Pravigard PAC

Pravastatin is an oral drug for lowering the cholesterol in the blood that contributes to the formation of plaques in the walls of arteries that obstruct the flow of blood, known as arteriosclerotic vascular disease. Obstruction of the flow of blood to the heart causes heart attacks. Obstruction of flow to the brain causes strokes. Pravastatin has been shown to reduce the occurrence of heart attacks, strokes and death caused by arteriosclerotic vascular disease. It belongs to a class of drugs called HMG-CoA reductase inhibitors, commonly called "statins." Other statins include simvastatin (Zocor), lovastatin (Mevacor), atorvastatin (Lipitor), rosuvastatin (Crestor) and fluvastatin (Lescol). Statins reduce cholesterol by inhibiting an enzyme in the liver (HMG-CoA reductase) that is necessary for the production of cholesterol. In the blood, statins lower total and LDL ("bad") cholesterol as well as triglycerides. LDL cholesterol is believed to be an important cause of arteriosclerotic vascular disease. Lowering LDL cholesterol levels slows progression or reduces the size of cholesterol-containing plaques in the arteries of the heart and brain as well as other tissues. Statins also increase HDL ("good") cholesterol, and higher levels of HDL cholesterol are associated with reduced arteriosclerotic vascular disease. Raising HDL cholesterol levels may slow the progression of arteriosclerotic vascular disease.

Scientists have discovered that inflammation of the coronary arteries also may contribute to arteriosclerotic vascular disease. Inflammation is associated with elevated levels of a protein called C-reactive protein in the blood. This C-reactive protein can be measured by a test, referred to as the "highly-sensitive" C-reactive protein test (Hs-CRP). Elevated levels of Hs-CRP predict the occurrence of heart attacks, strokes, and death. In fact, Hs-CRP is a better predictor of heart attacks, strokes, and death than cholesterol levels. Statins reduce the levels of Hs-CRP, and it has been suggested that statins may reduce arteriosclerotic vascular disease by reducing inflammation in addition to lowering levels of cholesterol. Pravastatin was approved by the FDA in October 1991.

The dose range of pravastatin is 10-80 mg daily. The usual starting dose in adults is 40 mg once daily. The maximum dose is 80 mg per day. The starting dose for patients with major liver or kidney dysfunction is 10 mg daily.

The dose for children (8-13 years old) is 20 mg daily, and the dose for adolescents (14-18 years old) is 40 mg daily.

Pravigard PAC

Pravigard PAC (Buffered Aspirin and Pravastatin Sodium) is indicated in patients for whom treatment with both PRAVACHOL and buffered aspirin is appropriate. As described in the labeling for PRAVACHOL and buffered aspirin below, the components of Pravigard PAC are both indicated to reduce the occurrence of cardiovascular events, including death, myocardial infarction or stroke, in patients who have clinical evidence of cardiovascular and/or cerebrovascular disease. Patients receiving treatment with Pravigard PAC should also be placed on a standard cholesterol-lowering diet and should continue on this diet during treatment.

Pravachol

In patients with clinically evident coronary heart disease, PRAVACHOL (pravastatin sodium) is indicated to:

• reduce the risk of total mortality by reducing coronary death
• reduce the risk of myocardial infarction
• reduce the risk of undergoing myocardial revascularization procedures
• reduce the risk of stroke and stroke/transient ischemic attack (TIA)
• slow the progression of coronary atherosclerosis

PRAVACHOL is indicated as an adjunct to diet to reduce elevated Total-C, LDL-C, Apo B, and TG levels and to increase HDL-C in patients with primary hypercholesterolemia and mixed dyslipidemia (Fredrickson Type IIa and IIb).

Prior to initiating therapy with PRAVACHOL, secondary causes for hypercholesterolemia (e.g., poorly controlled diabetes mellitus, hypothyroidism, nephrotic syndrome, dysproteinemias, obstructive liver disease, other drug therapy, alcoholism) should be excluded, and a lipid profile performed to measure Total-C, LDL-C, HDL-C, and TG. Lipid determinations should be performed at intervals of no less than four weeks and dosage adjusted according to the patient’s response to therapy.

The National Cholesterol and Education Program (NCEP - see below) recommends an LDL-C goal of <100 mg/dL in patients who have established CHD or CHD risk equivalents (diabetes, peripheral arterial disease, abdominal aortic aneurysm, symptomatic carotid artery disease, or multiple risk factors conferring a 10-year risk for CHD >20%).

After the LDL-C goal has been achieved, if the TG is still ≥200 mg/dL, non-HDL-C (Total-C minus HDL-C) becomes a secondary target of therapy. In patients with CHD or CHD risk equivalents the non-HDL-C goal is <130 mg/dL.

At the time of hospitalization for an acute coronary event, consideration can be given to initiating drug therapy at discharge if the LDL-C is ≥130 mg/dL (see NCEP Guidelines, above).

Buffered Aspirin

Aspirin is indicated to: (1) reduce the combined risk of death and nonfatal stroke in patients who have had ischemic stroke or transient ischemia of the brain due to fibrin platelet emboli, (2) reduce the risk of vascular mortality in patients with a suspected acute MI, (3) reduce the combined risk of death and nonfatal MI in patients with a previous MI or unstable angina pectoris, and (4) reduce the combined risk of MI and sudden death in patients with chronic stable angina pectoris.

Aspirin is indicated in patients who have undergone revascularization procedures (i.e., CABG, PTCA, or carotid endarterectomy) when there is a preexisting condition for which aspirin is already indicated.

Pravachol

Hypersensitivity to any component of this medication.

Active liver disease or unexplained, persistent elevations in liver function tests (see WARNINGS: Pravachol: Liver Enzymes).

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. Cholesterol and other products of cholesterol biosynthesis are essential components for fetal development (including synthesis of steroids and cell membranes). Since HMG-CoA reductase inhibitors decrease cholesterol synthesis and possibly the synthesis of other biologically active substances derived from cholesterol, they are contraindicated during pregnancy and in nursing mothers. Pravastatin 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 class of drug, therapy should be discontinued immediately and the patient apprised of the potential hazard to the fetus (see PRECAUTIONS: Pregnancy: Pravachol).

Buffered Aspirin

Aspirin is contraindicated in patients with known allergy to nonsteroidal anti-inflammatory drug products and in patients with the syndrome of asthma, rhinitis, and nasal polyps. Aspirin may cause severe urticaria, angioedema, or bronchospasm (asthma).

Aspirin should not be used in children or teenagers for viral infections, with or without fever, because of the risk of Reye’s Syndrome with concomitant use of aspirin in certain viral illnesses.

Pravachol

To date, there has been limited experience with overdosage of pravastatin. If an overdose occurs, it should be treated symptomatically with laboratory monitoring and supportive measures should be instituted as required. (See WARNINGS: Pravachol.)

Buffered Aspirin

Salicylate toxicity may result from acute ingestion (overdose) or chronic intoxication. The early signs of salicylic overdose (salicylism), including tinnitus (ringing in the ears), occur at plasma concentrations approaching 200 µg/mL. Plasma concentrations of aspirin above 300 µg/mL are clearly toxic. Severe toxic effects are associated with levels about 400 µg/mL. (See CLINICAL PHARMACOLOGY: Pharmacokinetics/Metabolism: Buffered Aspirin:Distribution.) A single lethal dose of aspirin in adults is not known with certainty but death may be expected at 30 g. For real or suspected overdose, a Poison Control Center should be contacted immediately. Careful medical management is essential.

In acute overdose, severe acid-base and electrolyte disturbances may occur and are complicated by hyperthermia and dehydration. Respiratory alkalosis occurs early while hyperventilation is present, but is quickly followed by metabolic acidosis.

Treatment consists primarily of supporting vital functions, increasing salicylate elimination, and correcting the acid-base disturbance. Gastric emptying and/or lavage is recommended as soon as possible after ingestion, even if the patient has vomited spontaneously. After lavage and/or emesis, administration of activated charcoal, as a slurry, is beneficial, if less than 3 hours have passed since ingestion. Charcoal adsorption should not be employed prior to emesis and lavage.

Severity of aspirin intoxication is determined by measuring the blood salicylate level. Acid-base status should be closely followed with serial blood gas and serum pH measurements. Fluid and electrolyte balance should also be maintained.

In severe cases, hyperthermia and hypovolemia are the major immediate threats to life. Children should be sponged with tepid water. Replacement fluid should be administered intravenously and augmented with correction of acidosis. Plasma electrolytes and pH should be monitored to promote alkaline diuresis of salicylate if renal function is normal. Infusion of glucose may be required to control hypoglycemia.

Hemodialysis and peritoneal dialysis can be performed to reduce the body drug content. In patients with renal insufficiency or in cases of life-threatening intoxication, dialysis is usually required. Exchange transfusion may be indicated in infants and young children.

PRAVIGARD™ PAC (PRAH-vih-gard Pak)
(Buffered Aspirin and Pravastatin Sodium) tablets

Read the patient information that comes with Pravigard PAC before you start taking it and each time you get a refill. There may be new information. This information does not take the place of talking to your doctor about your medical condition or your treatment.

What is the most important information about Pravigard PAC?

What is Pravigard PAC?

Pravigard PAC has 2 medicines in it, buffered aspirin and pravastatin sodium (PRAVACHOL®).

Buffered aspirin stops part of the normal blood clotting process and so keeps clots or plugs from forming in your blood vessels. Buffered aspirin has aspirin in it along with other ingredients that may lower your chance of getting an upset stomach.

PRAVACHOL is a prescription medicine that lowers cholesterol in your blood. It lowers your "bad" LDL cholesterol and raises your "good" HDL cholesterol. High cholesterol can lead to plugs or clots in your blood vessels.

Pravigard PAC is for people who may be helped by having their cholesterol lowered and who also have 1 or more of these problems:

• a heart attack in the past
• chest pain from heart problems (also called angina)
• had a bypass operation or angioplasty to open the blood vessels of the heart
• blood flow problems to the brain (such as strokes, near-strokes, or mini-strokes)

You need to follow your doctor’s advice and take Pravigard PAC every day for it to lower your chances of dying from your heart disease, having a heart attack, or having a stroke. Pravigard PAC is part of a treatment program that should also include a low-fat diet and exercise. If you stop taking Pravigard PAC, it will not help you anymore. You must tell your doctor if you stop taking Pravigard PAC.

Pravigard PAC should not be used by:

• children younger than 18 years of age
• pregnant women (see below under “Who should not take Pravigard PAC?”)

Who should not take Pravigard PAC?

Do not take Pravigard PAC if you:

• have certain liver or kidney problems. If you have liver or kidney problems, check with your doctor.
• are pregnant or planning to become pregnant. Pravigard PAC can reach your baby and may harm it. If you are pregnant, stop taking Pravigard PAC right away and tell your doctor.
• are breast feeding. Pravigard PAC can pass into your breast milk and may harm your baby. You may need to choose between breast feeding or taking Pravigard PAC.
• are 18 years of age or younger. Children younger than 18 years should not use any product with aspirin in it. Children can get a rare but very serious medical problem called Reye's Syndrome if they take aspirin when they are sick.
• are allergic to any medicines called "nonsteroidal anti-inflammatory drugs" (NSAIDs) or to any of the ingredients in Pravigard PAC. The active ingredients are PRAVACHOL and buffered aspirin. See the end of this leaflet for a list of all the ingredients in Pravigard PAC. Ask your doctor or pharmacist if you need a list of NSAIDs.

Pravigard PAC may not be right for you or you may need extra care while taking Pravigard PAC. Before you start Pravigard PAC, tell your doctor if you:

• have bleeding problems
• have unexplained muscle aches or weakness
• have stomach problems such as heartburn, upset stomach, stomach pain, or ulcers
• drink 3 or more alcoholic drinks every day
• have asthma (wheezing) along with nasal polyps (small growths in your nose)

Tell your doctor about all of your medical problems or conditions such as a serious injury, a serious infection, or major surgery.

Can Pravigard PAC affect my other medicines?

Tell your doctor about all the medicines you take, including other medicines that contain aspirin, prescription and non-prescription medicines, vitamins, and herbal supplements. Some medicines, like those listed below, can cause serious side effects if you take them while you are taking Pravigard PAC. Be extra sure to tell your doctor if you take any of the following kinds of medicines:

• blood thinners. Blood thinners can increase your chance of bleeding since the aspirin in Pravigard PAC also blocks normal blood clotting.
• certain medicines for high cholesterol or high triglycerides called fibrates

Pravigard PAC may affect how some of your other medicines work. If you take a high blood pressure medicine called an ACE inhibitor, you may need to have your blood pressure checked more often.

How should I take Pravigard PAC?

• Take Pravigard PAC exactly as your doctor prescribes it.
• The usual dose of Pravigard PAC is 1 aspirin tablet with 1 PRAVACHOL tablet once a day. Pravigard PAC comes in different strengths and your doctor may adjust your dose. Do not change your dose without talking to your doctor.
• If you miss a dose, take it as soon as you remember. Do not take 2 doses in the same day.
• You can take Pravigard PAC with or without food.
• Take Pravigard PAC with a full glass of water, unless your doctor has told you to keep your fluids low.
• If you take too much Pravigard PAC, call your doctor or Poison Control Center right away.

Some people may need to stop taking Pravigard PAC for a short time. Call your doctor if you plan to have any surgery, medical, or dental procedures. You may be told to stop taking Pravigard PAC for a while to lower your chance of bleeding.

Some people may need to stop taking Pravigard PAC completely, or for a long time (see "What are the possible side effects of Pravigard PAC?").

What activities should I avoid while taking Pravigard PAC?

• Do not get pregnant. If you do, tell your doctor right away.
• Do not breast feed your baby.

What are the possible side effects of Pravigard PAC?

Pravigard PAC contains buffered aspirin and PRAVACHOL. You should be aware of the following serious side effects:

• Muscle damage: Rarely, patients taking PRAVACHOL, have experienced serious muscle damage. If you have unexplained muscle pain or weakness while taking Pravigard PAC, tell your doctor right away. The following can be signs of serious muscle damage that can lead to kidney damage:
  • muscle problems like weakness, tenderness, or pain that don’t have a good reason for happening to you
  • a fever or you feel more tired than usual
  • passing brown or dark-colored urine
• Liver damage: Rare cases of liver function abnormalities have been reported with PRAVACHOL. Your doctor may do blood tests to check your liver before you start taking Pravigard PAC, and while you take it.
• Bleeding: Aspirin can make it harder for your blood to clot. Call your doctor if you have any unusual bleeding.
• Stomach problems: Aspirin may cause stomach ulcers or stomach bleeding. Tell your doctor if you get any of the following:
  • heartburn that is new or won't go away
  • nausea or vomiting. Call your doctor right away if you see blood or something that looks like coffee grounds when you vomit.
  • stomach pain that is new or won't go away
  • bowel movements or stools that look like black tar

Allergic reactions: In people who are allergic to aspirin or NSAIDs, aspirin may cause a severe allergic reaction with hives, facial swelling, asthma (wheezing) or shock. Call a doctor or get emergency help right away if you get any of these symptoms.

Common side effects with Pravigard PAC are rash, stomach pain, upset stomach, muscle ache, and headache.

These are not all the possible side effects of Pravigard PAC. For more information, ask your doctor or pharmacist.

Talk to your doctor or pharmacist if you think you have side effects from taking Pravigard PAC.

General information about the safe and effective use of Pravigard PAC.

Do not use Pravigard PAC for a condition for which it was not prescribed. Do not give Pravigard PAC to other people, even if they have the same symptoms that you have. Keep Pravigard PAC and all other medicines out of the reach of children. This leaflet summarizes the most important information about Pravigard PAC. If you would like more information talk with your doctor. You can ask your doctor or pharmacist for information about Pravigard PAC that is written for health professionals.

What are the ingredients of Pravigard PAC?

Active Ingredients:

The active ingredient in buffered aspirin is aspirin. The active ingredient in PRAVACHOL is pravastatin sodium.

Inactive Ingredients:

The inactive ingredients in buffered aspirin are calcium carbonate, magnesium oxide, magnesium carbonate, benzoic acid, citric acid, corn starch, FD&C Blue No. 1, hypromellose, magnesium stearate, mineral oil, polysorbate 20, povidone, propylene glycol, simethicone emulsion, sodium phosphate, sorbitan monolaurate, titanium dioxide, carnauba wax, and zinc stearate. The inactive ingredients in PRAVACHOL are croscarmellose sodium, lactose, magnesium oxide, magnesium stearate, microcrystalline cellulose, and povidone. The 20 mg tablets and the 80 mg tablets have Yellow Ferric Oxide. The 40 mg tablets have Green Lake Blend (D&C Yellow No. 10-Aluminum Lake and FD&C Blue No. 1-Aluminum Lake).

Bristol-Myers Squibb Company
Princeton, New Jersey 08543 USA

1148286A3
Issued June 2003

Pravastatin is a cholesterol-lowering medication that blocks the production of cholesterol (a type of fat) in the body.

Pravastatin reduces low-density lipoprotein (LDL) cholesterol and total cholesterol in the blood. Lowering your cholesterol can help prevent heart disease and hardening of the arteries, conditions that can lead to heart attack, stroke, and vascular disease.

Aspirin is a pain reliever and fever reducer. It also reduces swelling.

Pravigard Pac is used to treat high cholesterol and lower the risk of stroke, heart attack, or other heart complications in people with coronary heart disease.

Pravigard Pac may also be used for other purposes not listed in this medication guide.

• liver disease;

• asthma with nasal polyps;

• aspirin-sensitive asthma or other allergic reactions; or

• if you are pregnant or breast-feeding.

Before taking Pravigard Pac, tell your doctor if you are allergic to any drugs, or if you have:

• diabetes;

• underactive thyroid;

• kidney disease;

• congestive heart failure;

• a recent history of stomach or intestinal bleeding;

• a bleeding or blood clotting disorder such as hemophilia;

• a muscle disorder; or

• if you are a heavy drinker (3 or more alcoholic beverages per day).

If you have any of these conditions, you may need a dose adjustment or special tests to safely take Pravigard Pac.

• chest pain;

• muscle pain, tenderness, or weakness with fever or flu symptoms and dark colored urine;

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

• black, bloody, or tarry stools;

• coughing up blood or vomit that looks like coffee grounds; or

• easy bruising or bleeding, unusual weakness.

Less serious side effects include:

• mild stomach pain, constipation, diarrhea;

• heartburn, gas, bloating, upset stomach;

• tired feeling;

• headache;

• stuffy nose, cold or flu symptoms;

• skin rash; or

• general pain.

This is not a complete list of side effects and others may occur. Tell your doctor about any unusual or bothersome side effect.