LIPITOR safety information
IMPORTANT SAFETY INFORMATION

LIPITOR® (atorvastatin calcium) tablets are contraindicated in patients with a known hypersensitivity to any component of this product; in patients with active liver disease or unexplained persistent elevations of hepatic transaminases; in women who are or may become pregnant or who are breastfeeding. Advise females of reproductive potential of the risk to a fetus, to use effective contraception during treatment, and to inform their healthcare provider of a known or suspected pregnancy.

Rare cases of rhabdomyolysis with acute renal failure secondary to myoglobinuria have been reported with LIPITOR® (atorvastatin calcium) tablets and other statins. Tell patients to promptly report muscle pain, tenderness, or weakness. Predisposing factors include advanced age (≥65), uncontrolled hypothyroidism, and renal impairment. Patients with a history of renal impairment merit closer monitoring. In cases of myopathy or rhabdomyolysis, therapy should be temporarily withheld or discontinued.

The concomitant use of higher doses of LIPITOR® (atorvastatin calcium) tablets with certain drugs such as cyclosporine and strong CYP3A4 inhibitors (eg, clarithromycin, itraconazole, and HIV protease inhibitors) increases the risk of myopathy/rhabdomyolysis. Lower doses of LIPITOR should be considered. Physicians should carefully monitor patients for signs or symptoms of myopathy early during therapy and when titrating the dose of either drug.

It is recommended that liver function tests be performed prior to the initiation of therapy and repeated as clinically indicated thereafter.

Increases in HbA1c and fasting serum glucose levels have been reported with HMG-CoA reductase inhibitors, including LIPITOR® (atorvastatin calcium) tablets.

In a post hoc analysis of the SPARCL study in patients without CHD who had a stroke or TIA within the preceding 6 months, a higher incidence of hemorrhagic stroke was seen in the LIPITOR® 80 mg (atorvastatin calcium) tablets group compared with placebo (2.3% vs 1.4%). Some baseline characteristics, including hemorrhagic and lacunar stroke on study entry, were associated with a higher incidence of hemorrhagic stroke in the LIPITOR group.

The most commonly reported adverse reactions with LIPITOR® (atorvastatin calcium) tablets in placebo-controlled trials were: nasopharyngitis, arthralgia, diarrhea, pain in extremity, and urinary tract infection.

INDICATIONS

LIPITOR® (atorvastatin calcium) tablets are indicated as an adjunct to diet to:

  • Reduce the risk of myocardial infarction (MI), stroke, revascularization procedures, and angina in adult patients with multiple risk factors but without clinically evident coronary heart disease (CHD); to reduce the risk of MI and stroke in adult patients with type 2 diabetes and without clinically evident CHD, but with multiple risk factors; to reduce the risk of nonfatal MI, fatal and nonfatal stroke, revascularization procedures, hospitalization for congestive heart failure, and angina in adult patients with clinically evident CHD

  • Reduce elevated total-C, LDL-C, apo B, and TG levels; and to increase HDL-C in patients with primary hypercholesterolemia (heterozygous familial and nonfamilial) and mixed dyslipidemia

  • Reduce elevated TG in adult patients with hypertriglyceridemia and primary dysbetalipoproteinemia

  • Reduce total-C and LDL-C in patients with homozygous familial hypercholesterolemia (HoFH)

  • Reduce elevated total-C, LDL-C, and apo B levels in pediatric patients, 10 years to 17 years of age, with heterozygous familial hypercholesterolemia (HeFH) after failing an adequate trial of diet therapy

Limitations of Use: LIPITOR has not been studied in conditions where the major lipoprotein abnormality is elevation of chylomicrons (Fredrickson Types I and V).

Please see Full Prescribing Information and Patient Information.

FAQs

Frequently Asked Questions (FAQs)

About LIPITOR

Q: What is LIPITOR® (atorvastatin calcium) indicated for?

A: LIPITOR tablets are indicated as an adjunct to diet to:

  • Reduce the risk of myocardial infarction (MI), stroke, revascularization procedures, and angina in adult patients with multiple risk factors but without clinically evident coronary heart disease (CHD); to reduce the risk of MI and stroke in adult patients with type 2 diabetes and without clinically evident CHD, but with multiple risk factors; to reduce the risk of nonfatal MI, fatal and nonfatal stroke, revascularization procedures, hospitalization for congestive heart failure, and angina in adult patients with clinically evident CHD

  • Reduce elevated total-C, LDL-C, apo B, and TG levels; and to increase HDL-C in patients with primary hypercholesterolemia (heterozygous familial and nonfamilial) and mixed dyslipidemia

  • Reduce elevated TG in adult patients with hypertriglyceridemia and primary dysbetalipoproteinemia

  • Reduce total-C and LDL-C in patients with homozygous familial hypercholesterolemia (HoFH)

  • Reduce elevated total-C, LDL-C, and apo B levels in pediatric patients, 10 years to 17 years of age, with heterozygous familial hypercholesterolemia (HeFH) after failing an adequate trial of diet therapy

Limitations of Use

LIPITOR has not been studied in conditions where the majority lipoprotein abnormality is elevation of chylomicrons (Fredrickson Types I and V).

Q: How is LIPITOR administered?

A: LIPITOR can be administered as a single dose at any time of the day, with or without food.

Q: What is the recommended starting dose for LIPITOR?

A: Hyperlipidemia (Heterozygous Familial and Nonfamilial) and Mixed Dyslipidemia (Fredrickson Types IIa and IIb)

  • The recommended starting dose of LIPITOR is 10 or 20 mg once daily. Patients who require a large reduction in LDL-C (more than 45%) may be started at 40 mg once daily. The starting dose and maintenance doses of LIPITOR should be individualized according to patient characteristics such as goal of therapy and response (see current NCEP Guidelines). After initiation and/or upon titration of LIPITOR, lipid levels should be analyzed within 2 to 4 weeks and dosage adjusted accordingly.

Heterozygous Familial Hypercholesterolemia in Pediatric Patients (10-17 years of age)

  • The recommended starting dose of LIPITOR is 10 mg/day; the maximum recommended dose is 20 mg/day (doses greater than 20 mg have not been studied in this patient population).

Homozygous Familial Hypercholesterolemia

  • The dosage of LIPITOR in patients with homozygous FH is 10 to 80 mg daily. LIPITOR should be used as an adjunct to other lipid-lowering treatments (e.g., LDL apheresis) in these patients or if such treatments are unavailable.

Concomitant Lipid-Lowering Therapy

  • LIPITOR may be used with bile acid resins. The combination of HMG-CoA reductase inhibitors (statins) and fibrates should generally be used with caution.

Dosage in Patients Taking Cyclosporine, Clarithromycin, Itraconazole, or Certain Protease Inhibitors

  • In patients taking cyclosporine or the HIV protease inhibitors (tipranavir plus ritonavir) or the hepatitis C protease inhibitor (telaprevir), therapy with LIPITOR should be avoided. In patients with HIV taking lopinavir plus ritonavir, caution should be used when prescribing LIPITOR and the lowest dose necessary employed. In patients taking clarithromycin, itraconazole, or in patients with HIV taking a combination of saquinavir plus ritonavir, darunavir plus ritonavir, fosamprenavir, or fosamprenavir plus ritonavir, therapy with LIPITOR should be limited to 20 mg, and appropriate clinical assessment is recommended to ensure that the lowest dose necessary of LIPITOR is employed. In patients taking the HIV protease inhibitor nelfinavir or the hepatitis C protease inhibitor boceprevir, therapy with LIPITOR should be limited to 40 mg, and appropriate clinical assessment is recommended to ensure that the lowest dose necessary of LIPITOR is employed.
Q: What dosage strengths of LIPITOR are available?

A: LIPITOR is available in 10-, 20-, 40-, and 80-mg tablets. The dose range of LIPITOR is 10 to 80 mg once daily.

Q: What are the contraindications for LIPITOR?

A: LIPITOR is contraindicated in patients with:

  • Active liver disease, which may include unexplained persistent elevations in hepatic transaminase levels.
  • Hypersensitivity to any component of this medication.

Pregnancy

  • Women who are pregnant or may become pregnant. LIPITOR may cause fetal harm when administered to a pregnant woman. Serum cholesterol and triglycerides increase during normal pregnancy, and cholesterol or cholesterol derivatives are essential for fetal development. Atherosclerosis is a chronic process and discontinuation of lipid-lowering drugs during pregnancy should have little impact on the outcome of long-term therapy of primary hypercholesterolemia. There are no adequate and well-controlled studies of LIPITOR use during pregnancy; however in rare reports, congenital anomalies were observed following intrauterine exposure to statins. In rat and rabbit animal reproduction studies, atorvastatin revealed no evidence of teratogenicity. LIPITOR SHOULD BE ADMINISTERED TO WOMEN OF CHILDBEARING AGE ONLY WHEN SUCH PATIENTS ARE HIGHLY UNLIKELY TO CONCEIVE AND HAVE BEEN INFORMED OF THE POTENTIAL HAZARDS. If the patient becomes pregnant while taking this drug, LIPITOR should be discontinued immediately and the patient apprised of the potential hazard to the fetus.

Nursing mothers

  • It is not known whether atorvastatin is excreted into human milk; however a small amount of another drug in this class does pass into breast milk. Because statins have the potential for serious adverse reactions in nursing infants, women who require LIPITOR treatment should not breastfeed their infants.
Q: Are there any dose adjustments for special populations?

A:Pregnancy

Pregnancy category X

  • LIPITOR is contraindicated in women who are or may become pregnant. Serum cholesterol and triglycerides increase during normal pregnancy. Lipid lowering drugs offer no benefit during pregnancy because cholesterol and cholesterol derivatives are needed for normal fetal development. Atherosclerosis is a chronic process, and discontinuation of lipid-lowering drugs during pregnancy should have little impact on long-term outcomes of primary hypercholesterolemia therapy.
  • There are no adequate and well-controlled studies of atorvastatin use during pregnancy. There have been rare reports of congenital anomalies following intrauterine exposure to statins. In a review of about 100 prospectively followed pregnancies in women exposed to other statins, the incidences of congenital anomalies, spontaneous abortions, and fetal deaths/stillbirths did not exceed the rate expected in the general population. However, this study was only able to exclude a three-to-four-fold increased risk of congenital anomalies over background incidence. In 89% of these cases, drug treatment started before pregnancy and stopped during the first trimester when pregnancy was identified.
  • Statins may cause fetal harm when administered to a pregnant woman. LIPITOR should be administered to women of childbearing potential only when such patients are highly unlikely to conceive and have been informed of the potential hazards. If the woman becomes pregnant while taking LIPITOR, it should be discontinued immediately and the patient advised again as to the potential hazards to the fetus and the lack of known clinical benefit with continued use during pregnancy.

Nursing Mothers

  • It is not known whether atorvastatin is excreted in human milk, but a small amount of another drug in this class does pass into breast milk. Because another drug in this class passes into human milk and because statins have a potential to cause serious adverse reactions in nursing infants, women requiring LIPITOR treatment should be advised not to nurse their infants.

Pediatric Use

  • Safety and effectiveness in patients 10–17 years of age with heterozygous familial hypercholesterolemia have been evaluated in a controlled clinical trial of 6 months' duration in adolescent boys and postmenarchal girls. Patients treated with LIPITOR had an adverse experience profile generally similar to that of patients treated with placebo. The most common adverse experiences observed in both groups, regardless of causality assessment, were infections. Doses greater than 20 mg have not been studied in this patient population. In this limited controlled study, there was no significant effect on growth or sexual maturation in boys or on menstrual cycle length in girls [see Clinical Studies (14.6); Adverse Reactions, Pediatric Patients (ages 10–17 years) (6.3); and Dosage and Administration, Heterozygous Familial Hypercholesterolemia in Pediatric Patients (10–17 years of age) (2.2)]. Adolescent females should be counseled on appropriate contraceptive methods while on LIPITOR therapy [see Contraindications, Pregnancy (4.3) and Use in Specific Populations, Pregnancy (8.1)]. LIPITOR has not been studied in controlled clinical trials involving pre-pubertal patients or patients younger than 10 years of age.
  • Clinical efficacy with doses up to 80 mg/day for 1 year have been evaluated in an uncontrolled study of patients with homozygous FH including 8 pediatric patients.

Geriatric Use

  • Of the 39,828 patients who received LIPITOR in clinical studies, 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 subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older adults cannot be ruled out. Since advanced age (≥65 years) is a predisposing factor for myopathy, LIPITOR should be prescribed with caution in the elderly.

Hepatic Impairment

  • LIPITOR is contraindicated in patients with active liver disease, which may include unexplained persistent elevations in hepatic transaminase levels.
Q: Are there any potential drug interactions?

A: The risk of myopathy during treatment with statins is increased with concurrent administration of fibric acid derivatives, lipid-modifying doses of niacin, cyclosporine, or strong CYP 3A4 inhibitors (e.g., clarithromycin, HIV protease inhibitors, and itraconazole).

Strong Inhibitors of CYP 3A4

  • LIPITOR is metabolized by cytochrome P450 3A4. Concomitant administration of LIPITOR with strong inhibitors of CYP 3A4 can lead to increases in plasma concentrations of atorvastatin. The extent of interaction and potentiation of effects depend on the variability of effect on CYP 3A4.

Clarithromycin: Atorvastatin AUC was significantly increased with concomitant administration of LIPITOR 80 mg with clarithromycin (500 mg twice daily) compared to that of LIPITOR alone [see Clinical Pharmacology (12.3)]. Therefore, in patients taking clarithromycin, caution should be used when the LIPITOR dose exceeds 20 mg.

Combination of Protease Inhibitors: Atorvastatin AUC was significantly increased with concomitant administration of LIPITOR with several combinations of HIV protease inhibitors, as well as with the hepatitis C protease inhibitor telaprevir, compared to that of LIPITOR alone [see Clinical Pharmacology (12.3)]. Therefore, in patients taking the HIV protease inhibitor tipranavir plus ritonavir, or the hepatitis C protease inhibitor telaprevir, concomitant use of LIPITOR should be avoided. In patients taking the HIV protease inhibitor lopinavir plus ritonavir, caution should be used when prescribing LIPITOR and the lowest dose necessary should be used. In patients taking the HIV protease inhibitors saquinavir plus ritonavir, darunavir plus ritonavir, fosamprenavir, or fosamprenavir plus ritonavir, the dose of LIPITOR should not exceed 20 mg and should be used with caution [see Warnings and Precautions, Skeletal Muscle (5.1) and Dosage and Administration (2.6)]. In patients taking the HIV protease inhibitor nelfinavir or the hepatitis C protease inhibitor boceprevir, the dose of LIPITOR should not exceed 40 mg and close clinical monitoring is recommended.

Itraconazole: Atorvastatin AUC was significantly increased with concomitant administration of LIPITOR 40 mg and itraconazole 200 mg [see Clinical Pharmacology (12.3)]. Therefore, in patients taking itraconazole, caution should be used when the LIPITOR dose exceeds 20 mg.

Grapefruit Juice

  • Contains one or more components that inhibit CYP 3A4 and can increase plasma concentrations of atorvastatin, especially with excessive grapefruit juice consumption (>1.2 liters per day).

Cyclosporine

  • Atorvastatin and atorvastatin-metabolites are substrates of the OATP1B1 transporter. Inhibitors of the OATP1B1 (e.g., cyclosporine) can increase the bioavailability of atorvastatin. Atorvastatin AUC was significantly increased with concomitant administration of LIPITOR 10 mg and cyclosporine 5.2 mg/kg/day compared to that of LIPITOR alone [see Clinical Pharmacology (12.3)]. The co-administration of LIPITOR with cyclosporine should be avoided.

Gemfibrozil

  • Due to an increased risk of myopathy/rhabdomyolysis when HMG-CoA reductase inhibitors are co-administered with gemfibrozil, concomitant administration of LIPITOR with gemfibrozil should be avoided.

Other Fibrates

  • Because it is known that the risk of myopathy during treatment with HMG-CoA reductase inhibitors is increased with concurrent administration of other fibrates, LIPITOR should be administered with caution when used concomitantly with other fibrates.

Niacin

  • The risk of skeletal muscle effects may be enhanced when LIPITOR is used in combination with niacin; a reduction in LIPITOR dosage should be considered in this setting.

Rifampin or other Inducers of Cytochrome P450 3A4

  • Concomitant administration of LIPITOR with inducers of cytochrome P450 3A4 (e.g., efavirenz, rifampin) can lead to variable reductions in plasma concentrations of atorvastatin. Due to the dual interaction mechanism of rifampin, simultaneous co-administration of LIPITOR with rifampin is recommended, as delayed administration of LIPITOR after administration of rifampin has been associated with a significant reduction in atorvastatin plasma concentrations.

Digoxin

  • When multiple doses of LIPITOR and digoxin were co-administered, steady state plasma digoxin concentrations increased by approximately 20%. Patients taking digoxin should be monitored appropriately.

Oral Contraceptives

  • Co-administration of LIPITOR and an oral contraceptive increased AUC values for norethindrone and ethinyl estradiol [see Clinical Pharmacology (12.3)]. These increases should be considered when selecting an oral contraceptive for a woman taking LIPITOR.

Warfarin

  • LIPITOR had no clinically significant effect on prothrombin time when administered to patients receiving chronic warfarin treatment.

Colchicine

  • Cases of myopathy, including rhabdomyolysis, have been reported with atorvastatin co-administered with colchicine, and caution should be exercised when prescribing atorvastatin with colchicine.
Q: What are the potential adverse events?

A: The five most common adverse reactions in patients treated with LIPITOR that led to treatment discontinuation and occurred at a rate greater than placebo were:

  • Myalgia
  • Diarrhea
  • Nausea
  • Alanine aminotransferase increase
  • Hepatic enzyme increase

The most commonly reported adverse reactions (incidence ≥2% and greater than placebo), regardless of causality, in patients treated with LIPITOR in placebo-controlled trials (n=8755) were:

  • Nasopharyngitis
  • Arthralgia
  • Diarrhea
  • Pain in extremity
  • Urinary tract infection

Please see the Full Prescribing Information for a complete list of adverse events. For more information on the safety profile of LIPITOR, click here.

Q: What concerns are there regarding toxicity?

A: 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 (0–24) 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 (0–24) values of approximately 6 times the mean human plasma drug exposure after an 80-mg oral dose.

In vitro, LIPITOR was not mutagenic or clastogenic in the following tests with and without metabolic activation: the Ames test with Salmonella typhimurium and Escherichia coli, the HGPRT forward mutation assay in Chinese hamster lung cells, and the chromosomal aberration assay in Chinese hamster lung cells. LIPITOR was negative in the in vivo mouse micronucleus test.

Studies in 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 LIPITOR 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. LIPITOR caused no adverse effects on semen parameters, or reproductive organ histopathology in dogs given doses of 10, 40, or 120 mg/kg for two years.

Q: How does LIPITOR act to reduce elevated total-C, LDL-C, apo-B, and TG levels; and to increase HDL-C in patients with primary hypercholesterolemia?

A: LIPITOR 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. Cholesterol and triglycerides circulate in the bloodstream as part of lipoprotein complexes. With ultracentrifugation, these complexes separate into HDL (high-density lipoprotein), IDL (intermediate-density lipoprotein), LDL (low-density lipoprotein), and VLDL (very-low-density lipoprotein) fractions. Triglycerides (TG) and cholesterol in the liver are incorporated into VLDL and released into the plasma for delivery to peripheral tissues. LDL is formed from VLDL and is catabolized primarily through the high-affinity LDL receptor. Clinical and pathologic studies show that elevated plasma levels of total cholesterol (total-C), LDL-cholesterol (LDL-C), and apolipoprotein B (apo B) promote human atherosclerosis and are risk factors for developing cardiovascular disease, while increased levels of HDL-C are associated with a decreased cardiovascular risk.

Q: Does LIPITOR have a co-pay card/patient assistance program?

A: Yes. With the LIPITOR Savings Card, your eligible patients may pay as little as $4 a month, with a maximum yearly savings of $2500, depending on insurance.* Patients pay $30 if they have other commercial/private insurance, Medicare Part D, or no insurance.

To receive more information about the LIPITOR Savings Program, click here.

*Terms and Conditions apply.

Patients may pay less by receiving the generic.

Patients with Medicare Part D must agree not to use any prescription benefits to purchase LIPITOR.

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