Pravachol

HMG-CoA Reductase Inhibitors (Statins)

May be administered without regard to meals.
Pravastatin may be taken once-daily. The product labeling states that pravastatin may be taken anytime of day, but guidelines suggest administration in the evening. Pravastatin has been shown to be similarly effective (slightly less effective, but not significantly different) in lowering cholesterol when administered in the morning versus evening.

hepatoma / Delayed / 0-1.0
hepatic necrosis / Delayed / 0-1.0
hepatic failure / Delayed / 0-1.0
cirrhosis / Delayed / 0-1.0
immune-mediated necrotizing myopathy / Delayed / 0-1.0
rhabdomyolysis / Delayed / 0-0.1
renal failure (unspecified) / Delayed / Incidence not known
myoglobinuria / Delayed / Incidence not known
renal tubular obstruction / Delayed / Incidence not known
pancreatitis / Delayed / Incidence not known
lupus-like symptoms / Delayed / Incidence not known
Stevens-Johnson syndrome / Delayed / Incidence not known
angioedema / Rapid / Incidence not known
toxic epidermal necrolysis / Delayed / Incidence not known
hemolytic anemia / Delayed / Incidence not known
vasculitis / Delayed / Incidence not known
erythema multiforme / Delayed / Incidence not known
anaphylactoid reactions / Rapid / Incidence not known
myasthenia gravis / Delayed / Incidence not known

angina / Early / 0.1-3.1
chest pain (unspecified) / Early / 0.3-2.6
constipation / Delayed / 1.2-2.4
dyspnea / Early / 1.6-1.6
blurred vision / Early / 1.6-1.6
elevated hepatic enzymes / Delayed / 0-1.2
myasthenia / Delayed / 0-1.0
memory impairment / Delayed / 0-1.0
depression / Delayed / 1.0-1.0
edema / Delayed / 0-1.0
dysuria / Early / 0.7-1.0
cataracts / Delayed / 0-1.0
myopathy / Delayed / 0-0.1
hepatitis / Delayed / Incidence not known
cholestasis / Delayed / Incidence not known
jaundice / Delayed / Incidence not known
amnesia / Delayed / Incidence not known
confusion / Early / Incidence not known
eosinophilia / Delayed / Incidence not known
thrombocytopenia / Delayed / Incidence not known
anemia / Delayed / Incidence not known
leukopenia / Delayed / Incidence not known
peripheral neuropathy / Delayed / Incidence not known
diabetes mellitus / Delayed / Incidence not known
hyperglycemia / Delayed / Incidence not known
interstitial lung disease / Delayed / Incidence not known

musculoskeletal pain / Early / 1.4-6.0
pyrosis (heartburn) / Early / 2.0-3.5
dyspepsia / Early / 2.0-3.5
fatigue / Early / 1.9-3.4
flatulence / Early / 1.2-2.7
dizziness / Early / 1.0-2.2
rash / Early / 1.3-2.1
diarrhea / Early / 2.0-2.0
abdominal pain / Early / 1.6-2.0
nausea / Early / 1.6-2.0
vomiting / Early / 1.6-2.0
muscle cramps / Delayed / 2.0-2.0
headache / Early / 1.7-1.9
diplopia / Early / 1.6-1.6
myalgia / Early / 0.6-1.4
infection / Delayed / 1.3-1.3
anorexia / Delayed / 0-1.0
vertigo / Early / 0-1.0
paresthesias / Delayed / 0-1.0
insomnia / Early / 0-1.0
anxiety / Delayed / 1.0-1.0
tremor / Early / 0-1.0
urticaria / Rapid / 0-1.0
alopecia / Delayed / 0-1.0
xerosis / Delayed / 0-1.0
pruritus / Rapid / 0-1.0
cough / Delayed / 0.1-1.0
nocturia / Early / 0.7-1.0
libido increase / Delayed / 0-1.0
libido decrease / Delayed / 0-1.0
increased urinary frequency / Early / 0.7-1.0
flushing / Rapid / 0-1.0
fever / Early / 0-1.0
rhinitis / Early / 0.1-0.1
dysgeusia / Early / Incidence not known
weakness / Early / Incidence not known
drowsiness / Early / Incidence not known
nightmares / Early / Incidence not known
chills / Rapid / Incidence not known
photosensitivity / Delayed / Incidence not known
purpura / Delayed / Incidence not known
malaise / Early / Incidence not known
arthralgia / Delayed / Incidence not known
influenza / Delayed / Incidence not known
gynecomastia / Delayed / Incidence not known
Co-Enzyme Q-10 deficiency / Delayed / Incidence not known

Pravachol

Rx

Oral HMG Co-A reductase inhibitor (statin)
Used for hypercholesterolemia, hyperlipoproteinemia, hypertriglyceridemia, primary or secondary prevention of coronary heart disease, and for stroke prophylaxis in adults; used for heterozygous familial hypercholesterolemia in adult and pediatric patients 8 years and older
Hepatotoxicity, myopathy, rhabdomyolysis, and immune-mediated necrotizing myopathy have occurred with statin therapy

40 or 80 mg PO once daily.

10 or 20 mg PO once daily.

40 to 80 mg PO once daily. Max: 80 mg/day. Assess LDL-C 4 to 12 weeks after pravastatin initiation or dose adjustment and adjust dosage as necessary. Lipid panels should be repeated every 3 to 12 months as needed. For patients unable to achieve LDL-C goal level on pravastatin therapy, consider switching to a high-intensity statin (if tolerated) or adding another lipid-lowering agent. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.

40 mg PO once daily is the FDA-approved dosage. Alternatively, 10 mg PO once daily initially, then titrated up in 10 mg increments every 2 months (Max: 60 mg/day) was studied in a small observational study of 30 patients with familial hypercholesterolemia (ages 4.1 to 18.5 years). Pravastatin was started at 10 mg in all patients regardless of age or size; the dosage was increased gradually if the target total cholesterol concentration of 194 mg/dL or less was not achieved. At 2 years, doses of pravastatin in patients available for follow-up were as follows: 10 mg, n = 1; 20 mg, n = 4; 40 mg, n = 2; 50 mg, n = 4; 60 mg, n = 3. Decreases in mean serum total cholesterol, LDL, and triglyceride concentrations reported in observational and placebo-controlled studies were 18% to 26%, 24% to 32%, and 6% to 34%, respectively, after 2 years of treatment. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.

20 mg PO once daily is the FDA-approved dosage. Alternatively, 10 mg PO once daily initially, then titrated up in 10 mg increments every 2 months (Max: 60 mg/day) was studied in a small observational study of 30 patients with familial hypercholesterolemia (ages 4.1 to 18.5 years). Pravastatin was started at 10 mg in all patients regardless of age or size; the dosage was increased gradually if the target total cholesterol concentration of 194 mg/dL or less was not achieved. At 2 years, doses of pravastatin in patients available for follow-up were as follows: 10 mg, n = 1; 20 mg, n = 4; 40 mg, n = 2; 50 mg, n = 4; 60 mg, n = 3. Decreases in mean serum total cholesterol, LDL, and triglyceride concentrations reported in observational and placebo-controlled studies were 18% to 26%, 24% to 32%, and 6% to 34%, respectively, after 2 years of treatment. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.

Pharmacologic therapy is not generally recommended for young children; however, 10 mg PO once daily initially, then titrated up in 10 mg increments every 2 months (Max: 60 mg/day) was studied in a small observational study of 30 patients with familial hypercholesterolemia (ages 4.1 to 18.5 years). Pravastatin was started at 10 mg in all patients regardless of age or size; the dosage was increased gradually if the target total cholesterol concentration of 194 mg/dL or less was not achieved. At 2 years, doses of pravastatin in patients available for follow-up were as follows: 10 mg, n = 1; 20 mg, n = 4; 40 mg, n = 2; 50 mg, n = 4; 60 mg, n = 3. Mean serum total cholesterol, LDL, and triglyceride concentrations were decreased by 26%, 32%, and 34%, respectively, after 2 years of treatment. Although pharmacologic therapy is not routinely recommended for patients younger than 10 years of age, it may be considered in patients with severe primary hyperlipidemia or high level risk factors (e.g. diabetes, organ transplant, obesity, hypertension, chronic renal disease, strong family history of premature cardiovascular disease). Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.

40 to 80 mg PO once daily. Max: 80 mg/day. Assess LDL-C 4 to 12 weeks after pravastatin initiation or dose adjustment and adjust dosage as necessary. Lipid panels should be repeated every 3 to 12 months as needed. For patients unable to achieve LDL-C goal level on pravastatin therapy, consider switching to a high-intensity statin (if tolerated) or adding another lipid-lowering agent. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.

40 to 80 mg PO once daily. Max: 80 mg/day. Assess LDL-C 4 to 12 weeks after pravastatin initiation or dose adjustment and adjust dosage as necessary. Lipid panels should be repeated every 3 to 12 months as needed. For patients unable to achieve LDL-C goal level on pravastatin therapy, consider switching to a high-intensity statin (if tolerated) or adding another lipid-lowering agent.   Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.

Dosage not established. 40 mg PO once daily for 14 days has been used. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.

†Indicates off-label use

Contraindicated in patients with acute hepatic failure and decompensated cirrhosis (hepatic decompensation, e.g., Child-Pugh class C).

Adults:
Mild to moderate renal impairment: Dosage adjustments are not needed; the dosage is the same as for adults with normal renal function.
Severe renal impairment (estimated CrCl less than 30 mL/minute): 10 mg PO once daily initially; monitor closely. May adjust based on clinical response/tolerance. Max: 40 mg PO once daily.
 
Pediatric patients 8 to 17 years:
Specific recommendations for dosage adjustment in pediatric patients with renal impairment are not available.

Amoxicillin; Clarithromycin; Omeprazole: (Major) Do not exceed 40 mg per day of pravastatin if coadministration with clarithromycin cannot be avoided. Concurrent use increases the risk of myopathy and rhabdomyolysis. Coadministration of clarithromycin increased the AUC and Cmax of pravastatin by 110% and 128%, respectively.
Atazanavir: (Moderate) Concurrent use of atazanavir with pravastatin may result in elevated pravasatin serum concentrations. Pravastatin is a substrate for the drug transporter organic anion transporting polypeptide (OATP1B1); atazanavir is an inhibitor of OATP1B1. Monitor for increased toxicities if these drugs are given together, such as myopathy.
Atazanavir; Cobicistat: (Major) The plasma concentrations of pravastatin may be elevated when administered concurrently with cobicistat. Clinical monitoring for adverse effects, such as rhabdomyolysis or GI effects, is recommended during coadministration. Cobicistat is a organic anion transporting polypeptide (OATP) inhibitor, while pravastatin is a OATP1B1 substrate. (Moderate) Concurrent use of atazanavir with pravastatin may result in elevated pravasatin serum concentrations. Pravastatin is a substrate for the drug transporter organic anion transporting polypeptide (OATP1B1); atazanavir is an inhibitor of OATP1B1. Monitor for increased toxicities if these drugs are given together, such as myopathy.
Azithromycin: (Moderate) Azithromycin has the potential to increase pravastatin exposure when used concomitantly. Coadminister pravastatin and azithromycin cautiously due to a potential increased risk of myopathies.
Bempedoic Acid: (Major) Do not exceed a pravastatin dose of 40 mg/day in patients taking bempedoic acid due to increased risk of myopathy, including rhabdomyolysis. For patients chronically receiving pravastatin 60 mg/day or greater who need to be started on bempedoic acid, consider switching to an alternative statin with less potential for interaction. Carefully weigh the benefits of combined use of bempedoic acid and pravastatin against the potential risks. Bempedoic acid increases the pravastatin AUC and Cmax by 2-fold.
Bempedoic Acid; Ezetimibe: (Major) Do not exceed a pravastatin dose of 40 mg/day in patients taking bempedoic acid due to increased risk of myopathy, including rhabdomyolysis. For patients chronically receiving pravastatin 60 mg/day or greater who need to be started on bempedoic acid, consider switching to an alternative statin with less potential for interaction. Carefully weigh the benefits of combined use of bempedoic acid and pravastatin against the potential risks. Bempedoic acid increases the pravastatin AUC and Cmax by 2-fold.
Bortezomib: (Minor) Monitor patients for the development of peripheral neuropathy when receiving bortezomib in combination with other drugs that can cause peripheral neuropathy like HMG-CoA reductase inhibitors; the risk of peripheral neuropathy may be additive.
Cholestyramine: (Moderate) Administer pravastatin 1 hour before or 4 hours after a dose of cholestyramine if both agents are used together. Bile acid-sequestering agents, such as cholestyramine, have been shown to significantly reduce serum concentrations of pravastatin. Coadministration with cholestyramine decreases the AUC of pravastatin by about 40-50%.
Cimetidine: (Moderate) Use HMG-CoA reductase inhibitors with caution with concomitant drugs that may decrease the levels or activity of endogenous steroids, such as cimetidine. Evaluate patients with signs and symptoms of endocrine dysfunction appropriately. HMG-CoA reductase inhibitors interfere with cholesterol synthesis and theoretically might blunt adrenal and/or gonadal steroid production.
Clarithromycin: (Major) Do not exceed 40 mg per day of pravastatin if coadministration with clarithromycin cannot be avoided. Concurrent use increases the risk of myopathy and rhabdomyolysis. Coadministration of clarithromycin increased the AUC and Cmax of pravastatin by 110% and 128%, respectively.
Clofarabine: (Moderate) Concomitant use of clofarabine, a substrate of OAT1 and OAT3, and pravastatin, a substrate of OAT protein (OATP), may result in altered clofarabine levels. Therefore, monitor for signs of clofarabine toxicity such as gastrointestinal toxicity (e.g., nausea, vomiting, diarrhea, mucosal inflammation), hematologic toxicity, and skin toxicity (e.g., hand and foot syndrome, rash, pruritus) in patients also receiving OATP substrates.
Cobicistat: (Major) The plasma concentrations of pravastatin may be elevated when administered concurrently with cobicistat. Clinical monitoring for adverse effects, such as rhabdomyolysis or GI effects, is recommended during coadministration. Cobicistat is a organic anion transporting polypeptide (OATP) inhibitor, while pravastatin is a OATP1B1 substrate.
Colchicine: (Major) Use caution and the lowest HMG-CoA reductase inhibitor dose necessary if coadministration with colchicine is necessary due to an increased risk of myopathy and rhabdomyolysis. Carefully weigh the potential benefits and risk of combined therapy. Closely monitor patients for signs and symptoms of muscle pain, tenderness, or weakness especially during the initial months of therapy and during upward titration of either drug. There is no assurance that period monitoring of creatinine phosphokinase (CPK) will prevent the occurrence of myopathy. Case reports exist describing the development of myotoxicity with the concurrent administration of colchicine and HMG-CoA reductase inhibitors (e.g., simvastatin, atorvastatin, fluvastatin, lovastatin, pravastatin).
Colestipol: (Major) Bile acid-sequestering agents, such as colestipol, have been shown to significantly reduce serum concentrations of pravastatin. Coadministration of the bile acid-sequestering agent cholestyramine decreases the AUC of pravastatin by about 40-50%. Administering pravastatin 1 hour before or 4 hours after a dose of cholestyramine is advised if both agents are used together.
Cyclosporine: (Major) FDA-approved labeling recommends limiting the dose of pravastatin to 20 mg/day if coadministered with cyclosporine. However, guidelines recommend limiting the pravastatin dose to 40 mg/day in patients receiving cyclosporine. Concomitant administration increases the risk of myopathy and rhabdomyolysis. During pharmacokinetic trials, a single dose of cyclosporine increased the AUC and Cmax of pravastatin by 282% and 327%, respectively. However, neither myopathy nor significant increases in CPK levels have been observed in 3 reports involving 100 post-transplant (cardiac or renal) patients treated for up to 2 years with pravastatin (10 to 40 mg) and cyclosporine. Some of these patients also received other concomitant immunosuppressive therapies.
Daclatasvir: (Moderate) Caution and close monitoring is advised if daclatasvir is administered with HMG-CoA reductase inhibitors (Statins). Use of these drugs together may result in elevated Statin serum concentrations, potentially resulting in adverse effects such as myopathy and rhabdomyolysis.
Daptomycin: (Major) Temporarily suspend HMG-CoA reductase inhibitors in patients taking daptomycin as cases of rhabdomyolysis have been reported with concomitant use. Both agents can cause myopathy and rhabdomyolysis when given alone and the risk may be increased when given together.
Darolutamide: (Moderate) Monitor for an increase in pravastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with darolutamide is necessary. Concomitant use may increase pravastatin exposure. Pravastatin is an OATP1B1/3 substrate; darolutamide is an OATP1B1/3 inhibitor.
Darunavir: (Major) The risk of myopathy, including rhabdomyolysis, may be increased when darunavir is given in combination with pravastatin. If treatment with darunavir is required, consider using an alternate HMG-CoA reductase inhibitor (such as pitavastatin or fluvastatin). When concurrent administration is unavoidable, initiate pravastatin at the lowest possible dose with gradual dose increases based on clinical response. Carefully monitor for any signs or symptoms of muscle pain, weakness, or tenderness especially in the initial months of therapy and any time the dosage of either drug is titrated upward. When pravastatin is coadministered with darunavir (in the FDA approved dosage regimen), its AUC is increased by 81% and its Cmax is increased by 63%.
Darunavir; Cobicistat: (Major) The plasma concentrations of pravastatin may be elevated when administered concurrently with cobicistat. Clinical monitoring for adverse effects, such as rhabdomyolysis or GI effects, is recommended during coadministration. Cobicistat is a organic anion transporting polypeptide (OATP) inhibitor, while pravastatin is a OATP1B1 substrate. (Major) The risk of myopathy, including rhabdomyolysis, may be increased when darunavir is given in combination with pravastatin. If treatment with darunavir is required, consider using an alternate HMG-CoA reductase inhibitor (such as pitavastatin or fluvastatin). When concurrent administration is unavoidable, initiate pravastatin at the lowest possible dose with gradual dose increases based on clinical response. Carefully monitor for any signs or symptoms of muscle pain, weakness, or tenderness especially in the initial months of therapy and any time the dosage of either drug is titrated upward. When pravastatin is coadministered with darunavir (in the FDA approved dosage regimen), its AUC is increased by 81% and its Cmax is increased by 63%.
Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Major) The plasma concentrations of pravastatin may be elevated when administered concurrently with cobicistat. Clinical monitoring for adverse effects, such as rhabdomyolysis or GI effects, is recommended during coadministration. Cobicistat is a organic anion transporting polypeptide (OATP) inhibitor, while pravastatin is a OATP1B1 substrate. (Major) The risk of myopathy, including rhabdomyolysis, may be increased when darunavir is given in combination with pravastatin. If treatment with darunavir is required, consider using an alternate HMG-CoA reductase inhibitor (such as pitavastatin or fluvastatin). When concurrent administration is unavoidable, initiate pravastatin at the lowest possible dose with gradual dose increases based on clinical response. Carefully monitor for any signs or symptoms of muscle pain, weakness, or tenderness especially in the initial months of therapy and any time the dosage of either drug is titrated upward. When pravastatin is coadministered with darunavir (in the FDA approved dosage regimen), its AUC is increased by 81% and its Cmax is increased by 63%.
Elexacaftor; tezacaftor; ivacaftor: (Moderate) Monitor for an increase in pravastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with elexacaftor is necessary. Concomitant use may increase pravastatin exposure. Pravastatin is an OATP1B1/3 substrate; elexacaftor is an OATP1B1/3 inhibitor.
Eltrombopag: (Moderate) Eltrombopag is an inhibitor of the transporter OATP1B1. Drugs that are substrates for this transporter, such as pravastatin, may exhibit an increase in systemic exposure if coadministered with eltrombopag; monitor patients for adverse reactions if these drugs are coadministered.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Major) The plasma concentrations of pravastatin may be elevated when administered concurrently with cobicistat. Clinical monitoring for adverse effects, such as rhabdomyolysis or GI effects, is recommended during coadministration. Cobicistat is a organic anion transporting polypeptide (OATP) inhibitor, while pravastatin is a OATP1B1 substrate.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) The plasma concentrations of pravastatin may be elevated when administered concurrently with cobicistat. Clinical monitoring for adverse effects, such as rhabdomyolysis or GI effects, is recommended during coadministration. Cobicistat is a organic anion transporting polypeptide (OATP) inhibitor, while pravastatin is a OATP1B1 substrate.
Enasidenib: (Moderate) Monitor for an increase in pravastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with enasidenib is necessary. Concomitant use may increase pravastatin exposure. Pravastatin is an OATP1B1/3 substrate; enasidenib is an OATP1B1/3 inhibitor.
Encorafenib: (Moderate) Monitor for an increase in pravastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with encorafenib is necessary. Concomitant use may increase pravastatin exposure. Pravastatin is an OATP1B1/3 substrate; encorafenib is an OATP1B1/3 inhibitor.
Erythromycin: (Moderate) Monitor for evidence of myopathy during coadministration of pravastatin and erythromycin. With concurrent therapy of erythromycin, the risk of myopathy increases. The pravastatin labeling recommends caution during concurrent use.
Etravirine: (Moderate) Concomitant use of etravirine and pravastatin has no effect on the serum concentration of pravastatin; however, the risk of myopathy, including rhabdomyolysis, may be increased when antiretrovirals are given in combination with HMG-CoA reductase inhibitors.
Everolimus: (Moderate) Carefully weigh the benefits of combined use of everolimus and pravastatin against the potential risks. The risk of myopathy/rhabdomyolysis may increase with concurrent use. Although FDA-approved labeling for everolimus state that dosage adjustments are not necessary, guidelines recommend limiting the dose of pravastatin to 40 mg/day if combined with everolimus. In a drug interaction study in healthy subjects, the pharmacokinetics of pravastatin were not significantly altered by single dose administration of everolimus.
Fenofibrate: (Moderate) Monitor for an increase in pravastatin-related adverse reactions if coadministration with fenofibrate is necessary. Concomitant use increases the risk for rhabdomyolysis and has been shown to increase the overall exposure of pravastatin by 13%.
Fenofibric Acid: (Moderate) Monitor for an increase in pravastatin-related adverse reactions if coadministration with fenofibric acid is necessary. Concomitant use increases the risk for rhabdomyolysis and has been shown to increase the overall exposure of pravastatin by 13%.
Fostemsavir: (Moderate) Monitor for pravastatin-related adverse reactions (i.e., myopathy/rhabdomyolysis) during concomitant use of fostemsavir as concurrent use may increase exposure of pravastatin. Pravastatin is a substrate for the transporters OATP1B1/3 and fostemsavir is an inhibitor of OATP1B1/3.
Gemfibrozil: (Major) Avoid concomitant use of pravastatin and gemfibrozil due to increased risk for rhabdomyolysis. The benefit of combined therapy with gemfibrozil and HMG-CoA reductase inhibitors does not outweigh the risks for most patients. If combination therapy with gemfibrozil and an HMG-CoA reductase inhibitor is necessary, consider an alternative statin. Coadministration has also been shown to increase the overall exposure of pravastatin by 2-fold; pravastatin is an OATP1B1 substrate and gemfibrozil is an OATP1B1 inhibitor.
Glecaprevir; Pibrentasvir: (Major) Reduce pravastatin dose by 50% when coadministered with glecaprevir due to an increased risk of myopathy, including rhabdomyolysis. Pravastatin is a substrate of the drug transporters OATP1B1 and OATP1B3; glecaprevir is an inhibitor of these transporters. Coadministration may increase the plasma concentrations of pravastatin. In drug interaction studies, coadministration of pravastatin with glecaprevir; pibrentasvir resulted in more than a 2-fold increase in the AUC of pravastatin. (Major) Reduce pravastatin dose by 50% when coadministered with pibrentasvir due to an increased risk of myopathy, including rhabdomyolysis. Coadministration may increase the plasma concentrations of pravastatin. Pravastatin is a substrate of the drug transporters OATP1B1 and OATP1B3; pibrentasvir is an inhibitor of these transporters. In drug interaction studies, coadministration of pravastatin with glecaprevir; pibrentasvir resulted in more than a 2-fold increase in the AUC of pravastatin.
Idelalisib: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with pravastatin, a CYP3A substrate, as pravastatin toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Moderate) Rifampin has been reported to significantly increase the plasma clearance and decrease the serum concentrations of atorvastatin, simvastatin and fluvastatin, with the potential for reduced antilipemic efficacy. Although not studied, a similar interaction can be expected between other rifamycins (e.g., rifabutin, rifapentine) and other HMG-CoA reductase inhibitors (Statins). To evaluate this interaction, monitor serum lipid concentrations during coadministration of rifamycins with HMG-CoA reductase inhibitors.
Isoniazid, INH; Rifampin: (Moderate) Rifampin has been reported to significantly increase the plasma clearance and decrease the serum concentrations of atorvastatin, simvastatin and fluvastatin, with the potential for reduced antilipemic efficacy. Although not studied, a similar interaction can be expected between other rifamycins (e.g., rifabutin, rifapentine) and other HMG-CoA reductase inhibitors (Statins). To evaluate this interaction, monitor serum lipid concentrations during coadministration of rifamycins with HMG-CoA reductase inhibitors.
Lansoprazole; Amoxicillin; Clarithromycin: (Major) Do not exceed 40 mg per day of pravastatin if coadministration with clarithromycin cannot be avoided. Concurrent use increases the risk of myopathy and rhabdomyolysis. Coadministration of clarithromycin increased the AUC and Cmax of pravastatin by 110% and 128%, respectively.
Lanthanum Carbonate: (Major) To limit absorption problems, HMG-CoA reductase inhibitors ("statins") should not be taken within 2 hours of dosing with lanthanum carbonate. Oral drugs known to interact with cationic antacids, like statin cholesterol treatments, may also be bound by lanthanum carbonate. Separate the times of administration appropriately. Monitor the patient's lipid profile to ensure the appropriate response to statin therapy is obtained.
Leflunomide: (Major) Consider reducing the dose of HMG-CoA reductase inhibitors ("Statins" including atorvastatin, fluvastatin, lovastatin, pitavastatin, pravastatin, rosuvastatin, or simvastatin) during use of leflunomide and monitor patients closely for signs and symptoms of myopathy. For a patient taking leflunomide, the dose of rosuvastatin should not exceed 10 mg once daily. Patients should be advised to report promptly unexplained muscle pain, tenderness, or weakness, particularly if accompanied by malaise or fever. Following oral administration, leflunomide is metabolized to an active metabolite, teriflunomide, which is responsible for essentially all of leflunomide's in vivo activity. Teriflunomide is an inhibitor of the organic anion transporting polypeptide OATP1B1, and some statins are substrates for the OATP transporters. Teriflunomide may increase the exposure (AUC) of these statins. Increased concentrations of the statins increases the risk for myopathy and other statin-related side effects.
Leniolisib: (Moderate) Monitor for an increase in pravastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with leniolisib is necessary. Concomitant use may increase pravastatin exposure. Pravastatin is an OATP1B1/3 substrate; leniolisib is an OATP1B1/3 inhibitor.
Letermovir: (Moderate) Closely monitor for pravastatin-related adverse events (myopathy, rhabdomyolysis) and consider a pravastatin dose reduction if administered with letermovir. Do not exceed a pravastatin dose of 20 mg daily if the patient is also receiving cyclosporine. The magnitude of this interaction may be increased if letermovir is given with cyclosporine. Concurrent administration of letermovir, an organic anion-transporting polypeptide (OATP1B1/3) inhibitor, with pravastatin, an OATP1B1/3 substrate, may result in a clinically relevant increase in pravastatin plasma concentration.
Maralixibat: (Minor) Maralixibat may reduce the oral absorption of HMG-CoA reductase inhibitors, also known as statins, which may reduce their efficacy. This risk is greatest with maralixibat doses greater than 4.75 mg. Monitor statin therapy and adjust the dose as needed based on clinical response. Maralixibat is a OATP2B1 inhibitor and statins are OATP2B1 substrates.
Midostaurin: (Moderate) Monitor for an increase in pravastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with midostaurin is necessary. Concomitant use may increase pravastatin exposure. Pravastatin is an OATP1B1/3 substrate; midostaurin is an OATP1B1 inhibitor.
Nanoparticle Albumin-Bound Sirolimus: (Moderate) Carefully weigh the benefits of combined use of sirolimus and pravastatin against the potential risks. The risk of myopathy/rhabdomyolysis may increase with concurrent use. Guidelines recommend limiting the dose of pravastatin to 40 mg/day if combined with sirolimus.
Niacin, Niacinamide: (Major) There is no clear indication for routine use of niacin in combination with pravastatin. The addition of niacin to a statin has not been shown to reduce cardiovascular morbidity or mortality. In addition, lipid-modifying doses (1 g/day or more) of niacin increase the risk of myopathy and rhabdomyolysis when combined with pravastatin. If coadministered, consider lower starting and maintenance does of pravastatin. Monitor patients closely for myopathy or rhabdomyolysis, particularly in the early months of treatment or after upward dose titration of either drug. Consider monitoring serum creatinine phosphokinase (CPK) and potassium periodically in such situations. Discontinue pravastatin immediately if myopathy is diagnosed or suspected.
Niacin; Simvastatin: (Major) There is no clear indication for routine use of niacin in combination with pravastatin. The addition of niacin to a statin has not been shown to reduce cardiovascular morbidity or mortality. In addition, lipid-modifying doses (1 g/day or more) of niacin increase the risk of myopathy and rhabdomyolysis when combined with pravastatin. If coadministered, consider lower starting and maintenance does of pravastatin. Monitor patients closely for myopathy or rhabdomyolysis, particularly in the early months of treatment or after upward dose titration of either drug. Consider monitoring serum creatinine phosphokinase (CPK) and potassium periodically in such situations. Discontinue pravastatin immediately if myopathy is diagnosed or suspected.
Nitisinone: (Moderate) Monitor for increased pravastatin-related adverse effects if coadministered with nitisinone. Increased pravastatin exposure is possible. Nitisinone inhibits OAT3. Pravastatin is an OAT3 substrate.
Omeprazole; Amoxicillin; Rifabutin: (Minor) Rifampin has been reported to significantly increase the plasma clearance and decrease the serum concentrations of simvastatin and fluvastatin, with the potential for reduced antilipemic efficacy. Although not studied, a similar interaction can be expected between other rifamycins (e.g., rifabutin, rifapentine) and other HMG-CoA reductase inhibitors (Statins). To evaluate this interaction, monitor serum lipid concentrations during coadministration of rifamycins with HMG-CoA reductase inhibitors.
Orlistat: (Moderate) Serum concentrations of pravastatin increased by approximately 30% when administered with orlistat in a parallel study of 24 normal-weight, mildly hypercholesterolemic subjects. Orlistat produced additive lipid-lowering effects when used concomittantly with pravastatin. However, another study failed to show any changes in pravastatin pharmacokinetics when coadministered with orlistat. Use caution and monitor patients carefully if using these drugs together.
Probenecid; Colchicine: (Major) Use caution and the lowest HMG-CoA reductase inhibitor dose necessary if coadministration with colchicine is necessary due to an increased risk of myopathy and rhabdomyolysis. Carefully weigh the potential benefits and risk of combined therapy. Closely monitor patients for signs and symptoms of muscle pain, tenderness, or weakness especially during the initial months of therapy and during upward titration of either drug. There is no assurance that period monitoring of creatinine phosphokinase (CPK) will prevent the occurrence of myopathy. Case reports exist describing the development of myotoxicity with the concurrent administration of colchicine and HMG-CoA reductase inhibitors (e.g., simvastatin, atorvastatin, fluvastatin, lovastatin, pravastatin).
Raltegravir: (Moderate) Raltegravir use has been associated with elevated creatinine kinase concentrations; myopathy and rhabdomyolysis have been reported. Use raltegravir cautiously with drugs that increase the risk of myopathy or rhabdomyolysis such as HMG-CoA reductase inhibitors (Statins).
Red Yeast Rice: (Contraindicated) Since compounds in red yeast rice claim to have HMG-CoA reductase inhibitor activity, red yeast rice should not be used in combination with HMG-CoA reductase inhibitors. The administration of more than one HMG-CoA reductase inhibitor at one time would be duplicative therapy and perhaps increase the risk of drug-related toxicity including myopathy and rhabdomyolysis.
Rifabutin: (Minor) Rifampin has been reported to significantly increase the plasma clearance and decrease the serum concentrations of simvastatin and fluvastatin, with the potential for reduced antilipemic efficacy. Although not studied, a similar interaction can be expected between other rifamycins (e.g., rifabutin, rifapentine) and other HMG-CoA reductase inhibitors (Statins). To evaluate this interaction, monitor serum lipid concentrations during coadministration of rifamycins with HMG-CoA reductase inhibitors.
Rifampin: (Moderate) Rifampin has been reported to significantly increase the plasma clearance and decrease the serum concentrations of atorvastatin, simvastatin and fluvastatin, with the potential for reduced antilipemic efficacy. Although not studied, a similar interaction can be expected between other rifamycins (e.g., rifabutin, rifapentine) and other HMG-CoA reductase inhibitors (Statins). To evaluate this interaction, monitor serum lipid concentrations during coadministration of rifamycins with HMG-CoA reductase inhibitors.
Sirolimus: (Moderate) Carefully weigh the benefits of combined use of sirolimus and pravastatin against the potential risks. The risk of myopathy/rhabdomyolysis may increase with concurrent use. Guidelines recommend limiting the dose of pravastatin to 40 mg/day if combined with sirolimus.
Sofosbuvir; Velpatasvir; Voxilaprevir: (Moderate) Plasma concentrations of pravastatin have been shown to increase when pravastatin is administered concurrently with voxilaprevir. To prevent adverse effects, i.e., myopathy or rhabdomyolysis, the pravastatin dose should not exceed 40 mg when given with voxilaprevir. Pravastatin is a substrate of the Organic Anion Transporting Polypeptides 1B1/1B3 (OATP1B1/1B3). Voxilaprevir is an OATP1B1/1B3 inhibitor.
Tacrolimus: (Moderate) Carefully weigh the benefits of combined use of tacrolimus and pravastatin against the potential risk of statin-induced myopathy/rhabdomyolysis. Guidelines recommend lower doses of statins in combination with tacrolimus. A maximum dose of pravastatin40 mg/day is recommended.
Teriflunomide: (Major) Consider reducing the dose of HMG-CoA reductase inhibitors ("Statins" including atorvastatin, fluvastatin, lovastatin, pitavastatin, pravastatin, rosuvastatin, or simvastatin) during use of teriflunomide and monitor patients closely for signs and symptoms of myopathy. For a patient taking teriflunomide, the dose of rosuvastatin should not exceed 10 mg once daily. Patients should be advised to report promptly unexplained muscle pain, tenderness, or weakness, particularly if accompanied by malaise or fever. Teriflunomide is an inhibitor of the organic anion transporting polypeptide OATP1B1, and some statins are substrates for the OATP transporters. Teriflunomide may increase the exposure (AUC) of these statins. Increased concentrations of the statins increases the risk for myopathy and other statin-related side effects.
Trofinetide: (Moderate) Monitor for an increase in pravastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with trofinetide is necessary. Concomitant use may increase pravastatin exposure. Pravastatin is an OATP1B1/3 substrate; trofinetide is an OATP1B1/3 inhibitor.
Voclosporin: (Moderate) Monitor for an increase in pravastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with voclosporin is necessary. Concomitant use may increase pravastatin exposure. Pravastatin is an OATP1B1/3 substrate; voclosporin is an OATP1B1/3 inhibitor.
Vonoprazan; Amoxicillin; Clarithromycin: (Major) Do not exceed 40 mg per day of pravastatin if coadministration with clarithromycin cannot be avoided. Concurrent use increases the risk of myopathy and rhabdomyolysis. Coadministration of clarithromycin increased the AUC and Cmax of pravastatin by 110% and 128%, respectively.
Warfarin: (Moderate) Coadministration of pravastatin (40 mg) has been reported to have no clinically significant effect on prothrombin time in normal elderly subjects previously stabilized on warfarin. However, per prescribing information for warfarin sodium (Coumadin), all HMG-CoA reductase inhibitors (statins), including pravastatin, have been associated with potentiation of warfarin's clinical effect. However, it appears that pravastatin may be less likely to significantly interact with warfarin based on drug interaction studies. In general, it is prudent to monitor INR at baseline, at initiation of pravastatin, and after subsequent dosage changes. Adjust warfarin dosage based on INR and clinical response. Once a stable INR is documented, the INR can be monitored at the intervals otherwise recommended based on the indication for anticoagulation and co-existing conditions.

Pravachol/Pravastatin/Pravastatin Sodium Oral Tab: 10mg, 20mg, 40mg, 80mg

80 mg/day PO.

80 mg/day PO.

14 to 18 years: 40 mg/day PO is the FDA-approved maximum dose; however, higher doses were reported in a small study (exact maximum dosage for this age group was not defined, overall maximum for the study was 60 mg/day).
13 years: 20 mg/day PO is the FDA-approved maximum dose; however, higher doses were reported in a small study (exact maximum dosage for this age was not defined, overall maximum for the study was 60 mg/day).

 8 to 12 years: 20 mg/day PO is the FDA-approved maximum dose; however, higher doses were reported in a small study (exact maximum dosage for this age group was not defined, overall maximum for the study was 60 mg/day).
4 to 7 years: Safety and efficacy have not been established; however, doses of 10 mg/day PO or more were reported in a small study (exact maximum dosage for this age group was not defined, overall maximum for the study was 60 mg/day).
1 to 3 years: Safety and efficacy have not been established.

Safety and efficacy have not been established.

Safety and efficacy have not been established.

Pravastatin is a reversible inhibitor of hydroxymethylglutaryl-Coenzyme A (HMG-CoA) reductase. HMG-CoA reductase is the rate-limiting hepatic enzyme responsible for converting HMG-CoA to mevalonate, a precursor of sterols including cholesterol. Inhibition of HMG-CoA reductase lowers the amount of mevalonate and subsequently reduces cholesterol levels in hepatic cells. This, in turn, results in upregulation of LDL-receptors and increased hepatic uptake of LDL-cholesterol (LDL-C) from the blood. Sustained inhibition of cholesterol synthesis in the liver also decreases levels of very-low-density lipoproteins (VLDL), the precursor for LDL. The result is a reduction of circulating total cholesterol and LDL-C. Minor effects are also seen on HDL cholesterol (increase) and triglycerides (decrease).
HMG-CoA reductase inhibitors have also been reported to decrease endogenous coeznzyme Q10 (CoQ10) serum concentrations; the clinical significance of these effects is unknown.

Pravastatin is administered orally. It is approximately 50% protein bound and undergoes extensive first-pass extraction by the liver (extraction ratio 0.66). The major metabolic pathways for pravastatin are: (a) isomerization of 6-epi pravastatin and the 3-alpha-hydroxyisomer of pravastatin (SQ 31,906) and (b) enzymatic ring hydroxylation to the metabolite SQ 31,945. Metabolites do not possess significant clinical activity. After oral administration, roughly 20% of an oral dose is eliminated in the urine and 70% in the feces. After intravenous administration of radiolabeled pravastatin to normal volunteers, approximately 47% of total body clearance was via renal excretion and 53% by non-renal routes (i.e., biliary excretion and biotransformation). The elimination half-life of pravastatin in approximately 1.6 to 1.8 hours in humans and the elimination half-life for total radioactivity (pravastatin plus metabolites) is 77 hours.
 
Affected cytochrome P450 isoenzymes and drug transporters: OATP1B1, OATP1B3, OAT3, and MRP2
Pravastatin is a substrate for the drug transporters OATP1B1, OATP1B3, OAT3, and MRP2. In vitro and in vivo data with known CYP3A4 inhibitors suggest that pravastatin is not a clinically significant CYP3A4 substrate, in contrast to 'statins' which are primarily metabolized by the CYP3A4 isoenzyme (e.g., atorvastatin, lovastatin, simvastatin). For example, diltiazem (CYP3A4 inhibitor and substrate) has no effect on the pharmacokinetics of pravastatin. Pravastatin may be considered an alternative HMG-CoA reductase inhibitor for patients requiring therapy with potent CYP3A4 inhibitors.

Pravastatin is rapidly absorbed from the GI tract. Unlike lovastatin or simvastatin, pravastatin does not require hydrolysis for activation. Peak plasma concentrations are achieved in 1 to 1.5 hours. The average absorption is 34%, but due to significant first-pass elimination (extraction ratio 0.66), bioavailability is 17%. While the presence of food reduces AUC by 31% and Cmax by 49%, the lipid-lowering effect was similar whether pravastatin was taken with or 1 hour prior to meals. Systemic bioavailability of pravastatin following a bedtime dose was 60% lower than the bioavailability following morning administration. Despite this difference in bioavailability, the efficacy of pravastatin is slightly higher (but not statistically significantly different) with evening dosing relative to morning dosing. This may be explained by more extensive uptake of the drug by hepatocytes, the site of action, and/or diurnal variation in cholesterol synthesis.

After intravenous administration of radiolabeled pravastatin to normal volunteers, approximately 47% of total body clearance occurs via renal excretion. Non-renal clearance (e.g., biliary, metabolic biotransformation) accounts for about 53% of total body clearance.

Pravastatin therapy should be discontinued once pregnancy is identified in most patients. Alternatively, consider the ongoing therapeutic needs of the individual patient, particularly those at very high risk for cardiovascular events during pregnancy, such as those with homozygous familial hypercholesterolemia or with established cardiovascular disease. Based on the mechanism of action, pravastatin may cause fetal harm when administered to pregnant patients due to decreases in the synthesis of cholesterol and possibly other biologically active substances derived from cholesterol. Cholesterol and other products of the cholesterol biosynthesis pathway are essential components for fetal development, including synthesis of steroids and cell membranes. The U.S. Food and Drug Administration (FDA) completed a review of data from case series, prospective and retrospective observational cohort studies over decades of statin use in pregnant patients and concluded that these studies have not identified a drug-associated risk of major congenital malformations associated with statin use during pregnancy.  In a Medicaid cohort linkage study of 1,152 statin-exposed pregnant women, no significant teratogenic effects were observed following maternal statin use during the first trimester of pregnancy after adjusting for potential confounders (i.e., maternal age, diabetes mellitus, hypertension, obesity, alcohol use, and tobacco use); the relative risk (RR) of congenital malformations was 1.07 (95% confidence interval (CI), 0.85 to 1.37). In addition, after accounting for confounders, there were no statistically significant increases in organ-specific malformations. In the study, statin treatment was started prior to pregnancy and was discontinued within the first trimester after pregnancy was detected in a majority of patients. In another cohort study of 469 patients who were dispensed statins during pregnancy, it was determined that there was no increase in congenital anomalies after adjustment for maternal age and comorbidities; however, statin use was associated with an increased risk of preterm labor (RR, 1.99 [95% CI, 1.46 to 2.71]) and low birth weight (RR, 1.51 [95% CI, 1.05 to 2.16]). In a published, retrospective cohort study of 281 statin-exposed pregnant women, patients on statin therapy had a miscarriage rate of 25% compared to 21% for pregnant women not on statin therapy (n = 2,643); adjusted hazard ratio was 1.64 (95% CI, 1.1 to 2.46). The FDA also re-reviewed non-clinical, animal data statin development programs and concluded that statins have a limited potential to cause malformations or embryofetal lethality, and limited potential to affect nervous system development during embryofetal development during the pre- and post-natal period. In animal reproduction studies, fetal skeletal abnormalities, offspring mortality, and developmental delays did occur when pregnant rats were administered 10 to 12 times the maximum recommended human dose during organogenesis to parturition. Overall, available data have not identified a drug-associated risk of major congenital malformations, but published data are insufficient to determine if there is a drug-associated risk of miscarriage. Temporary discontinuation of lipid-lowering therapy, such as pravastatin, should have minimal impact on the long-term therapy of primary hyperlipidemia, as atherosclerosis is a chronic process. Advise pregnant patients and patients of child-bearing potential of the potential risk of statin therapy to the fetus and the importance of informing their health care provider of known or suspected pregnancy.

Pravastatin is not recommended for use during breast-feeding. There is no information about the presence of pravastatin in human or animal milk, the effects of the drug on the breastfed infant, or the effects of the drug on milk production. Cholesterol and other products of the cholesterol biosynthesis pathway are essential components for infant growth and development, including synthesis of steroids and cell membranes. HMG-CoA reductase inhibitors decrease the synthesis of cholesterol and possibly other products of the cholesterol biosynthesis pathway. The importance of continued pravastatin therapy to the mother should be considered in making the decision whether to discontinue breast-feeding or to discontinue the medication. If pharmacotherapy for hypercholesterolemia is necessary in the nursing mother, an alternative agent such as a nonabsorbable resin(cholestyramine, colesevelam, or colestipol) may be considered. These agents do not enter the bloodstream and thusly will not be excreted during lactation. However, resins bind fat-soluble vitamins and prolonged use may result in deficiencies of these vitamins in the mother and her nursing infant.