Fibricor

Fenofibric acid helps reduce cholesterol and triglycerides (fatty acids) in the blood. High levels of these types of fat in the blood are associated with an increased risk of atherosclerosis (clogged arteries).

Fenofibric acid is used to treat high cholesterol and high triglyceride levels. It is sometimes given together with other cholesterol-lowering medications.

Fenofibric acid may also be used for purposes not listed in this medication guide.

Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

You should not take fenofibric acid if you are allergic to it, or if you have:

• severe kidney disease (or if you are on dialysis);

• liver disease;

• gallbladder disease; or

• if you are breast-feeding a baby.

To make sure you can safely take fenofibric acid, tell your doctor if you have any of these other conditions:

• kidney disease;

• diabetes; or

• underactive thyroid.

FDA pregnancy category C. It is not known whether fenofibric acid will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant while using this medication.

Do not breast-feed while you are taking fenofibric acid.

Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

In rare cases, fenofibric acid can cause a condition that results in the breakdown of skeletal muscle tissue, leading to kidney failure. Stop taking fenofibric acid and call your doctor right away if you have unexplained muscle pain, tenderness, or weakness especially if you also have fever, unusual tiredness, and dark colored urine.

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Stop using fenofibric acid and call your doctor at once if you have a serious side effect such as:

• sharp stomach pain spreading to your back or shoulder blade;

• stomach pain just after eating a meal;

• nausea, upper stomach pain, itching, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes);

• pain, swelling, warmth, or redness in one or both legs; or

• chest pain, sudden cough, wheezing, rapid breathing, fast heart rate.

Less serious side effects may include:

• headache, dizziness;

• back pain;

• joint pain;

• diarrhea, upset stomach; or

• cold symptoms such as stuffy nose, sneezing, sore throat.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

This section provides information on the proper use of a number of products that contain fenofibric acid. It may not be specific to Fibricor. Please read with care.

Use this medicine only as directed by your doctor. Do not use more of it, do not use it more often, or do not use it for a longer time than your doctor ordered.

This medicine should come with a Medication Guide. Read and follow these instructions carefully. Ask your doctor if you have any questions.

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

Swallow the delayed-release capsule whole. Do not open, crush, break, or chew it.

You may take this medicine with or without food.

This medicine will not cure your high cholesterol problem, but it does help control it. You must continue to take it as directed if you expect to keep your cholesterol levels down.

If you are also using cholestyramine, colesevelam, or colestipol, you must take fenofibric acid at least 1 hour before or 4 to 6 hours after you take these medicines.

Dosing

The dose of this medicine 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 this medicine. 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 (delayed-release capsules):
  • For high triglycerides:
    • Adults—At first, 45 to 135 milligrams (mg) once a day. Your doctor may adjust your dose if needed.
    • Children—Use and dose must be determined by your doctor.
  • For mixed dyslipidemia or primary hypercholesterolemia:
    • Adults—135 milligrams (mg) once a day.
    • Children—Use and dose must be determined by your doctor.

Missed Dose

If you miss a dose of this medicine, 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.

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.

• If you have an allergy to fenofibrate or any other part of Fibricor (fenofibrate and derivatives tablets).
• 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 have any of these health problems: Gallbladder disease, kidney disease, liver disease, or rise in liver enzymes.
• If you are breast-feeding. Do not breast-feed while you take this medicine.

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

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 this medicine with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Headache.
• Back pain.
• Belly pain.

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-FDA-1088. You may also report side effects at http://www.fda.gov/medwatch.

• 35-mg: White, round tablets. Debossed "AR 787".
• 105-mg: White, modified oval tablets. Debossed "AR 788".

There is no specific treatment for overdose with Fibricor. General supportive care of the patient is indicated, including monitoring of vital signs and observation of clinical status, should an overdose occur. If indicated, elimination of unabsorbed drug should be achieved by emesis or gastric lavage; usual precautions should be observed to maintain the airway. Because Fibricor is highly bound to plasma proteins, hemodialysis should not be considered.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenesis

Two dietary carcinogenicity studies have been conducted in rats with fenofibrate. In the first 24-month study, Wistar rats were dosed with fenofibrate at 10, 45, and 200 mg/kg/day, approximately 0.3, 1, and 6 times the maximum recommended human (MRHD) dose, based on body surface area comparisons (mg/m2). At a dose of 200 mg/kg/day (6 times the MRHD), the incidence of liver carcinomas was significantly increased in both sexes. A statistically significant increase in pancreatic carcinomas was observed in males at 1, and 6 times the MRHD; an increase in pancreatic adenomas and benign testicular interstitial cell tumors was observed at 6 times the MRHD in males. In a second 24-month rat carcinogenicity study in a different strain of rats (Sprague-Dawley), doses of 10 and 60 mg/kg/day (0.3 and 2 times the MRHD) produced significant increases in the incidence of pancreatic acinar adenomas in both sexes and increases in testicular interstitial cell tumors in males at 2 times the MRHD.

A 117-week carcinogenicity study was conducted in rats comparing three drugs: fenofibrate 10 and 60 mg/kg/day (0.3 and 2 times the MRHD of fenofibrate), clofibrate (400 mg/kg/day; 2 times the human dose), and gemfibrozil (250 mg/kg/day; 2 times the human dose, based on mg/meter2 surface area). Fenofibrate increased pancreatic acinar adenomas in both sexes. Clofibrate increased hepatocellular carcinoma and pancreatic acinar adenomas in males and hepatic neoplastic nodules in females. Gemfibrozil increased hepatic neoplastic nodules in males and females, while all three drugs increased testicular interstitial cell tumors in males.

In a 21-month study in CF-1 mice, fenofibrate 10, 45, and 200 mg/kg/day (approximately 0.2, 1, and 3 times the human dose on the basis of mg/sq meter surface area) significantly increased the liver carcinomas in both sexes at doses that result in exposure to fenofibric acid that is 3 times the MRHD. In a second 18-month study at 10, 60, and 200 mg/kg/day, fenofibrate significantly increased the liver carcinomas in male mice and liver adenomas in female mice at 3 times the MRHD of fenofibrate.

Electron microscopy studies have demonstrated peroxisomal proliferation following fenofibrate administration to the rat. An adequate study to test for peroxisome proliferation in humans has not been done, but changes in peroxisome morphology and numbers have been observed in humans after treatment with other members of the fibrate class when liver biopsies were compared before and after treatment in the same individual.

Mutagenesis

Fenofibrate has been demonstrated to be devoid of mutagenic potential in the following tests: Ames, mouse lymphoma, chromosomal aberration and unscheduled DNA synthesis in primary rat hepatocytes.

Impairment of Fertility

In fertility studies, rats were given oral dietary doses of fenofibrate. Males received 61 days prior to mating and females 15 days prior to mating through weaning which resulted in no adverse effect on fertility at doses up to 300 mg/kg/day (approximately 10 times the MRHD of fenofibrate, based on mg/m2 surface area comparisons).

More frequent side effects include: thrombophlebitis, abnormal hepatic function tests, and increased serum alanine aminotransferase. See below for a comprehensive list of adverse effects.

Applies to fenofibric acid: oral delayed release capsule, oral tablet

General

The most frequently reported side effects were abnormal liver function tests, AST increased, ALT increased, creatine phosphokinase increased, and rhinitis.[Ref]

Musculoskeletal

Common (1% to 10%): Back pain, arthralgia, myalgia, pain in extremity
Postmarketing reports: Rhabdomyolysis, muscle spasm[Ref]

Gastrointestinal

Common (1% to 10%): Abdominal pain, nausea, constipation, diarrhea, dyspepsia
Postmarketing reports: Pancreatitis[Ref]

Hepatic

Common (1% to 10%): Liver function tests abnormal, ALT increased, AST increased
Postmarketing reports: Hepatitis, cirrhosis[Ref]

Respiratory

Common (1% to 10%): Respiratory disorder, rhinitis, nasopharyngitis, sinusitis, upper respiratory tract infection[Ref]

Nervous system

Common (1% to 10%): Headache, dizziness[Ref]

Other

Common (1% to 10%): Creatine phosphokinase increased, pain
Postmarketing reports: Asthenia[Ref]

Hematologic

Postmarketing reports: Anemia, hemoglobin decreased, hematocrit decreased, WBC decreased[Ref]

Renal

Postmarketing reports: Acute renal failure, renal failure[Ref]

Metabolic

Postmarketing reports: High density lipoprotein cholesterol levels severely depressed[Ref]

Some side effects of Fibricor may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.