How should I take atorvastatin calcium tablets? |
|
What should I avoid while taking atorvastatin calcium tablets? |
|
What are the possible side effects of atorvastatin calcium tablets? Your chances of getting muscle problems are higher if you: The most common side effects of atorvastatin calcium tablets include: Talk to your healthcare provider or pharmacist if you have side effects that bother you or that will not go away. These are not all the side effects of atorvastatin calcium tablets. Call your healthcare provider for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. |
|
How do I store atorvastatin calcium tablets? |
|
General information about the safe and effective use of atorvastatin calcium
tablets. |
|
What are the ingredients in atorvastatin calcium tablets? Manufactured for: By: Annora Pharma Pvt. Ltd. |
This Patient Package Information has been approved by the U.S. Food and Drug Administration
Revised: 07/2025
DOSAGE & ADMINISTRATION SECTION
2 DOSAGE AND ADMINISTRATION
2.1 Important Dosage Information
• 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.
2.2 Recommended Dosage in Adult Patients
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.
2.3 Recommended Dosage in Pediatric Patients 10 Years of Age and Older with
HeFH
The recommended starting dosage of atorvastatin calcium tablets are 10 mg once daily. The dosage range is 10 mg to 20 mg once daily.
2.4 Recommended Dosage in Pediatric Patients 10 Years of Age and Older with
HoFH
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.
2.5 Dosage Modifications Due to Drug Interactions
Concomitant use of atorvastatin calcium tablets with the following drugs
requires dosage modification of atorvastatin calcium tablets [see Warnings and Precautions ( 5.1) and Drug Interactions ( 7.1)].
Anti-Viral Medications
• 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.
Select Azole Antifungals or Macrolide Antibiotics
• 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, see Drug Interactions ( 7.1).
• Take orally once daily with or without food ( 2.1).
• Assess LDL-C when clinically appropriate, as early as 4 weeks after
initiating atorvastatin calcium tablets, and adjust dosage if necessary (
2.1).
• Adults( 2.2):
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.
• Pediatric Patients Aged 10 Years of Age and Older withHeFH:Recommended
starting dosage is 10 mg once daily; dosage range is 10 to 20 mg once daily (
2.3).
• Pediatric Patients Aged 10 Years of Age and Older withHoFH:Recommended
starting dosage is 10 to 20 mg once daily; dosage range is 10 to 80 mg once
daily ( 2.4).
• See full prescribing information for atorvastatin calcium tablets dosage
modifications due to drug interactions ( 2.5).
DOSAGE FORMS & STRENGTHS SECTION
3 DOSAGE FORMS AND STRENGTHS
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
Tablets: 10 mg; 20 mg; 40 mg; 80 mg of atorvastatin ( 3).
USE IN SPECIFIC POPULATIONS SECTION
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
Risk Summary
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 [see Clinical Pharmacology ( 12.1)] . In addition,
treatment of hyperlipidemia is not generally necessary during pregnancy.
Atherosclerosis is a chronic process and the discontinuation of lipid-lowering
drugs during pregnancy should have little impact on the outcome of long-term
therapy of primary hyperlipidemia for most patients.
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
(see Data). In animal reproduction studies, no adverse developmental effects
were observed in pregnant rats or rabbits orally administered atorvastatin at
doses that resulted in up to 30 and 20 times, respectively, the human exposure
at the maximum recommended human dose (MRHD) of 80 mg, based on body surface
area (mg/m 2). In rats administered atorvastatin during gestation and
lactation, decreased postnatal growth and development delay were observed at
doses ≥ 6 times the MRHD (see Data).
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.
Data
Human Data
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.
Animal Data
Atorvastatin was administered to pregnant rats and rabbits during
organogenesis at oral doses up to 300 mg/kg/day and 100 mg/kg/day,
respectively. Atorvastatin was not teratogenic in rats at doses up to 300
mg/kg/day or in rabbits at doses up to 100 mg/kg/day. These doses resulted in
multiples of about 30 times (rat) or 20 times (rabbit) the human exposure at
the MRHD based on surface area (mg/m 2). In rats, the maternally toxic dose of
300 mg/kg resulted in increased post-implantation loss and decreased fetal
body weight. At the maternally toxic doses of 50 and 100 mg/kg/day in rabbits,
there was increased post-implantation loss, and at 100 mg/kg/day fetal body
weights were decreased.
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.
8.2 Lactation
Risk Summary
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 (see Data). Statins, including atorvastatin calcium, decrease cholesterol
synthesis and possibly the synthesis of other biologically active substances
derived from cholesterol and may cause harm to the breastfed infant.
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 [see Use in Specific Populations ( 8.1), Clinical Pharmacology ( 12.1)].
Data
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).
8.4 Pediatric Use
The safety and effectiveness of atorvastatin calcium as an adjunct to diet to
reduce LDL-C have been established pediatric patients 10 years of age and
older with HeFH. Use of atorvastatin calcium for this indication is based on a
double-blind, placebo-controlled clinical trial in 187 pediatric patients 10
years of age and older with HeFH. In this limited controlled trial, there was
no significant effect on growth or sexual maturation in the males or females
or on menstrual cycle length in females.
The safety and effectiveness of atorvastatin calcium as an adjunct to other
LDL-C-lowering therapies to reduce LDL-C have been established pediatric
patients 10 years of age and older with HoFH. Use of atorvastatin calcium for
this indication is based on a trial without a concurrent control group in 8
pediatric patients 10 years of age and older with HoFH [see Clinical Studies ( 14)].
The safety and effectiveness of atorvastatin calcium have not been established
in pediatric patients younger than 10 years of age with HeFH or HoFH, or in
pediatric patients with other types of hyperlipidemia (other than HeFH or
HoFH).
8.5 Geriatric Use
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 [see Warnings and Precautions ( 5.1) and Clinical Pharmacology ( 12.3)].
8.6 Renal Impairment
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 [see Warnings and Precautions ( 5.1) and Clinical Pharmacology ( 12.3)].
8.7 Hepatic Impairment
In patients with chronic alcoholic liver disease, plasma concentrations of atorvastatin calcium are markedly increased. C maxand AUC are each 4-fold greater in patients with Childs-Pugh A disease. C maxand AUC are approximately 16-fold and 11-fold increased, respectively, in patients with Childs-Pugh B disease. Atorvastatin calcium is contraindicated in patients with acute liver failure or decompensated cirrhosis [see Contraindications ( 4)].
• Pregnancy:May cause fetal harm. ( 8.1).
• Lactation:Breastfeeding not recommended during treatment with atorvastatin
calcium ( 8.2).
OVERDOSAGE SECTION
10 OVERDOSAGE
No specific antidotes for atorvastatin calcium are known. Contact Poison Control (1-800-222-1222) for latest recommendations. Due to extensive drug binding to plasma proteins, hemodialysis is not expected to significantly enhance atorvastatin calcium clearance.
DESCRIPTION SECTION
11 DESCRIPTION
Atorvastatin is an inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG- CoA) reductase.
Atorvastatin calcium is 1 H-Pyrrole-1-heptanoic acid, 2-(4-fluorophenyl)- β,δ-dihydroxy-5-(1-methylethyl)-3-phenyl-4-[(phenylamino) carbonyl]-, calcium salt (2:1), [R-(R*, R*)] trihydrate. The molecular formula of atorvastatin calcium is (C 33H 34FN 2O 5) 2Ca 2+•3H 2O and its molecular weight is 1209.42. Its structural formula is:
Atorvastatin calcium, USP is a white to off-white powder. Atorvastatin calcium is very slightly soluble in pH 1.2, pH 4.5 and pH 6.8 buffers; freely soluble in methanol; slightly soluble in ethanol; practically insoluble in acetonitrile.
Atorvastatin Calcium Tablets, USP for oral use contain atorvastatin 10 mg, 20 mg, 40 mg, or 80 mg (equivalent to 10.825 mg, 21.649 mg, 43.299 mg or 86.597 mg atorvastatin calcium trihydrate, USP) and the following inactive ingredients: calcium carbonate, croscarmellose sodium, hydroxypropyl cellulose, lactose monohydrate, magnesium stearate, microcrystalline cellulose, polysorbate 80 and film coating contains hypromellose, polyethylene glycol, talc and titanium dioxide.
USP dissolution test is pending.
CLINICAL PHARMACOLOGY SECTION
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
Atorvastatin calcium is a selective, competitive inhibitor of HMG-CoA reductase, the rate-limiting enzyme that converts 3-hydroxy-3-methylglutaryl- coenzyme A to mevalonate, a precursor of sterols, including cholesterol. In animal models, atorvastatin calcium lowers plasma cholesterol and lipoprotein levels by inhibiting HMG-CoA reductase and cholesterol synthesis in the liver and by increasing the number of hepatic LDL receptors on the cell surface to enhance uptake and catabolism of LDL; atorvastatin calcium also reduces LDL production and the number of LDL particles.
12.2 Pharmacodynamics
Atorvastatin calcium, as well as some of its metabolites, are pharmacologically active in humans. The liver is the primary site of action and the principal site of cholesterol synthesis and LDL clearance. Drug dosage, rather than systemic drug concentration, correlates better with LDL-C reduction. Individualization of drug dosage should be based on therapeutic response [see Dosage and Administration ( 2)].
12.3 Pharmacokinetics
Absorption
Atorvastatin calcium is rapidly absorbed after oral administration; maximum
plasma concentrations occur within 1 to 2 hours. Extent of absorption
increases in proportion to atorvastatin calcium dose. The absolute
bioavailability of atorvastatin (parent drug) is approximately 14% and the
systemic availability of HMG-CoA reductase inhibitory activity is
approximately 30%. The low systemic availability is attributed to presystemic
clearance in gastrointestinal mucosa and/or hepatic first-pass metabolism.
Although food decreases the rate and extent of drug absorption by
approximately 25% and 9%, respectively, as assessed by C maxand AUC, LDL-C
reduction is similar whether atorvastatin calcium is given with or without
food. Plasma atorvastatin calcium concentrations are lower (approximately 30%
for C maxand AUC) following evening drug administration compared with morning.
However, LDL-C reduction is the same regardless of the time of day of drug
administration.
Distribution
Mean volume of distribution of atorvastatin calcium is approximately 381
liters. Atorvastatin calcium is ≥98% bound to plasma proteins. A blood/plasma
ratio of approximately 0.25 indicates poor drug penetration into red blood
cells.
Elimination
Metabolism
Atorvastatin calcium is extensively metabolized to ortho- and parahydroxylated
derivatives and various beta-oxidation products. In vitroinhibition of HMG-CoA
reductase by ortho- and parahydroxylated metabolites is equivalent to that of
atorvastatin calcium. Approximately 70% of circulating inhibitory activity for
HMG-CoA reductase is attributed to active metabolites. In vitrostudies suggest
the importance of atorvastatin calcium metabolism by cytochrome P450 3A4,
consistent with increased plasma concentrations of atorvastatin calcium in
humans following co-administration with erythromycin, a known inhibitor of
this isozyme [see Drug Interactions ( 7.1)]. In animals, the ortho-hydroxy
metabolite undergoes further glucuronidation.
Excretion
Atorvastatin calcium and its metabolites are eliminated primarily in bile
following hepatic and/or extra-hepatic metabolism; however, the drug does not
appear to undergo enterohepatic recirculation. Mean plasma elimination half-
life of atorvastatin calcium in humans is approximately 14 hours, but the
half-life of inhibitory activity for HMG-CoA reductase is 20 to 30 hours due
to the contribution of active metabolites. Less than 2% of a dose of
atorvastatin calcium is recovered in urine following oral administration.
Specific Populations
Geriatric
Plasma concentrations of atorvastatin calcium are higher (approximately 40%
for C maxand 30% for AUC) in healthy elderly subjects (age ≥65 years) than in
young adults.
Pediatric
Apparent oral clearance of atorvastatin in pediatric subjects appeared similar
to that of adults when scaled allometrically by body weight as the body weight
was the only significant covariate in atorvastatin population PK model with
data including pediatric HeFH patients (ages 10 years to 17 years of age,
n=29) in an open-label, 8-week study.
Gender
Plasma concentrations of atorvastatin calcium in females differ from those in
males (approximately 20% higher for C maxand 10% lower for AUC); however,
there is no clinically significant difference in LDL-C reduction with
atorvastatin calcium between males and females.
Renal Impairment
Renal disease has no influence on the plasma concentrations or LDL-C reduction
of atorvastatin calcium [see Use in Specific Populations ( 8.6)].
While studies have not been conducted in patients with end-stage renal
disease, hemodialysis is not expected to significantly enhance clearance of
atorvastatin calcium since the drug is extensively bound to plasma proteins.
Hepatic Impairment
In patients with chronic alcoholic liver disease, plasma concentrations of
atorvastatin calcium are markedly increased. C maxand AUC are each 4-fold
greater in patients with Childs-Pugh A disease. C maxand AUC are approximately
16-fold and 11-fold increased, respectively, in patients with Childs-Pugh B
disease [see Use in Specific Populations ( 8.7)].
Drug Interactions
Atorvastatin is a substrate of the hepatic transporters, OATP1B1 and OATP1B3
transporter. Metabolites of atorvastatin are substrates of OATP1B1.
Atorvastatin is also identified as a substrate of the efflux transporter BCRP,
which may limit the intestinal absorption and biliary clearance of
atorvastatin.
****Table 5: Effect of Co-administered Drugs on the Pharmacokinetics of Atorvastatin
|
Co-administered drug and dosage regimen |
Atorvastatin | ||
|
Dosage (mg) |
Ratio of AUC**&** |
Ratio of Cmax& | |
|
#Cyclosporine 5.2 mg/kg/day, stable dose |
10 mg QD afor 28 days |
8.69 |
10.66 |
|
#Tipranavir 500 mg BID b/ritonavir 200 mg BID b, 7 days |
10 mg SD c |
9.36 |
8.58 |
|
#Glecaprevir 400 mg QD a/pibrentasvir 120 mg QD a, 7 days |
10 mg QD afor 7 days |
8.28 |
22.00 |
|
#Telaprevir 750 mg q8h f, 10 days |
20 mg SD c |
7.88 |
10.60 |
|
#, ‡Saquinavir 400 mg BID b/ritonavir 400 mg BID b, 15 days |
40 mg QD afor 4 days |
3.93 |
4.31 |
|
#Elbasvir 50 mg QD a/grazoprevir 200 mg QD a, 13 days |
10 mg SD c |
1.94 |
4.34 |
|
#Simeprevir 150 mg QD a, 10 days |
40 mg SD c |
2.12 |
1.70 |
|
#Clarithromycin 500 mg BID b, 9 days |
80 mg QD afor 8 days |
4.54 |
5.38 |
|
#Darunavir 300 mg BID b/ritonavir 100 mg BID b, 9 days |
10 mg QD afor 4 days |
3.45 |
2.25 |
|
#Itraconazole 200 mg QD a, 4 days |
40 mg SD c |
3.32 |
1.20 |
|
#Letermovir 480 mg QD a, 10 days |
20 mg SD c |
3.29 |
2.17 |
|
#Fosamprenavir 700 mg BID b/ritonavir 100 mg BID b, 14 days |
10 mg QD afor 4 days |
2.53 |
2.84 |
|
#Fosamprenavir 1400 mg BID b, 14 days |
10 mg QD afor 4 days |
2.30 |
4.04 |
|
#Nelfinavir 1250 mg BID b, 14 days |
10 mg QD afor 28 days |
1.74 |
2.22 |
|
#Grapefruit Juice, 240 mL QD a,* |
40 mg SD c |
1.37 |
1.16 |
|
Diltiazem 240 mg QD a, 28 days |
40 mg SD c |
1.51 |
1.00 |
|
Erythromycin 500 mg QID e, 7 days |
10 mg SD c |
1.33 |
1.38 |
|
Amlodipine 10 mg, single dose |
80 mg SD c |
1.18 |
0.91 |
|
Cimetidine 300 mg QID e, 2 weeks |
10 mg QD afor 2 weeks |
1.00 |
0.89 |
|
Colestipol 10 g BID b, 24 weeks |
40 mg QD afor 8 weeks |
NA |
0.74** |
|
Maalox TC ®30 mL QID e, 17 days |
10 mg QD afor 15 days |
0.66 |
0.67 |
|
Efavirenz 600 mg QD a, 14 days |
10 mg for 3 days |
0.59 |
1.01 |
|
#Rifampin 600 mg QD a, 7 days (co-administered) † |
40 mg SD c |
1.12 |
2.90 |
|
#Rifampin 600 mg QD a, 5 days (doses separated) † |
40 mg SD c |
0.20 |
0.60 |
|
#Gemfibrozil 600 mg BID b, 7 days |
40 mg SD c |
1.35 |
1.00 |
|
#Fenofibrate 160 mg QD a, 7 days |
40 mg SD c |
1.03 |
1.02 |
|
Boceprevir 800 mg TID d, 7 days |
40 mg SD c |
2.32 |
2.66 |
&Represents ratio of treatments (co-administered drug plus atorvastatin vs.
atorvastatin alone).
#See Sections 5.1 and 7 for clinical significance.
*Greater increases in AUC (ratio of AUC up to 2.5) and/or Cmax (ratio of Cmax up to 1.71) have been reported with excessive grapefruit consumption (≥ 750 mL to 1.2 liters per day).
** Ratio based on a single sample taken 8 to 16 h post dose.
†Due to the dual interaction mechanism of rifampin, simultaneous co-
administration of atorvastatin with rifampin is recommended, as delayed
administration of atorvastatin after administration of rifampin has been
associated with a significant reduction in atorvastatin plasma concentrations.
‡The dose of saquinavir plus ritonavir in this study is not the clinically
used dose. The increase in atorvastatin exposure when used clinically is
likely to be higher than what was observed in this study. Therefore, caution
should be applied and the lowest dose necessary should be used.
aOnce daily
bTwice daily
cSingle dosage
dThree times daily
eFour times daily
fEvery 8 hours
****Table 6: Effect of Atorvastatin on the Pharmacokinetics of Co- administered Drugs
|
Atorvastatin |
Co-administered drug and dosage regimen | ||
|
Drug/Dosage (mg) |
Ratio of AUC |
Ratio of C****max | |
|
80 mg QD afor 15 days |
Antipyrine, 600 mg SD c |
1.03 |
0.89 |
|
80 mg QD afor 10 days |
#Digoxin 0.25 mg QD a, 20 days |
1.15 |
1.20 |
|
40 mg QD afor 22 days |
Oral contraceptive QD a, 2 months -norethindrone 1 mg |
1.28 |
1.23 |
|
10 mg SD c |
Tipranavir 500 mg |
1.08 |
0.96 |
|
10 mg QD afor 4 days |
Fosamprenavir 1400 mg BID b, 14 days |
0.73 |
0.82 |
|
10 mg QD afor 4 days |
Fosamprenavir 700 mg |
0.99 |
0.94 |
#See Section 7 for clinical significance.
aOnce daily
bTwice daily
cSingle dosage
Atorvastatin calcium had no clinically significant effect on prothrombin time
when administered to patients receiving chronic warfarin treatment.
NONCLINICAL TOXICOLOGY SECTION
13 NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
In a 2-year carcinogenicity study in rats at dose levels of 10, 30, and 100 mg/kg/day, 2 rare tumors were found in muscle in high-dose females: in one, there was a rhabdomyosarcoma and, in another, there was a fibrosarcoma. This dose represents a plasma AUC (0 to 24) value of approximately 16 times the mean human plasma drug exposure after an 80 mg oral dose.
A 2-year carcinogenicity study in mice given 100, 200, or 400 mg/kg/day resulted in a significant increase in liver adenomas in high-dose males and liver carcinomas in high-dose females. These findings occurred at plasma AUC (0 to 24) values of approximately 6 times the mean human plasma drug exposure after an 80 mg oral dose.
In vitro, atorvastatin was not mutagenic or clastogenic in the following tests with and without metabolic activation: the Ames test with Salmonella typhimuriumand Escherichia coli, the HGPRT forward mutation assay in Chinese hamster lung cells, and the chromosomal aberration assay in Chinese hamster lung cells. Atorvastatin was negative in the in vivomouse micronucleus test.
In female rats, atorvastatin at doses up to 225 mg/kg (56 times the human exposure) did not cause adverse effects on fertility. Studies in male rats performed at doses up to 175 mg/kg (15 times the human exposure) produced no changes in fertility. There was aplasia and aspermia in the epididymis of 2 of 10 rats treated with 100 mg/kg/day of atorvastatin for 3 months (16 times the human AUC at the 80 mg dose); testis weights were significantly lower at 30 and 100 mg/kg and epididymal weight was lower at 100 mg/kg. Male rats given 100 mg/kg/day for 11 weeks prior to mating had decreased sperm motility, spermatid head concentration, and increased abnormal sperm. Atorvastatin caused no adverse effects on semen parameters, or reproductive organ histopathology in dogs given doses of 10, 40, or 120 mg/kg for 2 years.
HOW SUPPLIED SECTION
16 HOW SUPPLIED/STORAGE AND HANDLING
Atorvastatin Calcium Tablets, USP are supplied as follows:
|
Strength |
How Supplied |
NDC |
Tablet Description |
|
10 mg of atorvastatin |
bottles of 1000 |
NDC 82009-176-10 |
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 |
bottles of 1000 |
NDC 82009-177-10 |
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 |
bottles of 1000 |
NDC 82009-178-10 |
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 |
bottles of 1000 |
NDC 82009-179-10 |
white to off-white, oval, biconvex film coated tablets debossed with '80' on one side and 'A 56' on other side |
Storage
Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature].
INFORMATION FOR PATIENTS SECTION
17 PATIENT COUNSELING INFORMATION
Advise the patient to read the FDA-approved patient labeling (Patient Information).
Myopathy and Rhabdomyolysis
Advise patients that atorvastatin calcium may cause myopathy and rhabdomyolysis. Inform patients that the risk is also increased when taking certain types of medication or consuming large quantities of grapefruit juice and they should discuss all medication, both prescription and over the counter, with their healthcare provider. Instruct patients to promptly report any unexplained muscle pain, tenderness or weakness particularly if accompanied by malaise or fever [see Warnings and Precautions ( 5.1), Drug Interactions ( 7.1)].
Hepatic Dysfunction
Inform patients that atorvastatin calcium may cause liver enzyme elevations
and possibly liver failure. Advise patients to promptly report fatigue,
anorexia, right upper abdominal discomfort, dark urine or jaundice [see Warnings and Precautions ( 5.3)].
Increases in HbA1c and Fasting Serum Glucose Levels
Inform patients that increases in HbA1c and fasting serum glucose levels may
occur with atorvastatin calcium. Encourage patients to optimize lifestyle
measures, including regular exercise, maintaining a healthy body weight, and
making healthy food choices [see Warnings and Precautions ( 5.4)].
Pregnancy
Advise pregnant patients and patients who can become pregnant of the potential risk to a fetus. Advise patients to inform their healthcare provider of a known or suspected pregnancy to discuss if atorvastatin calcium should be discontinued [see Use in Specific Populations ( 8.1)].
Lactation
Advise patients that breastfeeding is not recommended during treatment with
atorvastatin calcium [see Use in Specific Populations ( 8.2)].
Missed Doses
If a dose is missed, advise patients not to take the missed dose and resume
with the next scheduled dose.
Manufactured for:
Quallent****Pharmaceuticals Health LLC
Grand Cayman, Cayman Islands
By: Annora Pharma Pvt. Ltd.
Sangareddy - 502313,
Telangana, India.
Revised: 07/2025