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Special Alerts
HMG-CoA Reductase Inhibitors: Liver Enzyme Monitoring Requirements Removed and Warning Updates
February 2012
The U.S. Food and Drug Administration (FDA) has approved important labeling changes for HMG-CoA reductase inhibitors.
Routine monitoring of liver enzymes has been removed from the drug labeling. The incidence of serious liver injury associated with the currently marketed HMG-CoA reductase inhibitors is very low and routine periodic monitoring of serum alanine aminotransferase (ALT) does not appear to detect or prevent serious liver injury, but may cause interruptions in therapy for patients with isolated increases in ALT levels, placing them at risk for cardiovascular events. Baseline liver function tests are still recommended prior to initiation of HMG-CoA Reductase Inhibitor therapy.
Based upon review of postmarketing events through the AERS database and clinical trials, updated details regarding cognitive adverse events and glycemic regulation have been added to the labels. Although rare, reversible memory impairment (including confusion, forgetfulness, amnesia, and memory loss) can occur with HMG-CoA reductase inhibitors. These cognitive symptoms have been reported at variable times during therapy (1 day to years after initiation) and are reversible with discontinuation; resolution usually occurs within ~3 weeks. Cases have not been associated with fixed or progressive dementia; nor have they been associated with age, specific HMG CoA reductase inhibitor, dose or concomitant medication use.
Additionally, HMG-CoA reductase inhibitors have been associated with increases in glycosylated hemoglobin and fasting plasma glucose. Subgroup analyses of randomized, controlled, clinical trials, an observational study, and meta-analyses have observed an association between new onset diabetes and the use of an HMG CoA reductase inhibitor.
For additional information, please refer to http://www.fda.gov/Drugs/DrugSafety/ucm293101.htm.
Pronunciation
(prav a STAT in)
Generic Available (U.S.)
Yes
Index Terms
Brand Names: U.S.
Brand Names: Canada
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
Use with dietary therapy for the following:
Primary prevention of coronary events: In hypercholesterolemic patients without established coronary heart disease to reduce cardiovascular morbidity (myocardial infarction, coronary revascularization procedures) and mortality.
Secondary prevention of cardiovascular events in patients with established coronary heart disease: To slow the progression of coronary atherosclerosis; to reduce cardiovascular morbidity (myocardial infarction, coronary vascular procedures) and to reduce mortality; to reduce the risk of stroke and transient ischemic attacks
Hyperlipidemias: Reduce elevations in total cholesterol, LDL-C, apolipoprotein B, and triglycerides (elevations of 1 or more components are present in Fredrickson type IIa, IIb, III, and IV hyperlipidemias)
Heterozygous familial hypercholesterolemia (HeFH): In pediatric patients, 8-18 years of age, with HeFH having LDL-C ≥190 mg/dL or LDL ≥160 mg/dL with positive family history of premature cardiovascular disease (CVD) or 2 or more CVD risk factors in the pediatric patient
Pregnancy Risk Factor
X
Pregnancy Considerations
Cholesterol biosynthesis may be important in fetal development. Contraindicated in pregnancy. Administer to women of childbearing potential only when conception is highly unlikely and patients have been informed of potential hazards.
Lactation
Enters breast milk/contraindicated
Contraindications
Hypersensitivity to pravastatin or any component of the formulation; active liver disease; unexplained persistent elevations of serum transaminases; pregnancy; breast-feeding
Warnings/Precautions
Concerns related to adverse effects:
• Diabetes mellitus: Increases in Hb A1c and fasting blood glucose have been reported with HMG-CoA reductase inhibitors; however, the benefits of statin therapy far outweigh the risk of dysglycemia.
• 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.
• Myopathy/rhabdomyolysis: Patients receiving HMG-CoA reductase inhibitors have developed rhabdomyolysis with acute renal failure and/or myopathy; patients should be monitored closely. This risk is dose-related and is increased with concurrent use of other drugs which may cause rhabdomyolysis (including colchicine, gemfibrozil, fibric acid derivatives, or niacin at doses ≥1 g/day). Discontinue in any patient in which CPK levels are markedly elevated (>10 times ULN) or if myopathy is suspected/diagnosed. 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). However, based upon current evidence, HMG-CoA reductase inhibitor therapy should be continued in the perioperative period unless risk outweighs cardioprotective benefit. Use caution in patients with renal impairment, inadequately treated hypothyroidism, and those taking other drugs associated with myopathy (eg, colchicine); these patients are predisposed to myopathy. Patients should be instructed to report unexplained muscle pain, tenderness, weakness, or brown urine.
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.
Concurrent drug therapy issues:
• High potential for interactions: Concomitant use of pravastatin with some drugs may require cautious use or may require dosage adjustments (see Drug Interactions).
Special Populations:
• Elderly: Use with caution in patients with advanced age, these patients are predisposed to myopathy.
• Pediatrics: Treatment is not recommended in patients <8 years of age.
Other warnings/precautions:
• Hyperlipidemia: Secondary causes of hyperlipidemia should be ruled out prior to therapy.
• Liver function tests: Must be monitored by periodic laboratory assessment.
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: Rash (4%)
Gastrointestinal: Nausea/vomiting (7%), diarrhea (6%), heartburn (3%)
Hepatic: Transaminases increased (>3x normal on two occasions: 1%)
Neuromuscular & skeletal: Myalgia (2%)
Respiratory: Cough (3%)
Miscellaneous: Influenza (2%)
<1%: Allergy, alopecia, appetite decreased, dermatitis, dry skin, edema, fever, flushing, insomnia, lens opacity, libido change, muscle weakness, neuropathy, paresthesia, pruritus, sexual dysfunction, taste disturbance, tremor, urticaria, vertigo
Postmarketing and/or case reports: Amnesia (reversible), anaphylaxis, angioedema, cholestatic jaundice, cirrhosis, cognitive impairment (reversible), confusion (reversible), cranial nerve dysfunction, dermatomyositis, erythema multiforme, ESR increase, fulminant hepatic necrosis, gynecomastia, hemolytic anemia, hepatitis, hepatoma, lupus erythematosus-like syndrome, memory disturbance (reversible), memory impairment (reversible), myopathy, pancreatitis, peripheral nerve palsy, polymyalgia rheumatica, positive ANA, purpura, rhabdomyolysis, Stevens-Johnson syndrome, vasculitis
Additional class-related events or case reports (not necessarily reported with pravastatin therapy): Angioedema, blood glucose increased, cataracts, depression, diabetes mellitus (new onset), dyspnea, eosinophilia, erectile dysfunction, facial paresis, glycosylated hemoglobin (Hb A1c) increased, hypersensitivity reaction, impaired extraocular muscle movement, impotence, interstitial lung disease, leukopenia, malaise, memory loss, ophthalmoplegia, paresthesia, peripheral neuropathy, photosensitivity, psychic disturbance, skin discoloration, thrombocytopenia, thyroid dysfunction, toxic epidermal necrolysis, transaminases increased, vomiting
Metabolism/Transport Effects
Substrate of CYP3A4 (minor), P-glycoprotein, SLCO1B1; Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Inhibits CYP2C9 (weak), CYP2D6 (weak), CYP3A4 (weak)
Drug Interactions
Antacids: May decrease the serum concentration of HMG-CoA Reductase Inhibitors. Risk C: Monitor therapy
Antifungal Agents (Azole Derivatives, Systemic): May decrease the metabolism of HMG-CoA Reductase Inhibitors. Management: Consider use of HMG-CoA reductase inhibitors posing the least rhabdomyolysis risk (e.g. fluva- or pravastatin), and monitor for signs/symptoms of rhabdomyolysis. Do not use keto- or itraconazole with lova- or simvastatin, or posaconazole with simvastatin. Risk D: Consider therapy modification
ARIPiprazole: CYP3A4 Inhibitors (Weak) may increase the serum concentration of ARIPiprazole. Management: Monitor for increased aripiprazole systemic exposure/affects with concomitant use of a weak CYP3A4 inhibitor. Decrease aripiprazole dose to 25% of the usual dose in patients receiving both a CYP3A4 and a CYP2D6 inhibitor (regardless of potencies). Risk C: Monitor therapy
ARIPiprazole: CYP2D6 Inhibitors (Weak) may increase the serum concentration of ARIPiprazole. Management: Monitor for increased aripiprazole pharmacologic effects. Aripiprazole dose adjustments may or may not be required based on concomitant therapy and/or indication. Consult product labeling for specific recommendations. Risk C: Monitor therapy
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. Risk D: Consider therapy modification
Colchicine: May enhance the myopathic (rhabdomyolysis) effect of HMG-CoA Reductase Inhibitors. Colchicine may increase the serum concentration of HMG-CoA Reductase Inhibitors. Risk D: Consider therapy modification
Conivaptan: May increase the serum concentration of CYP3A4 Substrates (Low risk). Risk C: Monitor therapy
CycloSPORINE: May increase the serum concentration of HMG-CoA Reductase Inhibitors. Management: Use of cyclosporine with simvastatin, lovastatin, or pitavastatin is contraindicated. U.S. and Canadian recommendations for some statins may differ, see appropriate prescribing information. Monitor closely for myotoxicity with concurrent use. Risk D: Consider therapy modification
CycloSPORINE (Systemic): May increase the serum concentration of HMG-CoA Reductase Inhibitors. Management: Use of cyclosporine with simvastatin, lovastatin, or pitavastatin is contraindicated. U.S. and Canadian recommendations for some statins may differ, see appropriate prescribing information. Monitor closely for myotoxicity with concurrent use. Risk D: Consider therapy modification
DAPTOmycin: HMG-CoA Reductase Inhibitors 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. Risk D: Consider therapy modification
Efavirenz: May decrease the serum concentration of Pravastatin. Risk C: Monitor therapy
Eltrombopag: May increase the serum concentration of OATP1B1/SLCO1B1 Substrates. Management: According to eltrombopag prescribing information, consideration of a preventative dose reduction may be warranted. Risk D: Consider therapy modification
Fenofibrate: May enhance the adverse/toxic effect of HMG-CoA Reductase Inhibitors. Risk C: Monitor therapy
Fenofibric Acid: May enhance the adverse/toxic effect of HMG-CoA Reductase Inhibitors. Risk C: Monitor therapy
Fosphenytoin: May decrease the serum concentration of HMG-CoA Reductase Inhibitors. Risk D: Consider therapy modification
Gemfibrozil: May enhance the myopathic (rhabdomyolysis) effect of Pravastatin. Gemfibrozil may increase the serum concentration of Pravastatin. Management: Avoid concomitant use of pravastatin and gemfibrozil or consider micronized fenofibrate instead of gemfibrozil. If use with gemfibrozil can not be avoided, consider pravastatin dosage reductions and monitor closely for signs/symptoms of rhabdomyolysis. Risk D: Consider therapy modification
Lanthanum: HMG-CoA Reductase Inhibitors may decrease the serum concentration of Lanthanum. Management: Administer HMG-CoA reductase inhibitors at least two hours before or after lanthanum. Risk D: Consider therapy modification
Niacin: May enhance the adverse/toxic effect of HMG-CoA Reductase Inhibitors. Management: This is of greatest concern with niacin doses of 1 g or greater daily. Avoid simvastatin 80 mg in combination with niacin 1 g or greater in Chinese patients. Canadian labeling contraindicates use of niacin with rosuvastatin 40 mg. Risk D: Consider therapy modification
Niacinamide: May enhance the adverse/toxic effect of HMG-CoA Reductase Inhibitors. Risk C: Monitor therapy
PARoxetine: Pravastatin may enhance the adverse/toxic effect of PARoxetine. Specifically, blood glucose elevations may occur with the combination. Risk C: Monitor therapy
P-glycoprotein/ABCB1 Inducers: May decrease the serum concentration of P-glycoprotein/ABCB1 Substrates. P-glycoprotein inducers may also further limit the distribution of p-glycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.). Risk C: Monitor therapy
P-glycoprotein/ABCB1 Inhibitors: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates. P-glycoprotein inhibitors may also enhance the distribution of p-glycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.). Risk C: Monitor therapy
Phenytoin: May decrease the serum concentration of HMG-CoA Reductase Inhibitors. Risk D: Consider therapy modification
Pimozide: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Pimozide. Risk X: Avoid combination
Protease Inhibitors: May increase the serum concentration of HMG-CoA Reductase Inhibitors. Limited data suggest pravastatin may slightly decrease protease inhibitor concentrations. Management: Lovastatin and simvastatin are contraindicated with protease inhibitors; also, avoid rosuvastatin with indinavir. Use lowest possible HMG-CoA reductase inhibitor dose and monitor for signs of toxicity if these agents are used concomitantly. Risk D: Consider therapy modification
Red Yeast Rice: May enhance the adverse/toxic effect of HMG-CoA Reductase Inhibitors. Risk X: Avoid combination
Rifamycin Derivatives: May decrease the serum concentration of HMG-CoA Reductase Inhibitors. 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. Risk D: Consider therapy modification
Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy
Trabectedin: HMG-CoA Reductase Inhibitors may enhance the myopathic (rhabdomyolysis) effect of Trabectedin. Risk C: Monitor therapy
Vitamin K Antagonists (eg, warfarin): HMG-CoA Reductase Inhibitors may enhance the anticoagulant effect of Vitamin K Antagonists. Risk C: Monitor therapy
Ethanol/Nutrition/Herb Interactions
Ethanol: Consumption of large amounts of ethanol may increase the risk of liver damage with HMG-CoA reductase inhibitors.
Food: Red yeast rice contains an estimated 2.4 mg lovastatin per 600 mg rice.
Herb/Nutraceutical: St John's wort may decrease pravastatin levels.
Storage
Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Protect from moisture and light.
Mechanism of Action
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.
Pharmacodynamics/Kinetics
Onset of action: Several days
Peak effect: 4 weeks
Absorption: Rapidly absorbed; average absorption 34%
Protein binding: 50%
Metabolism: Hepatic multiple metabolites; primary metabolite is 3α-hydroxy-iso-pravastatin (2.5% to 10% activity of parent drug)
Bioavailability: 17%
Half-life elimination: 77 hours (including all metabolites); pravastatin: ∼2-3 hours (Pan, 1990); 3α-hydroxy-iso-pravastatin: ~1.5 hours (Gustavson, 2005)
Time to peak, serum: 1-1.5 hours
Excretion: Feces (70%); urine (≤20%, 8% as unchanged drug)
Dosage
Oral: Note: Doses should be individualized according to the baseline LDL-cholesterol levels, the recommended goal of therapy, and patient response; adjustments should be made at intervals of 4 weeks or more; doses may need adjusted based on concomitant medications
Children: HeFH:
8-13 years: 20 mg/day
14-18 years: 40 mg/day
Dosage adjustment for pravastatin with concomitant medications (clarithromycin, cyclosporine): Refer to adult dosing.
Adults: Hyperlipidemias, primary prevention of coronary events, secondary prevention of cardiovascular events: Initial: 40 mg once daily; titrate dosage to response; usual range: 10-80 mg; (maximum dose: 80 mg once daily)
Dosage adjustment for pravastatin with concomitant medications:
Clarithromycin: Limit daily pravastatin dose to 40 mg/day
Cyclosporine: Initial: 10 mg pravastatin daily, titrate with caution (maximum dose: 20 mg/day)
Elderly: No specific dosage recommendations. Clearance is reduced in the elderly, resulting in an increase in AUC between 25% to 50%. However, substantial accumulation is not expected.
Dosing adjustment in renal impairment: Significant impairment: Initial dose: 10 mg/day
Dosing adjustment in hepatic impairment: Contraindicated in active liver disease or in patients with unexplained persistent elevations of serum transaminases
Administration: Oral
May be administered without regard to meals.
Monitoring Parameters
Obtain baseline LFTs and total cholesterol profile; creatine phosphokinase due to possibility of myopathy. Repeat LFTs when clinically indicated; baseline CPK (recheck CPK in any patient with symptoms suggestive of myopathy). Monitor LDL-C at intervals no less than 4 weeks.
Dietary Considerations
May be taken without regard to meals. 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 an estimated 2.4 mg lovastatin per 600 mg rice.
Patient Education
Take at same time each day, with or without food. Follow prescribed cholesterol-lowering diet and exercise regimen. Avoid excess alcohol. You will have periodic blood tests to assess effectiveness. Avoid excessive alcohol. Report unusual muscle cramping or weakness, yellowing of skin or eyes, easy bruising or bleeding, or unusual fatigue.
Geriatric Considerations
Effective and well tolerated in the elderly. No specific dosage recommendations. Clearance is reduced in the elderly, resulting in an increase in AUC between 25% to 50%; however, substantial accumulation is not expected.
The definition of and, therefore, when to treat hyperlipidemia in elderly is a controversial issue. The National Cholesterol Education Program recommends that all adults maintain a plasma cholesterol <160 mg/dL. For the elderly with one additional risk factor, goal LDL would be <130 mg/dL. It is the authors' belief that pharmacologic treatment be reserved for those who are unable to obtain a desirable plasma cholesterol concentration by diet alone and for whom the benefits of treatment are believed to outweigh the potential adverse effects, drug interactions, and cost of treatment. Age ≥65 years is a risk factor for myopathy.
Anesthesia and Critical Care Concerns/Other Considerations
Clinical Pearls/Comments: Based on current research and clinical guidelines (Fleisher, 2009), HMG-CoA reductase inhibitors should be continued in the perioperative period. Postoperative discontinuation of statin therapy is associated with an increased risk of cardiac morbidity and mortality.
Cardiovascular Considerations
Primary Prevention: HMG-CoA reductase inhibitors are effective in primary and secondary prevention of cardiovascular events in patients with hyperlipidemia. For primary prevention, a patient's major risk factors (cigarette smoking, hypertension or currently taking antihypertensives, low HDL-C, family history, age, gender) should be evaluated. Patients with multiple risk factors (≥2) require more intensive therapy guided by the calculation of a 10-year absolute CHD risk (eg, the percent probability of having a CHD event in next 10 years). An individual's 10-year absolute CHD risk can be calculated at www.med-decisions.com/cvtool/phys/phys.html. LDL cholesterol goals, therapeutic lifestyle changes, and drug therapy are determined based upon a patient's risk factor profile.
Primary prevention trials show that cholesterol-lowering drugs reduce the risk of major coronary events, coronary death, and cerebrovascular events even in the first 6-12 months of use. The WOSCOP trial suggested a trend towards enhanced survival using pravastatin in their patients (mean LDL-cholesterol of 192 mg/dL and no history of MI). In a recent trial (Sever, 2003), patients with HTN and at least three other risk factors were randomized to 10 mg daily of atorvastatin or placebo. These patients had a total nonfasting cholesterol <250 mg/dL before treatment. LDL-C levels were 132 mg/dL before treatment and fell to an average of 90 mg/dL in the atorvastatin-treated group. There was a significant reduction in stroke, cardiovascular events, and coronary events in the atorvastatin-treated group as compared to the placebo group. There was no difference in mortality between the groups.
HMG-CoA reductase inhibitors decrease C-reactive protein (CRP), an inflammatory marker and an acute phase reactant. Elevated levels of high sensitive CRP (hsCRP), which detects CRP levels as low as 0.175 mg/L, have been shown to be associated with an increased risk of cardiovascular events. Recently, the JUPITER trial demonstrated that the use of rosuvastatin in healthy patients (men ≥50 years and women ≥60 years) without a history of cardiovascular disease with LDL <130 mg/dL and a hsCRP level ≥2 mg/L reduced the risk of major cardiovascular events (eg, nonfatal MI, stroke, death from cardiovascular causes), The number needed to treat over 5 years to prevent 1 cardiovascular event is 25. Current guidelines do not recommend drug treatment for patients with an LDL <130 mg/dL. However, identification of the patient at higher risk of cardiovascular events within this subgroup using hsCRP is now important given that statins may prevent the occurrence of these serious cardiovascular events (Ridker, 2008).
Secondary Prevention: Secondary prevention trials indicate that “statin” therapy reduces mortality, major coronary events, coronary artery procedures, and stroke. The Heart Protection Study proved that lowering serum cholesterol levels reduces the rate of major vascular events among high-risk individuals with documented vascular disease (CHD, cerebrovascular, peripheral vascular) or diabetes regardless of initial cholesterol concentrations. PROVE IT is a randomized, double-blind trial evaluating hospitalized patients with acute coronary syndrome to determine the effects of intense LDL-C lowering therapy. Four thousand patients with an LDL-C levels of 106 mg/dL were randomized to pravastatin 40 mg daily or atorvastatin 80 mg daily. After 2 years, the combined cardiovascular endpoint (death, MI, unstable angina requiring hospitalization, revascularization and stroke) was ~26% in the pravastatin patients (median LDL-C 95 mg/dL) and ~22% in the atorvastatin treated patients (median LDL-C 62 mg/dL).
LaRosa and colleagues assessed the efficacy and safety of lowering LDL cholesterol <100 mg/dL in patients with stable coronary heart disease (LaRosa, 2005). Ten thousand and one patients with baseline LDL levels <130 mg/dL were randomized to atorvastatin 10 mg or 80 mg daily and followed for a median of 4.9 years. The primary endpoint was the occurrence of the first major cardiovascular event (death from CVD, MI, resuscitation after cardiac arrest, or stroke). A primary event occurred in 434 patients (8.7%) receiving 80 mg daily (mean LDL 77 mg/dL) and 548 patients (10.9%) receiving 10 mg dose (mean LDL 101 mg/dL) (95% CI, 0.69-0.89; p <0.001). There was no mortality difference between the two treatment groups.
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. These nonlipid effects may be beneficial when HMG-CoA reductase inhibitors are introduced early in the management of acute coronary syndromes (de Denus, 2002).
Myopathy: Currently-marketed HMG-CoA reductase inhibitors appear to have a similar potential for causing myopathy. Incidence of severe myopathy is about 0.08% to 0.09%. The factors that increase risk include advanced age (especially >80 years of age), women more frequently than men, small body frame, frailty, multisystem disease (eg, chronic renal insufficiency especially due to diabetes), multiple medications, drug interactions (use with caution or avoid). The combination of a HMG-CoA reductase inhibitor plus nicotinic acid seems to carry a lower risk of myopathy than does a HMG-CoA reductase inhibitor plus a fibrate. Other medications, when used concurrently, may enhance the risk of myopathy associated with statins; these include drugs that inhibit CYP3A4 isoenzymes (lovastatin, simvastatin, atorvastatin) or CYP2C9 isoenzymes (fluvastatin). HMG-CoA reductase inhibitors may exacerbate exercise-induced skeletal muscle injury. Many experts favor getting a baseline creatine kinase (CK) measurement before initiating therapy (asymptomatic CK elevations are common). Obtain a CK measurement if patient complains of muscle soreness, tenderness, or pain.
Dental Health: Effects on Dental Treatment
No significant effects or complications reported
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Mental Health: Effects on Mental Status
May cause dizziness
Mental Health: Effects on Psychiatric Treatment
None reported
Nursing: Physical Assessment/Monitoring
Use caution with history of hepatic disease. Assess risk potential for interactions with other prescriptions or herbal products patient may be taking that may increase risk of myopathy or rhabdomyolysis. Evaluate lipid profile prior to treatment and at regular intervals; evaluate LFTs when clinically indicated. Teach proper diet and exercise regimen.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, oral, as sodium: 10 mg, 20 mg, 40 mg, 80 mg
Pravachol®: 10 mg, 20 mg, 40 mg, 80 mg
Pricing: U.S. (www.drugstore.com)
Tablets (Pravachol)
10 mg (30): $139.99
20 mg (30): $121.99
40 mg (30): $169.98
80 mg (30): $191.66
Tablets (Pravastatin Sodium)
10 mg (30): $18.99
20 mg (30): $27.99
40 mg (30): $25.99
80 mg (30): $119.99
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