Pravastatin


Continuing Education Activity

Pravastatin is a medication used in the management and treatment of primary hypercholesterolemia, hyperlipidemia, and mixed dyslipidemia. It falls under the class of competitive hydroxymethylglutaryl coenzyme-A (HMG Co-A) reductase inhibitors. This activity reviews the indications, action, and contraindications for pravastatin as a valuable agent in the treatment and management of primary hypercholesterolemia, hyperlipidemia, and mixed dyslipidemia. This activity will highlight the mechanism of action, adverse effects, and other vital factors such as dosing, pharmacodynamics, pharmacokinetics, monitoring, relevant interactions pertinent for members of the interprofessional team in the treatment and care of patients with hyperlipidemia and related conditions.

Objectives:

  • Identify the mechanism of action of pravastatin.
  • Describe the adverse effects and contraindications of pravastatin.
  • Review the toxicity of pravastatin.
  • Summarize interprofessional team strategies for improving care coordination and communication to advance pravastatin and improve outcomes.

Indications

Pravastatin is an FDA-approved HMG Co-A reductase inhibitor indicated for the treatment of primary hypercholesterolemia, hyperlipidemia, and mixed dyslipidemia. Indications also include the prevention of cardiovascular events in patients diagnosed with coronary artery disease. Pravastatin can improve total mortality by decreasing the risk of coronary death, myocardial infarction, and slow the progression of coronary atherosclerosis. Pravastatin is most beneficial when prescribed as adjunctive therapy with a low-fat diet (i.e., a strict cholesterol-lowering diet including food such as fruits, vegetables, fish, beans, and nuts) and regular exercise. The medication is also safe and effective for the geriatrics population and in children over the age of seven. However, drug safety and efficacy remain unestablished in infants, and it is highly contraindicated in pregnant women. The medication is also effective management for individuals with familial heterozygous hypercholesterolemia. Off-label, pravastatin may be used for cerebral vasospasm prophylaxis after subarachnoid hemorrhage in adults.[1][2]

Mechanism of Action

Pravastatin falls under the class of competitive hydroxymethylglutaryl Coenzyme-A (HMG Co-A) reductase inhibitors. It is readily absorbed and less potent in comparison to atorvastatin and simvastatin. The drug selectively acts on the rate-limiting step in cholesterol biosynthesis by inhibiting HMG Co-A reductase; this results in the upregulation of hepatic LDL (low-density lipoprotein) receptors enhancing LDL metabolism and clearance, which subsequently lowers the total plasma cholesterol in circulation. It also causes a reduction in VLDL, triglycerides, and apolipoprotein B and increases HDL (high-density lipoprotein)-cholesterol levels. 

Statins such as pravastatin get metabolized in the liver via the extensive first-pass extraction path, and elimination is primarily through feces. When administered orally, pravastatin has a bioavailability of 17% and a half-life of between 2.6 to 3.2 hours. 

Some limited studies have shown when coadministering pravastatin with cholestyramine (bile-binding resin), the drug may decrease LDL levels to half and further slow the progression of atherosclerosis and reduce the risk of coronary death.[3][4][5]

Administration

Pravastatin is available as an oral tablet and is administered once daily with or without food. HMG Co-A inhibitors are most effective when taken at bedtime due to their effect on hepatic cholesterol synthesis. The drug should be swallowed whole with water and not crushed. The clinician can make dose adjustments on 4-week intervals based on individual response.[6]

Hyperlipidemia, hypercholesterolemia, and mixed dyslipidemia:

  • In adults and geriatrics population; 40 mg PO daily (do not exceed 80mg/day)
  • In children eight and above; 20 mg PO daily (do not exceed 60mg/day)

Stroke or myocardial infarction prophylaxis and secondary prevention of cardiovascular mortality and acute coronary events:

  • In adults; 40 mg PO daily (do not exceed 80 mg/day)

Patients with severe renal impairment:

  • 10 mg PO daily

Patients with hepatic impairment: *avoid HMG Co-A inhibitors

Adverse Effects

Some common adverse effects associated with pravastatin therapy include nausea and vomiting, dizziness, arthralgia, myalgia, headache, constipation, diarrhea, abdominal pain, flushing, dyspepsia, insomnia, increased creatine phosphokinase, and urinary tract infection. Fatigue, pruritus, rash, cough, heartburn, and flu-like symptoms may also present in patients taking pravastatin.  

Some potentially serious adverse effects that require adjustment of dose or frequency of administration may include chest pain, edema, hepatitis, jaundice, renal impairment, blurred vision, and confusion.[7][8]

Contraindications

Pravastatin is contraindicated in patients with HMG Co-A reductase inhibitor hypersensitivity or suspected reaction to any component of the medication. Statins such as pravastatin are highly contraindicated in individuals with any active form of liver disease (i.e., hepatitis, hepatic encephalopathy, jaundice, hepatic impairment) or persistently elevated serum transaminase levels. Safety measures are necessary for patients with a recent history of hepatic disease or a history of heavy alcohol use. These patients should be closely monitored for any signs of liver impairment and treated accordingly. Pravastatin therapy requires discontinuation in patients with signs or symptoms of muscle weakness or myalgias or suspected rhabdomyolysis. In patients taking fibrates, niacin, or cyclosporine, the risk of myopathy may increase when on statins; thus, prompt dose adjustment is necessary. Diabetic patients should receive counsel to use precaution when on pravastatin therapy due to the increased risk of hyperglycemia.  

Pregnant or breastfeeding women should avoid HMG Co-A inhibitors due to the elevated risk of teratogenicity and excretion into breast milk. Caution is necessary for the geriatrics population due to advanced age being a predisposing factor for myopathy. Avoid pravastatin therapy with cytochrome P450 inducers and inhibitors due to its effect on drug absorption.[9][10][11]

Monitoring

Patients taking pravastatin should undergo monitoring for the relief of symptoms and any adverse effects pertaining to the medication. A complete list of patient medications should be revised extensively before prescribing the drug. Renal function (UA, BUN, and creatinine) should be regularly monitored in individuals with renal impairment and dosing just be corrected. It is crucial to monitor the hepatic function (LFTs) to avoid administering the medication in patients with active liver disease or persistently elevated serum transaminases. Creatine phosphokinase (CPK) levels need close monitoring for any signs of myopathy or rhabdomyolysis associated with the medication. The patient's blood pressure and cardiac function (heart rate) should have routinely checked at each physician visit, and dose adjustments should checking accordingly. A complete lipid panel (total cholesterol, LDL, TGs) is regularly necessary, and dose adjustment can take place at intervals of four weeks. Diet and exercise regime should also have revisions with the patient at each clinic visit for optimal results.  

Pravastatin should be stored in a cool, dry place and away from light.[12][13]

Toxicity

Rhabdomyolysis and other muscle symptoms can be indicative of toxicity. Several studies and case reports have also suggested an association between statin therapy and neuromuscular disorders such as dermatomyositis, polymyositis, and necrotizing myopathies. If rhabdomyolysis is ruled out and other muscle symptom pathologies are suspected, the statin-associated muscle symptoms clinical index (SAMS-CI) must be administered to determine if muscle symptoms are due to statin therapy. Stopping the use of statin, administration of replacement vitamin D (associated with myopathy), and switching statins are all viable options depending on the etiology of myopathy.[14][15]

Enhancing Healthcare Team Outcomes

An interprofessional team consisting of physicians, nurses, and pharmacists is needed to successfully manage patients treated with HMG Co-A reductase inhibitors such as pravastatin. Providers must be knowledgable regarding the symptoms of toxicity. Other specialty physicians, such as a nephrologist and toxicologist, may be consulted to ensure the best patient outcome. Patient education is necessary for individuals with hepatic or renal impairment, clinicians and pharmacists must advise patients to report any signs or symptoms of hepatic injury (abnormal fatigue, weight loss, RUQ pain, jaundice). Pharmacists should also check for drug interactions and inform the prescriber of any concerns. The primary care physician or the nurse practitioner must also counsel the patient on the importance of reading labels to avoid overdosing to prevent any drug-related toxicities. Pravastatin therapy requires a communicative team dynamic, coordinating to manage any adverse effects and provide optimal patient care successfully to obtain the best outcomes. [Level 5] 


Article Details

Article Author

Gursharan Sidhu

Article Editor:

Amit Sapra

Updated:

2/23/2021 7:38:25 AM

PubMed Link:

Pravastatin

References

[1]

Pravastatin 2012;     [PubMed PMID: 31643964]

[2]

Statins 2012;     [PubMed PMID: 31643398]

[3]

Wagmann L,Hemmer S,Caspar AT,Meyer MR, Method development for quantitative determination of seven statins including four active metabolites by means of high-resolution tandem mass spectrometry applicable for adherence testing and therapeutic drug monitoring. Clinical chemistry and laboratory medicine. 2019 Oct 30;     [PubMed PMID: 31665111]

[4]

Carmena R,Betteridge DJ, Diabetogenic Action of Statins: Mechanisms. Current atherosclerosis reports. 2019 Apr 30;     [PubMed PMID: 31037345]

[5]

Expanded table: statins. The Medical letter on drugs and therapeutics. 2019 Sep 23;     [PubMed PMID: 31599870]

[6]

Lipid-lowering drugs. The Medical letter on drugs and therapeutics. 2019 Feb 11;     [PubMed PMID: 30845106]

[7]

Gosho M, Rhabdomyolysis risk from the use of two-drug combination of antidyslipidemic drugs with antihypertensive and antidiabetic medications: a signal detection analysis. Fundamental     [PubMed PMID: 30575126]

[8]

Hori E,Kikuchi C,Imaeda K,Okayama N,Suzuki T,Matsunaga T, [Effect of Statins on Glycemic Status and Plasma Adiponectin Concentrations in Patients with Type 2 Diabetes Mellitus and Hypercholesterolemia]. Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan. 2019 May 1;     [PubMed PMID: 30773524]

[9]

Muhammad ZA,Ahmad T,Baloch N, Can alternate-day Statin regimen minimize its adverse effects on muscle and tendon? A systematic review. JPMA. The Journal of the Pakistan Medical Association. 2019 Jul;     [PubMed PMID: 31308572]

[10]

Williams B,Brown D, Direct to consumer Internet advertising of statins: an assessment of safety. Pharmacoepidemiology and drug safety. 2012 Apr;     [PubMed PMID: 22298504]

[11]

Andrus MR,East J, Use of statins in patients with chronic hepatitis C. Southern medical journal. 2010 Oct;     [PubMed PMID: 20818300]

[12]

Charlton M, Obesity, hyperlipidemia, and metabolic syndrome. Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society. 2009 Nov;     [PubMed PMID: 19877024]

[13]

Ochs-Balcom HM,Nguyen LM,Ma C,Isackson PJ,Luzum JA,Kitzmiller JP,Tarnopolsky M,Weisman M,Christopher-Stine L,Peltier W,Wortmann RL,Vladutiu GD, Clinical features related to statin-associated muscle symptoms. Muscle     [PubMed PMID: 30549046]

[14]

Stein EA,Ballantyne CM,Windler E,Sirnes PA,Sussekov A,Yigit Z,Seper C,Gimpelewicz CR, Efficacy and tolerability of fluvastatin XL 80 mg alone, ezetimibe alone, and the combination of fluvastatin XL 80 mg with ezetimibe in patients with a history of muscle-related side effects with other statins. The American journal of cardiology. 2008 Feb 15;     [PubMed PMID: 18312764]

[15]

Ovesjö ML,Skilving I,Bergman P,Rane A,Ekström L,Björkhem-Bergman L, Low Vitamin D Levels and Genetic Polymorphism in the Vitamin D Receptor are Associated with Increased Risk of Statin-Induced Myopathy. Basic     [PubMed PMID: 26423691]