Pravachol

Eat a low-fat, low-cholesterol diet. Be sure to follow all exercise and dietary recommendations made by your doctor or dietitian. You can also visit the National Cholesterol Education Program (NCEP) website for additional dietary information at http://www.nhlbi.nih.gov/health/public/heart/chol/chol_tlc.pdf.

Pravachol is a prescription medication used to treat high cholesterol levels. Pravachol belongs to a group of drugs called HMG-CoA reductase inhibitors, also known as statins. These work by blocking cholesterol production in the body.

This medication comes in tablet form and is usually taken once a day, with or without food.

Common side effects of Pravachol include muscle pain, headache, nausea, and vomiting.

• Bristol-Myers Squibb Co.

Serious side effects have been reported with Pravachol.  See the “Drug Precautions” section.

Common side effects of Pravachol include the following:

• diarrhea
• nausea
• vomiting
• headache
• upper airway infection
• muscle pain

This is not a complete list of Pravachol side effects. Ask your doctor or pharmacist for more information.

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

Tell your doctor if you are breastfeeding or plan to breastfeed.

Many HMG-CoA reductase inhibitors have been detected in human breast milk. Because of the possibility for adverse reactions in nursing infants from Pravachol , a choice should be made whether to stop nursing or to stop use of this medication. The importance of the drug to the mother should be considered.

• Store Pravachol at room temperature between 20° to 25°C (68° to 77°F).
• Protect from moisture and light.
• Keep Pravachol and all medicines out of the reach of children.

General

• Patients should be placed on a standard lipid-lowering diet before initiation of pravastatin therapy and should remain on this diet during treatment with the drug.1

Monitoring during Antilipemic Therapy

• Manufacturer recommends obtaining lipoprotein concentrations within 4 weeks following initiation of pravastatin and adjusting dosage accordingly.1 ACC/AHA cholesterol management guideline recommends obtaining lipoprotein concentrations within 4–12 weeks following initiation of statin therapy (to assess response and adherence) and monitoring every 3–12 months thereafter as clinically indicated.350

• Periodically reinforce adherence to lifestyle modifications.350

Administration

Oral Administration

Administer orally at any time of day without regard to meals.1

Dosage

Available as pravastatin sodium; dosage expressed in terms of pravastatin.1

Pediatric Patients

Children 8–13 years of age: 20 mg once daily.1 Dosages >20 mg daily have not been evaluated.1

Adolescents 14–18 years of age: 40 mg once daily.1 Dosages >40 mg daily have not been evaluated.1

Re-evaluate in adulthood and modify therapy appropriately.1

Adults

Select appropriate statin intensity to achieve optimal ASCVD risk reduction.350 Giving maximally tolerated statin intensity is preferred over giving lower statin dosages in combination with nonstatin drugs, a strategy not yet shown to reduce ASCVD risk.350

Although 80 mg once daily is an FDA-labeled dosage, it was not evaluated in randomized controlled studies reviewed by the ACC/AHA expert panel.350

ACC/AHA cholesterol management guideline recommends initiating high-intensity statin therapy (i.e., with atorvastatin or rosuvastatin) unless contraindicated.350

ACC/AHA cholesterol management guideline recommends moderate-intensity statin therapy (e.g., pravastatin 40–80 mg once daily).350

If estimated 10-year ASCVD risk ≥7.5%, consider high-intensity statin therapy (i.e., with atorvastatin or rosuvastatin) unless contraindicated.350

In patients <40 or >75 years of age, consider potential benefits, adverse effects, drug interactions, and patient preferences when deciding to initiate, continue, or intensify statin therapy.350

Estimated 10-year ASCVD risk ≥7.5%: ACC/AHA cholesterol management guideline recommends moderate- (e.g., pravastatin 40–80 mg once daily) to high-intensity statin therapy (i.e., with atorvastatin or rosuvastatin).350

Estimated 10-year ASCVD risk of 5 to <7.5%: ACC/AHA cholesterol management guideline states may consider moderate-intensity statin therapy.350

Consider potential benefits, adverse effects, drug interactions, and patient preferences before initiating statin therapy.350

ACC/AHA cholesterol management guideline recommends high-intensity statin therapy (i.e., with atorvastatin or rosuvastatin) unless contraindicated.350

In patients at increased risk for developing statin-associated adverse effects or in whom high-intensity statin therapy is inappropriate or contraindicated, consider moderate-intensity statin therapy (e.g., pravastatin 40–80 mg once daily) if tolerated.350

Patients >75 years of age: Individualize therapy based on potential benefits, adverse effects, drug interactions, and patient preferences; may consider moderate-intensity statin therapy if tolerated.350

Initially, 40 mg once daily.1 If antilipemic response is inadequate, increase dosage to 80 mg daily.1 Adjust dosage at intervals of ≥4 weeks until the desired effect on lipoprotein concentrations is observed.1

ACC/AHA cholesterol management guideline states may consider decreasing statin dosage when LDL-cholesterol concentrations are <40 mg/dL on 2 consecutive measurements; however, no data to suggest that LDL-cholesterol concentrations <40 mg/dL increase risk of adverse effects.350

Special Populations

Hepatic Impairment

No specific dosage recommendations at this time.1

Use with caution in patients who consume substantial amounts of alcohol, have a recent (<6 months) history of liver disease, or exhibit manifestations of liver disease (e.g., unexplained increases in aminotransferase concentrations, jaundice).1

Contraindicated in patients with active liver disease or unexplained, persistent increases in serum aminotransferase concentrations.1

Renal Impairment

Initially, 10 mg once daily in patients with severe renal impairment.1

Minimally metabolized by CYP3A4; pharmacokinetic interaction unlikely.1

Specific Drugs

Storage

Oral

Tight containers at 25°C (may be exposed to 15–30°C); protect from light and moisture.1

• Tell all of your health care providers that you take this medicine. This includes your doctors, nurses, pharmacists, and dentists.
• Have blood work checked as you have been told by the doctor. Talk with the doctor.
• Follow the diet and workout plan that your doctor told you about.
• Do not take more than what your doctor told you to take. Taking more than you are told may raise your chance of very bad side effects.
• If you have high blood sugar (diabetes), you will need to watch your blood sugar closely.
• If you take cholestyramine or colestipol, take them at least 4 hours before or 1 hour after Pravachol.
• Avoid or limit drinking alcohol to less than 3 drinks a day. Drinking too much alcohol may raise your chance of liver disease.
• If you are 65 or older, use this medicine with care. You could have more side effects.
• This medicine may cause harm to the unborn baby if you take it while you are pregnant. If you are pregnant or you get pregnant while taking Pravachol, call your doctor right away.
• Use birth control that you can trust to prevent pregnancy while taking this medicine.

Use Pravachol as ordered by your doctor. Read all information given to you. Follow all instructions closely.

• To gain the most benefit, do not miss doses.
• Keep taking this medicine as you have been told by your doctor or other health care provider, even if you feel well.
• Take with or without food.

What do I do if I miss a dose?

• Take a missed dose as soon as you think about it.
• If it is close to the time for your next dose, skip the missed dose and go back to your normal time.
• Do not take 2 doses at the same time or extra doses.

Pravachol® Tablets are supplied as:

20 mg tablets: Yellow, rounded, rectangular-shaped, biconvex with a “P” embossed on one side and “Pravachol 20” engraved on the opposite side.

40 mg tablets: Green, rounded, rectangular-shaped, biconvex with a “P” embossed on one side and “Pravachol 40” engraved on the opposite side.

80 mg tablets: Yellow, oval-shaped tablet with “BMS” on one side and “80” on the other side.

Pregnancy

Risk Summary

Pravachol is contraindicated for use in pregnant woman because of the potential for fetal harm. As safety in pregnant women has not been established and there is no apparent benefit to therapy with Pravachol during pregnancy, Pravachol should be immediately discontinued as soon as pregnancy is recognized [see Contraindications (4.3)]. Limited published data on the use of Pravachol in pregnant women are insufficient to determine a drug-associated risk of major congenital malformations or miscarriage. In animal reproduction studies, no evidence of fetal malformations was seen in rabbits or rats exposed to 10 times to 120 times, respectively, the maximum recommended human dose (MRHD) of 80 mg/day. Fetal skeletal abnormalities, offspring mortality, and developmental delays occurred when pregnant rats were administered 10 times to 12 times the MRHD during organogenesis to parturition [see Data]. Advise pregnant women of the potential risk to a fetus.

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.

Data

Human Data

Limited published data on pravastatin have not shown an increased risk of major congenital malformations or miscarriage.

Rare reports of congenital anomalies have been received following intrauterine exposure to other statins. In a review2 of approximately 100 prospectively followed pregnancies in women exposed to simvastatin or lovastatin, the incidences of congenital anomalies, spontaneous abortions, and fetal deaths/stillbirths did not exceed what would be expected in the general population. The number of cases is adequate to exclude a ≥3 to 4-fold increase in congenital anomalies over the background incidence. In 89% of the prospectively followed pregnancies, drug treatment was initiated prior to pregnancy and was discontinued at some point in the first trimester when pregnancy was identified.

Animal Data

Embryofetal and neonatal mortality was observed in rats given pravastatin during the period of organogenesis or during organogenesis continuing through weaning.

In pregnant rats given oral gavage doses of 4, 20, 100, 500, and 1000 mg/kg/day from gestation days 7 through 17 (organogenesis) increased mortality of offspring and increased cervical rib skeletal anomalies were observed at ≥100 mg/kg/day systemic exposure, 10 times the human exposure at 80 mg/day MRHD based on body surface area (mg/m2).

In other studies, no teratogenic effects were observed when pravastatin was dosed orally during organogenesis in rabbits (gestation days 6 through 18) up to 50 mg/kg/day or in rats (gestation days 7 through 17) up to 1000 mg/kg/day. Exposures were 10 times (rabbit) or 120 times (rat) the human exposure at 80 mg/day MRHD based on body surface area (mg/m2).

In pregnant rats given oral gavage doses of 10, 100, and 1000 mg/kg/day from gestation day 17 through lactation day 21 (weaning), increased mortality of offspring and developmental delays were observed at ≥100 mg/kg/day systemic exposure, corresponding to 12 times the human exposure at 80 mg/day MRHD, based on body surface area (mg/m2).

In pregnant rats, pravastatin crosses the placenta and is found in fetal tissue at 30% of the maternal plasma levels following administration of a single dose of 20 mg/day orally on gestation day 18, which corresponds to exposure 2 times the MRHD of 80 mg daily based on body surface area (mg/m2). In lactating rats, up to 7 times higher levels of pravastatin are present in the breast milk than in the maternal plasma, which corresponds to exposure 2 times the MRHD of 80 mg/day based on body surface area (mg/m2).

Lactation

Risk Summary

Pravastatin use is contraindicated during breastfeeding [see Contraindications (4.4)]. Based on one lactation study in published literature, pravastatin is present in human milk. There is no available information on the effects of the drug on the breastfed infant or the effects of the drug on milk production. Because of the potential for serious adverse reactions in a breastfed infant, advise patients that breastfeeding is not recommended during treatment with Pravachol.

Females and Males of Reproductive Potential

Contraception:

Females

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

Pediatric Use

The safety and effectiveness of Pravachol in children and adolescents from 8 to 18 years of age have been evaluated in a placebo-controlled study of 2 years duration. Patients treated with pravastatin had an adverse experience profile generally similar to that of patients treated with placebo with influenza and headache commonly reported in both treatment groups. [See Adverse Reactions (6.4).] Doses greater than 40 mg have not been studied in this population. Children and adolescent females of childbearing potential should be counseled on appropriate contraceptive methods while on pravastatin therapy [see Contraindications (4.3) and Use in Specific Populations (8.1)]. For dosing information [see Dosage and Administration (2.4)].

Double-blind, placebo-controlled pravastatin studies in children less than 8 years of age have not been conducted.

Geriatric Use

Two secondary prevention trials with pravastatin (CARE and LIPID) included a total of 6593 subjects treated with pravastatin 40 mg for periods ranging up to 6 years. Across these 2 studies, 36.1% of pravastatin subjects were aged 65 and older and 0.8% were aged 75 and older. The beneficial effect of pravastatin in elderly subjects in reducing cardiovascular events and in modifying lipid profiles was similar to that seen in younger subjects. The adverse event profile in the elderly was similar to that in the overall population. Other reported clinical experience has not identified differences in responses to pravastatin between elderly and younger patients.

Mean pravastatin AUCs are slightly (25%-50%) higher in elderly subjects than in healthy young subjects, but mean maximum plasma concentration (Cmax), time to maximum plasma concentration (Tmax), and half-life (t½) values are similar in both age groups and substantial accumulation of pravastatin would not be expected in the elderly [see Clinical Pharmacology (12.3)].

Since advanced age (≥65 years) is a predisposing factor for myopathy, Pravachol should be prescribed with caution in the elderly [see Warnings and Precautions (5.1) and Clinical Pharmacology (12.3)].

Homozygous Familial Hypercholesterolemia

Pravastatin has not been evaluated in patients with rare homozygous familial hypercholesterolemia. In this group of patients, it has been reported that statins are less effective because the patients lack functional LDL receptors.

Pravachol® (pravastatin sodium) is one of a class of lipid-lowering compounds, the statins, which reduce cholesterol biosynthesis. These agents are competitive inhibitors of HMG-CoA reductase, the enzyme catalyzing the early rate-limiting step in cholesterol biosynthesis, conversion of HMG-CoA to mevalonate.

Pravastatin sodium is designated chemically as 1-Naphthalene-heptanoic acid, 1,2,6,7,8,8a-hexahydro-β,δ,6-trihydroxy-2-methyl-8-(2-methyl-1-oxobutoxy)-, monosodium salt, [1S-[1α(βS*,δS*),2α,6α,8β(R*),8aα]]-.

Structural formula:

Pravastatin sodium is an odorless, white to off-white, fine or crystalline powder. It is a relatively polar hydrophilic compound with a partition coefficient (octanol/water) of 0.59 at a pH of 7.0. It is soluble in methanol and water (>300 mg/mL), slightly soluble in isopropanol, and practically insoluble in acetone, acetonitrile, chloroform, and ether.

Pravachol is available for oral administration as 20 mg, 40 mg, and 80 mg tablets. Inactive ingredients include: croscarmellose sodium, lactose, magnesium oxide, magnesium stearate, microcrystalline cellulose, and povidone. The 20 mg and 80 mg tablets also contain Yellow Ferric Oxide and the 40 mg tablet also contains Green Lake Blend (mixture of D&C Yellow No. 10-Aluminum Lake and FD&C Blue No. 1-Aluminum Lake).

90 tablets
NDC 0003-5194-10
40 mg
Pravachol®
(pravastatin sodium) Tablets
Rx only
Bristol-Myers Squibb

You should not use Pravachol if you are allergic to pravastatin, or if you have:

• liver disease; or

• if you are pregnant or breast-feeding.

To make sure Pravachol is safe for you, tell your doctor if you have:

• kidney disease;

• abnormal liver function tests;

• a thyroid disorder; or

• if you drink more than 2 alcoholic beverages daily.

Pravastatin can cause a condition that results in the breakdown of skeletal muscle tissue, leading to kidney failure. This condition may be more likely to occur in older adults and in people who have kidney disease or poorly controlled hypothyroidism (underactive thyroid).

This medicine can harm an unborn baby or cause birth defects. Do not use if you are pregnant. Stop taking Pravachol and tell your doctor right away if you become pregnant. Use effective birth control to prevent pregnancy while you are taking this medicine.

Pravastatin can pass into breast milk and may harm a nursing baby. Do not breast-feed while using this medicine.

This medicine is not approved for use by anyone younger than 8 years old.

You should not take pravastatin if you are pregnant or breast-feeding, or if you have liver disease.

Stop taking this medication and tell your doctor right away if you become pregnant.

Serious drug interactions can occur when certain medicines are used together with pravastatin. Tell each of your healthcare providers about all medicines you use now, and any medicine you start or stop using.

In rare cases, pravastatin can cause a condition that results in the breakdown of skeletal muscle tissue, leading to kidney failure. 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.