Atorvastatin

Lipitor can cause serious side effects. Stop taking the drug and call your doctor right away if you have any of these serious side effects:

• Unexplained muscle pain, tenderness, or weakness
• Confusion, memory problems, or other cognitive issues
• Fever, unusual tiredness, and dark-colored urine
• Swelling, weight gain, urinating less than usual or not at all
• Increased thirst, increased urination, hunger, dry mouth, fruity breath odor, drowsiness, dry skin, blurred vision, weight loss
• Nausea, upper stomach pain, itching, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes)

Less serious side effects from Lipitor may include mild muscle pain, diarrhea, or mild nausea.

Allergic Reaction to Lipitor

Get emergency medical help if you take Lipitor and have signs of a severe allergic reaction (anaphylaxis) including hives, difficulty breathing, or swelling of your face, lips, tongue, or throat.

Yes

• Tablets of 10, 20, 40, and 80 mg

• Tablets should be stored at room temperature, 20 C to 25 C (68 F to 77 F).

• All statins, including atorvastatin, prevent the production of cholesterol in the liver by blocking HMG-CoA reductase, an enzyme that makes cholesterol. Statins reduce total cholesterol as well as LDL cholesterol in blood. LDL cholesterol is believed to be the "bad" cholesterol that is primarily responsible for the development of coronary artery disease. Reducing LDL cholesterol levels retards progression and may even reverse coronary artery disease. Atorvastatin also raises the concentrations of HDL ("good") cholesterol that protects against coronary artery disease and reduces the concentration of triglycerides in the blood. (High blood concentrations of triglycerides also have been associated with coronary artery disease.)

• The FDA approved atorvastatin in December 1996.

Atorvastatin may be found in some form under the following brand names:

• Caduet

• Lipitor

• Liptruzet

Tell your doctor about all the medicines you take including prescription and non-prescription medicines, vitamins, and herbal supplements. Especially tell your doctor if you take:

• antifungal medications such as itraconazole (Sporanox) and ketoconazole (Nizoral)
• cimetidine (Tagamet)
• clarithromycin (Biaxin)
• colchicine (Colcrys)
• digoxin (Lanoxin)
• diltiazem (Cardizem, Cartia, Taztia, Tiazac)
• erythromycin (E.E.S., E-Mycin, Erythrocin)
• efavirenz (Sustiva, in Atripla)
• oral contraceptives (birth control pills)
• other cholesterol-lowering medications such as fenofibrate (Tricor), gemfibrozil (Lopid), and niacin (nicotinic acid, Niacor, Niaspan)
• certain HIV protease inhibitors such as darunavir (Prezista), fosamprenavir (Lexiva), lopinavir (in Kaletra), nelfinavir (Viracept), saquinavir (Invirase), ritonavir (Norvir, in Kaletra) and tipranavir (Aptivus)
• medications that suppress the immune system such as cyclosporine (Neoral, Sandimmune)
• rifampin (Rifadin, Rimactane)
• spironolactone (Aldactone)
• telaprevir (Incivek)

This is not a complete list of atorvastatin drug interactions. Ask your doctor or pharmacist for more information.

Statin medications, including atorvastatin, carry a rare but serious risk of:

• liver damage
• memory loss or confusion
• increase in blood sugar levels (hyperglycemia)
• type 2 diabetes
• immune-mediated muscle breakdown

Certain statins can increase risk of muscle weakness as well.  It is important to consult your physician to discuss the benefits and risks associated with using this medication.

Do not take atorvastatin if you:

• are pregnant or think you may be pregnant, or are planning to become pregnant. Atorvastatin may harm your unborn baby. If you get pregnant, stop taking atorvastatin and call your doctor right away.
• are breastfeeding. Atorvastatin can pass into your breast milk and may harm your baby.
• have liver problems.
• are allergic to atorvastatin or any of its ingredients. 

Atorvastatin has not been studied in children under 10 years of age.

• Talk to your doctor before you start any new medicines. This includes prescription and non-prescription medicines, vitamins, and herbal supplements. atorvastatin and certain other medicines can interact causing serious side effects.
• Do not get pregnant. If you get pregnant, stop taking atorvastatin right away and call your doctor.

Tell your doctor if you are breastfeeding. Atorvastatin can pass into your breast milk and may harm your baby.

The atorvastatin dose your doctor recommends will depend on several factors including your age, the medical condition being treated, other medical conditions you have, and the medications you are taking.

The recommended starting atorvastatin dose is 10 or 20 mg once daily. For some people with extremely high cholesterol, the starting atorvastatin dose may be as high as 40 mg.

After several weeks the atorvastatin dose may be increased as necessary to achieve the desired cholesterol levels. If you are experiencing side effects, your doctor may reduce your atorvastatin dose. The recommended dosage range of atorvastatin is 10 to 80 mg once daily.

For children (ages 10 to 17), the maximum recommended daily atorvastatin dose is 20 mg.

Take atorvastatin only as directed by your doctor. Do not use more of it, do not use it more often, and do not use it or for a longer time than your doctor ordered.

In addition to atorvastatin, your doctor may change your diet to one that is low in fat, sugar, and cholesterol. Carefully follow your doctor's orders about any special diet.

Take atorvastatin at the same time each day.

Swallow the tablet whole. Do not break, crush, or chew it. Take atorvastatin with or without food.

Do not drink large amounts of alcohol with atorvastatin. This could cause unwanted effects on the liver.

Tell your doctor if you regularly drink grapefruit juice. Drinking large amounts of grapefruit juice (more than 1.2 liters each day) while you take atorvastatin may increase your risk of muscle injury and could result in kidney problems.

Dosing

The dose of atorvastatin will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of atorvastatin. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

• For oral dosage form (tablets):
  • For high cholesterol:
    • Adults—At first, 10 or 20 milligrams (mg) once a day. Some patients may need to start at 40 mg per day. Your doctor may increase your dose as needed. However, the dose is usually not more than 80 mg per day.
    • Children 10 to 17 years of age—At first, 10 mg once a day. Your doctor may increase your dose as needed. However, the dose is usually not more than 20 mg per day.
    • Children younger than 10 years of age)—Use and dose must be determined by your doctor.

Missed Dose

If you miss a dose of atorvastatin, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

However, do not take 2 doses of atorvastatin within 12 hours.

Storage

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Ask your healthcare professional how you should dispose of any medicine you do not use.

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

• Cough
• difficulty with swallowing
• dizziness
• fast heartbeat
• fever
• hives
• itching
• muscle cramps, pain, stiffness, swelling, or weakness
• puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue
• skin rash
• tightness in the chest
• unusual tiredness or weakness
• wheezing

• Blistering, peeling, or loosening of the skin
• chills
• dark-colored urine
• diarrhea
• joint pain
• large, hive-like swelling on the face, eyelids, lips, tongue, throat, hands, legs, feet, or sex organs
• red skin lesions, often with a purple center sore
• red, irritated eyes
• sore throat
• sores, ulcers, or white spots in the mouth or on the lips

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Headache
• hoarseness
• lower back or side pain
• pain or tenderness around the eyes and cheekbones
• painful or difficult urination
• stuffy or runny nose

• Abdominal or stomach pain
• back pain
• belching or excessive gas
• constipation
• general feeling of discomfort or illness
• heartburn, indigestion, or stomach discomfort
• lack or loss of strength
• loss of appetite
• nausea
• shivering
• sweating
• trouble sleeping
• vomiting

• Appetite increased
• black, tarry stools
• bloody nose
• bloody or cloudy urine
• blurred vision
• continuing ringing or buzzing or other unexplained noise in the ears
• difficult, burning, or painful urination
• difficulty seeing at night
• excessive muscle tone or tension
• fruit-like breath odor
• groin or scrotum pain
• inability to have or keep an erection
• increased body movements
• increased sensitivity of the eyes to light
• increased sensitivity to touch or pain
• increased thirst
• increased urination
• loss of bladder control
• loss of sexual ability, drive, or desire
• menstrual bleeding occurring earlier or lasting longer than usual
• mental depression
• nervousness
• nightmares
• pale skin
• paranoia
• pinpoint red spots on the skin
• slurred speech
• swollen or tender lymph glands in the neck, armpit, or groin
• unable to move or feel face
• unusual bleeding or bruising
• weight loss

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

• It is used to prevent heart attacks.
• It is used to prevent strokes.
• It is used to prevent chest pain.
• It is used to lower bad cholesterol and raise good cholesterol (HDL).
• It is used to lower triglycerides.
• It is used to slow the progress of heart disease.
• It may be given to you for other reasons. Talk with the doctor.

• If you have an allergy to atorvastatin or any other part of atorvastatin.
• If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
• If you are pregnant or may be pregnant. Do not take this medicine if you are pregnant.
• If you are breast-feeding. Do not breast-feed while you take atorvastatin.
• If you have any of these health problems: Active liver disease or a rise in liver enzymes.
• If you are taking any of these drugs: Cyclosporine, gemfibrozil, telaprevir, or tipranavir plus ritonavir.

This is not a list of all drugs or health problems that interact with this medicine.

Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take atorvastatin with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

Pregnancy

Risk Summary 
Atorvastatin calcium is contraindicated for use in pregnant women since safety in pregnant women has not been established and there is no apparent benefit of lipid lowering drugs during pregnancy. Because HMG-CoA reductase inhibitors decrease cholesterol synthesis and possibly the synthesis of other biologically active substances derived from cholesterol, Atorvastatin calcium may cause fetal harm when administered to a pregnant woman. Atorvastatin calcium should be discontinued as soon as pregnancy is recognized [see Contraindications (4)]. Limited published data on the use of Atorvastatin are insufficient to determine a drug-associated risk of major congenital malformations or miscarriage. In animal reproduction studies in rats and rabbits there was no evidence of embryo-fetal toxicity or congenital malformations at doses 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/m2). In rats administered Atorvastatin during gestation and lactation, decreased postnatal growth and development was 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 2-4% and 15-20%, respectively. 

Data
Human Data
Limited published data on Atorvastatin calcium from observational studies, meta-analyses and case reports have not shown an increased risk of major congenital malformations or miscarriage. Rare reports of congenital anomalies have been received following intrauterine exposure to other HMG-CoA reductase inhibitors. In a review of approximately 100 prospectively followed pregnancies in women exposed to simvastatin or lovastatin, the incidences of congenital anomalies, spontaneous abortions, and fetal deaths/stillbirths did not exceed what would be expected in the general population. The number of cases is adequate to exclude a ≥3to 4-fold increase in congenital anomalies over the background incidence. In 89% of the prospectively followed pregnancies, drug treatment was initiated prior to pregnancy and was discontinued at some point in the first trimester when pregnancy was identified.

Animal Data
Atorvastatin crosses the rat placenta and reaches a level in fetal liver equivalent to that of maternal plasma. Atorvastatin was administered to pregnant rats and rabbits during organogenesis at oral doses up to 300mg/kg/day and 100mg/kg/day, respectively. Atorvastatin was not teratogenic in rats at doses up to 300mg/kg/day or in rabbits at doses up to 100mg/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/m2). In rats, the maternally toxic dose of 300mg/kg resulted in increased post-implantation loss and decreased fetal body weight. At the maternally toxic doses of 50 and 100mg/kg/day in rabbits, there was increased post-implantation loss, and at 100mg/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 225mg/kg/day, a dose at which maternal toxicity was observed. Pup body weight was decreased through postnatal day 21at 100 mg/kg/day, and through postnatal day 91 at 225 mg/kg/day. Pup development was delayed (rotorod performance at 100mg/kg/dayand acoustic startle at 225 mg/kg/day; pinnae detachment and eye-opening at 225mg/kg/day). These doses correspond to 6 times (100 mg/kg) and 22times (225 mg/kg) the human exposure at the MRHD, based on AUC.

Lactation

Risk Summary

Atorvastatin calcium use is contraindicated during breastfeeding [see Contraindications (4)]. There is no available information on the effects of the drug on the breastfed infant or the effects of the drug on milk production. It is not known whether Atorvastatin is present in human milk, but it has been shown that another drug in this class passes into human milk and Atorvastatin is present in rat milk. Because of the potential for serious adverse reactions in a breastfed infant, advise women that breastfeeding is not recommended during treatment with Atorvastatin calcium.

Females and Males of Reproductive Potential

Atorvastatin calcium may cause fetal harm when administered to a pregnant woman. Advise females of reproductive potential to use effective contraception during treatment with Atorvastatin calcium [see Use in Specific Populations (8.1)].

Pediatric Use

Heterozygous Familial Hypercholesterolemia (HeFH)

The safety and effectiveness of Atorvastatin calcium have been established in pediatric patients, 10 years to 17 years of age, with HeFH as an adjunct to diet to reduce total cholesterol, LDL-C, and apo B levels when, after an adequate trial of diet therapy, the following are present:

• LDL-C ≥ 190 mg/dL, or
• LDL-C ≥ 160 mg/dL and
  • a positive family history of FH, or premature CVD in a first, or second-degree relative, or
  • two or more other CVD risk factors are present.

Use of Atorvastatin calcium for this indication is supported by evidence from [see Dosage and Administration (2.2), Adverse Reactions (6.1), Clinical Pharmacology (12.3), and Clinical Studies (14.6)]:

• A placebo-controlled clinical trial of 6 months duration in 187 boys and postmenarchal girls,10 years to 17 years of age. Patients treated with 10 mg or 20 mg daily Atorvastatin calcium had an adverse reaction profile generally similar to that of patients treated with placebo. In this limited controlled study, there was no significant effect on growth or sexual maturation in boys or on menstrual cycle length in girls.
• A three year open-label uncontrolled trial that included 163 pediatric patients 10 to 15years of age with HeFH who were titrated to achieve a target LDL-C < 130 mg/dL. The safety and efficacy of Atorvastatin calcium in lowering LDL-C appeared generally consistent with that observed for adult patients, despite limitations of the uncontrolled study design

Advise postmenarchal girls of contraception recommendations, if appropriate for the patient [see Use in Specific Populations (8.1), (8.3)].

The long-term efficacy of Atorvastatin calcium therapy initiated in childhood to reduce morbidity and mortality in adulthood has not been established.

The safety and efficacy of Atorvastatin calcium have not been established in pediatric patients younger than 10 years of age with HeFH.

Homozygous Familial Hypercholesterolemia (HoFH)

Clinical efficacy of Atorvastatin calcium with dosages up to 80mg/day for 1 year was evaluated in an uncontrolled study of patients with HoFH including 8 pediatric patients [see Clinical Studies (14.5)].

Geriatric Use

Of the 39,828 patients who received Atorvastatin calcium 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, Atorvastatin calcium should be prescribed with caution in the elderly.

Hepatic Impairment

Atorvastatin calcium is contraindicated in patients with active liver disease which may include unexplained persistent elevations in hepatic transaminase levels [see Contraindications (4) and Clinical Pharmacology (12.3)].

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 typhimurium and 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 vivo mouse 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 as permia 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 80mg dose); testis weights were significantly lower at 30 and 100mg/kg and epididymal weight was lower at 100mg/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 two years.

Inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, the rate-limiting enzyme in cholesterol synthesis (reduces the production of mevalonic acid from HMG-CoA); this then results in a compensatory increase in the expression of LDL receptors on hepatocyte membranes and a stimulation of LDL catabolism. In addition to the ability of HMG-CoA reductase inhibitors to decrease levels of high-sensitivity C-reactive protein (hsCRP), they also possess pleiotropic properties including improved endothelial function, reduced inflammation at the site of the coronary plaque, inhibition of platelet aggregation, and anticoagulant effects (de Denus 2002; Ray 2005).

Absorption

Oral: Rapidly absorbed; extensive first-pass metabolism in GI mucosa and liver

Distribution

Vd: ~381 L

Metabolism

Hepatic via CYP3A4; forms active ortho- and parahydroxylated derivatives and an inactive beta-oxidation product; plasma concentrations are elevated in patients with chronic alcoholic liver disease and Childs-Pugh class A and B liver disease

Excretion

Bile (following hepatic and/or extra-hepatic metabolism; does not appear to undergo enterohepatic recirculation); urine (<2% as unchanged drug)

Note: Doses should be individualized according to the baseline LDL-cholesterol concentrations and patient response; adjustments should be made at intervals of 4 weeks

Heterozygous familial hypercholesterolemia: Children ≥10 years and Adolescents (females postmenarche): Oral: 10 mg once daily (maximum: 20 mg/day)

Dosage adjustment for atorvastatin with concomitant medications: Refer to adult dosing.

Administer with or without food; may take without regard to time of day. The manufacturer’s labeling states tablets should not be broken; however, available data do not indicate any safety or efficacy concerns with this practice.

Store at 20°C to 25°C (68°F to 77°F).

Acipimox: May enhance the myopathic (rhabdomyolysis) effect of HMG-CoA Reductase Inhibitors. Monitor therapy

Aliskiren: AtorvaSTATin may increase the serum concentration of Aliskiren. Monitor therapy

Amiodarone: May increase the serum concentration of AtorvaSTATin. Monitor therapy

Antacids: May decrease the serum concentration of HMG-CoA Reductase Inhibitors. Monitor therapy

Antihepaciviral Combination Products: May increase the serum concentration of AtorvaSTATin. Avoid combination

Aprepitant: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy

ARIPiprazole: CYP3A4 Inhibitors (Weak) may increase the serum concentration of ARIPiprazole. Management: Monitor for increased aripiprazole pharmacologic effects. Aripiprazole dose adjustments may or may not be required based on concomitant therapy and/or indication. Consult full interaction monograph for specific recommendations. Monitor therapy

Asunaprevir: May increase the serum concentration of HMG-CoA Reductase Inhibitors. Monitor therapy

Azithromycin (Systemic): May enhance the myopathic (rhabdomyolysis) effect of AtorvaSTATin. Monitor therapy

Bexarotene (Systemic): May decrease the serum concentration of AtorvaSTATin. Monitor therapy

Bezafibrate: May enhance the myopathic (rhabdomyolysis) effect of HMG-CoA Reductase Inhibitors. Bezafibrate may increase the serum concentration of HMG-CoA Reductase Inhibitors. More specifically, bezafibrate may increase the serum concentration of fluvastatin Management: Monitor patients closely for myopathy with concomitant use of bezafibrate and HMG-CoA reductase inhibitors. Concomitant use is contraindicated in patients predisposed to myopathy and alternative therapy should be considered. Consider therapy modification

Bile Acid Sequestrants: May decrease the serum concentration of AtorvaSTATin. Monitor therapy

Boceprevir: May increase the serum concentration of AtorvaSTATin. Management: Limit the atorvastatin maximum adult dose to 40 mg daily in patients receiving boceprevir. Monitor clinical response to ensure that the lowest necessary atorvastatin dose is used. Consider therapy modification

Bosentan: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy

Cimetidine: AtorvaSTATin may enhance the adverse/toxic effect of Cimetidine. Specifically, there is a theoretical potential for enhanced effects on reducing endogenous steroid activity. Monitor therapy

Ciprofibrate: May enhance the adverse/toxic effect of HMG-CoA Reductase Inhibitors. Management: Avoid the use of HMG-CoA reductase inhibitors and ciprofibrate if possible. If concomitant therapy is considered, benefits should be carefully weighed against the risks, and patients should be monitored closely for signs/symptoms of muscle toxicity. Consider therapy modification

Clarithromycin: May increase the serum concentration of AtorvaSTATin. Management: Limit atorvastatin to a maximum dose of 20 mg/day (for adults) when used with clarithromycin. If this combination is used, monitor patients more closely for evidence of atorvastatin toxicity. Consider therapy modification

Cobicistat: May increase the serum concentration of AtorvaSTATin. Management: Initiate atorvastatin at the lowest recommended dose and titrate slowly as needed while monitoring closely for evidence of atorvastatin toxicity. Consider therapy modification

Colchicine: May enhance the myopathic (rhabdomyolysis) effect of HMG-CoA Reductase Inhibitors. Colchicine may increase the serum concentration of HMG-CoA Reductase Inhibitors. Consider therapy modification

Conivaptan: May increase the serum concentration of CYP3A4 Substrates. Avoid combination

CycloSPORINE (Systemic): May increase the serum concentration of AtorvaSTATin. Avoid combination

CYP3A4 Inducers (Moderate): May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy

CYP3A4 Inducers (Strong): May increase the metabolism of CYP3A4 Substrates. Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. Consider therapy modification

CYP3A4 Inhibitors (Moderate): May decrease the metabolism of CYP3A4 Substrates. Monitor therapy

CYP3A4 Inhibitors (Strong): May decrease the metabolism of CYP3A4 Substrates. Consider therapy modification

Cyproterone: May increase the serum concentration of HMG-CoA Reductase Inhibitors. Management: Avoid use of statins metabolized by CYP3A4 (eg, simvastatin) and consider avoiding fluvastatin as well in patients receiving high dose cyproterone (300 mg/day). Consider use of pravastatin, rosuvastatin, or pitavastatin if statin therapy is needed. Consider therapy modification

Dabigatran Etexilate: AtorvaSTATin may decrease the serum concentration of Dabigatran Etexilate. Monitor therapy

Dabrafenib: May decrease the serum concentration of CYP3A4 Substrates. Management: Seek alternatives to the CYP3A4 substrate when possible. If concomitant therapy cannot be avoided, monitor clinical effects of the substrate closely (particularly therapeutic effects). Consider therapy modification

Daclatasvir: May increase the serum concentration of HMG-CoA Reductase Inhibitors. Monitor therapy

Danazol: May increase the serum concentration of HMG-CoA Reductase Inhibitors. Management: Concurrent use of simvastatin with danazol is contraindicated. Initiate lovastatin at an adult maximum dose of 10 mg/day, and do not exceed 20 mg/day, when danazol is given concomitantly. Fluvastatin, pravastatin and rosuvastatin may pose lower risk. Consider therapy modification

DAPTOmycin: HMG-CoA Reductase Inhibitors may enhance the adverse/toxic effect of DAPTOmycin. Specifically, the risk of skeletal muscle toxicity may be increased. Management: Consider temporarily stopping HMG-CoA reductase inhibitor therapy prior to daptomycin. If used together, regular (i.e., at least weekly) monitoring of CPK concentrations is recommended. Consider therapy modification

Dasatinib: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy

Deferasirox: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy

Digoxin: AtorvaSTATin may increase the serum concentration of Digoxin. Monitor therapy

DilTIAZem: AtorvaSTATin may increase the serum concentration of DilTIAZem. DilTIAZem may increase the serum concentration of AtorvaSTATin. Management: Consider using lower atorvastatin doses when used together with diltiazem. Consider therapy modification

Dofetilide: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Dofetilide. Monitor therapy

Dronedarone: May increase the serum concentration of AtorvaSTATin. Monitor therapy

Efavirenz: May decrease the serum concentration of AtorvaSTATin. Monitor therapy

Elbasvir: May increase the serum concentration of AtorvaSTATin. Management: Limit the dose of atorvastatin to a maximum of 20 mg/day when used together with elbasvir and grazoprevir. Monitor closely for evidence of statin-related toxicities such as myalgia or myopathy. Consider therapy modification

Eltrombopag: May increase the serum concentration of OATP1B1/SLCO1B1 Substrates. Monitor therapy

Enzalutamide: May decrease the serum concentration of CYP3A4 Substrates. Management: Concurrent use of enzalutamide with CYP3A4 substrates that have a narrow therapeutic index should be avoided. Use of enzalutamide and any other CYP3A4 substrate should be performed with caution and close monitoring. Consider therapy modification

Erythromycin (Systemic): May increase the serum concentration of AtorvaSTATin. Monitor therapy

Etravirine: May decrease the serum concentration of HMG-CoA Reductase Inhibitors. This applies to atorvastatin, lovastatin and simvastatin. Conversely, levels of fluvastatin may be increased. Management: Dose adjustment of the HMG-CoA reductase inhibitor may be warranted. No interaction is expected with rosuvastatin, pravastatin, or pitavastatin. Monitor therapy

Fenofibrate and Derivatives: May enhance the adverse/toxic effect of HMG-CoA Reductase Inhibitors. Monitor therapy

Flibanserin: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Flibanserin. Monitor therapy

Fluconazole: May increase the serum concentration of AtorvaSTATin. Monitor therapy

Fosaprepitant: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy

Fosphenytoin: May decrease the serum concentration of HMG-CoA Reductase Inhibitors. Consider therapy modification

Fusidic Acid (Systemic): May enhance the adverse/toxic effect of HMG-CoA Reductase Inhibitors. Specifically, the risk for muscle toxicities, including rhabdomyolysis may be significantly increased. Management: Avoid concurrent use whenever possible. Use is listed as contraindicated in product characteristic summaries in several countries, although UK labeling suggests that use could be considered under exceptional circumstances and with close supervision. Avoid combination

Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates. Avoid combination

Gemfibrozil: May enhance the myopathic (rhabdomyolysis) effect of AtorvaSTATin. Gemfibrozil may increase the serum concentration of AtorvaSTATin. Avoid combination

Glecaprevir and Pibrentasvir: May increase the serum concentration of AtorvaSTATin. Avoid combination

Grapefruit Juice: May increase the serum concentration of HMG-CoA Reductase Inhibitors. Management: Avoid concurrent use of GFJ with lovastatin or simvastatin. Avoid high quantities of GFJ with atorvastatin. Consider using a lower statin dose or a statin that is less likely to interact when possible. Consider therapy modification

Grazoprevir: May increase the serum concentration of AtorvaSTATin. Management: Limit the dose of atorvastatin to a maximum of 20 mg/day when used together with elbasvir and grazoprevir. Monitor closely for evidence of statin-related toxicities such as myalgia or myopathy. Consider therapy modification

HYDROcodone: CYP3A4 Inhibitors (Weak) may increase the serum concentration of HYDROcodone. Monitor therapy

Idelalisib: May increase the serum concentration of CYP3A4 Substrates. Avoid combination

Itraconazole: May increase the serum concentration of AtorvaSTATin. Management: Limit atorvastatin to a maximum adult dose of 20 mg/day in patients receiving itraconazole. Assess clinical response to ensure that the lowest necessary dose of atorvastatin is used. Consider use of fluva-, rosuva-, pitava-, or pravastatin when possible. Consider therapy modification

Ketoconazole (Systemic): AtorvaSTATin may enhance the adverse/toxic effect of Ketoconazole (Systemic). Specifically, there is a theoretical potential for additive effects on reducing endogenous steroid concentrations. Ketoconazole (Systemic) may increase the serum concentration of AtorvaSTATin. Management: Administer ketoconazole with atorvastatin cautiously, and monitor for toxic effects of atorvastatin (e.g., myalgia, rhabdomyolysis, liver function test abnormalities). Consider use of fluva-, rosuva-, pitava-, or pravastatin when possible. Consider therapy modification

Lanthanum: HMG-CoA Reductase Inhibitors may decrease the serum concentration of Lanthanum. Management: Administer HMG-CoA reductase inhibitors at least two hours before or after lanthanum. Consider therapy modification

Lomitapide: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Lomitapide. Management: Patients on lomitapide 5 mg/day may continue that dose. Patients taking lomitapide 10 mg/day or more should decrease the lomitapide dose by half. The lomitapide dose may then be titrated up to a max adult dose of 30 mg/day. Consider therapy modification

Midazolam: AtorvaSTATin may increase the serum concentration of Midazolam. Monitor therapy

MiFEPRIStone: May increase the serum concentration of CYP3A4 Substrates. Management: Minimize doses of CYP3A4 substrates, and monitor for increased concentrations/toxicity, during and 2 weeks following treatment with mifepristone. Avoid cyclosporine, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, and tacrolimus. Consider therapy modification

Mitotane: May decrease the serum concentration of CYP3A4 Substrates. Management: Doses of CYP3A4 substrates may need to be adjusted substantially when used in patients being treated with mitotane. Consider therapy modification

Netupitant: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy

Niacin: May enhance the adverse/toxic effect of HMG-CoA Reductase Inhibitors. Monitor therapy

Niacinamide: May enhance the adverse/toxic effect of HMG-CoA Reductase Inhibitors. Monitor therapy

NiMODipine: CYP3A4 Inhibitors (Weak) may increase the serum concentration of NiMODipine. Monitor therapy

Palbociclib: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy

PAZOPanib: AtorvaSTATin may enhance the hepatotoxic effect of PAZOPanib. AtorvaSTATin may increase the serum concentration of PAZOPanib. Avoid combination

P-glycoprotein/ABCB1 Inhibitors: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates. P-glycoprotein inhibitors may also enhance the distribution of p-glycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.). Monitor therapy

Phenytoin: May decrease the serum concentration of HMG-CoA Reductase Inhibitors. Consider therapy modification

Pimozide: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Pimozide. Avoid combination

Posaconazole: May increase the serum concentration of AtorvaSTATin. Avoid combination

Protease Inhibitors: May increase the serum concentration of AtorvaSTATin. Management: See full monograph for recommended dose limits. Avoid atorvastatin with tipranavir/ritonavir. Consider therapy modification

QuiNINE: May increase the serum concentration of HMG-CoA Reductase Inhibitors. Management: Consider using a lower starting dose and lower maintenance/maximum doses of atorvastatin, simvastatin, or lovastatin when used together with quinine. Consider therapy modification

Raltegravir: May enhance the myopathic (rhabdomyolysis) effect of HMG-CoA Reductase Inhibitors. Monitor therapy

Ranolazine: May increase the serum concentration of AtorvaSTATin. Monitor therapy

Red Yeast Rice: May enhance the adverse/toxic effect of HMG-CoA Reductase Inhibitors. Avoid combination

Repaglinide: HMG-CoA Reductase Inhibitors may increase the serum concentration of Repaglinide. Monitor therapy

Rifamycin Derivatives: May decrease the serum concentration of HMG-CoA Reductase Inhibitors. Management: Consider use of noninteracting antilipemic agents (note: pitavastatin concentrations may increase with rifamycin treatment). Monitor for altered HMG-CoA reductase inhibitor effects. Rifabutin and fluvastatin, or possibly pravastatin, may pose lower risk. Consider therapy modification

Rupatadine: May enhance the adverse/toxic effect of HMG-CoA Reductase Inhibitors. Specifically, the risk for increased CPK and/or other muscle toxicities may be increased. Monitor therapy

Sarilumab: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy

Siltuximab: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy

Simeprevir: May increase the serum concentration of AtorvaSTATin. Management: The maximum atorvastatin dose should not exceed 40 mg/day with concurrent use of simeprevir, and use of the lowest necessary atorvastatin dose is recommended. Consider therapy modification

Spironolactone: AtorvaSTATin may enhance the adverse/toxic effect of Spironolactone. Specifically, there is a theoretical potential for enhanced effects on reducing endogenous steroid activity. Monitor therapy

St John's Wort: May increase the metabolism of HMG-CoA Reductase Inhibitors. Management: Consider avoiding the concomitant administration of St Johns Wort with interacting HMG-CoA reductase inhibitors in order to avoid the potential for decreased antilipemic effects. Monitor for decreased effects during concomitant therapy. Consider therapy modification

St John's Wort: May decrease the serum concentration of CYP3A4 Substrates. Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. Consider therapy modification

Stiripentol: May increase the serum concentration of CYP3A4 Substrates. Management: Use of stiripentol with CYP3A4 substrates that are considered to have a narrow therapeutic index should be avoided due to the increased risk for adverse effects and toxicity. Any CYP3A4 substrate used with stiripentol requires closer monitoring. Consider therapy modification

Telaprevir: May increase the serum concentration of AtorvaSTATin. Avoid combination

Telithromycin: May increase the serum concentration of AtorvaSTATin. Management: Consider limiting atorvastatin to a max (adult) dose of 20 mg/day when used with telithromycin. Although not a specific recommendation in atorvastatin labeling, this is consistent with dosing for other strong CYP3A4 inhibitors, including clarithromycin. Consider therapy modification

Teriflunomide: May increase the serum concentration of OATP1B1/SLCO1B1 Substrates. Monitor therapy

Ticagrelor: May increase the serum concentration of AtorvaSTATin. Monitor therapy

Tipranavir: May increase the serum concentration of AtorvaSTATin. Avoid combination

Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy

Trabectedin: HMG-CoA Reductase Inhibitors may enhance the myopathic (rhabdomyolysis) effect of Trabectedin. Monitor therapy

Velpatasvir: May increase the serum concentration of AtorvaSTATin. Monitor therapy

Verapamil: AtorvaSTATin may increase the serum concentration of Verapamil. Verapamil may increase the serum concentration of AtorvaSTATin. Management: Consider using lower atorvastatin doses when used together with verapamil. Consider therapy modification

Voriconazole: May increase the serum concentration of AtorvaSTATin. Management: Monitor for toxic effects of atorvastatin (e.g., myalgia, rhabdomyolysis, liver function test abnormalities) during concomitant treatment, and reduce atorvastatin dose when possible. Consider use of fluva-, rosuva-, pitava-, or pravastatin when possible. Consider therapy modification

Voxilaprevir: May increase the serum concentration of HMG-CoA Reductase Inhibitors. Management: Use the lowest statin dose possible if combined with voxilaprevir and monitor patients for increased statin effects/toxicities. Avoid concomitant use of voxilaprevir with rosuvastatin or pitavastatin, and limit pravastatin doses to 40 mg daily. Consider therapy modification

Certain other drugs can increase your risk of serious muscle problems, and it is very important that your doctor knows if you are using any of them. Tell your doctor about all your current medicines and any you start or stop using, especially:

• antibiotic or antifungal medicine;

• birth control pills;

• cholesterol-lowering medication;

• heart medication; or

• medicine to treat HIV or AIDS.

This list is not complete. Other drugs may interact with atorvastatin, including prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible interactions are listed in this medication guide.

-Initial dose: 10 mg or 20 mg orally once a day; an initial dose of 40 mg may be used in patients who require a reduction in low density lipoprotein (LDL-C) of more than 45%
-Maintenance dose: 10 mg to 80 mg orally once a day

Comments:
-Following initiation and/or upon titration, lipid levels should be evaluated within 2 to 4 weeks and dosages adjusted accordingly.

Uses: As an adjunct to diet in the following conditions: to reduced total cholesterol (total-C), LDL-C, apolipoprotein B (apo B), and triglyceride (TG) levels, and to increase high density lipoprotein (HDL-C) in patients with primary hypercholesterolemia (heterozygous familial and nonfamilial) and mixed dyslipidemia (Fredrickson Types IIa and IIb); for the treatment of elevated TG levels (Fredrickson Type IV); and for the treatment of primary dysbetalipoproteinemia (Fredrickson Type III) in patients who do not respond adequately to diet

-Initial dose: 10 mg or 20 mg orally once a day; an initial dose of 40 mg may be used in patients who require a reduction in low density lipoprotein (LDL-C) of more than 45%
-Maintenance dose: 10 mg to 80 mg orally once a day

Comments:
-Following initiation and/or upon titration, lipid levels should be evaluated within 2 to 4 weeks and dosages adjusted accordingly.

Uses: As an adjunct to diet in the following conditions: to reduced total cholesterol (total-C), LDL-C, apolipoprotein B (apo B), and triglyceride (TG) levels, and to increase high density lipoprotein (HDL-C) in patients with primary hypercholesterolemia (heterozygous familial and nonfamilial) and mixed dyslipidemia (Fredrickson Types IIa and IIb); for the treatment of elevated TG levels (Fredrickson Type IV); and for the treatment of primary dysbetalipoproteinemia (Fredrickson Type III) in patients who do not respond adequately to diet

• Atorvastatin, in conjunction with dietary measures, may be used for the treatment of high cholesterol in people at increased risk of cardiovascular disease if initial dietary measures fail to lower cholesterol.
• Atorvastatin is also used to lower the risk of coronary events (such as a heart attack, stroke, or angina) in patients at high risk of these events. This includes people with pre-existing coronary heart disease, diabetes, peripheral vessel disease, a previous history of stroke and stroke-like events or heart attack, or with multiple risk factors (such as older age, smoking, high blood pressure, low HDL-C, family history of heart disease).
• Possibly more effective than other statins.
• Generic atorvastatin is available.