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Pravastatin

Medically reviewed by Drugs.com. Last updated on Jun 15, 2020.

Pronunciation

(prav a STAT in)

Index Terms

  • Pravastatin Sodium

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Tablet, Oral, as sodium:

Pravachol: 20 mg

Pravachol: 40 mg [contains fd&c blue #1 aluminum lake, fd&c yellow #10 aluminum lake]

Pravachol: 80 mg [DSC]

Generic: 10 mg, 20 mg, 40 mg, 80 mg

Brand Names: U.S.

  • Pravachol

Pharmacologic Category

  • Antilipemic Agent, HMG-CoA Reductase Inhibitor

Pharmacology

Pravastatin is a competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, which is the rate-limiting enzyme involved in de novo cholesterol synthesis. In addition to the ability of HMG-CoA reductase inhibitors to decrease levels of high-sensitivity C-reactive protein (hsCRP), they also possess pleiotropic properties including improved endothelial function, reduced inflammation at the site of the coronary plaque, inhibition of platelet aggregation, and anticoagulant effects (de Denus 2002; Ray 2005).

Absorption

Rapidly absorbed; average absorption 34%

Distribution

Vd: 0.46 L/kg

Metabolism

Hepatic multiple metabolites; primary metabolite is 3 alpha-hydroxy-iso-pravastatin (2.5% to 10% activity of parent drug); extensive first-pass metabolism

Excretion

Feces (70%); urine (~20%, 8% as unchanged drug)

Onset of Action

Several days; Peak effect: 4 weeks; LDL-reduction: 40 mg/day: 34% (for each doubling of this dose, LDL-C is lowered by ~6%)

Time to Peak

Serum: 1-1.5 hours

Half-Life Elimination

Children and Adolescents (4.9-15.6 years): 1.6 hours; range: 0.85 to 4.2 hours (Hedman 2003)

Adults: 77 hours (including all metabolites); Pravastatin: ~2 to 3 hours (Pan 1990); 3 alpha hydroxy-iso-pravastatin: ~1.5 hours (Gustavson 2005)

Protein Binding

~50%

Special Populations: Elderly

Mean AUC was approximately 27% greater and mean cumulative urinary excretion was approximately 19% lower in elderly men. Mean AUC was approximately 46% higher and mean cumulative urinary excretion was approximately 18% lower in elderly women.

Use: Labeled Indications

Heterozygous familial hypercholesterolemia: To reduce elevated total cholesterol (total-C), LDL-C, apoB, and triglyceride levels, and to increase HDL-C in patients with primary hypercholesterolemia.

Heterozygous familial hypercholesterolemia (pediatrics): Adjunct to diet in children and adolescents ≥8 years of age with heterozygous familial hypercholesterolemia if after an adequate trial of diet therapy the following findings are present: LDL-C ≥190 mg/dL, LDL ≥160 mg/dL with positive family history of premature cardiovascular disease (CVD), or LDL ≥160 mg/dL with 2 or more other CVD risk factors.

Homozygous familial hypercholesterolemia: To reduce total-C and LDL-C in patients with homozygous familial hypercholesterolemia as an adjunct to other lipid-lowering treatments (eg, LDL apheresis) or if such treatments are unavailable.

Prevention of atherosclerotic cardiovascular disease:

Primary prevention of atherosclerotic cardiovascular disease: To reduce the risk of myocardial infarction (MI), stroke, revascularization procedures, and angina in adults without a history of coronary heart disease (CHD) but who have multiple CHD risk factors.

Secondary prevention in patients with established atherosclerotic cardiovascular disease: To reduce the risk of MI, stroke, revascularization procedures, and angina in patients with a history of CHD.

Off Label Uses

Transplantation, post heart or post kidney

Based on the 2010 International Society of Heart and Lung Transplantation guidelines for the care of heart transplant recipients, pravastatin is effective and recommended following heart transplant, regardless of cholesterol levels, to reduce cardiac allograft vasculopathy and improve long-term outcomes [ISHLT [Costanzo 2010]].

Based on the 2013 Kidney Disease: Improving Global Outcomes clinical practice guideline for lipid management in chronic kidney disease, pravastatin is suggested following kidney transplant to reduce cardiovascular events (eg, myocardial infarction, stroke, cardiovascular death) [KDIGO 2013].

Contraindications

Hypersensitivity to pravastatin or any component of the formulation; active liver disease; unexplained persistent elevations of serum transaminases; pregnancy; breast-feeding

Dosing: Adult

Note: Use in conjunction with lifestyle modification (eg, diet and exercise). When choosing to initiate therapy and selecting dose intensity, consider the following: age, baseline LDL-C, 10-year atherosclerotic cardiovascular disease (ASCVD) risk, risk-enhancing factors, potential adverse effects, and drug interactions. Pravastatin is considered a moderate-intensity statin at doses of 40 to 80 mg/day (generally reduces LDL-C by ~30% to 49%). If LDL-C must be lowered ≥50%, select an alternative high-intensity statin (atorvastatin or rosuvastatin). Assess response ~1 to 3 months after initiation of therapy or dose adjustment and every 3 to 12 months thereafter (ACC/AHA [Grundy 2019]; ACC/AHA [Stone 2014]).

Heterozygous familial hypercholesterolemia (alternative agent):

Note: Use of pravastatin should be limited to patients unable to tolerate a high-intensity statin. Multiple lipid-lowering therapies may be needed if statin monotherapy is not effective. Referral to a lipid specialist should be considered if treatment goals are not met (ACC/AHA [Grundy 2019]; Rosenson 2020a).

Patients unable to tolerate high-intensity therapy (eg, appropriate dose of atorvastatin or rosuvastatin):

Moderate-intensity therapy: Oral: 40 to 80 mg once daily (ACC/AHA [Grundy 2019]; ACC/AHA [Stone 2014]).

Homozygous familial hypercholesterolemia (alternative agent):

Note: Use of pravastatin should be limited to patients unable to tolerate a high-intensity statin. Multiple lipid-lowering therapies may be needed if statin monotherapy is not effective. Referral to a lipid specialist should be considered if treatment goals are not met (ACC/AHA [Grundy 2019]; Rosenson 2020a).

Patients unable to tolerate high-intensity therapy (eg, appropriate dose of atorvastatin or rosuvastatin):

Moderate-intensity therapy: Oral: 40 to 80 mg once daily (ACC/AHA [Grundy 2019]; ACC/AHA [Stone 2014]).

Prevention of atherosclerotic cardiovascular disease:

Note: If LDL-C goal (eg, percent reduction or absolute goal) is not met with the initial dose, may consider up-titration based on estimated 10-year ASCVD risk (see ACC/AHA ASCVD Risk Estimator Plus online), LDL-C response, and tolerability. If LDL-C goal is not met with maximally tolerated dose, consider switching to a high-intensity statin (atorvastatin or rosuvastatin); additional lipid-lowering therapy may be warranted (ACC/AHA [Grundy 2019]; ACC/AHA [Stone 2014]).

Primary prevention:

Patients without diabetes, 40 to 75 years of age, and LDL-C 70 to 189 mg/dL:

ASCVD 10-year risk 5% to <7.5%:

Note: Depending on baseline LDL-C and presence of risk-enhancing factors, consider statin therapy after shared decision-making with patient. Some experts suggest shared decision-making if ASCVD 10-year risk is 5% to 10%; however, in patients with a baseline LDL-C ≥160 mg/dL, statin therapy is usually recommended (Pignone 2020).

Moderate-intensity therapy: Oral: 40 to 80 mg once daily to reduce LDL-C by 30% to 49% (ACC/AHA [Grundy 2019]; ACC/AHA [Stone 2014]).

ASCVD 10-year risk ≥7.5% to <20%:

Note: Depending on baseline LDL-C and presence of risk-enhancing factors, consider statin therapy after shared decision-making with patient. Some experts suggest initiating moderate-intensity statin therapy in most patients if ASCVD 10-year risk is >10% to <20% and LDL-C is >100 mg/dL (Pignone 2020).

Moderate-intensity therapy: Oral: 40 to 80 mg once daily to reduce LDL-C by 30% to 49%; higher-risk patients with multiple risk-enhancing factors may benefit from high-intensity statin therapy (ie, with atorvastatin or rosuvastatin) to reduce LDL-C by ≥50% (ACC/AHA [Grundy 2019]).

ASCVD 10-year risk ≥20% (alternative agent):

Note: Use of pravastatin should be limited to patients unable to tolerate a high-intensity statin (ACC/AHA [Grundy 2019]; Rosenson 2020a).

Patients unable to tolerate high-intensity therapy (eg, appropriate dose of atorvastatin or rosuvastatin):

Moderate-intensity therapy: Oral: 40 to 80 mg once daily (ACC/AHA [Grundy 2019]; ACC/AHA [Stone 2014]).

Patients with diabetes:

Age 40 to 75 years without additional ASCVD risk factors:

Moderate-intensity therapy: Oral: 40 to 80 mg once daily to reduce LDL-C by 30% to 49% (ACC/AHA [Grundy 2019; ACC/AHA [Stone 2014]).

ASCVD 10-year risk ≥20% or multiple ASCVD risk factors (alternative agent):

Note: Use of pravastatin should be limited to patients unable to tolerate a high-intensity statin (ACC/AHA [Grundy 2019]; Rosenson 2020a).

Patients unable to tolerate high-intensity therapy (eg, appropriate dose of atorvastatin or rosuvastatin):

Moderate-intensity therapy: Oral: 40 to 80 mg once daily (ACC/AHA [Grundy 2019]; ACC/AHA [Stone 2014]).

Patients with LDL-C ≥190 mg/dL and 20 to 75 years of age (regardless of ASCVD risk estimate or coexisting diabetes mellitus) (alternative agent):

Note: Use of pravastatin should be limited to patients unable to tolerate a high-intensity statin (ACC/AHA [Grundy 2019]; Rosenson 2020a).

Patients unable to tolerate high-intensity therapy (eg, appropriate dose of atorvastatin or rosuvastatin):

Moderate-intensity therapy: Oral: 40 to 80 mg once daily (ACC/AHA [Grundy 2019]; ACC/AHA [Stone 2014]).

Secondary prevention in patients with established atherosclerotic cardiovascular disease (eg, coronary heart disease, cerebrovascular disease [ischemic stroke or transient ischemic attack], peripheral arterial disease) (alternative agent):

Note: Use of pravastatin should be limited to patients unable to tolerate a high-intensity statin (ACC/AHA [Grundy 2019]; Rosenson 2020a). Patients with high-risk ASCVD may require additional therapies to achieve LDL-C goal (eg, <70 mg/dL or <50 mg/dL if very high risk) (ACC/AHA [Grundy 2019]; ACC/AHA [Stone 2014]; Rosenson 2020b).

Patients unable to tolerate high-intensity therapy (eg, appropriate dose of atorvastatin or rosuvastatin):

Moderate-intensity therapy: Oral: 40 to 80 mg once daily (ACC/AHA [Grundy 2019]; ACC/AHA [Stone 2014]).

Transplantation, post heart or post kidney (off-label use):

Note: Initiate after transplant regardless of baseline cholesterol levels. Certain immunosuppressive drugs can induce or exacerbate hypercholesterolemia; significant drug interactions between statins and immunosuppressant drugs are frequent; some interactions can increase statin serum concentrations and risk of toxicity (eg, myopathy) (AHA [Wiggins 2016]; Brennan 2020; Eisen 2020; ISHLT [Costanzo 2010]; KDIGO 2013). Consult drug interactions database for more detailed information.

Oral: Initial: 20 mg once daily starting 1 to 2 weeks after transplant; increase dose based on response, tolerability, and concomitant drugs up to 40 mg once daily (AHA [Wiggins 2016]; Brennan 2020; Eisen 2020; ISHLT [Costanzo 2010]).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

Note: Dosage should be individualized according to the baseline LDL-C level, the recommended goal of therapy, and patient response; adjustments should be made at intervals of 4 weeks.

Hyperlipidemia or heterozygous familial and nonfamilial hypercholesterolemia:

Note: Begin treatment if, after adequate trial (6 to 12 months) of intensive lifestyle modification emphasizing body weight normalization and diet, the following are present (AACE [Jellinger 2017]):

LDL-C ≥190 mg/dL or

LDL-C remains ≥160 mg/dL and two or more cardiovascular risk factors: Family history of premature atherosclerotic cardiovascular disease (<55 years of age), overweight, obesity, or other elements of insulin resistance syndrome or

LDL-C ≥130 mg/dL and diabetes mellitus (Daniels 2008; NHLBI 2011).

Therapy may also be considered for children 8 to 9 years of age meeting the above criteria or for children with diabetes mellitus and LDL-C ≥130 mg/dL (Daniels 2008).

Children and Adolescents 8 to 13 years: Oral: 20 mg once daily; lower doses (5 and 10 mg/day) have been evaluated and less efficacy observed compared to 20 mg doses (NHLBI 2011; Vuorio 2017); doses >20 mg have not been studied (Vuorio 2017).

Adolescents 14 to 18 years: Oral: 40 mg once daily; lower doses have been evaluated and less efficacy observed; doses >40 mg have not been studied (NHLBI 2011; Vuorio 2017).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing adjustment for toxicity: Muscle symptoms (potential myopathy): Children ≥8 years and Adolescents: Discontinue use until symptoms can be evaluated; check CPK level; based on experience in adult patients, also evaluate patient for conditions that may increase the risk for muscle symptoms (eg, hypothyroidism, reduced renal or hepatic function, rheumatologic disorders such as polymyalgia rheumatica, steroid myopathy, vitamin D deficiency, or primary muscle diseases). Upon resolution (symptoms and any associated CPK abnormalities), resume the original or consider a lower dose of pravastatin and retitrate. If muscle symptoms recur, discontinue pravastatin use. After muscle symptom resolution, may then reinitiate a different statin at an initial low dose; gradually increase if tolerated. Based on experience in adult patients, if muscle symptoms or elevated CPK persists for 2 months in the absence of continued statin use, consider other causes of muscle symptoms. If determined to be due to another condition aside from statin use, may resume statin therapy at the original dose (NHLBI 2011; Stone 2013).

Dosing: Adjustment for Toxicity

Severe muscle symptoms or fatigue: Promptly discontinue use; evaluate CPK, creatinine, and urinalysis for myoglobinuria (ACC/AHA [Stone 2014]).

Mild to moderate muscle symptoms: Discontinue use until symptoms can be evaluated; evaluate patient for conditions that may increase the risk for muscle symptoms (eg, hypothyroidism, reduced renal or hepatic function, rheumatologic disorders such as polymyalgia rheumatica, steroid myopathy, vitamin D deficiency, primary muscle diseases). Upon resolution, resume the original or lower dose of pravastatin. If muscle symptoms recur, discontinue pravastatin use. After muscle symptom resolution, may then use a low dose of a different statin; gradually increase if tolerated. In the absence of continued statin use, if muscle symptoms or elevated CPK continues after 2 months, consider other causes of muscle symptoms. If determined to be due to another condition aside from statin use, may resume statin therapy at the original dose (ACC/AHA [Stone 2014]).

Administration

Oral: Administer without regard to meals.

Dietary Considerations

Before initiation of therapy, patients should be placed on a standard cholesterol-lowering diet for 6 weeks and the diet should be continued during drug therapy.

Red yeast rice contains variable amounts of several compounds that are structurally similar to HMG-CoA reductase inhibitors, primarily monacolin K (or mevinolin) which is structurally identical to lovastatin; concurrent use of red yeast rice with HMG-CoA reductase inhibitors may increase the incidence of adverse and toxic effects (Lapi 2008; Smith 2003).

Storage

Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Protect from light.

Drug Interactions

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

Antihepaciviral Combination Products: May increase the serum concentration of Pravastatin. Management: Limit the pravastatin dose to a maximum of 40 mg per day when used with antihepaciviral combination products and monitor patients for evidence of pravastatin toxicities (eg, myopathy). Consider therapy modification

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

Bempedoic Acid: May increase the serum concentration of Pravastatin. Management: Avoid coadministration of bempedoic acid with pravastatin doses greater than 40 mg due to the potential for increased pravastatin concentrations and pravastatin-related myopathy. Consider therapy modification

Bezafibrate: May enhance the myopathic (rhabdomyolysis) effect of HMG-CoA Reductase Inhibitors (Statins). Bezafibrate may increase the serum concentration of HMG-CoA Reductase Inhibitors (Statins). More specifically, bezafibrate may increase the serum concentration of fluvastatin Consider therapy modification

Bile Acid Sequestrants: May decrease the serum concentration of Pravastatin. Management: Administer pravastatin at least 1 hour before or 4 hours after administration of bile-acid resins (eg, cholestyramine, colestipol, colesevelam) to minimize the risk for any significant interaction. Consider therapy modification

CarBAMazepine: May decrease the serum concentration of Pravastatin. Monitor therapy

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

Clarithromycin: May increase the serum concentration of Pravastatin. Management: Limit pravastatin to a maximum of 40 mg/day when used in combination with clarithromycin. If this combination is used, monitor patients more closely for evidence of pravastatin toxicity. Consider therapy modification

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

CycloSPORINE (Systemic): May increase the serum concentration of Pravastatin. Pravastatin may increase the serum concentration of CycloSPORINE (Systemic). Management: Initiate pravastatin dose at 10 mg daily and limit the maximum pravastatin dose to 20 mg daily in patients who are also receiving cyclosporine. Monitor for pravastatin toxicities (eg, myalgia, myopathy, rhabdomyolysis) if combined. Consider therapy modification

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

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

Darunavir: May increase the serum concentration of Pravastatin. This effect has been demonstrated with darunavir/ritonavir and may occur with darunavir/cobicistat. The individual contributions of darunavir, ritonavir, and cobicistat are unknown. Monitor therapy

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

Eltrombopag: May increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates. Monitor therapy

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

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

Fosphenytoin-Phenytoin: May decrease the serum concentration of HMG-CoA Reductase Inhibitors (Statins). Management: Consider avoiding coadministration of fosphenytoin/phenytoin and statins. If combined, monitor for decreased therapeutic effects of statins if fosphenytoin/phenytoin is initiated/dose increased. Consider therapy modification

Fostemsavir: May increase the serum concentration of HMG-CoA Reductase Inhibitors (Statins). Management: Use the lowest possible starting statin dose and monitor patients closely for statin-related adverse effects (eg, muscle aches and pains) during coadministration with fostemsavir. Consider therapy modification

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

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

Glecaprevir and Pibrentasvir: May increase the serum concentration of HMG-CoA Reductase Inhibitors (Statins). Management: Use the lowest statin dose possible if combined with glecaprevir/pibrentasvir and monitor for increased statin effects/toxicities. Avoid concomitant use with atorva-, simva-, or lovastatin. Limit rosuvastatin to 10 mg daily and reduce pravastatin dose 50% Consider therapy modification

Itraconazole: May increase the serum concentration of Pravastatin. Monitor therapy

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

Letermovir: May increase the serum concentration of HMG-CoA Reductase Inhibitors (Statins). Monitor therapy

Nelfinavir: May decrease the serum concentration of Pravastatin. Monitor therapy

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

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

PARoxetine: Pravastatin may enhance the adverse/toxic effect of PARoxetine. Specifically, blood glucose elevations may occur with the combination. Monitor therapy

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

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

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

RifAMPin: May decrease the serum concentration of Pravastatin. Monitor therapy

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

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

Saquinavir: May decrease the serum concentration of Pravastatin. This effect has only been demonstrated with saquinavir/ritonavir. The individual contributions of saquinavir and ritonavir are unknown. Monitor therapy

Simeprevir: May increase the serum concentration of Pravastatin. Monitor therapy

Telithromycin: May increase the serum concentration of Pravastatin. Monitor therapy

Teriflunomide: May increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates. Monitor therapy

Tolvaptan: May increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates. Management: Avoid concomitant use of OATP1B1/1B3 substrates in patients receiving the Jynarque brand of tolvaptant. Concentrations and effects of the OATP1B1/1B3 substrate would be expected to increase with combined use. Consider therapy modification

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

Vitamin K Antagonists (eg, warfarin): HMG-CoA Reductase Inhibitors (Statins) may enhance the anticoagulant effect of Vitamin K Antagonists. Monitor therapy

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

Adverse Reactions

As reported in short-term trials; safety and tolerability with long-term use were similar to placebo.

1% to 10%:

Cardiovascular: Chest pain (4%)

Central nervous system: Headache (2% to 6%), fatigue (4%), dizziness (1% to 3%)

Dermatologic: Skin rash (4%)

Gastrointestinal: Nausea (≤7%), vomiting (≤7%), diarrhea (6%), heartburn (3%)

Genitourinary: Cystitis (interstitial; Huang 2015)

Hepatic: Increased serum transaminases (>3x normal on 2 occasions: 1%)

Infection: Influenza (2%)

Neuromuscular & skeletal: Myalgia (2%)

Respiratory: Cough (3%)

<1%, postmarketing, and/or case reports: Alopecia, amnesia (reversible), anaphylaxis, angioedema, cataract, change in libido, cholestatic jaundice, cognitive dysfunction (reversible), confusion (reversible), cranial nerve dysfunction, decreased appetite, dermatitis, dermatomyositis, dysgeusia, edema, erythema multiforme, fever, flushing, fulminant hepatic necrosis, gynecomastia, hemolytic anemia, hepatic cirrhosis, hepatic neoplasm, hepatitis, hypersensitivity reaction, increased erythrocyte sedimentation rate, insomnia, lupus-like syndrome, memory impairment (reversible), myasthenia, myopathy, neuropathy, pancreatitis, paresthesia, peripheral nerve palsy, polymyalgia rheumatica, positive ANA titer, pruritus, purpura, rhabdomyolysis, sexual disorder, Stevens-Johnson syndrome, tremor, urticaria, vasculitis, vertigo, xeroderma

Warnings/Precautions

Concerns related to adverse effects:

• Diabetes mellitus: Increases in HbA1c and fasting blood glucose have been reported with HMG-CoA reductase inhibitors; however, the benefits of statin therapy far outweigh the risk of dysglycemia.

• Endocrine effects: Reduced cholesterol synthesis as a result of therapy could theoretically lead to reduced adrenal or gonadal steroid hormone production; clinical trial data is inconsistent in regards to the effect on basal steroid hormone levels. Patients with signs/symptoms of endocrine dysfunction should be evaluated as clinically indicated; use caution with concomitant medications (eg, spironolactone, cimetidine, ketoconazole) that may reduce steroid hormone levels/activity.

• Hepatotoxicity: Postmarketing reports of fatal and nonfatal hepatic failure are rare. If serious hepatotoxicity with clinical symptoms and/or hyperbilirubinemia or jaundice occurs during treatment, interrupt therapy. If an alternate etiology is not identified, do not restart pravastatin. Liver enzyme tests should be obtained at baseline and as clinically indicated; routine periodic monitoring of liver enzymes is not necessary. Ethanol may enhance the potential of adverse hepatic effects; instruct patients to avoid excessive ethanol consumption.

• Myopathy/rhabdomyolysis: Rhabdomyolysis with acute renal failure secondary to myoglobinuria and/or myopathy have been reported; patients should be monitored closely. This risk is dose-related and is increased with concurrent use of erythromycin, cyclosporine, fibric acid derivatives (eg, gemfibrozil), or niacin (doses ≥1 g/day). Temporarily withhold therapy in patients experiencing conditions predisposing to the development of renal failure secondary to rhabdomyolysis (eg, sepsis, hypotension, major surgery, trauma, uncontrolled epilepsy; severe metabolic, endocrine, or electrolyte disorders). Discontinue therapy in any patient in which CPK levels are markedly elevated (>10 times ULN) or if myopathy is suspected/diagnosed; consider treatment with immunosuppressants and additional neuromuscular and serologic testing. Prior to initiating a different HMG-CoA reductase inhibitor, consider risk of immune-mediated necrotizing myopathy; monitor closely. Use caution in patients with inadequately treated hypothyroidism, those taking other drugs associated with myopathy (eg, colchicine), and ≥65 years of age; these patients are predisposed to myopathy. Patients should be instructed to report unexplained muscle pain, tenderness, weakness, or brown urine, particularly if accompanied by malaise or fever.

Disease-related concerns:

• Hepatic impairment and/or ethanol use: Use with caution in patients who consume large amounts of ethanol or have a history of liver disease. Use is contraindicated in patients with active liver disease or unexplained transaminase elevations.

• Renal impairment: Use with caution in patients with renal impairment; these patients are predisposed to myopathy.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Special Populations:

• Elderly: Use with caution in patients with advanced age, these patients are predisposed to myopathy.

• Surgical patients: The manufacturer recommends temporary discontinuation for elective major surgery, acute medical or surgical conditions, or in any patient experiencing an acute or serious condition predisposing to renal failure (eg, sepsis, hypotension, trauma, uncontrolled seizures). Based on current research and clinical guidelines, HMG-CoA reductase inhibitors should be continued in the perioperative period for noncardiac and cardiac surgery (ACC/AHA [Fleisher 2014]; ACC/AHA [Hillis 2011]). Perioperative discontinuation of statin therapy is associated with an increased risk of cardiac morbidity and mortality.

Other warnings/precautions:

• Appropriate use: Has not been studied in homozygous familial hypercholesterolemia (statins may be less effective due to lack of functional LDL receptors).

• Hyperlipidemia: Secondary causes of hyperlipidemia should be ruled out prior to therapy.

Monitoring Parameters

ACC/AHA Blood Cholesterol Guideline recommendations (ACC/AHA [Grundy 2019]; ACC/AHA [Stone 2014]):

Lipid panel (total cholesterol, HDL, LDL, triglycerides): Lipid profile (fasting or nonfasting) before initiating treatment. Fasting lipid profile should be rechecked 4 to 12 weeks after starting therapy and every 3 to 12 months thereafter. If 2 consecutive LDL levels are <40 mg/dL, consider decreasing the dose.

Hepatic transaminase levels: Baseline measurement of hepatic transaminase levels (AST and ALT); measure AST, ALT, total bilirubin, and alkaline phosphatase if symptoms suggest hepatotoxicity (eg, unusual fatigue or weakness, loss of appetite, abdominal pain, dark-colored urine or yellowing of skin or sclera) during therapy.

CPK: CPK should not be routinely measured. Baseline CPK measurement is reasonable for some individuals (eg, family history of statin intolerance or muscle disease, clinical presentation, concomitant drug therapy that may increase risk of myopathy). May measure CPK in any patient with symptoms suggestive of myopathy (pain, tenderness, stiffness, cramping, weakness, or generalized fatigue).

Evaluate for new-onset diabetes mellitus during therapy; if diabetes develops, continue statin therapy and encourage adherence to a heart-healthy diet, physical activity, a healthy body weight, and tobacco cessation.

If patient develops a confusional state or memory impairment, may evaluate patient for nonstatin causes (eg, exposure to other drugs), systemic and neuropsychiatric causes, and the possibility of adverse effects associated with statin therapy.

Manufacturer's labeling: Consider neuromuscular and serologic testing if immune-mediated necrotizing myopathy is suspected.

Reproductive Considerations

Pravastatin is contraindicated in females who may become pregnant.

Adequate contraception is recommended if an HMG-CoA reductase inhibitor is required in females of reproductive potential. Females planning a pregnancy should discontinue the HMG-CoA reductase inhibitor 1 to 2 months prior to attempting to conceive (AHA/ACC [Grundy 2019]).

Pregnancy Considerations

Pravastatin is contraindicated in pregnant females.

Pravastatin was found to cross the placenta in an ex vivo study using term human placentas (Nanovskaya 2013). There are reports of congenital anomalies following maternal use of HMG-CoA reductase inhibitors in pregnancy; however, maternal disease, differences in specific agents used, and the low rates of exposure limit the interpretation of the available data (Godfrey 2012; Lecarpentier 2012). Cholesterol biosynthesis may be important in fetal development; serum cholesterol and triglycerides increase normally during pregnancy. The discontinuation of lipid lowering medications temporarily during pregnancy is not expected to have significant impact on the long term outcomes of primary hypercholesterolemia treatment.

Pravastatin should be discontinued immediately if an unplanned pregnancy occurs during treatment.

Patient Education

What is this drug used for?

• It is used to lower bad cholesterol and raise good cholesterol (HDL).

• It is used to lower triglycerides.

• It is used to slow the progress of heart disease.

• It is used to prevent heart attacks.

• It is used to prevent strokes.

• It may be given to you for other reasons. Talk with the 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

• Dizziness

• Loss of strength and energy

• Diarrhea

• Nausea

• Vomiting

• Stuffy nose

• Sore throat

• Cough

• Runny nose

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Liver problems like dark urine, feeling tired, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or yellow skin or eyes.

• Chest pain

• Vision changes

• Unable to pass urine

• Change in amount of urine passed

• Muscle pain

• Muscle tenderness

• Muscle weakness

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a limited summary of general information about the medicine’s uses from the patient education leaflet and is not intended to be comprehensive. This limited summary does NOT include all information available about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not intended to provide medical advice, diagnosis or treatment and does not replace information you receive from the healthcare provider. For a more detailed summary of information about the risks and benefits of using this medicine, please speak with your healthcare provider and review the entire patient education leaflet.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

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