Mevacor

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Mevacor

Classes

HMG-CoA Reductase Inhibitors (Statins)

Administration

NOTE: Patients receiving lovastatin therapy should also be placed on a standard cholesterol-lowering diet, and this diet should be continued throughout therapy. Serum lipoprotein concentrations should be determined periodically and dosage adjusted according to individual response and established NCEP treatment guidelines.
 

Oral Administration

Avoid administration with grapefruit juice to avoid potential increases in drug serum concentrations. Evening dosing of lovastatin is preferable to optimize cholesterol-lowering effects.

Oral Solid Formulations

Immediate-release tablets: Administer with the evening meal to maximize oral bioavailability.
Extended-release tablets: Administer Altoprev tablets in the evening at bedtime, preferably without food. Food decreases the absorption of Altoprev. Tablets should be swallowed whole; do not crush or chew.

Adverse Reactions
Severe

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

Moderate

constipation / Delayed / 2.0-3.5
elevated hepatic enzymes / Delayed / 0.1-1.9
blurred vision / Early / 0.9-1.2
confusion / Early / 0-1.0
amnesia / Delayed / 0-1.0
memory impairment / Delayed / 0-1.0
chest pain (unspecified) / Early / 0.5-1.0
myopathy / Delayed / Incidence not known
myasthenia / Delayed / Incidence not known
cholestasis / Delayed / Incidence not known
hepatitis / Delayed / Incidence not known
jaundice / Delayed / Incidence not known
depression / Delayed / Incidence not known
eosinophilia / Delayed / Incidence not known
thrombocytopenia / Delayed / Incidence not known
leukopenia / Delayed / Incidence not known
dyspnea / Early / Incidence not known
cataracts / Delayed / Incidence not known
peripheral neuropathy / Delayed / Incidence not known
hyperglycemia / Delayed / Incidence not known
diabetes mellitus / Delayed / Incidence not known
impotence (erectile dysfunction) / Delayed / Incidence not known

Mild

infection / Delayed / 2.0-16.0
headache / Early / 2.1-8.0
arthralgia / Delayed / 0.5-6.0
sinusitis / Delayed / 4.0-6.0
influenza / Delayed / 5.0-5.0
back pain / Delayed / 5.0-5.0
flatulence / Early / 3.7-4.5
asthenia / Delayed / 1.2-3.0
myalgia / Early / 1.8-3.0
diarrhea / Early / 2.0-3.0
abdominal pain / Early / 2.0-2.5
nausea / Early / 1.9-2.5
dizziness / Early / 0.5-2.0
dyspepsia / Early / 1.0-1.6
rash / Early / 0.8-1.3
muscle cramps / Delayed / 0.6-1.1
vomiting / Early / 0.5-1.0
xerostomia / Early / 0.5-1.0
gastroesophageal reflux / Delayed / 0.5-1.0
insomnia / Early / 0.5-1.0
paresthesias / Delayed / 0.5-1.0
pruritus / Rapid / 0.5-1.0
alopecia / Delayed / 0.5-1.0
ocular irritation / Rapid / 0.5-1.0
fatigue / Early / Incidence not known
drowsiness / Early / Incidence not known
fever / Early / Incidence not known
weakness / Early / Incidence not known
vertigo / Early / Incidence not known
anxiety / Delayed / Incidence not known
dysgeusia / Early / Incidence not known
tremor / Early / Incidence not known
urticaria / Rapid / Incidence not known
purpura / Delayed / Incidence not known
photosensitivity / Delayed / Incidence not known
malaise / Early / Incidence not known
flushing / Rapid / Incidence not known
chills / Rapid / Incidence not known
gynecomastia / Delayed / Incidence not known
libido decrease / Delayed / Incidence not known
Co-Enzyme Q-10 deficiency / Delayed / Incidence not known

Common Brand Names

Altoprev, Mevacor

Dea Class

Rx

Description

Oral antilipemic agent; HMG-CoA reductase inhibitor; used for hypercholesterolemia.

Dosage And Indications
For general dosing information in persons requiring moderate-intensity statin therapy. Oral dosage (immediate-release) Adults

40 or 80 mg PO once daily.

For general dosing information in persons requiring low-intensity statin therapy. Oral dosage (immediate-release) Adults

20 mg PO once daily.

For the treatment of hypercholesterolemia, including hyperlipidemia, hyperlipoproteinemia, or hypertriglyceridemia, as an adjunct to dietary control. Oral dosage (immediate-release tablets) Adults

Initially, 10 to 20 mg PO once daily with the evening meal. Patients requiring LDL reductions of 20% or more to achieve their goal may begin with 20 mg PO once daily, while patients requiring lower reductions may begin with 10 mg PO once daily. The recommended dosing range is 10 to 80 mg/day PO in single or 2 divided doses. The maximum daily dose is 80 mg/day PO. At a dosage range of 10 to 80 mg/day, the mean LDL reduction range is 21% to 42%. Dividing the daily dosage into 2 doses is slightly more effective than once daily dosing. Dosage adjustments should be made at intervals of four weeks or more to attain desired cholesterol reduction. Geriatric patients may have greater LDL reductions at the usual dose compared to younger adults. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.

Adolescents and Children 10 years and older including girls who are at least 1 year post-menarche

Initially, 10 to 20 mg PO once daily with the evening meal. Patients requiring reductions in LDL cholesterol of 20% or more to achieve their goal can be started at 20 mg PO once daily, while patients requiring lower reductions may begin with 10 mg PO once daily. Maximum dosage is 40 mg/day PO. Dosage adjustments should be made at intervals of 4 weeks or more to attain desired cholesterol reduction. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. NOTE: Lovastatin may be used as an adjunct to diet in adolescents and children 10 years and older (including girls at least 1 year post-menarche) when either: 1) the LDL remains 190 mg/dL or higher or 2) the LDL remains higher than 160 mg/dL and there is an increased risk for cardiovascular disease (e.g., positive family history of premature cardiovascular disease or 2 or more other risk factors are present).

Oral dosage (lovastatin extended-release tablets; Altoprev) Adults

Initially, 20 to 60 mg PO once daily (mean LDL reduction range: 30% to 41%), given in the evening at bedtime. Food reduces absorption of the extended-release tablets. For patients requiring smaller LDL reductions, lovastatin extended-release is not recommended; immediate-release lovastatin should be considered. Dosage adjustments should be made at intervals of 4 weeks or more to attain desired cholesterol reduction. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.[28604] [43289]

Geriatric or Patients with complicated medical conditions (e.g., renal insufficiency, diabetes)

The manufacturer recommends 20 mg PO once daily, given in the evening at bedtime. Higher doses should be used only after careful consideration of the potential risks and benefits. For patients requiring smaller cholesterol reductions, the extended-release dosage form is not recommended; immediate-release lovastatin should be considered. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.

For slowing the progression of coronary atherosclerosis. Oral dosage (immediate-release tablets) Adults

Initially, 20 mg PO once daily with the evening meal. The recommended dosing range is 10 to 80 mg/day PO in single or two divided doses. The maximum daily dose is 80 mg/day PO. At the usual dosage range of 20 to 80 mg/day PO, the mean LDL reduction range is 27% to 42%. Dosage adjustments should be made at intervals of 4 weeks or more to attain desired cholesterol reduction. In patients with coronary artery disease, a study of lovastatin 80 mg/day significantly reduced coronary artery stenosis. Geriatric patients may have greater LDL reductions at the usual dose compared to younger adults. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.

Oral dosage (lovastatin extended-release tablets; Altoprev) Adults

Initially, 20 to 60 mg PO once daily (mean LDL reduction range: 30% to 41%), given in the evening at bedtime. Food reduces absorption of the extended-release tablets. For patients requiring smaller LDL reductions, lovastatin extended-release tablets are not recommended; immediate-release lovastatin should be considered. Dosage adjustments should be made at intervals of four weeks or more to attain desired cholesterol reduction.[43289] Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.

Geriatric or Patients with complicated medical conditions (e.g., renal insufficiency, diabetes)

Initially, 20 mg PO once daily given in the evening at bedtime. Higher doses should be used only after careful consideration of the potential risks and benefits. For patients requiring smaller cholesterol reductions, the extended-release dosage form is not recommended; immediate-release lovastatin should be considered. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.

For myocardial infarction prophylaxis (primary prevention). Oral dosage (immediate-release tablets) Adults

Initially, 20 to 40 mg PO once daily with the evening meal.[25813] The recommended dosing range is 10 to 80 mg/day PO in single or two divided doses. The maximum daily dose is 80 mg/day PO. At the usual dosage range of 20 to 80 mg/day PO, the mean LDL reduction range is 27% to 42%. Dosage adjustments should be made at intervals of four weeks or more to attain desired cholesterol reduction. In the AFCAPS/TexCAPS primary prevention study, lovastatin reduced the risk for the first acute major coronary event in adult men and women with average total and LDL cholesterol levels and below average HDL cholesterol levels. After an average of 5.2 years, lovastatin reduced the incidence of first acute major coronary event by 37%, fatal or nonfatal myocardial infarction by 40%, unstable angina by 32%, and coronary revascularization procedures by 33%, respectively.[25813] Geriatric patients may have greater LDL reductions at usual doses compared to younger adults. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.[28604]

Oral dosage (lovastatin extended-release tablets; Altoprev) Adults

Initially, 20 to 60 mg PO once daily (mean LDL reduction range: 30% to 41%), given in the evening at bedtime. Food reduces absorption of the extended-release tablets. For patients requiring smaller cholesterol reductions, the extended-release dosage form is not recommended; immediate-release lovastatin should be considered. Dosage adjustments should be made at intervals of 4 weeks or more to attain desired cholesterol reduction. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.[43289]

Geriatric or Patients with complicated medical conditions (e.g., renal insufficiency, diabetes)

20 mg PO once daily given in the evening at bedtime. Higher doses up to 60 mg/day should be used only after careful consideration of the potential risks and benefits. For patients requiring smaller cholesterol reductions, the extended-release dosage form is not recommended; immediate-release lovastatin should be considered. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.

For slowing the progression of atherosclerosis in patients with carotid artery disease (i.e., stroke prophylaxis†). Oral dosage (immediate-release tablets) Adults

Initially, 20 mg PO once daily with the evening meal. The recommended dosing range is 10 to 80 mg/day PO in single or 2 divided doses. The maximum daily dose is 80 mg/day PO.[28604] At the usual dosage range of 20 to 80 mg/day PO, the mean LDL reduction range is 27% to 42%. Dosage adjustments should be made at intervals of 4 weeks or more to attain desired cholesterol reduction. Lovastatin, in doses of 20 to 40 mg PO per day, was compared with low-dose warfarin in patients with early carotid disease. Lovastatin was shown to significantly reduce cardiovascular events which included coronary heart disease death, stroke, and non-fatal myocardial infarction. Although these cardiovascular events were analyzed collectively and therefore no direct conclusions can be drawn regarding stroke prophylaxis specifically, this study focused on patients with documented carotid disease and the resulting change in mean carotid artery intimal-medial thickness in the carotid artery. All patients were encouraged to take aspirin daily.[24359] Geriatric patients may have greater LDL reductions at usual doses compared to younger adults. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.

Oral dosage (lovastatin extended-release tablets; Altoprev) Adults

Initially, 20 to 60 mg PO once daily (mean LDL reduction range: 30% to 41%), given in the evening at bedtime. Food reduces absorption of the extended-release tablets. For patients requiring smaller LDL reductions, lovastatin extended-release is not recommended; immediate-release lovastatin should be considered. Dosage adjustments should be made at intervals of 4 weeks or more to attain desired cholesterol reduction. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.

Geriatric or Patients with complicated medical conditions (e.g., renal insufficiency, diabetes)

20 mg PO once daily given in the evening at bedtime. Higher doses should be used only after careful consideration of the potential risks and benefits. For patients requiring smaller cholesterol reductions, the extended-release dosage form is not recommended; immediate-release lovastatin should be considered. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.

†Indicates off-label use

Dosing Considerations
Hepatic Impairment

Not recommended in patients with hepatic disease (see Contraindications).

Renal Impairment

CrCl >= 30 ml/min: No dosage adjustment needed.
CrCl < 30 ml/min: Using dosages > 20 mg/day should be carefully considered.
 
Intermittent hemodialysis
The dialyzability of lovastatin and its metabolites is unknown.

Drug Interactions

Abrocitinib: (Moderate) Monitor for an increase in lovastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with abrocitinib is necessary. Concomitant use may increase lovastatin exposure. Lovastatin is a P-gp substrate; abrocitinib is a P-gp inhibitor.
Adagrasib: (Contraindicated) Coadministration of lovastatin and adagrasib is contraindicated due to the risk of elevated plasma concentrations of lovastatin leading to myopathy and rhabdomyolysis. Lovastatin is a sensitive CYP3A and P-gp substrate and adagrasib is a strong CYP3A and P-gp inhibitor. Coadministration with another strong CYP3A inhibitor increased lovastatin exposure by 11 to 36-fold.
Amiodarone: (Major) In general, in patients taking amiodarone, the lovastatin adult dose should not exceed 40 mg/day PO. Lovastatin doses greater than 40 mg/day should only be used in patients taking amiodarone in whom the benefit is expected to outweigh the increased risk of myopathy. Amiodarone may inhibit lovastatin metabolism via hepatic CYP3A4 isoenzymes. Monitor for signs and symptoms of myopathy in patients receiving amiodarone concurrently with any dose of lovastatin.
Amlodipine: (Moderate) Carefully weigh the benefits of combined use of amlodipine and lovastatin against the potential risks. Lovastatin exposure may increase resulting in increased risk of myopathy/rhabdomyolysis. Although FDA-approved labeling for amlodipine or lovastatin do not suggest dose adjustments, guidelines recommend limiting the dose of lovastatin to 20 mg/day if combined with amlodipine. Lovastatin is a CYP3A4 substrate; amlodipine is a weak CYP3A4 inhibitor.
Amlodipine; Atorvastatin: (Moderate) Carefully weigh the benefits of combined use of amlodipine and lovastatin against the potential risks. Lovastatin exposure may increase resulting in increased risk of myopathy/rhabdomyolysis. Although FDA-approved labeling for amlodipine or lovastatin do not suggest dose adjustments, guidelines recommend limiting the dose of lovastatin to 20 mg/day if combined with amlodipine. Lovastatin is a CYP3A4 substrate; amlodipine is a weak CYP3A4 inhibitor.
Amlodipine; Benazepril: (Moderate) Carefully weigh the benefits of combined use of amlodipine and lovastatin against the potential risks. Lovastatin exposure may increase resulting in increased risk of myopathy/rhabdomyolysis. Although FDA-approved labeling for amlodipine or lovastatin do not suggest dose adjustments, guidelines recommend limiting the dose of lovastatin to 20 mg/day if combined with amlodipine. Lovastatin is a CYP3A4 substrate; amlodipine is a weak CYP3A4 inhibitor.
Amlodipine; Celecoxib: (Moderate) Carefully weigh the benefits of combined use of amlodipine and lovastatin against the potential risks. Lovastatin exposure may increase resulting in increased risk of myopathy/rhabdomyolysis. Although FDA-approved labeling for amlodipine or lovastatin do not suggest dose adjustments, guidelines recommend limiting the dose of lovastatin to 20 mg/day if combined with amlodipine. Lovastatin is a CYP3A4 substrate; amlodipine is a weak CYP3A4 inhibitor.
Amlodipine; Olmesartan: (Moderate) Carefully weigh the benefits of combined use of amlodipine and lovastatin against the potential risks. Lovastatin exposure may increase resulting in increased risk of myopathy/rhabdomyolysis. Although FDA-approved labeling for amlodipine or lovastatin do not suggest dose adjustments, guidelines recommend limiting the dose of lovastatin to 20 mg/day if combined with amlodipine. Lovastatin is a CYP3A4 substrate; amlodipine is a weak CYP3A4 inhibitor.
Amlodipine; Valsartan: (Moderate) Carefully weigh the benefits of combined use of amlodipine and lovastatin against the potential risks. Lovastatin exposure may increase resulting in increased risk of myopathy/rhabdomyolysis. Although FDA-approved labeling for amlodipine or lovastatin do not suggest dose adjustments, guidelines recommend limiting the dose of lovastatin to 20 mg/day if combined with amlodipine. Lovastatin is a CYP3A4 substrate; amlodipine is a weak CYP3A4 inhibitor.
Amlodipine; Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) Carefully weigh the benefits of combined use of amlodipine and lovastatin against the potential risks. Lovastatin exposure may increase resulting in increased risk of myopathy/rhabdomyolysis. Although FDA-approved labeling for amlodipine or lovastatin do not suggest dose adjustments, guidelines recommend limiting the dose of lovastatin to 20 mg/day if combined with amlodipine. Lovastatin is a CYP3A4 substrate; amlodipine is a weak CYP3A4 inhibitor.
Amoxicillin; Clarithromycin; Omeprazole: (Contraindicated) The concurrent use of lovastatin and clarithromycin is contraindicated due to the risk of myopathy and rhabdomyolysis. If no alternative to a short course of treatment with clarithromycin therapy is available, lovastatin use must be suspended during clarithromycin treatment. Lovastatin is metabolized by CYP3A4, and clarithromycin is a strong inhibitor of CYP3A4.
Aprepitant, Fosaprepitant: (Moderate) Use caution if lovastatin and aprepitant, fosaprepitant are used concurrently and monitor for an increase in lovastatin-related adverse effects, including myopathy and rhabdomyolysis, for several days after administration of a multi-day aprepitant regimen. Lovastatin is a CYP3A4 substrate. Aprepitant, when administered as a 3-day oral regimen (125 mg/80 mg/80 mg), is a moderate CYP3A4 inhibitor and inducer and may increase plasma concentrations of lovastatin. For example, a 5-day oral aprepitant regimen increased the AUC of another CYP3A4 substrate, midazolam (single dose), by 2.3-fold on day 1 and by 3.3-fold on day 5. After a 3-day oral aprepitant regimen, the AUC of midazolam (given on days 1, 4, 8, and 15) increased by 25% on day 4, and then decreased by 19% and 4% on days 8 and 15, respectively. As a single 125 mg or 40 mg oral dose, the inhibitory effect of aprepitant on CYP3A4 is weak, with the AUC of midazolam increased by 1.5-fold and 1.2-fold, respectively. After administration, fosaprepitant is rapidly converted to aprepitant and shares many of the same drug interactions. However, as a single 150 mg intravenous dose, fosaprepitant only weakly inhibits CYP3A4 for a duration of 2 days; there is no evidence of CYP3A4 induction. Fosaprepitant 150 mg IV as a single dose increased the AUC of midazolam (given on days 1 and 4) by approximately 1.8-fold on day 1; there was no effect on day 4. Less than a 2-fold increase in the midazolam AUC is not considered clinically important.
Atazanavir: (Contraindicated) Concurrent use of lovastatin and anti-retroviral protease inhibitors is contraindicated. The risk of developing myopathy, rhabdomyolysis, and acute renal failure is substantially increased if lovastatin is administered concomitantly with anti-retroviral protease inhibitors. Lovastatin is a substrate of CYP3A4 and anti-retroviral protease inhibitors are strong inhibitors of CYP3A4; therefore, coadministration may result in substantial increases in plasma concentrations of lovastatin.
Atazanavir; Cobicistat: (Contraindicated) Concomitant use of lovastatin with cobicistat is contraindicated due to the potential for myopathy, including rhabdomyolysis. Coadministration is expected to significantly increase lovastatin plasma concentrations. Lovastatin is a substrate for CYP3A4; cobicistat is a strong inhibitor of CYP3A. Coadministration with another strong CYP3A4 inhibitor increased lovastatin exposure by 11 to 36-fold. (Contraindicated) Concurrent use of lovastatin and anti-retroviral protease inhibitors is contraindicated. The risk of developing myopathy, rhabdomyolysis, and acute renal failure is substantially increased if lovastatin is administered concomitantly with anti-retroviral protease inhibitors. Lovastatin is a substrate of CYP3A4 and anti-retroviral protease inhibitors are strong inhibitors of CYP3A4; therefore, coadministration may result in substantial increases in plasma concentrations of lovastatin.
Barbiturates: (Moderate) Barbiturates are significant hepatic CYP3A4 inducers. Monitor for potential reduced cholesterol-lowering efficacy when barbiturates are co-administered with HMG-CoA reductase inhibitors metabolized by CYP3A4 including lovastatin.
Berotralstat: (Moderate) Monitor for an increase in lovastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with berotralstat is necessary. Coadministration may increase the exposure of lovastatin. Lovastatin is a sensitive substrate of CYP3A4 and berotralstat is a moderate CYP3A4 inhibitor.
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.
Bosentan: (Moderate) Co-administration of bosentan may decrease the plasma concentrations of lovastatin, a CYP3A4 substrate. The possibility of reduced anti-lipemic efficacy should be considered. Patients receiving CYP3A4 metabolized statins should have cholesterol levels monitored after adding bosentan therapy to evaluate the need for anti-lipemic dosage adjustment.
Cannabidiol: (Moderate) Monitor for an increase in lovastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with cannabidiol is necessary. Concomitant use may increase lovastatin exposure. Lovastatin is a P-gp substrate; cannabidiol is a P-gp inhibitor.
Capmatinib: (Moderate) Monitor for an increase in lovastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with capmatinib is necessary. Concomitant use may increase lovastatin exposure. Lovastatin is a substrate of P-gp; capmatinib is an inhibitor of P-gp.
Carbamazepine: (Minor) Carbamazepine, which is a CYP3A4 inducer, may decrease the efficacy of HMG-Co-A reductase inhibitors which are CYP3A4 substrates, such as lovastatin. Monitor for potential reduced cholesterol-lowering efficacy when these drugs are co-administered with HMG-CoA reductase inhibitors which are metabolized by CYP3A4.
Ceritinib: (Contraindicated) Coadministration of lovastatin and ceritinib is contraindicated due to the risk of elevated plasma concentrations of lovastatin leading to myopathy and rhabdomyolysis. Lovastatin is a sensitive CYP3A4 substrate and ceritinib is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased lovastatin exposure by 11 to 36-fold.
Cilostazol: (Moderate) Cilostazol may interact with lovastatin, but it is not clear if the interaction could be clinically significant. In healthy volunteers, peak plasma concentrations of lovastatin did not change with co-administration of cilostazol. However, peak plasma concentrations and the AUC of lovastatin's active metabolite did increase. Also, the peak plasma concentrations and AUC of cilostazol were decreased by roughly 15% when lovastatin was co-administered.
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: (Contraindicated) The concurrent use of lovastatin and clarithromycin is contraindicated due to the risk of myopathy and rhabdomyolysis. If no alternative to a short course of treatment with clarithromycin therapy is available, lovastatin use must be suspended during clarithromycin treatment. Lovastatin is metabolized by CYP3A4, and clarithromycin is a strong inhibitor of CYP3A4.
Cobicistat: (Contraindicated) Concomitant use of lovastatin with cobicistat is contraindicated due to the potential for myopathy, including rhabdomyolysis. Coadministration is expected to significantly increase lovastatin plasma concentrations. Lovastatin is a substrate for CYP3A4; cobicistat is a strong inhibitor of CYP3A. Coadministration with another strong CYP3A4 inhibitor increased lovastatin exposure by 11 to 36-fold.
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).
Conivaptan: (Moderate) Monitor for an increase in lovastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with conivaptan is necessary. Coadministration may increase the exposure of lovastatin. Lovastatin is a CYP3A and P-gp substrate and conivaptan is a moderate CYP3A and P-gp inhibitor.
Crizotinib: (Moderate) Monitor for an increase in lovastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with crizotinib is necessary. Lovastatin is a sensitive substrate of CYP3A4 and crizotinib is a moderate CYP3A inhibitor.
Cyclosporine: (Major) Avoid the concurrent use of cyclosporine and lovastatin. Cyclosporine may increase the risk of myopathy, rhabdomyolysis and acute renal failure in patients taking lovastatin. In uncontrolled clinical studies of lovastatin, myopathy was reported more frequently in patients receiving concomitant therapy with cyclosporine. Cyclosporine may reduce the clearance of the HMG-CoA reductase inhibitors (statins), Cyclosporine has been shown to increase the AUC of HMG-CoA reductase inhibitors, presumably due to CYP3A4 inhibition.
Dabigatran: (Moderate) Consider a statin other than lovastatin or simvastatin if HMG-CoA reductase inhibition is necessary for a patient receiving dabigatran. Increased serum concentrations of dabigatran are possible when coadministered with lovastatin. If use together is medically necessary, patients should be monitored for increased adverse effects of dabigatran and an increased risk for bleeding. A mechanism for this interaction may be the inhibition of P-gp by lovastatin; dabigatran is a P-gp substrate. In one clinical trial, patients receiving dabigatran with lovastatin or simvastatin experienced a higher risk of major hemorrhage relative to the use of other statins that are not P-gp inhibitors. P-gp inhibition and renal impairment are the major independent factors that result in increased exposure to dabigatran.
Dabrafenib: (Major) The concomitant use of dabrafenib and lovastatin may lead to decreased lovastatin concentrations and loss of efficacy. Use of an alternative agent is recommended. If concomitant use of these agents together is unavoidable, monitor patients for loss of lovastatin efficacy. Dabrafenib is a moderate CYP3A4 inducer and lovastatin is a sensitive CYP3A4 substrate. Concomitant use of dabrafenib with a single dose of another sensitive CYP3A4 substrate decreased the AUC value of the sensitive CYP3A4 substrate by 65%.
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.
Danazol: (Major) The risk of myopathy and rhabdomyolysis is increased if danazol is used with lovastatin. In adult patients taking danazol, the initial lovastatin dose should not exceed 10 mg/day PO, and the total lovastatin dose should not exceed 20 mg/day PO. A single case report has documented the onset of myositis which progressed to rhabdomyolysis with myoglobinuria after danazol was added to a regimen containing lovastatin. Although other drugs were in use concurrently, a drug interaction between danazol and lovastatin is suspected since danazol (CYP3A4 inhibitor) is known to inhibit lovastatin metabolism. If concurrent use of lovastatin and danazol is desired, carefully weigh the benefit of lovastatin against the risk of 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.
Darunavir: (Contraindicated) Concurrent use of lovastatin and anti-retroviral protease inhibitors is contraindicated. The risk of developing myopathy, rhabdomyolysis, and acute renal failure is substantially increased if lovastatin is administered concomitantly with anti-retroviral protease inhibitors. Lovastatin is a substrate of CYP3A4 and anti-retroviral protease inhibitors are strong inhibitors of CYP3A4; therefore, coadministration may result in substantial increases in plasma concentrations of lovastatin.
Darunavir; Cobicistat: (Contraindicated) Concomitant use of lovastatin with cobicistat is contraindicated due to the potential for myopathy, including rhabdomyolysis. Coadministration is expected to significantly increase lovastatin plasma concentrations. Lovastatin is a substrate for CYP3A4; cobicistat is a strong inhibitor of CYP3A. Coadministration with another strong CYP3A4 inhibitor increased lovastatin exposure by 11 to 36-fold. (Contraindicated) Concurrent use of lovastatin and anti-retroviral protease inhibitors is contraindicated. The risk of developing myopathy, rhabdomyolysis, and acute renal failure is substantially increased if lovastatin is administered concomitantly with anti-retroviral protease inhibitors. Lovastatin is a substrate of CYP3A4 and anti-retroviral protease inhibitors are strong inhibitors of CYP3A4; therefore, coadministration may result in substantial increases in plasma concentrations of lovastatin.
Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Contraindicated) Concomitant use of lovastatin with cobicistat is contraindicated due to the potential for myopathy, including rhabdomyolysis. Coadministration is expected to significantly increase lovastatin plasma concentrations. Lovastatin is a substrate for CYP3A4; cobicistat is a strong inhibitor of CYP3A. Coadministration with another strong CYP3A4 inhibitor increased lovastatin exposure by 11 to 36-fold. (Contraindicated) Concurrent use of lovastatin and anti-retroviral protease inhibitors is contraindicated. The risk of developing myopathy, rhabdomyolysis, and acute renal failure is substantially increased if lovastatin is administered concomitantly with anti-retroviral protease inhibitors. Lovastatin is a substrate of CYP3A4 and anti-retroviral protease inhibitors are strong inhibitors of CYP3A4; therefore, coadministration may result in substantial increases in plasma concentrations of lovastatin.
Delavirdine: (Contraindicated) The risk of myopathy, including rhabdomyolysis, may be increased when delavirdine is given in combination with HMG-CoA reductase inhibitors. Concomitant use of delavirdine and the CYP3A4 substrate lovastatin is not recommended. If treatment with an HMG-CoA reductase inhibitor is necessary, pravastatin should also be considered, since it is not significantly metabolized by CYP3A4 or CYP2C9 isoenzymes.
Diltiazem: (Major) Coadministration of diltiazem and lovastatin increases the risk for myopathy/rhabdomyolysis particularly with higher doses of lovastatin. In adult patients taking diltiazem, the initial lovastatin dose should not exceed 10 mg/day PO, and the total lovastatin dose should not exceed 20 mg/day PO. The benefits of the use of lovastatin in patients taking diltiazem should be carefully weighed against the risks of this combination.
Dronedarone: (Major) Although FDA-approved labeling for lovastatin recommends limiting the dose of lovastatin to 20 mg/day if combined with dronedarone, guidelines recommend limiting the lovastatin dose to 10 mg/day during concurrent use. Lovastatin exposure may increase resulting in increased risk of myopathy/rhabdomyolysis. Lovastatin is a CYP3A4 substrate; dronedarone is a moderate CYP3A4 inhibitor.
Duvelisib: (Moderate) Monitor for an increase in lovastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with duvelisib is necessary. Coadministration may increase the exposure of lovastatin. Lovastatin is a sensitive substrate of CYP3A4 and duvelisib is a moderate CYP3A4 inhibitor.
Efavirenz: (Minor) Efavirenz has potential to induce CYP3A4 isoenzymes which may decrease the efficacy of lovastatin.
Efavirenz; Emtricitabine; Tenofovir Disoproxil Fumarate: (Minor) Efavirenz has potential to induce CYP3A4 isoenzymes which may decrease the efficacy of lovastatin.
Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Minor) Efavirenz has potential to induce CYP3A4 isoenzymes which may decrease the efficacy of lovastatin.
Elacestrant: (Moderate) Monitor for an increase in lovastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with elacestrant is necessary. Concomitant use may increase lovastatin exposure. Lovastatin is a P-gp substrate; elacestrant is a P-gp inhibitor.
Elbasvir; Grazoprevir: (Moderate) The manufacturer of elbasvir; grazoprevir recommends caution during concurrent administration with lovastatin. Although this interaction has not been studied, use of these drugs together may result in elevated lovastatin plasma concentrations. Use the lowest effective lovastatin dose and monitor patients for statin-related adverse events (such as myopathy). Lovastatin is a substrate for the hepatic enzymes CYP3A; grazoprevir is a weak CYP3A inhibitor.
Elexacaftor; tezacaftor; ivacaftor: (Moderate) Monitor for lovastatin-related adverse reactions (i.e., myopathy/rhabdomyolysis) during coadministration of elexacaftor; tezacaftor; ivacaftor as concurrent use may increase exposure of lovastatin. Lovastatin is a substrate for the transporter OATP1B1; elexacaftor; tezacaftor; ivacaftor may inhibit uptake of OATP1B1. (Moderate) Monitoring for lovastatin-related adverse events (i.e., myopathy, rhabdomyolysis) is recommended if administered concurrently with ivacaftor. Coadministration can increase lovastatin exposure leading to increased or prolonged therapeutic effects and adverse events. Lovastatin is a CYP3A4 substrate; ivacaftor is a weak CYP3A4 inhibitor.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Contraindicated) Concomitant use of lovastatin with cobicistat is contraindicated due to the potential for myopathy, including rhabdomyolysis. Coadministration is expected to significantly increase lovastatin plasma concentrations. Lovastatin is a substrate for CYP3A4; cobicistat is a strong inhibitor of CYP3A. Coadministration with another strong CYP3A4 inhibitor increased lovastatin exposure by 11 to 36-fold.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Contraindicated) Concomitant use of lovastatin with cobicistat is contraindicated due to the potential for myopathy, including rhabdomyolysis. Coadministration is expected to significantly increase lovastatin plasma concentrations. Lovastatin is a substrate for CYP3A4; cobicistat is a strong inhibitor of CYP3A. Coadministration with another strong CYP3A4 inhibitor increased lovastatin exposure by 11 to 36-fold.
Enasidenib: (Moderate) Monitor for an increase in lovastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with enasidenib is necessary. Concomitant use may increase lovastatin exposure. Lovastatin is a substrate of P-gp; enasidenib is an inhibitor of P-gp.
Encorafenib: (Moderate) Coadministration of encorafenib with lovastatin may result in increased toxicity or decreased efficacy of lovastatin. Lovastatin is a sensitive CYP3A4 substrate. In vitro studies with encorafenib showed time-dependent inhibition of CYP3A4 and induction of CYP3A4. The clinical relevance of the in vivo effect of encorafenib on CYP3A4 is not established.
Erythromycin: (Contraindicated) Concurrent use of lovastatin and erythromycin is contraindicated. The risk of developing myopathy, rhabdomyolysis, and acute renal failure is substantially increased if lovastatin is administered concomitantly with strong CYP3A4 inhibitors including erythromycin. If no alternative to a short course of treatment with erythromycin is available, a brief suspension of lovastatin therapy during such treatment can be considered as there are no known adverse consequences to brief interruptions of long-term cholesterol-lowering therapy.
Eslicarbazepine: (Minor) In vivo studies suggest eslicarbazepine is an inducer of CYP3A4. Coadministration of CYP3A4 substrates, such as lovastatin, may result in decreased serum concentrations of the substrate. Monitor for decreased efficacy of lovastatin if coadministered with eslicarbazepine. Adjust the dose of lovastatin if clinically significant alterations in serum lipds are noted.
Etravirine: (Moderate) The risk of myopathy, including rhabdomyolysis, may be increased when antiretrovirals are given in combination with HMG-CoA reductase inhibitors. Concomitant use of etravirine and lovastatin (CYP3A4 substrate) may result in lower plasma concentrations of the HMG-CoA reductase inhibitor; dose adjustments may be necessary.
Fedratinib: (Moderate) Monitor for an increase in lovastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with fedratinib is necessary. Coadministration may increase the exposure of lovastatin. Lovastatin is a sensitive substrate of CYP3A4 and fedratinib is a moderate CYP3A4 inhibitor.
Fenofibrate: (Moderate) Concurrent use of fenofibrate and lovastatin may increase the risk of myopathy, rhabdomyolysis, and acute renal failure. The serious risk of myopathy and rhabdomyolysis should be weighed carefully against the benefit of further alteration in lipid concentrations by the combined use of fenofibrate or fenofibric acid and lovastatin.
Fenofibric Acid: (Moderate) Concurrent use of fenofibric acid and lovastatin may increase the risk of myopathy, rhabdomyolysis, and acute renal failure. The serious risk of myopathy and rhabdomyolysis should be weighed carefully against the benefit of further alteration in lipid concentrations by the combined use of fenofibric acid and lovastatin.
Fluconazole: (Moderate) Monitor for an increase in lovastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with fluconazole is necessary. Concomitant use may increase lovastatin exposure. Lovastatin is a sensitive substrate of CYP3A and fluconazole is a moderate CYP3A inhibitor.
Fosamprenavir: (Contraindicated) Concurrent use of lovastatin and anti-retroviral protease inhibitors is contraindicated. The risk of developing myopathy, rhabdomyolysis, and acute renal failure is substantially increased if lovastatin is administered concomitantly with anti-retroviral protease inhibitors. Lovastatin is a substrate of CYP3A4 and anti-retroviral protease inhibitors are strong inhibitors of CYP3A4; therefore, coadministration may result in substantial increases in plasma concentrations of lovastatin.
Fosphenytoin: (Moderate) Monitor for a decrease in lovastatin efficacy if concomitant use with phenytoin/fosphenytoin is necessary. Concomitant use may decrease lovastatin exposure. Lovastatin is a CYP3A substrate and phenytoin/fosphenytoin is a strong CYP3A inducer.
Fostemsavir: (Moderate) Monitor for lovastatin-related adverse reactions (i.e., myopathy/rhabdomyolysis) during concomitant use of fostemsavir as concurrent use may increase exposure of lovastatin. Lovastatin is a substrate for the transporter OATP1B1 and fostemsavir is an inhibitor of OATP1B1.
Futibatinib: (Moderate) Monitor for an increase in lovastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with futibatinib is necessary. Concomitant use may increase lovastatin exposure. Lovastatin is a P-gp substrate; futibatinib is a P-gp inhibitor.
Gemfibrozil: (Major) Avoid the concurrent use of gemfibrozil and lovastatin. The risk of myopathy and rhabdomyolysis is increased with combined gemfibrozil and HMG-CoA reductase inhibitor ("statin") therapy. Myopathy or rhabdomyolysis with or without acute renal failure have been reported as early as 3 weeks after initiation of combined therapy or after several months. There is no assurance that periodic monitoring of creatine kinase will prevent the occurrence of severe myopathy and kidney damage. In uncontrolled clinical studies of lovastatin, myopathy was reported more frequently in patients receiving concomitant therapy with gemfibrozil. Gemfibrozil may increase the risk of myopathy, rhabdomyolysis and acute renal failure in patients taking lovastatin. Data suggest that the addition of gemfibrozil to lovastatin therapy does not result in greater reductions in LDL-C than that achieved with lovastatin alone.
Gilteritinib: (Moderate) Monitor for an increase in lovastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with gilteritinib is necessary. Concomitant use may increase lovastatin exposure. Lovastatin is a P-gp substrate; gilteritinib is a P-gp inhibitor.
Glecaprevir; Pibrentasvir: (Major) Coadministration of glecaprevir with lovastatin is not recommended due to an increased risk of myopathy, including rhabdomyolysis. Coadministration may increase the plasma concentrations of lovastatin. Lovastatin is a substrate of the drug transporter OATP1B1; glecaprevir is an inhibitor of this transporter. In drug interaction studies, coadministration of lovastatin with glecaprevir; pibrentasvir resulted in 70% increase in the AUC of lovastatin. (Major) Coadministration of pibrentasvir with lovastatin is not recommended due to an increased risk of myopathy, including rhabdomyolysis. Coadministration may increase the plasma concentrations of lovastatin. Lovastatin is a substrate of the drug transporter OATP1B1; pibrentasvir is an inhibitor of this transporter. In drug interaction studies, coadministration of lovastatin with glecaprevir; pibrentasvir resulted in 70% increase in the AUC of lovastatin.
Grapefruit juice: (Major) Large quantities of grapefruit juice (>1 quart daily) should be avoided during lovastatin therapy due to the increased risk of myopathy. Grapefruit juice contains compounds that inhibit the CYP3A4 isozyme in the gut wall. Coadministration with grapefruit juice increases the plasma concentrations and AUC of lovastatin (and its beta-hydroxy acid metabolite) and may have a similar effect on the serum concentrations of simvastatin, atorvastatin, and cerivastatin, which are CYP3A4 substrates. Grapefruit juice should be avoided or minimized in patients taking these agents to avoid the potential for drug accumulation and toxicity (ie. myopathy and rhabdomyolysis).
Idelalisib: (Contraindicated) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with lovastatin, a CYP3A substrate, as lovastatin toxicities, such as myopathy, may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib. Consider an alternative to lovastatin. A single dose of 10 mg of rosuvastatin was administered alone and after idelailsib 150 mg for 12 doses in healthy subjects and no changes in exposure to rosuvastatin were observed.
Imatinib: (Major) Imatinib, STI-571 is a potent inhibitor of the cytochrome P450 3A4 isoenzyme. Concurrent use of lovastatin and imatinib may result in increased levels of lovastatin and potential toxicity. Concurrent use of simvastatin and imatinib resulted in 2- and 3.5-fold increases in simvastatin Cmax and AUC values, respectively.
Indinavir: (Contraindicated) Concurrent use of lovastatin and anti-retroviral protease inhibitors is contraindicated. The risk of developing myopathy, rhabdomyolysis, and acute renal failure is substantially increased if lovastatin is administered concomitantly with anti-retroviral protease inhibitors. Lovastatin is a substrate of CYP3A4 and anti-retroviral protease inhibitors are strong inhibitors of CYP3A4; therefore, coadministration may result in substantial increases in plasma concentrations of lovastatin.
Isavuconazonium: (Moderate) Concomitant use of isavuconazonium with lovastatin may result in increased serum concentrations of lovastatin. Lovastatin is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is an inhibitor of CYP3A4. Caution and close monitoring are advised if these drugs are used together.
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.
Isradipine: (Minor) Isradipine has been shown to increase the clearance of lovastatin. Lovastatin serum concentrations were correspondingly lower during isradipine administration. Lovastatin did not have any effect on isradipine pharmacokinetics. The clinical significance of this drug interaction is unclear at this time.
Itraconazole: (Contraindicated) Lovastatin is contraindicated for use during and for 2 weeks after itraconazole therapy due to the substantial increased risk of developing myopathy, rhabdomyolysis, and acute renal failure. In a small, double-blind study in healthy volunteers, lovastatin mean peak concentrations and lovastatin AUC increased by more than 20-fold when subjects were pretreated with itraconazole. Although side effects were not reported, one patient experienced a 10-fold increase in creatine kinase. One other case is noted of a patient who developed rhabdomyolysis when itraconazole was added to a stable regimen of lovastatin and niacin. Because pravastatin does not significantly rely on the CYP3A4 isoenzyme for metabolism, it is less likely to exhibit an interaction with the azole antifungals. Compared to a 19 to 20-fold increase in lovastatin AUC with concurrent itraconazole, the AUC of pravastatin is increased 1.7-fold when coadministered with itraconazole. The relatively small increase in pravastatin AUC during itraconazole therapy is postulated by the manufacturer to be due to inhibition of P-glycoprotein transport.
Ivacaftor: (Moderate) Monitoring for lovastatin-related adverse events (i.e., myopathy, rhabdomyolysis) is recommended if administered concurrently with ivacaftor. Coadministration can increase lovastatin exposure leading to increased or prolonged therapeutic effects and adverse events. Lovastatin is a CYP3A4 substrate; ivacaftor is a weak CYP3A4 inhibitor.
Ivosidenib: (Moderate) Monitor for loss of efficacy of lovastatin during coadministration of ivosidenib; a lovastatin dose adjustment may be necessary. Lovastatin is a sensitive substrate of CYP3A4; ivosidenib induces CYP3A4 and may lead to decreased lovastatin concentrations.
Ketoconazole: (Contraindicated) Concurrent use of lovastatin and ketoconazole is contraindicated. The risk of developing myopathy, rhabdomyolysis, and acute renal failure is substantially increased if lovastatin is administered concomitantly with strong CYP3A4 inhibitors including ketoconazole. If no alternative to a short course of treatment with ketoconazole is available, a brief suspension of lovastatin therapy during such treatment can be considered as there are no known adverse consequences to brief interruptions of long-term cholesterol-lowering therapy.
Lansoprazole; Amoxicillin; Clarithromycin: (Contraindicated) The concurrent use of lovastatin and clarithromycin is contraindicated due to the risk of myopathy and rhabdomyolysis. If no alternative to a short course of treatment with clarithromycin therapy is available, lovastatin use must be suspended during clarithromycin treatment. Lovastatin is metabolized by CYP3A4, and clarithromycin is a strong inhibitor of CYP3A4.
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.
Lasmiditan: (Moderate) Monitor for an increase in lovastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with lasmiditan is necessary. Concomitant use may increase lovastatin exposure. Lovastatin is a P-gp substrate; lasmiditan is a P-gp inhibitor.
Lefamulin: (Moderate) Monitor for an increase in lovastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with oral lefamulin is necessary. Coadministration may increase the exposure of lovastatin. Lovastatin is a sensitive substrate of CYP3A4 and oral lefamulin is a moderate CYP3A4 inhibitor; an interaction is not expected with intravenous lefamulin.
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.
Lenacapavir: (Moderate) Monitor for an increase in lovastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with lenacapavir is necessary. Concomitant use may increase lovastatin exposure. Lovastatin is a CYP3A and P-gp substrate and lenacapavir is a moderate CYP3A and P-gp inhibitor.
Letermovir: (Major) Close monitoring for lovastatin-related adverse events (i.e., myopathy, rhabdomyolysis) and consideration of a lovastatin dose reduction is recommended if administered concurrently with letermovir. Concurrent use is contraindicated if the patient is also receiving cyclosporine. A clinically relevant increase in the plasma concentration of lovastatin may occur during concurrent administration with letermovir. The magnitude of this interaction may be increased in patients who are also receiving cyclosporine. Lovastatin is a sensitive substrate of CYP3A4 and the organic anion-transporting polypeptide (OATP1B1). Both letermovir and cyclosporine are moderate CYP3A4 inhibitors and inhibitors of OATP1B1. The combined effect of letermovir and cyclosporine on CYP3A4 substrates may be similar to a strong CYP3A4 inhibitor.
Levamlodipine: (Moderate) Carefully weigh the benefits of combined use of amlodipine and lovastatin against the potential risks. Lovastatin exposure may increase resulting in increased risk of myopathy/rhabdomyolysis. Although FDA-approved labeling for amlodipine or lovastatin do not suggest dose adjustments, guidelines recommend limiting the dose of lovastatin to 20 mg/day if combined with amlodipine. Lovastatin is a CYP3A4 substrate; amlodipine is a weak CYP3A4 inhibitor.
Levoketoconazole: (Contraindicated) Concurrent use of lovastatin and ketoconazole is contraindicated. The risk of developing myopathy, rhabdomyolysis, and acute renal failure is substantially increased if lovastatin is administered concomitantly with strong CYP3A4 inhibitors including ketoconazole. If no alternative to a short course of treatment with ketoconazole is available, a brief suspension of lovastatin therapy during such treatment can be considered as there are no known adverse consequences to brief interruptions of long-term cholesterol-lowering therapy.
Lomitapide: (Major) The risk of developing myopathy, including rhabdomyolysis may be increased if lovastatin is administered concomitantly with lomitapide. Consider reducing the dose of lovastatin when initiating lomitapide. Although the interaction between lovastatin and lomitapide has not been studied, coadministration of lomitapide and simvastatin approximately doubles the exposure to simvastatin. Because the metabolizing enzymes and transporters responsible for the disposition of lovastatin and simvastatin are similar, increased exposure to lovastatin should also be expected.
Lonafarnib: (Contraindicated) Coadministration of lovastatin and lonafarnib is contraindicated due to the risk of elevated plasma concentrations of lovastatin leading to myopathy and rhabdomyolysis. Lovastatin is a P-gp substrate and sensitive CYP3A4 substrate; lonafarnib is a P-gp inhibitor and strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased lovastatin exposure by 11 to 36-fold.
Lopinavir; Ritonavir: (Contraindicated) Concurrent use of lovastatin and anti-retroviral protease inhibitors is contraindicated. The risk of developing myopathy, rhabdomyolysis, and acute renal failure is substantially increased if lovastatin is administered concomitantly with anti-retroviral protease inhibitors. Lovastatin is a substrate of CYP3A4 and anti-retroviral protease inhibitors are strong inhibitors of CYP3A4; therefore, coadministration may result in substantial increases in plasma concentrations of lovastatin.
Lumacaftor; Ivacaftor: (Moderate) Lumacaftor; ivacaftor may decrease the systemic exposure of lovastatin; if used together, monitor serum lipid concentrations. Lovastatin is a substrate of CYP3A4. Lumacaftor is a strong CYP3A inducer.
Lumacaftor; Ivacaftor: (Moderate) Monitoring for lovastatin-related adverse events (i.e., myopathy, rhabdomyolysis) is recommended if administered concurrently with ivacaftor. Coadministration can increase lovastatin exposure leading to increased or prolonged therapeutic effects and adverse events. Lovastatin is a CYP3A4 substrate; ivacaftor is a weak CYP3A4 inhibitor.
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.
Maribavir: (Moderate) Monitor for an increase in lovastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with maribavir is necessary. Concomitant use may increase lovastatin exposure. Lovastatin is a P-gp substrate; maribavir is a P-gp inhibitor.
Mefenamic Acid: (Moderate) Mefenamic acid is a substrate for CYP2C9. Inhibitors of this enzyme, such as lovastatin, may lead to increased serum concentrations of mefenamic acid. If these drugs are administered concurrently, monitor for NSAID related side effects, such as fluid retention or GI irritation, or renal dysfunction and adjust the mefenamic acid dose, if needed.
Mifepristone: (Contraindicated) When mifepristone is used in the treatment of Cushing's syndrome, coadministration is contraindicated based on studies demonstrating significant lovastatin exposure increases which may lead to an increased risk of myopathy and rhabdomyolysis. Consider interruption of lovastatin therapy during use of mifepristone for pregnancy termination. Mifepristone inhibits CYP3A4; lovastatin is a CYP3A4 substrate. Coadministration of mifepristone increases serum levels drugs metabolized via CYP3A4 with narrow therapeutic indexes, such as lovastatin. Due to the slow elimination of mifepristone from the body, such interactions may be observed for a prolonged period after administration.
Mitapivat: (Moderate) Monitor for an increase in lovastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with mitapivat is necessary. Concomitant use may increase lovastatin exposure. Lovastatin is a P-gp substrate; mitapivat is a P-gp inhibitor.
Mitotane: (Major) Use caution if mitotane and lovastatin are used concomitantly, and monitor for decreased efficacy of lovastatin and a possible change in dosage requirements. Mitotane is a strong CYP3A4 inducer and lovastatin is a CYP3A4 substrate; coadministration may result in decreased plasma concentrations of lovastatin.
Nanoparticle Albumin-Bound Sirolimus: (Major) Guidelines recommend avoiding coadministration of lovastatin with sirolimus due to the potential for increased risk of myopathy/rhabdomyolysis. Consider use of an alternative statin such as atorvastatin, fluvastatin, pravastatin, or rosuvastatin with dose limitations in patients receiving sirolimus.
Nefazodone: (Contraindicated) Concurrent use of lovastatin and nefazodone is contraindicated. The risk of developing myopathy, rhabdomyolysis, and acute renal failure is substantially increased if lovastatin is administered concomitantly with nefazodone. Lovastatin is a substrate of CYP3A4 and nefazodone is a strong inhibitor of CYP3A4; therefore, coadministration may result in substantial increases in plasma concentrations of lovastatin.
Nelfinavir: (Contraindicated) Concurrent use of lovastatin and anti-retroviral protease inhibitors is contraindicated. The risk of developing myopathy, rhabdomyolysis, and acute renal failure is substantially increased if lovastatin is administered concomitantly with anti-retroviral protease inhibitors. Lovastatin is a substrate of CYP3A4 and anti-retroviral protease inhibitors are strong inhibitors of CYP3A4; therefore, coadministration may result in substantial increases in plasma concentrations of lovastatin.
Neratinib: (Moderate) Monitor for an increase in lovastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with neratinib is necessary. Concomitant use may increase lovastatin exposure. Lovastatin is a substrate of P-gp; neratinib is an inhibitor of P-gp.
Nevirapine: (Moderate) Monitor for reduced cholesterol-lowering efficacy of lovastatin if coadministration with nevirapine is necessary; a dose adjustment may be needed. Concomitant use may decrease lovastatin exposure. Lovastatin is a CYP3A substrate and nevirapine is a weak CYP3A inducer.
Niacin, Niacinamide: (Major) There is no clear indication for routine use of niacin in combination with lovastatin. 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 lovastatin. If coadministered, consider lower starting and maintenance does of lovastatin. 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 lovastatin immediately if myopathy is diagnosed or suspected.
Niacin; Simvastatin: (Major) There is no clear indication for routine use of niacin in combination with lovastatin. 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 lovastatin. If coadministered, consider lower starting and maintenance does of lovastatin. 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 lovastatin immediately if myopathy is diagnosed or suspected.
Nicardipine: (Moderate) Nicardipine is an inhibitor of CYP3A4 isoenzymes. Co-administration with nicardipine may lead to an increase in serum levels of drugs that are CYP3A4 substrates including lovastatin.
Nilotinib: (Moderate) Concomitant use of nilotinib and lovastatin may result in increased lovastatin levels. A lovastatin dose reduction may be necessary if these drugs are used together. Be alert for symptoms of statin-induced myopathy. Lovastatin is a CYP3A4 substrate; nilotinib is a moderate CYP3A4 inhibitor.
Nirmatrelvir; Ritonavir: (Contraindicated) Concomitant use of ritonavir-boosted nirmatrelvir and lovastatin is contraindicated. Discontinue use of lovastatin at least 12 hours before, during, and 5 days after treatment with ritonavir-boosted nirmatrelvir. Coadministration may increase lovastatin exposure resulting in increased toxicity. Lovastatin is a CYP3A substrate and nirmatrelvir is a CYP3A inhibitor. (Contraindicated) Concurrent use of lovastatin and anti-retroviral protease inhibitors is contraindicated. The risk of developing myopathy, rhabdomyolysis, and acute renal failure is substantially increased if lovastatin is administered concomitantly with anti-retroviral protease inhibitors. Lovastatin is a substrate of CYP3A4 and anti-retroviral protease inhibitors are strong inhibitors of CYP3A4; therefore, coadministration may result in substantial increases in plasma concentrations of lovastatin.
Olmesartan; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) Carefully weigh the benefits of combined use of amlodipine and lovastatin against the potential risks. Lovastatin exposure may increase resulting in increased risk of myopathy/rhabdomyolysis. Although FDA-approved labeling for amlodipine or lovastatin do not suggest dose adjustments, guidelines recommend limiting the dose of lovastatin to 20 mg/day if combined with amlodipine. Lovastatin is a CYP3A4 substrate; amlodipine is a weak CYP3A4 inhibitor.
Omeprazole; Amoxicillin; Rifabutin: (Minor) 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.
Oritavancin: (Moderate) Lovastatin is metabolized by CYP3A4; oritavancin is a weak CYP3A4 inducer. Plasma concentrations and efficacy of lovastatin may be reduced if these drugs are administered concurrently.
Oxcarbazepine: (Minor) Oxcarbazepine, which is a CYP3A4 inducer, may decrease the efficacy of HMG-Co-A reductase inhibitors which are CYP3A4 substrates including lovastatin. Monitor for potential reduced cholesterol-lowering efficacy when these drugs are co-administered with HMG-CoA reductase inhibitors which are metabolized by CYP3A4.
Pacritinib: (Moderate) Monitor for an increase in lovastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with pacritinib is necessary. Concomitant use may increase lovastatin exposure. Lovastatin is a P-gp substrate; pacritinib is a P-gp inhibitor.
Pazopanib: (Moderate) Pazopanib is a weak inhibitor of CYP3A4. Coadministration of pazopanib and lovastatin, a CYP3A4 substrate, may cause an increase in systemic concentrations of lovastatin. Use caution when administering these drugs concomitantly.
Perindopril; Amlodipine: (Moderate) Carefully weigh the benefits of combined use of amlodipine and lovastatin against the potential risks. Lovastatin exposure may increase resulting in increased risk of myopathy/rhabdomyolysis. Although FDA-approved labeling for amlodipine or lovastatin do not suggest dose adjustments, guidelines recommend limiting the dose of lovastatin to 20 mg/day if combined with amlodipine. Lovastatin is a CYP3A4 substrate; amlodipine is a weak CYP3A4 inhibitor.
Phenytoin: (Moderate) Monitor for a decrease in lovastatin efficacy if concomitant use with phenytoin is necessary. Concomitant use may decrease lovastatin exposure. Lovastatin is a CYP3A substrate and phenytoin is a strong CYP3A inducer.
Pirtobrutinib: (Moderate) Monitor for an increase in lovastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with pirtobrutinib is necessary. Concomitant use may increase lovastatin exposure. Lovastatin is a P-gp substrate; pirtobrutinib is a P-gp inhibitor.
Posaconazole: (Contraindicated) Concurrent use of lovastatin and posaconazole is contraindicated. The risk of developing myopathy, rhabdomyolysis, and acute renal failure is substantially increased if lovastatin is administered concomitantly with strong CYP3A4 inhibitors including posaconazole. If no alternative to a short course of treatment with posaconazole is available, a brief suspension of lovastatin therapy during such treatment can be considered as there are no known adverse consequences to brief interruptions of long-term cholesterol-lowering therapy.
Pretomanid: (Moderate) Monitor for an increase in lovastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with pretomanid is necessary. Concomitant use may increase lovastatin exposure. Lovastatin is a P-gp substrate; pretomanid is a P-gp inhibitor.
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).
Protease inhibitors: (Contraindicated) Concurrent use of lovastatin and anti-retroviral protease inhibitors is contraindicated. The risk of developing myopathy, rhabdomyolysis, and acute renal failure is substantially increased if lovastatin is administered concomitantly with anti-retroviral protease inhibitors. Lovastatin is a substrate of CYP3A4 and anti-retroviral protease inhibitors are strong inhibitors of CYP3A4; therefore, coadministration may result in substantial increases in plasma concentrations of lovastatin.
Quetiapine: (Moderate) In a published case, it has been hypothesized that the combination of lovastatin and quetiapine resulted in prolongation of the QTc interval. The suggested mechanism is competitive inhibition of the CYP3A4 isoenzyme leading to elevated quetiapine plasma concentrations. Both lovastatin and quetiapine are CYP3A4 substrates. The QTc interval returned to baseline when the lovastatin dose was reduced. The clinical significance and reproducibility of this interaction is unknown.
Quinine: (Moderate) Lovastatin is a CYP3A4 substrate; therefore, quinine has the potential to inhibit the metabolism of lovastatin leading to an increased potential of rhabdomyolysis. Patients receiving concomitant lovastatin and quinine should be monitored closely for muscle pain or weakness. Lower starting doses of lovastatin should be considered while patients are receiving quinine.
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).
Ranolazine: (Moderate) Carefully weigh the benefits of combined use of ranolazine and lovastatin against the potential risks. Lovastatin exposure may increase resulting in increased risk of myopathy/rhabdomyolysis. Although FDA-approved labeling for ranolazine and lovastatin do not provide specific dose adjustments, guidelines recommend limiting the dose of lovastatin to 20 mg/day if combined with ranolazine. Lovastatin is a CYP3A4 substrate; ranolazine is a weak CYP3A4 inhibitor.
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.
Ribociclib: (Contraindicated) Coadministration of lovastatin and ribociclib is contraindicated due to the risk of elevated plasma concentrations of lovastatin leading to myopathy and rhabdomyolysis. Lovastatin is a sensitive CYP3A4 substrate and ribociclib is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased lovastatin exposure by 11 to 36-fold.
Ribociclib; Letrozole: (Contraindicated) Coadministration of lovastatin and ribociclib is contraindicated due to the risk of elevated plasma concentrations of lovastatin leading to myopathy and rhabdomyolysis. Lovastatin is a sensitive CYP3A4 substrate and ribociclib is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased lovastatin exposure by 11 to 36-fold.
Rifabutin: (Minor) 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.
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.
Ritlecitinib: (Moderate) Monitor for an increase in lovastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with ritlecitinib is necessary. Concomitant use may increase lovastatin exposure. Lovastatin is a sensitive substrate of CYP3A and ritlecitinib is a moderate CYP3A inhibitor.
Ritonavir: (Contraindicated) Concurrent use of lovastatin and anti-retroviral protease inhibitors is contraindicated. The risk of developing myopathy, rhabdomyolysis, and acute renal failure is substantially increased if lovastatin is administered concomitantly with anti-retroviral protease inhibitors. Lovastatin is a substrate of CYP3A4 and anti-retroviral protease inhibitors are strong inhibitors of CYP3A4; therefore, coadministration may result in substantial increases in plasma concentrations of lovastatin.
Saquinavir: (Contraindicated) Concurrent use of lovastatin and anti-retroviral protease inhibitors is contraindicated. The risk of developing myopathy, rhabdomyolysis, and acute renal failure is substantially increased if lovastatin is administered concomitantly with anti-retroviral protease inhibitors. Lovastatin is a substrate of CYP3A4 and anti-retroviral protease inhibitors are strong inhibitors of CYP3A4; therefore, coadminist

ration may result in substantial increases in plasma concentrations of lovastatin.
Sarilumab: (Moderate) Utilize caution with concomitant use of sarilumab and CYP3A4 substrate drugs, such as lovastatin, where a decrease in effectiveness is undesirable. Monitor lipid panels and adjust therapy as indicated. Inhibition of IL-6 signaling by sarilumab may restore CYP450 activities to higher levels leading to increased metabolism of drugs that are CYP450 substrates as compared to metabolism prior to treatment. This effect on CYP450 enzyme activity may persist for several weeks after stopping sarilumab. A 45% decrease in exposure to another "statin" was noted in a drug interaction study. In vitro, sarilumab has the potential to affect expression of multiple CYP enzymes, including CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, and CYP3A4. Lovastatin is a CYP3A4 substrate.
Selpercatinib: (Moderate) Monitor for an increase in lovastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with selpercatinib is necessary. Concomitant use may increase lovastatin exposure. Lovastatin is a P-gp substrate; selpercatinib is a P-gp inhibitor.
Siltuximab: (Moderate) Caution is warranted in patients receiving siltuximab who are taking CYP3A4 substrates, such as lovastatin, in which a decreased effect would be undesirable. Monitor the patient's lipid profile as clinically indicated and adjust treatment as necessary. Cytochrome P450s in the liver are down regulated by infection and inflammation stimuli, including cytokines such as interleukin-6 (IL-6). Inhibition of IL-6 signaling by siltuximab may restore CYP450 activities to higher levels leading to increased metabolism of drugs that are CYP450 substrates as compared to metabolism prior to treatment. The effect of siltuximab on CYP450 enzyme activity can persist for several weeks after stopping therapy.
Sirolimus: (Major) Guidelines recommend avoiding coadministration of lovastatin with sirolimus due to the potential for increased risk of myopathy/rhabdomyolysis. Consider use of an alternative statin such as atorvastatin, fluvastatin, pravastatin, or rosuvastatin with dose limitations in patients receiving sirolimus.
Sodium Phenylbutyrate; Taurursodiol: (Moderate) Monitor for an increase in lovastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with taurursodiol is necessary. Concomitant use may increase lovastatin exposure. Lovastatin is a P-gp substrate; taurursodiol is a P-gp inhibitor.
Sotorasib: (Moderate) Monitor for an increase in lovastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with sotorasib is necessary. Concomitant use may increase lovastatin exposure. Lovastatin is a substrate of P-gp; sotorasib is an inhibitor of P-gp.
Sparsentan: (Moderate) Monitor for an increase in lovastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with sparsentan is necessary. Concomitant use may increase lovastatin exposure. Lovastatin is a P-gp substrate; sparsentan is a P-gp inhibitor.
St. John's Wort, Hypericum perforatum: (Moderate) St. John's Wort appears to induce several isoenzymes of the hepatic cytochrome P450 enzyme system. Co-administration of St. John's Wort could decrease the efficacy of some medications metabolized by these enzymes including lovastatin.
Stiripentol: (Moderate) Consider a dose adjustment of lovastatin when coadministered with stiripentol. Coadministration may alter plasma concentrations of lovastatin resulting in an increased risk of adverse reactions and/or decreased efficacy. Lovastatin is a sensitive CYP3A4 substrate. In vitro data predicts inhibition or induction of CYP3A4 by stiripentol potentially resulting in clinically significant interactions.
Tacrolimus: (Major) Guidelines recommend avoiding coadministration of lovastatin with tacrolimus due to the potential for increased risk of myopathy/rhabdomyolysis. Consider use of an alternative statin such as atorvastatin, fluvastatin, pravastatin, or rosuvastatin with dose limitations in patients receiving tacrolimus.
Telmisartan; Amlodipine: (Moderate) Carefully weigh the benefits of combined use of amlodipine and lovastatin against the potential risks. Lovastatin exposure may increase resulting in increased risk of myopathy/rhabdomyolysis. Although FDA-approved labeling for amlodipine or lovastatin do not suggest dose adjustments, guidelines recommend limiting the dose of lovastatin to 20 mg/day if combined with amlodipine. Lovastatin is a CYP3A4 substrate; amlodipine is a weak CYP3A4 inhibitor.
Tepotinib: (Moderate) Monitor for an increase in lovastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with tepotinib is necessary. Concomitant use may increase lovastatin exposure. Lovastatin is a substrate of P-gp; tepotinib is an inhibitor of P-gp.
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.
Tezacaftor; Ivacaftor: (Moderate) Monitoring for lovastatin-related adverse events (i.e., myopathy, rhabdomyolysis) is recommended if administered concurrently with ivacaftor. Coadministration can increase lovastatin exposure leading to increased or prolonged therapeutic effects and adverse events. Lovastatin is a CYP3A4 substrate; ivacaftor is a weak CYP3A4 inhibitor.
Ticagrelor: (Major) Avoid lovastatin doses higher than 40 mg/day when used concomitantly with ticagrelor as concomitant use will result in higher serum concentrations of lovastatin. Lovastatin is metabolized by CYP3A4 and ticagrelor is an inhibitor of CYP3A4.
Tipranavir: (Contraindicated) Concurrent use of lovastatin and anti-retroviral protease inhibitors is contraindicated. The risk of developing myopathy, rhabdomyolysis, and acute renal failure is substantially increased if lovastatin is administered concomitantly with anti-retroviral protease inhibitors. Lovastatin is a substrate of CYP3A4 and anti-retroviral protease inhibitors are strong inhibitors of CYP3A4; therefore, coadministration may result in substantial increases in plasma concentrations of lovastatin.
Tocilizumab: (Moderate) Utilize caution with concomitant use of tocilizumab and CYP3A4 substrate drugs, such as lovastatin, where a decrease in effectiveness is undesirable. Monitor lipid panels and adjust therapy as indicated. Inhibition of IL-6 signaling by tocilizumab may restore CYP450 activities to higher levels leading to increased metabolism of drugs that are CYP450 substrates as compared to metabolism prior to treatment. This effect on CYP450 enzyme activity may persist for several weeks after stopping tocilizumab. A 57% decrease in the exposure of another "statin" was noted 1 week after a single tocilizumab dose. In vitro, tocilizumab has the potential to affect expression of multiple CYP enzymes, including CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, and CYP3A4. Lovastatin is a CYP3A4 substrate.
Trandolapril; Verapamil: (Major) Coadministration of verapamil and lovastatin increases the risk for myopathy/rhabdomyolysis, particularly with higher doses of lovastatin. In patients taking verapamil, the initial lovastatin dose should not exceed 10 mg/day PO. While the FDA-approved product labeling for lovastatin products recommends a maximum lovastatin dosage of 20 mg/day when these agents are used together, the product labeling for verapamil suggests a maximum lovastatin dosage of 40 mg/day. The benefits of the use of lovastatin in patients taking verapamil should be carefully weighed against the risks of this combination. Specific dosage recommendations for pediatric patients receiving this combination are not available.
Tucatinib: (Contraindicated) Coadministration of lovastatin and tucatinib is contraindicated due to the risk of elevated plasma concentrations of lovastatin leading to myopathy and rhabdomyolysis. Lovastatin is a sensitive CYP3A4 substrate and tucatinib is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased lovastatin exposure by 11 to 36-fold.
Verapamil: (Major) Coadministration of verapamil and lovastatin increases the risk for myopathy/rhabdomyolysis, particularly with higher doses of lovastatin. In patients taking verapamil, the initial lovastatin dose should not exceed 10 mg/day PO. While the FDA-approved product labeling for lovastatin products recommends a maximum lovastatin dosage of 20 mg/day when these agents are used together, the product labeling for verapamil suggests a maximum lovastatin dosage of 40 mg/day. The benefits of the use of lovastatin in patients taking verapamil should be carefully weighed against the risks of this combination. Specific dosage recommendations for pediatric patients receiving this combination are not available.
Voclosporin: (Moderate) Monitor for an increase in lovastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with voclosporin is necessary. Concomitant use may increase lovastatin exposure. Lovastatin is a substrate of P-gp; voclosporin is an inhibitor of P-gp.
Vonoprazan; Amoxicillin; Clarithromycin: (Contraindicated) The concurrent use of lovastatin and clarithromycin is contraindicated due to the risk of myopathy and rhabdomyolysis. If no alternative to a short course of treatment with clarithromycin therapy is available, lovastatin use must be suspended during clarithromycin treatment. Lovastatin is metabolized by CYP3A4, and clarithromycin is a strong inhibitor of CYP3A4.
Voriconazole: (Contraindicated) Coadministration of lovastatin and voriconazole is contraindicated due to the risk of elevated plasma concentrations of lovastatin leading to myopathy and rhabdomyolysis. Lovastatin is a sensitive CYP3A4 substrate and voriconazole is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased lovastatin exposure by 11 to 36-fold.
Voxelotor: (Moderate) Monitor for an increase in lovastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with voxelotor is necessary. Concomitant use may increase lovastatin exposure. Lovastatin is a sensitive substrate of CYP3A and voxelotor is a moderate CYP3A inhibitor.
Warfarin: (Moderate) Monitor INR carefully in patients taking warfarin when lovastatin is initiated or a lovastatin dosage adjustment is made. Lovastatin's influence on warfarin's clinical effects is unclear. Bleeding and/or prolonged prothrombin time have been reported in a few patients when lovastatin was taken concurrently with coumarin anticoagulants. However, one small clinical trial found no effect on prothrombin time when lovastatin was given to patients receiving warfarin. Another HMG-CoA reductase inhibitor was found to increase the INR by < 2 seconds in healthy subjects taking low doses of warfarin. Alternatively, it appears that pravastatin and atorvastatin may be less likely to significantly interact with warfarin based on drug interaction studies.
Zafirlukast: (Minor) Zafirlukast inhibits the CYP3A4 isoenzymes and should be used cautiously in patients stabilized on drugs metabolized by CYP3A4, such as lovastatin.

How Supplied

Altoprev Oral Tab ER: 20mg, 40mg, 60mg
Lovastatin/Mevacor Oral Tab: 10mg, 20mg, 40mg

Maximum Dosage
Adults

80 mg/day PO immediate-release tablets (e.g., Mevacor); 60 mg/day PO extended-release tablets (Altoprev). Max 20 mg/day PO immediate-release or extended-release lovastatin if taking fibrates, niacin, danazol, or cyclosporine; max 40 mg/day PO immediate-release lovastatin if taking amiodarone or verapamil; max 20 mg/day PO extended-release lovastatin if taking amiodarone or verapamil.

Geriatric

80 mg/day PO immediate-release tablets (e.g., Mevacor); 60 mg/day PO extended-release tablets (Altoprev). Max 20 mg/day PO immediate-release or extended-release lovastatin if taking fibrates, niacin, danazol, or cyclosporine; max 40 mg/day PO immediate-release lovastatin if taking amiodarone or verapamil; max 20 mg/day PO extended-release lovastatin if taking amiodarone or verapamil.

Adolescents

40 mg/day PO immediate-release tablets (e.g., Mevacor). Safety and efficacy have not been established for extended-release tablets (e.g., Altoprev).

Children

10 years and older: 40 mg/day PO immediate-release tablets (e.g., Mevacor). Safety and efficacy have not been established for extended-release tablets (e.g., Altoprev).
Less than 10 years: Safety and efficacy have not been established.

Mechanism Of Action

Mechanism of Action: Lovastatin is a prodrug with little or no inherent activity but is hydrolyzed in vivo to mevinolinic acid. Mevinolinic acid, one of lovastatin's several active metabolites, is structurally similar to HMG-CoA (hydroxymethylglutaryl CoA). Once hydrolyzed, lovastatin competes with HMG-CoA for HMG-CoA reductase, a hepatic microsomal enzyme. Interference with the activity of this enzyme reduces the quantity of mevalonic acid, a precursor of cholesterol. This process occurs within the hepatocyte and is one of two mechanisms that generate cholesterol. Cholesterol also can be taken up from LDL by endocytosis. Since de novo synthesis of cholesterol is impaired by lovastatin, the second mechanism is augmented. Thus, lovastatin also enhances clearance of LDL. Lovastatin exerts its effects mainly on total cholesterol and LDL, with minor effects seen on HDL and triglycerides. Because peak cholesterol synthesis occurs in the early morning hours, evening dosing for lovastatin is preferable.HMG-CoA reductase inhibitors have been reported to decrease endogenous CoQ10 serum concentrations; the clinical significance of these effects is unknown.

Pharmacokinetics

Lovastatin is administered orally. Both lovastatin and its beta-hydroxyacid metabolite are highly bound to plasma proteins (more than 95%). Lovastatin crosses the blood-brain barrier and the placental barrier, and may be distributed into human milk. Lovastatin is a prodrug that is hydrolyzed to mevinolinic acid and metabolized to several other active derivatives via hepatic CYP3A4 isoenzymes. The major active metabolites present in human plasma are the beta-hydroxyacid (lovastatin acid), its 6'-hydroxy derivative, and two additional metabolites. The plasma half-life of mevinolinic acid is about 1.1 to 1.7 hours. Following a single dose of immediate-release lovastatin to adults with hypercholesterolemia, 83% is excreted in the feces as both active and inactive metabolites. Drug eliminated via the stool represents both unabsorbed drug and drug and metabolites secreted in the bile. Only 10% of a dose is eliminated renally.
 
Affected cytochrome P450 isoenzymes and drug transporters: CYP3A4
Lovastatin is a substrate of CYP3A4 hepatic metabolism, but does not affect the metabolism of CYP3A4 substrates. It has multiple significant drug interactions with CYP3A4 inhibitors, which may result in increased HMG-CoA reductase inhibition and toxicity including myopathy and rhabdomyolysis. There is evidence suggesting that lovastatin may be a P-gp substrate and inhibitor; however, the clinical relevance of this on drug-drug interactions has not been established.

Oral Route

Lovastatin is incompletely absorbed from the GI tract and undergoes extensive first-pass extraction in the liver. Lovastatin was purposely developed as a prodrug to concentrate active inhibitors in the liver during first-pass circulation. Only fewer than 5% (with considerable inter-individual variation) of active inhibitors reaches the systemic circulation following immediate-release lovastatin. Peak concentrations of active and total HMG Co-A reductase inhibitors occur within 2 to 4 hours after oral administration of immediate-release lovastatin. The presence of food in the GI tract enhances oral absorption. Lovastatin absorption appears to be increased by at least 30% by grapefruit juice; however, the effect is dependent on the amount of grapefruit juice consumed and the interval between grapefruit juice and lovastatin ingestion. When compared to 40 mg of immediate-release lovastatin, Altoprev 40 mg (extended-release lovastatin) produces a 3.9% greater LDL-reduction. At the same dosage (40 mg), Altoprev is also associated with greater lovastatin (prodrug) bioavailability, a lower lovastatin Cmax, prolonged absorption (increased Tmax), comparable exposure to the lovastatin acid metabolite, and similar exposure to active and total inhibitors of HMG-CoA reductase. Food decreases the bioavailability of Altoprev. When Altoprev is given with a meal, plasma concentrations of lovastatin and lovastatin acid are about 0.5 to 0.6 times those observed when administered in the fasting state. Diurnal variation in cholesterol synthesis has been documented; single daily doses of lovastatin (immediate-release or extended-release formulations) are most effective when given in the evening.

Pregnancy And Lactation
Pregnancy

Lovastatin is contraindicated for use in pregnancy because of the potential effects of HMG-CoA reductase inhibitors on cholesterol pathways and the potential for fetal harm. Cholesterol and other products of the cholesterol biosynthesis pathway are essential components for fetal development, including synthesis of steroids and cell membranes. Treatment should be immediately discontinued as soon as pregnancy is recognized. Lovastatin has been shown to cause malformations of vertebrae and ribs in fetal rats when given at doses 50 times the maximum recommended human dose, based on body surface area. In a prospective review of about 100 pregnancies in women exposed to simvastatin or another structurally related HMG-CoA reductase inhibitor, the incidence of congenital anomalies, spontaneous abortions, and fetal deaths/stillbirths did not exceed what would be expected in the general population. However, atherosclerosis is a chronic process and the discontinuation of lipid-lowering drugs during pregnancy should have little impact on the outcome of long-term therapy of primary hypercholesterolemia. If the patient becomes pregnant while taking this drug, lovastatin should be discontinued immediately and the patient should be apprised of the potential hazard to the fetus. Lovastatin should only be administered to females of child-bearing potential, including adolescents at least 1 year post-menarche, when such patients are highly unlikely to conceive and have been informed of the potential hazards. Contraception requirements are advised; females should be counseled regarding appropriate methods of contraception while on therapy. The effects of statins on spermatogenesis and fertility have not been studied in adequate numbers of patients. The effects, if any, of lovastatin on the pituitary-gonadal axis in pre-menopausal females are unknown. Patients treated with lovastatin who display clinical evidence of endocrine dysfunction should be evaluated appropriately.