Product Name
:
PRAVASTATIN-ELSaad
Chemical Name
:
Pravastatin Sodium
Therapeutic Category
:
Cardiovascular drugs
Pharmacologic Category
:
Antilipemic Agent, HMG-CoA Reductase Inhibitor
Pharmaceutical Form
:
Tablets
Composition
:
Pravastatin Sodium 10mg/ 20mg/ 40mg /80mg
Dosing
 
Dosing: Adult
Hyperlipidemias, primary prevention of coronary events, secondary prevention of cardiovascular events: Oral: Initial: 40 mg once daily; titrate dosage to response (usual range: 10-80 mg) (maximum dose: 80 mg once daily)
Dosage adjustment based on concomitant cyclosporine: Oral: Initial: 10 mg/day, titrate with caution (maximum dose: 20 mg/day)
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

Dosing: Pediatric

Heterozygous familial hypercholesterolemia (HeFH): Oral: Children:
8-13 years: 20 mg/day
14-18 years: 40 mg/day
Dosage adjustment based on concomitant cyclosporine: Refer to adult dosing.
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

Dosing: Geriatric

Refer to adult dosing.

Dosing: Renal Impairment

Initial: 10 mg/day

Dosing: Hepatic Impairment

Initial: 10 mg/day
Use
 
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
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% (Limited to important or life-threatening): Allergy, lens opacity, libido change, memory impairment, muscle weakness, neuropathy, paresthesia, taste disturbance, tremor, vertigo
Postmarketing and/or case reports: Anaphylaxis, angioedema, cholestatic jaundice, cirrhosis, cranial nerve dysfunction, dermatomyositis, erythema multiforme, ESR increase, fulminant hepatic necrosis, gynecomastia, hemolytic anemia, hepatitis, hepatoma, lupus erythematosus-like syndrome, 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, cataracts, depression, dyspnea, eosinophilia, erectile dysfunction, facial paresis, 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
Contraindications
 
Hypersensitivity to pravastatin or any component of the formulation; active liver disease; unexplained persistent elevations of serum transaminases; pregnancy; breast-feeding
Warnings / Precautions Drug
 
Concerns related to adverse Adverse Reactions Significant
• 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 lipid lowering medications. 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.
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/Warnings/Precautions
• Hyperlipidemia: Secondary causes of hyperlipidemia should be ruled out prior to therapy.
• Liver function tests: Must be monitored by periodic laboratory assessment.
Metabolism/Transport Effects
Substrate of CYP3A4 (minor), P-glycoprotein, SLCO1B1; Inhibits CYP2C9 (weak), 2D6 (weak), 3A4 (weak)
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
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 simvastain 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 simvastain 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: P-glycoprotein/ABCB1 Substrates may increase the serum concentration of P-glycoprotein/ABCB1 Inhibitors. 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
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. Rifamycin Derivatives may increase the serum concentration of HMG-CoA Reductase Inhibitors. 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.
Pregnancy
 
X
Pregnancy Implications
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
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)