The following drugs and medications are in some way related to, or used in the treatment of Sinus Symptoms. This service should be used as a supplement to, and NOT a substitute for, the expertise, skill, knowledge and judgment of healthcare practitioners.
Loratadine 10 mg
Antihistamine
temporarily relieves these symptoms due to hay fever or other upper respiratory allergies:
if you have ever had an allergic reaction to this product or any of its ingredients
liver or kidney disease. Your doctor should determine if you need a different dose.
do not take more than directed. Taking more than directed may cause drowsiness.
an allergic reaction to this product occurs. Seek medical help right away.
ask a health professional before use.
In case of overdose, get medical help or contact a Poison Control Center right away.
| adults and children 6 years and over | 1 tablet daily; not more than 1 tablet in 24 hours |
| children under 6 years of age | ask a doctor |
| consumers with liver or kidney disease | ask a doctor |
lactose monohydrate, magnesium stearate, povidone, pregelatinized starch
1-866-322-2439
Compare to active ingredient of Claritin®
Allergy Relief
Loratadine Tablets, 10 mg/Antihistamine
24 Hour Relief of:
Sneezing
Runny Nose
Itchy, Watery Eyes
Itchy Throat or Nose
Non-Drowsy*
Indoor & Outdoor Allergies
Actual Size
*When taken as directed. See Drug Facts Panel.
Allergy Relief Carton
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| Marketing Information | |||
| Marketing Category | Application Number or Monograph Citation | Marketing Start Date | Marketing End Date |
| ANDA | ANDA076301 | 12/15/2007 | |
| Labeler - DZA Brands LLC (090322194) |
Buttercup Syrup
Squill Liquid Extract 0.062% v/v
Capsicum Tincture 0.05% v/v
Oral Liquid
For coughs, colds, sore throats, hoarseness.
Route of administration: oral.
Adults: Two 5 ml spoonfuls three times a day and on retiring, when the cough is troublesome.
Children (over 2 years of age): One 5 ml spoonful three times a day and on retiring, when the cough is troublesome.
Children (under 2 years of age): Not recommended.
None known.
If symptoms persist, consult your doctor. Keep all medicines out of the reach and sight of children.
Patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency should not take this medicine.
None known.
As with all medicines, caution is required. If in doubt, consult your medical adviser.
None.
None known.
None known.
Traditional mixed constituents, syrup based remedy providing symptomatic relief by virtue of demulcent properties, a mild expectorant action and an aromatic “warming” flavour.
None available.
None.
Acacia Powder
Caramel Colour (E150)
Ethanol 96%
Levomenthol
Clove Oil
Peppermint Oil
Sodium methyl hydroxybenzoate (E219)
Sodium propyl hydroxybenzoate (E217)
Aniseed Flavour
Purified Water
Carmoisine (E122)
Sunset Yellow (E110)
Strong Ginger Tincture
Acetic Acid (80%)
Saccharin Sodium
Syrup (fructose, glucose and sucrose)
None known.
36 months (unopened).
28 days (after first opening the bottle).
None
75 ml bottle: R.O.P.P. aluminium cap.
150 ml bottle: R.O.P.P. aluminium cap.
200 ml bottle: White fluted plastic cap with viskring and aluminium foil wad.
All sizes are in clear glass flat bottles, with straight sides. Caps are twist off.
None
Chefaro UK Ltd,
4th Floor, Hamilton House,
Mabledon Place, Bloomsbury,
LONDON, WC1H 9BB
United Kingdom
PL 02855/0024
30th November 2004
14th November 2010
Tegretol Chewable Tablets may rarely cause severe blood problems (eg, aplastic anemia, agranulocytosis). Contact your doctor right away if you develop fever, chills, or sore throat; rash; ulcers or sores in the mouth; unusual bruising or bleeding; unusual tiredness; or swollen lymph nodes. Lab tests, including complete blood cell counts, will be performed before and during treatment with Tegretol Chewable Tablets. These tests will be used to check for side effects.
Tegretol Chewable Tablets may rarely cause serious and sometimes fatal skin reactions. Contact your doctor at once if you develop red, swollen, blistered, or peeling skin with or without fever. The risk of this reaction may be greater in Asian patients. Asian patients may need to have a blood test before they start Tegretol Chewable Tablets to determine whether they have a greater risk of developing a severe skin reaction.
Treating certain types of seizures. It is also used to treat severe pain of the jaw or cheek caused by a facial nerve problem (trigeminal neuralgia). It may also be used for other conditions as determined by your doctor.
Tegretol Chewable Tablets are an anticonvulsant. It works to control seizures by blocking certain nerve impulses in the brain. It works to treat trigeminal neuralgia by altering nerve impulses in certain facial nerves, which relieves pain.
Contact your doctor or health care provider right away if any of these apply to you.
Treatments for depression are getting better everyday and there are things you can start doing right away.
Some medical conditions may interact with Tegretol Chewable Tablets. Tell your doctor or pharmacist if you have any medical conditions, especially if any of the following apply to you:
Some MEDICINES MAY INTERACT with Tegretol Chewable Tablets. Tell your health care provider if you are taking any other medicines, especially any of the following:
This may not be a complete list of all interactions that may occur. Ask your health care provider if Tegretol Chewable Tablets may interact with other medicines that you take. Check with your health care provider before you start, stop, or change the dose of any medicine.
Use Tegretol Chewable Tablets as directed by your doctor. Check the label on the medicine for exact dosing instructions.
Ask your health care provider any questions you may have about how to use Tegretol Chewable Tablets.
All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome:
Dizziness; drowsiness; dry mouth; nausea; unsteadiness; vomiting.
Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); black, tarry, or bloody stools; calf pain, swelling, or tenderness; change in the amount of urine produced; chest pain; confusion; dark urine; decreased coordination; fainting; fast, slow, or irregular heartbeat; fever, chills, or sore throat; hallucinations; joint pain; light-headedness; loss of appetite; menstrual changes; new or worsening mental or mood changes (eg, aggression, agitation, anger, anxiety, depression, irritability, restlessness); pain, tenderness, or unusual swelling in the neck, groin, or under the arms; red or purple spots on your body; red, swollen, blistered, or peeling skin; severe or persistent dizziness or headache; severe or persistent nausea or vomiting; shortness of breath; speech problems; stomach pain; sudden, unusual weight gain; suicidal thoughts or actions; swelling of the hands, ankles, or feet; swollen lymph nodes; ulcers or sores in the mouth; trouble sleeping; uncontrolled muscle movements; unusual bruising or bleeding (eg, bleeding gums, nosebleeds); unusual tiredness or weakness; vision or eye problems; yellowing of the skin or eyes.
This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider. Call your doctor for medical advice about side effects. To report side effects to the appropriate agency, please read the Guide to Reporting Problems to FDA.
See also: Tegretol side effects (in more detail)
Contact 1-800-222-1222 (the American Association of Poison Control Centers), your local poison control center, or emergency room immediately. Symptoms may include decreased urination; fainting; fast or irregular heartbeat; loss of consciousness; muscle twitching or tremor; seizures; severe dizziness, headache, or drowsiness; severe nausea or vomiting; slow, shallow, or irregular breathing.
Store Tegretol Chewable Tablets at room temperature, between 59 and 86 degrees F (15 and 30 degrees C), in a tightly closed container. Store away from heat, moisture, and light. Do not store in the bathroom. Keep Tegretol Chewable Tablets out of the reach of children and away from pets.
This information is a summary only. It does not contain all information about Tegretol Chewable Tablets. If you have questions about the medicine you are taking or would like more information, check with your doctor, pharmacist, or other health care provider.
HYDRO 35 is a keratolytic emollient in a water and lipid based foam containing lactic acid which is a gentle, but potent, tissue softener for skin and nails. Each gram of HYDRO 35 contains Urea 35% as the active ingredient, and the following inactive ingredients: dimethicone, ethylparaben, glycerin, lactic acid, methylparaben, phenoxyethanol, polysorbate 20, povidone, propylene glycol, propylparaben, purified water, stearic acid, trolamine, and in propellants butane and propane.
Urea has the following chemical structure:
Topically applied urea dissolves the intercellular matrix of the skin which results in enhanced shedding of scaly, dry skin and thus a softening of the hyperkeratotic areas of the skin.
Urea topically applied to the nail plate has a similar effect on the intercellular matrix of the nail plate.
The mechanism of action of topically applied urea is not yet known.
For enzymatic debridement and promotion of normal healing of surface lesions, particularly where healing is retarded by local infection, necrotic tissue, fibrinous or purulent debris, or eschar. Topically applied urea is useful for the treatment of hyperkeratotic conditions such as dermatitis, psoriasis, xerosis, ichthyosis, eczema, keratosis, keratoderma, and dry, rough skin, as well as corns and calluses and damaged, ingrown and devitalized nails.
Known hypersensitivity to any of the listed ingredients.
HYDRO 35 is for external use only. It is not for ophthalmic, oral, anal or intravaginal use. Contact with eyes, lips and all mucous membranes should be avoided. HYDRO 35 should not be used by persons who have a known hypersensitivity to urea or any of the other listed ingredients.
HYDRO 35 should be used only as directed by a physician and should not be used to treat any condition other than that for which it is prescribed. If redness or irritation occurs, discontinue use and consult with prescribing physician.
Pregnancy (Category B) - Animal reproduction studies have not been performed with topically applied urea and it is not known whether HYDRO 35 can cause fetal harm when administered to a pregnant woman. Nevertheless, HYDRO 35 should be used by a pregnant woman only if necessary.
Nursing Mothers - It is not known whether topically applied urea is excreted in human milk. Due to the fact that many drugs are excreted in human milk, caution should be exercised by physicians when administering HYDRO 35 to nursing mothers.
KEEP THIS AND ALL OTHER MEDICATIONS OUT OF THE REACH OF CHILDREN.
Transient stinging, burning, itching or irritation is possible.
Unless otherwise directed by a prescribing physician,
HYDRO 35 should be applied to affected area twice a day.
HYDRO 35 should be rubbed into the skin until it is completely absorbed.
HYDRO 35 is supplied in a 150 gram or 5.3 ounce aerosolized canister bearing the NDC Number 23710-035-15 and a 22 gram or .79 ounce aerosolized canister bearing the NDC Number 23710-035-20. The 22g canister is a physician-dispensed sample product.
Store at controlled room temperature 15° - 25°C (59° - 77°F).
U.S. Patent Pending for HYDRO 35.
HYDRO 35 is manufactured for Quinnova Pharmaceuticals,
Inc., Newtown, PA 18940, (877) 660-6263,
www.QUINNOVA.com.
Prescribing Information as of May 2009.
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| HYDRO 35 urea in a water and lipid based foam containing lactic acid aerosol, foam | ||||||||||||||||||||||||||||||||||
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| Marketing Information | |||
| Marketing Category | Application Number or Monograph Citation | Marketing Start Date | Marketing End Date |
| unapproved other | 06/20/2009 | ||
| Labeler - Quinnova Pharmaceuticals, Inc. (607183766) |
| Establishment | |||
| Name | Address | ID/FEI | Operations |
| Bioglan Pharma AB Kosterogatan | 426994992 | manufacture | |
| Establishment | |||
| Name | Address | ID/FEI | Operations |
| Aerosol Scandinavia | 508349792 | manufacture | |
| Establishment | |||
| Name | Address | ID/FEI | Operations |
| Quinnova Pharmaceuticals, Inc. | 607183766 | import | |
Preventing cavities in children older than 6 months of age when the amount of fluoride in the water supply is too low.
Sodium Fluoride Drops are a mineral. It works by strengthening the teeth and decreasing the effects of acid and bacteria on the teeth.
Contact your doctor or health care provider right away if any of these apply to you.
Some medical conditions may interact with Sodium Fluoride Drops. Tell your doctor or pharmacist if you have any medical conditions, especially if any of the following apply to you:
Some MEDICINES MAY INTERACT with Sodium Fluoride Drops. However, no specific interactions with Sodium Fluoride Drops are known at this time.
Ask your health care provider if Sodium Fluoride Drops may interact with other medicines that you take. Check with your health care provider before you start, stop, or change the dose of any medicine.
Use Sodium Fluoride Drops as directed by your doctor. Check the label on the medicine for exact dosing instructions.
Ask your health care provider any questions you may have about how to use Sodium Fluoride Drops.
All medicines may cause side effects, but many people have no, or minor, side effects. When used in small doses, no COMMON side effects have been reported with Sodium Fluoride Drops. Seek medical attention right away if any of these SEVERE side effects occur:
Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue).
This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider. Call your doctor for medical advice about side effects. To report side effects to the appropriate agency, please read the Guide to Reporting Problems to FDA.
Contact 1-800-222-1222 (the American Association of Poison Control Centers), your local poison control center, or emergency room immediately. Symptoms may include bloody vomit or vomit that looks like coffee grounds; diarrhea; fast or irregular heartbeat; increased drooling; muscle weakness; nausea; seizures; slow or shallow breathing; sore tongue; stomach pain or cramping; tremor; vomiting.
Store Sodium Fluoride Drops at room temperature, between 68 and 77 degrees F (20 and 25 degrees C). Store away from heat, moisture, and light. Do not store in the bathroom. Keep Sodium Fluoride Drops out of the reach of children and away from pets.
This information is a summary only. It does not contain all information about Sodium Fluoride Drops. If you have questions about the medicine you are taking or would like more information, check with your doctor, pharmacist, or other health care provider.
Generic Name: varicella virus vaccine (Subcutaneous route)
var-i-SEL-a VYE-rus VAX-een
In the U.S.
In Canada
Available Dosage Forms:
Therapeutic Class: Vaccine
Varicella virus vaccine is an active immunizing agent that is given to protect against infection caused by the varicella-zoster virus (VZV). The vaccine works by causing the body to produce its own protection (antibodies) against the virus.
Varicella (commonly known as chickenpox) is an infection that is easily spread from one person to another. Chickenpox is usually a mild infection but sometimes it can cause serious problems, such as pneumonia, inflammation of the brain, and a rare disease called Reye's syndrome.
Immunization against chickenpox is recommended for anyone 12 months of age and older who has not had chickenpox. Immunization against chickenpox is not recommended for infants younger than 12 months of age.
You can be considered to be immune to chickenpox only if you have received the right number of varicella vaccine doses (1 dose if you are between 12 months and 12 years of age; or 2 doses if you are 13 years of age or older). You also are considered to be immune if you have a doctor's diagnosis of a previous chickenpox infection or if you have had a blood test showing that you are immune to varicella.
Varicella virus vaccine (Zostavax®) is also used for the prevention of herpes zoster (commonly known as shingles) in people 50 years of age and older.
This vaccine is to be administered only by or under the supervision of your doctor or other authorized health care professional.
In deciding to use a vaccine, the risks of taking the vaccine must be weighed against the good it will do. This is a decision you and your doctor will make. For this vaccine, the following should be considered:
Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.
Varivax® (for preventing chickenpox)—Appropriate studies performed to date have not demonstrated pediatric-specific problems that would limit the usefulness of varicella virus vaccine in children 1 year of age and older. However, varicella virus vaccine is not recommended for infants younger than 12 months of age.
Zostavax® (for preventing shingles)—This vaccine should not be used in children.
Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of varicella virus vaccine in the elderly.
Studies in women suggest that this medication poses minimal risk to the infant when used during breastfeeding.
Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are receiving this vaccine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.
Receiving this vaccine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.
Receiving this vaccine with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.
Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.
The presence of other medical problems may affect the use of this vaccine. Make sure you tell your doctor if you have any other medical problems, especially:
This section provides information on the proper use of a number of products that contain varicella virus vaccine. It may not be specific to Varivax. Please read with care.
A nurse or other trained health professional will give you or your child this vaccine. This vaccine is given as a shot under your skin (usually in the upper arms).
Children 12 months to 12 years of age may need a second shot within 3 months after receiving the first dose of Varivax®. Teenagers and adults should have a "booster" shot 4 to 8 weeks after the first dose of this vaccine.
Adults receiving Zostavax® should receive only one dose of the vaccine unless your doctor tells you otherwise.
This vaccine comes with a patient information insert. Make sure you understand all of the information in the insert. Ask your doctor if you have any questions.
Tell your doctor before receiving this vaccine if you are severely ill or if you have a fever greater than 101.3 °F.
This vaccine needs to be given on a fixed schedule. If you or your child missed the scheduled dose, call your doctor or your child’s doctor for another appointment as soon as possible.
It is very important that you or your child return to your doctor’s office at the right time if you or your child needs a second dose of the vaccine. Be sure to notify your doctor of any side effects that occur after your child receive this vaccine.
Do not become pregnant for 3 months after receiving varicella virus vaccine without first checking with your doctor. There is a chance that this vaccine may cause problems during pregnancy. If you think you have become pregnant, tell your doctor right away. Your doctor may want you to join a pregnancy registry for patients receiving this vaccine.
Zostavax® should not be used in place of Varivax®.
Zostavax® should not be used in children.
Tell your doctor that you or your child have received this vaccine:
This vaccine may cause serious types of allergic reactions, including anaphylaxis. Anaphylaxis can be life-threatening and requires immediate medical attention. Call your doctor right away if you have a rash; itching; hoarseness; trouble breathing; trouble swallowing; or any swelling of your hands, face, or mouth after you receive the vaccine.
Do not take aspirin or medicines that contain aspirin (such as certain cold medicines) for 6 weeks after receiving this vaccine. Carefully check the label of any pain, headache, or cold medicine you or your child use to be sure it does not contain aspirin or salicylic acid.
You or your child may be able to pass the virus to other people after getting this vaccine. You or your child should avoid close contact with people at high risk for getting chickenpox for 6 weeks after receiving this vaccine. People who are most at risk of catching the virus from you are pregnant women, newborn babies, and people whose bodies cannot fight infection (such as with bone marrow disease, cancer drug treatment, or AIDS). Talk to your doctor about this risk.
Do not take other medicines unless they have been discussed with your doctor. This includes prescription or nonprescription (over-the-counter [OTC]) medicines and herbal or vitamin supplements.
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 or nurse immediately if any of the following side effects occur:
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:
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.
See also: Varivax side effects (in more detail)
The information contained in the Thomson Reuters Micromedex products as delivered by Drugs.com is intended as an educational aid only. It is not intended as medical advice for individual conditions or treatment. It is not a substitute for a medical exam, nor does it replace the need for services provided by medical professionals. Talk to your doctor, nurse or pharmacist before taking any prescription or over the counter drugs (including any herbal medicines or supplements) or following any treatment or regimen. Only your doctor, nurse, or pharmacist can provide you with advice on what is safe and effective for you.
The use of the Thomson Reuters Healthcare products is at your sole risk. These products are provided "AS IS" and "as available" for use, without warranties of any kind, either express or implied. Thomson Reuters Healthcare and Drugs.com make no representation or warranty as to the accuracy, reliability, timeliness, usefulness or completeness of any of the information contained in the products. Additionally, THOMSON REUTERS HEALTHCARE MAKES NO REPRESENTATION OR WARRANTIES AS TO THE OPINIONS OR OTHER SERVICE OR DATA YOU MAY ACCESS, DOWNLOAD OR USE AS A RESULT OF USE OF THE THOMSON REUTERS HEALTHCARE PRODUCTS. ALL IMPLIED WARRANTIES OF MERCHANTABILITY AND FITNESS FOR A PARTICULAR PURPOSE OR USE ARE HEREBY EXCLUDED. Thomson Reuters Healthcare does not assume any responsibility or risk for your use of the Thomson Reuters Healthcare products.
Therapy with lipid-altering agents should be only one component of multiple risk factor intervention in individuals at significantly increased risk for atherosclerotic vascular disease due to hypercholesterolemia. Drug therapy is recommended as an adjunct to diet when the response to a diet restricted in saturated fat and cholesterol and other nonpharmacologic measures alone has been inadequate. In patients with CHD or multiple risk factors for CHD, Lipitor can be started simultaneously with diet.
In adult patients without clinically evident coronary heart disease, but with multiple risk factors for coronary heart disease such as age, smoking, hypertension, low HDL-C, or a family history of early coronary heart disease, Lipitor is indicated to:
In patients with type 2 diabetes, and without clinically evident coronary heart disease, but with multiple risk factors for coronary heart disease such as retinopathy, albuminuria, smoking, or hypertension, Lipitor is indicated to:
In patients with clinically evident coronary heart disease, Lipitor is indicated to:
Lipitor is indicated:
Lipitor has not been studied in conditions where the major lipoprotein abnormality is elevation of chylomicrons (Fredrickson Types I and V).
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 dosage range of Lipitor is 10 to 80 mg once daily. Lipitor can be administered as a single dose at any time of the day, with or without food. 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.
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). Doses should be individualized according to the recommended goal of therapy [see current NCEP Pediatric Panel Guidelines, Clinical Pharmacology (12), and Indications and Usage (1.2)]. Adjustments should be made at intervals of 4 weeks or more.
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.
Lipitor may be used with bile acid resins. The combination of HMG-CoA reductase inhibitors (statins) and fibrates should generally be used with caution [see Warnings and Precautions, Skeletal Muscle (5.1), Drug Interactions (7)].
Renal disease does not affect the plasma concentrations nor LDL-C reduction of Lipitor; thus, dosage adjustment in patients with renal dysfunction is not necessary [see Warnings and Precautions, Skeletal Muscle (5.1), Clinical Pharmacology, Pharmacokinetics (12.3)].
In patients taking cyclosporine, therapy should be limited to Lipitor 10 mg once daily. In patients taking clarithromycin, itraconazole, or in patients with HIV taking a combination of ritonavir plus saquinavir or lopinavir plus ritonavir, for doses of Lipitor exceeding 20 mg, appropriate clinical assessment is recommended to ensure that the lowest dose necessary of Lipitor is employed [see Warnings and Precautions, Skeletal Muscle (5.1), Drug Interactions (7)].
White, elliptical, film-coated tablets containing 10, 20, 40, and 80 mg atorvastatin calcium.
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 [see Use in Specific Populations (8.1)].
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 [see Use in Specific Populations (8.3)].
Rare cases of rhabdomyolysis with acute renal failure secondary to myoglobinuria have been reported with Lipitor and with other drugs in this class. A history of renal impairment may be a risk factor for the development of rhabdomyolysis. Such patients merit closer monitoring for skeletal muscle effects.
Atorvastatin, like other statins, occasionally causes myopathy, defined as muscle aches or muscle weakness in conjunction with increases in creatine phosphokinase (CPK) values >10 times ULN. The concomitant use of higher doses of atorvastatin with certain drugs such as cyclosporine and strong CYP3A4 inhibitors (e.g., clarithromycin, itraconazole, and HIV protease inhibitors) increases the risk of myopathy/rhabdomyolysis.
Myopathy should be considered in any patient with diffuse myalgias, muscle tenderness or weakness, and/or marked elevation of CPK. Patients should be advised to report promptly unexplained muscle pain, tenderness, or weakness, particularly if accompanied by malaise or fever. Lipitor therapy should be discontinued if markedly elevated CPK levels occur or myopathy is diagnosed or suspected.
The risk of myopathy during treatment with drugs in this class is increased with concurrent administration of cyclosporine, fibric acid derivatives, erythromycin, clarithromycin, combination of ritonavir plus saquinavir or lopinavir plus ritonavir, niacin, or azole antifungals. Physicians considering combined therapy with Lipitor and fibric acid derivatives, erythromycin, clarithromycin, a combination of ritonavir plus saquinavir or lopinavir plus ritonavir, immunosuppressive drugs, azole antifungals, or lipid-modifying doses of niacin should carefully weigh the potential benefits and risks and should carefully monitor patients for any signs or symptoms of muscle pain, tenderness, or weakness, particularly during the initial months of therapy and during any periods of upward dosage titration of either drug. Lower starting and maintenance doses of atorvastatin should be considered when taken concomitantly with the aforementioned drugs (see Drug Interactions (7)). Periodic creatine phosphokinase (CPK) determinations may be considered in such situations, but there is no assurance that such monitoring will prevent the occurrence of severe myopathy.
Prescribing recommendations for interacting agents are summarized in Table 1 [see also Dosage and Administration (2.6), Drug Interactions (7), Clinical Pharmacology (12.3)].
| Interacting Agents | Prescribing Recommendations |
|---|---|
| Cyclosporine | Do not exceed 10 mg atorvastatin daily |
| Clarithromycin, itraconazole, HIV protease inhibitors (ritonavir plus saquinavir or lopinavir plus ritonavir) | Caution when exceeding doses > 20mg atorvastatin daily. The lowest dose necessary should be used. |
Lipitor therapy should be temporarily withheld or discontinued in any patient with an acute, serious condition suggestive of a myopathy or having a risk factor predisposing to the development of renal failure secondary to rhabdomyolysis (e.g., severe acute infection, hypotension, major surgery, trauma, severe metabolic, endocrine and electrolyte disorders, and uncontrolled seizures).
Statins, like some other lipid-lowering therapies, have been associated with biochemical abnormalities of liver function. Persistent elevations (>3 times the upper limit of normal [ULN] occurring on 2 or more occasions) in serum transaminases occurred in 0.7% of patients who received Lipitor 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 function tests (LFT) 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 LFT elevations continued treatment with a reduced dose of Lipitor.
It is recommended that liver function tests be performed prior to and at 12 weeks following both the initiation of therapy and any elevation of dose, and periodically (e.g., semiannually) thereafter. Liver enzyme changes generally occur in the first 3 months of treatment with Lipitor. Patients who develop increased transaminase levels should be monitored until the abnormalities resolve. Should an increase in ALT or AST of >3 times ULN persist, reduction of dose or withdrawal of Lipitor is recommended.
Lipitor should be used with caution in patients who consume substantial quantities of alcohol and/or have a history of liver disease. Active liver disease or unexplained persistent transaminase elevations are contraindications to the use of Lipitor [see Contraindications (4.1)].
Statins interfere with cholesterol synthesis and theoretically might blunt adrenal and/or gonadal steroid production. Clinical studies have shown that Lipitor does not reduce basal plasma cortisol concentration or impair adrenal reserve. The effects of statins on male fertility have not been studied in adequate numbers of patients. The effects, if any, on the pituitary-gonadal axis in premenopausal women are unknown. Caution should be exercised if a statin is administered concomitantly with drugs that may decrease the levels or activity of endogenous steroid hormones, such as ketoconazole, spironolactone, and cimetidine.
Brain hemorrhage was seen in a female dog treated for 3 months at 120 mg/kg/day. Brain hemorrhage and optic nerve vacuolation were seen in another female dog that was sacrificed in moribund condition after 11 weeks of escalating doses up to 280 mg/kg/day. The 120 mg/kg dose resulted in a systemic exposure approximately 16 times the human plasma area-under-the-curve (AUC, 0–24 hours) based on the maximum human dose of 80 mg/day. A single tonic convulsion was seen in each of 2 male dogs (one treated at 10 mg/kg/day and one at 120 mg/kg/day) in a 2-year study. No CNS lesions have been observed in mice after chronic treatment for up to 2 years at doses up to 400 mg/kg/day or in rats at doses up to 100 mg/kg/day. These doses were 6 to 11 times (mouse) and 8 to 16 times (rat) the human AUC (0–24) based on the maximum recommended human dose of 80 mg/day.
CNS vascular lesions, characterized by perivascular hemorrhages, edema, and mononuclear cell infiltration of perivascular spaces, have been observed in dogs treated with other members of this class. A chemically similar drug in this class produced optic nerve degeneration (Wallerian degeneration of retinogeniculate fibers) in clinically normal dogs in a dose-dependent fashion at a dose that produced plasma drug levels about 30 times higher than the mean drug level in humans taking the highest recommended dose.
In a post-hoc analysis of the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) study where Lipitor 80 mg vs. placebo was administered in 4,731 subjects 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 group compared to placebo (55, 2.3% atorvastatin 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 nonfatal hemorrhagic stroke was significantly higher in the atorvastatin 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 group [see Adverse Reactions (6.1)].
The following serious adverse reactions are discussed in greater detail in other sections of the label:
Rhabdomyolysis and myopathy [see Warnings and Precautions (5.1)]
Liver enzyme abnormalities [see Warnings and Precautions (5.2)]
Because clinical trials are conducted under widely varying conditions, the adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.
In the Lipitor placebo-controlled clinical trial database of 16,066 patients (8755 Lipitor vs. 7311 placebo; age range 10–93 years, 39% women, 91% Caucasians, 3% Blacks, 2% Asians, 4% other) with a median treatment duration of 53 weeks, 9.7% of patients on Lipitor and 9.5% of the patients on placebo discontinued due to adverse reactions regardless of causality. 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 (0.7%), diarrhea (0.5%), nausea (0.4%), alanine aminotransferase increase (0.4%), and hepatic enzyme increase (0.4%).
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 (8.3%), arthralgia (6.9%), diarrhea (6.8%), pain in extremity (6.0%), and urinary tract infection (5.7%).
Table 2 summarizes the frequency of clinical adverse reactions, regardless of causality, reported in ≥ 2% and at a rate greater than placebo in patients treated with Lipitor (n=8755), from seventeen placebo-controlled trials.
| Adverse Reaction* | Any dose N=8755 | 10 mg N=3908 | 20 mg N=188 | 40 mg N=604 | 80 mg N=4055 | Placebo N=7311 |
|---|---|---|---|---|---|---|
| ||||||
| Nasopharyngitis | 8.3 | 12.9 | 5.3 | 7.0 | 4.2 | 8.2 |
| Arthralgia | 6.9 | 8.9 | 11.7 | 10.6 | 4.3 | 6.5 |
| Diarrhea | 6.8 | 7.3 | 6.4 | 14.1 | 5.2 | 6.3 |
| Pain in extremity | 6.0 | 8.5 | 3.7 | 9.3 | 3.1 | 5.9 |
| Urinary tract infection | 5.7 | 6.9 | 6.4 | 8.0 | 4.1 | 5.6 |
| Dyspepsia | 4.7 | 5.9 | 3.2 | 6.0 | 3.3 | 4.3 |
| Nausea | 4.0 | 3.7 | 3.7 | 7.1 | 3.8 | 3.5 |
| Musculoskeletal pain | 3.8 | 5.2 | 3.2 | 5.1 | 2.3 | 3.6 |
| Muscle Spasms | 3.6 | 4.6 | 4.8 | 5.1 | 2.4 | 3.0 |
| Myalgia | 3.5 | 3.6 | 5.9 | 8.4 | 2.7 | 3.1 |
| Insomnia | 3.0 | 2.8 | 1.1 | 5.3 | 2.8 | 2.9 |
| Pharyngolaryngeal pain | 2.3 | 3.9 | 1.6 | 2.8 | 0.7 | 2.1 |
Other adverse reactions reported in placebo-controlled studies 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.
Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT)
In ASCOT [see Clinical Studies (14.1)] involving 10,305 participants (age range 40–80 years, 19% women; 94.6% Caucasians, 2.6% Africans, 1.5% South Asians, 1.3% mixed/other) treated with Lipitor 10 mg daily (n=5,168) or placebo (n=5,137), the safety and tolerability profile of the group treated with Lipitor was comparable to that of the group treated with placebo during a median of 3.3 years of follow-up.
Collaborative Atorvastatin Diabetes Study (CARDS)
In CARDS [see Clinical Studies (14.1)] involving 2,838 subjects (age range 39–77 years, 32% women; 94.3% Caucasians, 2.4% South Asians, 2.3% Afro-Caribbean, 1.0% other) with type 2 diabetes treated with Lipitor 10 mg daily (n=1,428) or placebo (n=1,410), there was no difference in the overall frequency of adverse reactions or serious adverse reactions between the treatment groups during a median follow-up of 3.9 years. No cases of rhabdomyolysis were reported.
Treating to New Targets Study (TNT)
In TNT [see Clinical Studies (14.1)] involving 10,001 subjects (age range 29–78 years, 19% women; 94.1% Caucasians, 2.9% Blacks, 1.0% Asians, 2.0% other) with clinically evident CHD treated with Lipitor 10 mg daily (n=5006) or Lipitor 80 mg daily (n=4995), there were more serious adverse reactions and discontinuations due to adverse reactions in the high-dose atorvastatin group (92, 1.8%; 497, 9.9%, respectively) as compared to the low-dose group (69, 1.4%; 404, 8.1%, respectively) during a median follow-up of 4.9 years. Persistent transaminase elevations (≥3 × ULN twice within 4–10 days) occurred in 62 (1.3%) individuals with atorvastatin 80 mg and in nine (0.2%) individuals with atorvastatin 10 mg. Elevations of CK (≥ 10 × ULN) were low overall, but were higher in the high-dose atorvastatin treatment group (13, 0.3%) compared to the low-dose atorvastatin group (6, 0.1%).
Incremental Decrease in Endpoints through Aggressive Lipid Lowering Study (IDEAL)
In IDEAL [see Clinical Studies (14.1)] involving 8,888 subjects (age range 26–80 years, 19% women; 99.3% Caucasians, 0.4% Asians, 0.3% Blacks, 0.04% other) treated with Lipitor 80 mg/day (n=4439) or simvastatin 20–40 mg daily (n=4449), there was no difference in the overall frequency of adverse reactions or serious adverse reactions between the treatment groups during a median follow-up of 4.8 years.
Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL)
In SPARCL involving 4731 subjects (age range 21–92 years, 40% women; 93.3% Caucasians, 3.0% Blacks, 0.6% Asians, 3.1% other) without clinically evident CHD but with a stroke or transient ischemic attack (TIA) within the previous 6 months treated with Lipitor 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 × ULN twice within 4–10 days) in the atorvastatin group (0.9%) compared to placebo (0.1%). Elevations of CK (>10 × ULN) were rare, but were higher in the atorvastatin group (0.1%) compared to placebo (0.0%). Diabetes was reported as an adverse reaction in 144 subjects (6.1%) in the atorvastatin group and 89 subjects (3.8%) in the placebo group [see Warnings and Precautions (5.5)].
In a post-hoc analysis, Lipitor 80 mg reduced the incidence of ischemic stroke (218/2365, 9.2% vs. 274/2366, 11.6%) and increased the incidence of hemorrhagic stroke (55/2365, 2.3% vs. 33/2366, 1.4%) compared to placebo. The incidence of fatal hemorrhagic stroke was similar between groups (17 Lipitor vs. 18 placebo). The incidence of non-fatal hemorrhagic strokes was significantly greater in the atorvastatin group (38 non-fatal hemorrhagic strokes) as compared to the placebo group (16 non-fatal hemorrhagic strokes). Subjects who entered the study with a hemorrhagic stroke appeared to be at increased risk for hemorrhagic stroke [7 (16%) Lipitor vs. 2 (4%) placebo].
There were no significant differences between the treatment groups for all-cause mortality: 216 (9.1%) in the Lipitor 80 mg/day group vs. 211 (8.9%) in the placebo group. The proportions of subjects who experienced cardiovascular death were numerically smaller in the Lipitor 80 mg group (3.3%) than in the placebo group (4.1%). The proportions of subjects who experienced non-cardiovascular death were numerically larger in the Lipitor 80 mg group (5.0%) than in the placebo group (4.0%).
The following adverse reactions have been identified during postapproval use of Lipitor. 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.
Adverse reactions associated with Lipitor therapy reported since market introduction, that are not listed above, regardless of causality assessment, include the following: anaphylaxis, angioneurotic edema, bullous rashes (including erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis), rhabdomyolysis, fatigue, tendon rupture, hepatic failure, dizziness, memory impairment, depression, and peripheral neuropathy.
In a 26-week controlled study in boys and postmenarchal girls (n=140, 31% female; 92% Caucasians, 1.6% Blacks, 1.6% Asians, 4.8% other), the safety and tolerability profile of Lipitor 10 to 20 mg daily was generally similar to that of placebo [see Clinical Studies (14.6) and Use in Special Populations, Pediatric Use (8.4)].
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) [see Warnings and Precautions, Skeletal Muscle (5.1) and Clinical Pharmacology (12.3)].
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.
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).
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)]. In cases where co-administration of Lipitor with cyclosporine is necessary, the dose of Lipitor should not exceed 10 mg [see Warnings and Precautions, Skeletal Muscle (5.1)].
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.
When multiple doses of Lipitor and digoxin were coadministered, steady state plasma digoxin concentrations increased by approximately 20%. Patients taking digoxin should be monitored appropriately.
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.
Lipitor had no clinically significant effect on prothrombin time when administered to patients receiving chronic warfarin treatment.
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.
Atorvastatin crosses the rat placenta and reaches a level in fetal liver equivalent to that of maternal plasma. 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 based on surface area (mg/m2) [see Contraindications, Pregnancy (4.3)].
In a study in rats given 20, 100, or 225 mg/kg/day, from gestation day 7 through to lactation day 21 (weaning), there was decreased pup survival at birth, neonate, weaning, and maturity in pups of mothers dosed with 225 mg/kg/day. Body weight was decreased on days 4 and 21 in pups of mothers dosed at 100 mg/kg/day; pup body weight was decreased at birth and at days 4, 21, and 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 AUC at 80 mg/day.
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.
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. Nursing rat pups had plasma and liver drug levels of 50% and 40%, respectively, of that in their mother's milk. Animal breast milk drug levels may not accurately reflect human breast milk levels. 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 [seeContraindications (4)].
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 [see Clinical Studies, Homozygous Familial Hypercholesterolemia (14.5)].
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.
Lipitor is contraindicated in patients with active liver disease which may include unexplained persistent elevations in hepatic transaminase levels [see Contraindications (4) and Pharmacokinetics (12.3)].
There is no specific treatment for Lipitor overdosage. In the event of an overdose, the patient should be treated symptomatically, and supportive measures instituted as required. Due to extensive drug binding to plasma proteins, hemodialysis is not expected to significantly enhance Lipitor clearance.
Lipitor is a synthetic lipid-lowering agent. Atorvastatin is an inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase. This enzyme catalyzes the conversion of HMG-CoA to mevalonate, an early and rate-limiting step in cholesterol biosynthesis.
Atorvastatin calcium is [R-(R*, R*)]-2-(4-fluorophenyl)-ß, δ-dihydroxy-5-(1-methylethyl)-3-phenyl-4-[(phenylamino)carbonyl]-1H-pyrrole-1-heptanoic acid, calcium salt (2:1) trihydrate. The empirical formula of atorvastatin calcium is (C33H34 FN2O5)2Ca•3H2O and its molecular weight is 1209.42. Its structural formula is:
Atorvastatin calcium is a white to off-white crystalline powder that is insoluble in aqueous solutions of pH 4 and below. Atorvastatin calcium is very slightly soluble in distilled water, pH 7.4 phosphate buffer, and acetonitrile; slightly soluble in ethanol; and freely soluble in methanol.
Lipitor Tablets for oral administration contain 10, 20, 40, or 80 mg atorvastatin and the following inactive ingredients: calcium carbonate, USP; candelilla wax, FCC; croscarmellose sodium, NF; hydroxypropyl cellulose, NF; lactose monohydrate, NF; magnesium stearate, NF; microcrystalline cellulose, NF; Opadry White YS-1-7040 (hypromellose, polyethylene glycol, talc, titanium dioxide); polysorbate 80, NF; simethicone emulsion.
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.
In animal models, Lipitor 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; Lipitor also reduces LDL production and the number of LDL particles. Lipitor reduces LDL-C in some patients with homozygous familial hypercholesterolemia (FH), a population that rarely responds to other lipid-lowering medication(s).
A variety of clinical studies have demonstrated that elevated levels of total-C, LDL-C, and apo B (a membrane complex for LDL-C) promote human atherosclerosis. Similarly, decreased levels of HDL-C (and its transport complex, apo A) are associated with the development of atherosclerosis. Epidemiologic investigations have established that cardiovascular morbidity and mortality vary directly with the level of total-C and LDL-C, and inversely with the level of HDL-C.
Lipitor reduces total-C, LDL-C, and apo B in patients with homozygous and heterozygous FH, nonfamilial forms of hypercholesterolemia, and mixed dyslipidemia. Lipitor also reduces VLDL-C and TG and produces variable increases in HDL-C and apolipoprotein A-1. Lipitor reduces total-C, LDL-C, VLDL-C, apo B, TG, and non-HDL-C, and increases HDL-C in patients with isolated hypertriglyceridemia. Lipitor reduces intermediate density lipoprotein cholesterol (IDL-C) in patients with dysbetalipoproteinemia.
Like LDL, cholesterol-enriched triglyceride-rich lipoproteins, including VLDL, intermediate density lipoprotein (IDL), and remnants, can also promote atherosclerosis. Elevated plasma triglycerides are frequently found in a triad with low HDL-C levels and small LDL particles, as well as in association with non-lipid metabolic risk factors for coronary heart disease. As such, total plasma TG has not consistently been shown to be an independent risk factor for CHD. Furthermore, the independent effect of raising HDL or lowering TG on the risk of coronary and cardiovascular morbidity and mortality has not been determined.
Lipitor, 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)].
Absorption: Lipitor is rapidly absorbed after oral administration; maximum plasma concentrations occur within 1 to 2 hours. Extent of absorption increases in proportion to Lipitor 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 Cmax and AUC, LDL-C reduction is similar whether Lipitor is given with or without food. Plasma Lipitor concentrations are lower (approximately 30% for Cmax and AUC) following evening drug administration compared with morning. However, LDL-C reduction is the same regardless of the time of day of drug administration [see Dosage and Administration (2)].
Distribution: Mean volume of distribution of Lipitor is approximately 381 liters. Lipitor is ≥98% bound to plasma proteins. A blood/plasma ratio of approximately 0.25 indicates poor drug penetration into red blood cells. Based on observations in rats, Lipitor is likely to be secreted in human milk [see Contraindications, Nursing Mothers (4.4) and Use in Specific Populations, Nursing Mothers (8.3)].
Metabolism: Lipitor is extensively metabolized to ortho- and parahydroxylated derivatives and various beta-oxidation products. In vitro inhibition of HMG-CoA reductase by ortho- and parahydroxylated metabolites is equivalent to that of Lipitor. Approximately 70% of circulating inhibitory activity for HMG-CoA reduct
