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Pronunciation |
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(PRA
va stat
in) |
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U.S. Brand
Names |
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Pravachol® |
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Generic
Available |
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No |
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Synonyms |
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Pravastatin Sodium |
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Pharmacological Index |
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Antilipemic Agent (HMG-CoA Reductase Inhibitor) |
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Use |
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"Primary prevention" in hypercholesterolemic patients without
clinically-evident coronary heart disease to reduce the risk of myocardial
infarction, reduce the risk of undergoing myocardial revascularization
procedures, reduce the risk of cardiovascular mortality with no increase in
death from noncardiovascular causes
"Secondary prevention" in hypercholesterolemic patients with
clinically-evident coronary artery disease, including prior myocardial
infarction, to slow the progression of coronary atherosclerosis, and reduce the
risk of acute coronary events
"Secondary prevention" in patients with previous myocardial infarction, and
normal cholesterol levels; to reduce the risk of recurrent myocardial
infarction; reduce the risk of undergoing myocardial revascularization
procedures; and reduce the risk of stroke or transient ischemic attack (TIA)
Adjunct to diet to reduce elevated total cholesterol, LDL cholesterol,
apolipoprotein B (apo-B) and triglyceride levels, and increasing HDL-C in
patients with primary hypercholesterolemia and mixed dyslipidemia (Fredrickson
types IIa and IIb); Fredrickson type IV, type III (who do not respond adequately
to diet) |
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Pregnancy Risk
Factor |
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X |
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Contraindications |
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Hypersensitivity to pravastatin or any component; active liver disease;
unexplained persistent elevations of serum transaminases;
pregnancy |
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Warnings/Precautions |
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Liver function must be monitored by periodic laboratory assessment.
Rhabdomyolysis with acute renal failure has occurred with other HMG-CoA
reductase inhibitors. Risk is increased with concurrent use of clarithromycin,
danazol, diltiazem, fluvoxamine, indinavir, nefazodone, nelfinavir, ritonavir,
verapamil, troleandomycin, cyclosporine, fibric acid derivatives, erythromycin,
niacin, or azole antifungals. The risk of combining any of these drugs with
pravastatin is minimal. Temporarily discontinue in any patient experiencing an
acute or serious condition predisposing to renal failure secondary to
rhabdomyolysis. Use with caution in patients who consume large amounts of
alcohol or have a history of liver disease. |
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Adverse
Reactions |
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1% to 10%:
Central nervous system: Headache (1.7% to 6.2%), fatigue (3.8%), dizziness
(1% to 3.3%)
Cardiovascular: Chest pain (3.7%)
Dermatologic: Rash (4%)
Gastrointestinal: Nausea/vomiting (7.3%), diarrhea (6.2%), heartburn (2.9%)
Hepatic: Increased transaminases (>3x normal on two occasions - 1.3%)
Neuromuscular & skeletal: Myalgia (2.4%)
Respiratory: Cough (2.6%)
Miscellaneous: Influenza (2.4%)
<1%: Weakness, neuropathy, myopathy
Case reports: Lichenoid eruption, porphyria cutanea tarda
Additional class-related events or case reports (not necessarily reported
with pravastatin therapy): Myopathy, increased CPK (>10x normal),
rhabdomyolysis, renal failure (secondary to rhabdomyolysis), alteration in
taste, impaired extraocular muscle movement, facial paresis, tremor, memory
loss, vertigo, paresthesia, peripheral neuropathy, peripheral nerve palsy,
anxiety, depression, psychic disturbance, hypersensitivity reaction, angioedema,
anaphylaxis, systemic lupus erythematosus-like syndrome, polymyalgia rheumatica,
dermatomyositis, vasculitis, purpura, thrombocytopenia, leukopenia, hemolytic
anemia, positive ANA, increased ESR, eosinophilia, arthritis, urticaria,
photosensitivity, fever, chills, flushing, malaise, dyspnea, rash, toxic
epidermal necrolysis, erythema multiforme, Stevens-Johnson syndrome,
pancreatitis, hepatitis, cholestatic jaundice, fatty liver, cirrhosis, fulminant
hepatic necrosis, hepatoma, anorexia, vomiting, alopecia, pruritus, nodules,
skin discoloration, dryness of skin/mucous membranes, nail changes,
gynecomastia, decreased libido, erectile dysfunction, impotence, cataracts,
ophthalmoplegia, elevated transaminases, increased alkaline phosphatase,
increased GGT, hyperbilirubinemia, thyroid dysfunction |
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Overdosage/Toxicology |
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Very little adverse events; treatment is symptomatic |
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Drug
Interactions |
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CYP3A3/4 enzyme substrate
Cholestyramine and colestipol (bile acid sequestrants): Cholesterol-lowering
effects are additive.
Clofibrate and fenofibrate may increase the risk of myopathy and
rhabdomyolysis.
Colestipol reduces pravastatin absorption.
Gemfibrozil: Increased risk of myopathy and rhabdomyolysis.
Niacin may increase the risk of myopathy and rhabdomyolysis.
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Mechanism of
Action |
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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. |
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Pharmacodynamics/Kinetics |
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Onset of action: Several days
Absorption: Poor
Metabolism: In the liver to at least two metabolites
Bioavailability: 17%
Half-life, elimination: ~2-3 hours
Time to peak serum concentration: 1-1.5 hours
Elimination: Up to 20% excreted in urine (8% unchanged) |
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Usual Dosage |
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Adults: Oral: 10-40 mg once daily at bedtime. Dosing adjustment in renal
impairment:10 mg daily. |
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Dietary
Considerations |
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Before initiation of therapy, patients should be placed on a standard
cholesterol-lowering diet for 3-6 months and the diet should be continued during
drug therapy. |
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Monitoring
Parameters |
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Creatine phosphokinase due to possibility of myopathy |
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Cardiovascular
Considerations |
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HMG-CoA reductase inhibitors are effective in secondary prevention of
cardiovascular events in patients with hyperlipidemia. In these situations, the
target of therapy is a reduction in LDL cholesterol to <100 mg/dL. HMG-CoA
reductase inhibitors have also been shown to be effective in primary prevention
of coronary artery disease in individuals without established cardiovascular
disease but who have multiple risk factors. Selection of lipid-lowering therapy
should be based on the patient's lipid profile, concomitant disease states, and
the cost of therapy. The benefits of lipid-lowering are also compelling in women
and in the elderly. Important side effects relate to elevated liver enzymes and
rhabdomyolysis. LFTs need to be monitored at specified intervals.
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Mental Health: Effects
on Mental Status |
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May cause dizziness |
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Mental Health:
Effects on Psychiatric
Treatment |
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None reported |
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Dental Health: Local
Anesthetic/Vasoconstrictor
Precautions |
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No information available to require special precautions |
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Dental Health:
Effects on Dental Treatment |
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No effects of complications reported |
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Patient
Information |
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Take at bedtime since highest rate of cholesterol synthesis occurs between
midnight and 5 AM. Do not change dosage without consulting prescriber. Maintain
diet and exercise program as as prescribed. Have periodic ophthalmic exam while
taking pravastatin (check for cataracts). You may experience mild GI
disturbances (gas, diarrhea, constipation); inform prescriber if these are
severe, or if you experience severe muscle pain or tenderness accompanied with
malaise, blurred vision, or chest pain. Pregnancy/breast-feeding
precautions: Inform prescriber if you are pregnant. Do not get pregnant
during or for 1 month following therapy. Consult prescriber for instruction on
appropriate barrier contraceptive measures. This drug may cause severe fetal
defects. Do not breast-feed. |
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Nursing
Implications |
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Liver enzyme elevations may be observed during therapy with pravastatin;
diet, weight reduction, and exercise should be attempted prior to therapy with
pravastatin |
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Dosage Forms |
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Tablet, as sodium: 10 mg, 20 mg, 40 mg |
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References |
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Lintott CJ and Scott RS,
"HMG-CoA Reductase Inhibitor Use in the Aged: A Review of Clinical Experience,"
Drugs Aging, 1992, 2(6):518-29.
"Summary of the Second Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults,"
JAMA, 1993, 269(23):3015-23. |
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