Advicor

HMG-CoA Reductase Inhibitors/Statins and Other Lipid Modifying Agent Combinations

NOTE: Therapy with lipid-altering agents should be only one component of multiple risk factor intervention in individuals at significantly increased risk for atherosclerotic vascular disease due to hypercholesterolemia. Patients receiving lovastatin; niacin (Advicor) 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 treatment guidelines.
 

Oral Administration

Avoid administration with grapefruit juice to avoid potential increases in lovastatin serum concentrations.
Niacin-induced flushing of the skin may be reduced in frequency or severity by pretreatment with a dose (e.g., 325 mg) of aspirin (taken up to about 30 minutes prior to the niacin dose) or an NSAID product such as ibuprofen, if appropriate for the individual patient.
Administer Advicor at bedtime, with a low-fat snack. Since peak cholesterol synthesis occurs in the early morning hours, evening dosing is preferable. Advicor is administered with food to maximize the oral bioavailability of lovastatin, to limit GI side effects, and should help limit niacin-induced flushing.

Oral Solid Formulations

Administer lovastatin; niacin intact; do not break, chew or crush the tablets.

Severe

immune-mediated necrotizing myopathy / Delayed / 0-1.0
cirrhosis / Delayed / 0-1.0
hepatic failure / Delayed / 0-1.0
pancreatitis / Delayed / 0-1.0
hepatic necrosis / Delayed / 0-1.0
rhabdomyolysis / Delayed / Incidence not known
myoglobinuria / Delayed / Incidence not known
Stevens-Johnson syndrome / Delayed / Incidence not known
toxic epidermal necrolysis / Delayed / Incidence not known
hemolytic anemia / Delayed / Incidence not known
laryngeal edema / Rapid / Incidence not known
vasculitis / Delayed / Incidence not known
erythema multiforme / Delayed / Incidence not known
angioedema / Rapid / Incidence not known
lupus-like symptoms / Delayed / Incidence not known
peptic ulcer / Delayed / Incidence not known
macular edema / Delayed / Incidence not known
muscle paralysis / Delayed / Incidence not known

Moderate

hyperglycemia / Delayed / 46.0-65.0
cataracts / Delayed / 0.9-1.2
hepatitis / Delayed / 0-1.0
amnesia / Delayed / 0-1.0
memory impairment / Delayed / 0-1.0
confusion / Early / 0-1.0
thrombocytopenia / Delayed / Incidence not known
myopathy / Delayed / Incidence not known
peripheral edema / Delayed / Incidence not known
angina / Early / Incidence not known
leukopenia / Delayed / Incidence not known
edema / Delayed / Incidence not known
bullous rash / Early / Incidence not known
erythema / Early / Incidence not known
hypotension / Rapid / Incidence not known
orthostatic hypotension / Delayed / Incidence not known
eosinophilia / Delayed / Incidence not known
dyspnea / Early / Incidence not known
peripheral vasodilation / Rapid / Incidence not known
palpitations / Early / Incidence not known
sinus tachycardia / Rapid / Incidence not known
constipation / Delayed / Incidence not known
jaundice / Delayed / Incidence not known
cholestasis / Delayed / Incidence not known
elevated hepatic enzymes / Delayed / Incidence not known
blurred vision / Early / Incidence not known
amblyopia / Delayed / Incidence not known
impotence (erectile dysfunction) / Delayed / Incidence not known
diabetes mellitus / Delayed / Incidence not known
hyperuricemia / Delayed / Incidence not known
hypophosphatemia / Delayed / Incidence not known
peripheral neuropathy / Delayed / Incidence not known
dysphagia / Delayed / Incidence not known
dysarthria / Delayed / Incidence not known

Mild

flushing / Rapid / 53.0-83.0
headache / Early / 9.0-9.0
pruritus / Rapid / 7.0-7.0
nausea / Early / 7.0-7.0
diarrhea / Early / 6.0-6.0
asthenia / Delayed / 5.0-5.0
rash (unspecified) / Early / 5.0-5.0
abdominal pain / Early / 4.0-4.0
myalgia / Early / 3.0-3.0
vomiting / Early / 3.0-3.0
dyspepsia / Early / 3.0-3.0
muscle cramps / Delayed / Incidence not known
drowsiness / Early / Incidence not known
fatigue / Early / Incidence not known
weakness / Early / Incidence not known
vesicular rash / Delayed / Incidence not known
dizziness / Early / Incidence not known
arthralgia / Delayed / Incidence not known
maculopapular rash / Early / Incidence not known
photosensitivity / Delayed / Incidence not known
alopecia / Delayed / Incidence not known
purpura / Delayed / Incidence not known
chills / Rapid / Incidence not known
urticaria / Rapid / Incidence not known
malaise / Early / Incidence not known
syncope / Early / Incidence not known
diaphoresis / Early / Incidence not known
fever / Early / Incidence not known
anorexia / Delayed / Incidence not known
flatulence / Early / Incidence not known
ocular irritation / Rapid / Incidence not known
insomnia / Early / Incidence not known
skin hyperpigmentation / Delayed / Incidence not known

Advicor

Rx

Oral antilipemic combination product; not first-line therapy; indicated for primary hypercholesterolemia and mixed dyslipidemia in patients receiving lovastatin or niacin and who require further TG-lowering and/or HDL-raising.

For the treatment of primary hypercholesterolemia (heterozygous familial and nonfamilial) and mixed dyslipidemia (Frederickson Types IIa and IIb hyperlipoproteinemia) in patients receiving lovastatin or niacin and who require further TG-lowering and/or HDL-raising.
NOTE: Equivalent doses of Advicor may be substituted for niacin-equivalent doses of Niaspan, but should not be substituted for other niacin preparations. Since extended-release and regular-release dosage forms of niacin are not bioequivalent, the manufacturer recommends that patients previously receiving niacin products (other than Niaspan) be titrated with Niaspan prior to switching to Advicor.
Oral dosage (Advicor extended-release tablets) Adults

Dosage should be administered once daily PO at bedtime with a low-fat snack. The combination product is not indicated for initial therapy. Initial titration of the separate components is required first. Measure serum lipid concentrations at intervals of 4 weeks or more; adjust lovastatin or niacin dosage as tolerated to attain the target NCEP lipid goals. Patients already receiving a stable dosage of Niaspan may be switched directly to a niacin-equivalent dosage of Advicor. Patients already receiving a stable dosage of lovastatin may receive concomitant dosage titration with Niaspan, and then switch to Advicor once a stable dosage of Niaspan has been reached. The usual recommended starting dosage for Niaspan is 500 mg PO once daily at bedtime. Niaspan is titrated gradually to achieve clinical goals; the dosage may be increased by increments of 500 mg or less every 4 weeks (max: 2,000 mg/day). Once Advicor therapy is initiated, the dose of Advicor may be titrated by 500 mg of niacin per day every 4 weeks if needed based on serum lipid determinations. The maximum dosage is 40 mg/day PO lovastatin and 2,000 mg/day PO niacin. If Advicor therapy is discontinued for an extended period (more than 7 days), therapy should restarted with the lowest dose of Advicor.

Adult patients taking danazol, diltiazem, or verapamil

Initially, 10 mg/day PO lovastatin component with the evening meal. Do not exceed 20 mg/day PO of lovastatin because of the risk of developing myopathy and/or rhabdomyolysis.

Adult patients taking amiodarone

Initially, 10 to 20 mg PO lovastatin component once daily with the evening meal. Because of the risk of developing myopathy and/or rhabdomyolysis, do not exceed 40 mg/day PO lovastatin.

Hepatic Impairment

Not recommended in patients with active hepatic disease or unexplained elevations in hepatic enzymes (see Contraindications).

Renal Impairment

Lovastatin; niacin should be used with caution in patients with renal disease. In patients with pre-existing renal impairment, dosage escalation of lovastatin; niacin requires caution.
CrCl >= 30 ml/min: No dosage adjustment needed.
CrCl < 30 ml/min: Doses of lovastatin > 20 mg/day should be carefully considered.
 
Intermittent hemodialysis
The dialyzability of niacin, lovastatin, or lovastatin metabolites is unknown. See dosage for renal impairment.

Acarbose: (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin (nicotinic acid) is added or deleted to the medication regimen. Dosage adjustments may be necessary.
Acetohexamide: (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin (nicotinic acid) is added or deleted to the medication regimen. Dosage adjustments may be necessary.
Albiglutide: (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. When used at daily doses of 750 to 2,000 mg, niacin significantly lowers LDL cholesterol and triglycerides while increasing HDL cholesterol. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients on antidiabetic therapy for blood glucose control if niacin (nicotinic acid) is added or deleted to the medication regimen and adjust dosages as clinically warranted
Alogliptin: (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin (nicotinic acid) is added or deleted to the medication regimen. Dosage adjustments may be necessary.
Alogliptin; Metformin: (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin (nicotinic acid) is added or deleted to the medication regimen. Dosage adjustments may be necessary. (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin (nicotinic acid) is added or deleted to the medication regimen. Dosage adjustments may be necessary.
Alogliptin; Pioglitazone: (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin (nicotinic acid) is added or deleted to the medication regimen. Dosage adjustments may be necessary.
Alpha-blockers: (Moderate) Cutaneous vasodilation induced by niacin may become problematic if high-dose niacin is used concomitantly with other antihypertensive agents. This effect is of particular concern in the setting of acute myocardial infarction, unstable angina, or other acute hemodynamic compromise.
Alpha-glucosidase Inhibitors: (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin (nicotinic acid) is added or deleted to the medication regimen. Dosage adjustments may be necessary.
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; Atorvastatin: (Moderate) The risk of myopathy increases when HMG-Co-A reductase inhibitors are administered concurrently with antilipemic doses of niacin (i.e., 1 g per day or more). Patients undergoing combined therapy should be carefully monitored for myopathy or rhabdomyolysis, particularly in the early months of treatment or during periods of upward dose titration of either drug. Chinese patients receiving concomitant lipid-altering doses of niacin-containing products should not receive the 80 mg dose of simvastatin due to increased risk of myopathy. When possible, avoid concurrent use of HMG-reductase inhibitors with drugs known to increase the risk of developing rhabdomyolysis or acute renal failure. The serious risk of myopathy or rhabdomyolysis should be weighed carefully versus the benefits of combined 'statin' and fibrate therapy; there is no assurance that periodic monitoring of CK will prevent the occurrence of severe myopathy and renal damage.
Amoxicillin; Clarithromycin; Lansoprazole: (Severe) 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.
Amoxicillin; Clarithromycin; Omeprazole: (Severe) 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.
Amprenavir: (Severe) 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.
Angiotensin II receptor antagonists: (Moderate) Cutaneous vasodilation induced by niacin may become problematic if high-dose niacin is used concomitantly with other antihypertensive agents. This effect is of particular concern in the setting of acute myocardial infarction, unstable angina, or other acute hemodynamic compromise.
Angiotensin-converting enzyme inhibitors: (Moderate) Cutaneous vasodilation induced by niacin may become problematic if high-dose niacin is used concomitantly with other antihypertensive agents. This effect is of particular concern in the setting of acute myocardial infarction, unstable angina, or other acute hemodynamic compromise.
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.
Aspirin, ASA; Pravastatin: (Moderate) The risk of myopathy increases when HMG-Co-A reductase inhibitors are administered concurrently with antilipemic doses of niacin (i.e., 1 g per day or more). Patients undergoing combined therapy should be carefully monitored for myopathy or rhabdomyolysis, particularly in the early months of treatment or during periods of upward dose titration of either drug. Chinese patients receiving concomitant lipid-altering doses of niacin-containing products should not receive the 80 mg dose of simvastatin due to increased risk of myopathy. When possible, avoid concurrent use of HMG-reductase inhibitors with drugs known to increase the risk of developing rhabdomyolysis or acute renal failure. The serious risk of myopathy or rhabdomyolysis should be weighed carefully versus the benefits of combined 'statin' and fibrate therapy; there is no assurance that periodic monitoring of CK will prevent the occurrence of severe myopathy and renal damage.
Atazanavir: (Severe) 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: (Severe) 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. (Severe) 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.
Atorvastatin: (Moderate) The risk of myopathy increases when HMG-Co-A reductase inhibitors are administered concurrently with antilipemic doses of niacin (i.e., 1 g per day or more). Patients undergoing combined therapy should be carefully monitored for myopathy or rhabdomyolysis, particularly in the early months of treatment or during periods of upward dose titration of either drug. Chinese patients receiving concomitant lipid-altering doses of niacin-containing products should not receive the 80 mg dose of simvastatin due to increased risk of myopathy. When possible, avoid concurrent use of HMG-reductase inhibitors with drugs known to increase the risk of developing rhabdomyolysis or acute renal failure. The serious risk of myopathy or rhabdomyolysis should be weighed carefully versus the benefits of combined 'statin' and fibrate therapy; there is no assurance that periodic monitoring of CK will prevent the occurrence of severe myopathy and renal damage.
Atorvastatin; Ezetimibe: (Moderate) The risk of myopathy increases when HMG-Co-A reductase inhibitors are administered concurrently with antilipemic doses of niacin (i.e., 1 g per day or more). Patients undergoing combined therapy should be carefully monitored for myopathy or rhabdomyolysis, particularly in the early months of treatment or during periods of upward dose titration of either drug. Chinese patients receiving concomitant lipid-altering doses of niacin-containing products should not receive the 80 mg dose of simvastatin due to increased risk of myopathy. When possible, avoid concurrent use of HMG-reductase inhibitors with drugs known to increase the risk of developing rhabdomyolysis or acute renal failure. The serious risk of myopathy or rhabdomyolysis should be weighed carefully versus the benefits of combined 'statin' and fibrate therapy; there is no assurance that periodic monitoring of CK will prevent the occurrence of severe myopathy and renal damage.
Azelaic Acid; Copper; Folic Acid; Nicotinamide; Pyridoxine; Zinc: (Moderate) HMG-CoA reductase inhibitors have been administered safely with niacin (nicotinic acid) in some patients; however the risk of potential myopathy should be considered. Rare cases of rhabdomyolysis have been reported in patients taking niacin (nicotinic acid) in lipid-altering doses (i.e., >=1 g/day) and HMG-CoA reductase inhibitors (Statins) concurrently. The serious risk of myopathy or rhabdomyolysis should be carefully weighed against the potential risks. Patients undergoing combined therapy should be carefully monitored for myopathy or rhabdomyolysis, particularly in the early months of treatment or during periods of upward dose titration of either drug. Chinese patients receiving concomitant lipid-altering doses of niacin-containing products should not receive the 80 mg dose of simvastatin due to increased risk of myopathy.
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.
Beta-blockers: (Moderate) Cutaneous vasodilation induced by niacin may become problematic if high-dose niacin is used concomitantly with other antihypertensive agents. This effect is of particular concern in the setting of acute myocardial infarction, unstable angina, or other acute hemodynamic compromise.
Bile acid sequestrants: (Moderate) In vitro studies have shown that bile acid sequestrants bind niacin. Roughly 98% of niacin was bound to colestipol, and 10 to 30% of niacin was bound to cholestyramine. These results suggest that at least 4 to 6 hours should elapse between the ingestion of bile-acid-binding resins and the administration of niacin.
Boceprevir: (Severe) Concurrent use of lovastatin and boceprevir is contraindicated. The risk of developing myopathy, rhabdomyolysis, and acute renal failure is substantially increased if lovastatin is administered concomitantly with boceprevir. Lovastatin is a substrate of CYP3A4 and boceprevir is a strong inhibitor of CYP3A4; therefore, coadministration may result in substantial increases in plasma concentrations of lovastatin.
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.
Brigatinib: (Moderate) Monitor for decreased efficacy of lovastatin if coadministration with brigatinib is necessary. Lovastatin is a CYP3A substrate and brigatinib induces CYP3A in vitro; plasma concentrations of lovastatin may decrease.
Calcium-channel blockers: (Moderate) Cutaneous vasodilation induced by niacin may become problematic if high-dose niacin is used concomitantly with other antihypertensive agents, especially calcium-channel blockers. This effect is of particular concern in the setting of acute myocardial infarction, unstable angina, or other acute hemodynamic compromise.
Canagliflozin: (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin (nicotinic acid) is added or deleted to the medication regimen. Dosage adjustments may be necessary.
Canagliflozin; Metformin: (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin (nicotinic acid) is added or deleted to the medication regimen. Dosage adjustments may be necessary. (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin (nicotinic acid) is added or deleted to the medication regimen. Dosage adjustments may be necessary.
Carbamazepine: (Moderate) Niacin may inhibit the CYP3A4 metabolism of carbamazepine, resulting in elevated carbamazepine plasma concentrations. Serum carbamazepine concentrations should be monitored if niacin is added during carbamazepine therapy. It may be necessary to reduce the dose of 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.
Central-acting adrenergic agents: (Moderate) Cutaneous vasodilation induced by niacin may become problematic if high-dose niacin is used concomitantly with other antihypertensive agents. This effect is of particular concern in the setting of acute myocardial infarction, unstable angina, or other acute hemodynamic compromise. Clonidine has been shown to inhibit niacin-induced flushing. The interaction is harmless unless niacin augments the hypotensive actions of clonidine.
Ceritinib: (Major) Avoid coadministration of ceritinib with lovastatin due to increased lovastatin exposure. If coadministration is unavoidable, monitor for lovastatin-related adverse reactions. Ceritinib is a CYP3A4 inhibitor and lovastatin is primarily metabolized by CYP3A4.
Cerivastatin: (Severe) The risk of myopathy increases when HMG-Co-A reductase inhibitors are administered concurrently with antilipemic doses of niacin.
Chlorpropamide: (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin (nicotinic acid) is added or deleted to the medication regimen. Dosage adjustments may be necessary.
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: (Major) Because HMG-CoA reductase inhibitors may theoretically blunt adrenal and/or gonadal steroid production by interfering with cholesterol synthesis, the manufacturer recommends caution with concomitant administion of drugs that may decrease the concentrations or activity of endogenous hormones, such as cimetidine. It has also been reported that cimetidine could potentially increase the serum concentrations of HMG-CoA reductase inhibitors via the inhibition of the hepatic isoenzymes. Cimetidine does not alter the pharmacokinetics of atorvastatin, cerivastatin, or pravastatin. Clinical evidence of pharmacokinetic interactions with lovastatin and simvastatin is not available.
Clarithromycin: (Severe) 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.
Clopidogrel: (Minor) Theoretically, clopidogrel may interact with lovastatin. CYP3A4 is involved in the hepatic biotransformation of clopidogrel to its active metabolite. Atorvastatin, a CYP3A4 substrate, has been reported to attenuate the antiplatelet activity of clopidogrel possibly by the competitive inhibition of CYP3A4 metabolism of clopidogrel to its active metabolite; however, conflicting data exists. The clinical significance of this theoretical interaction is not known. Lovastatin also is a CYP3A4 substrate and may theoretically be involved in the competitive inhibition of the CYP3A4 metabolism of clopidogrel. Patients should be monitored for a possible decrease in efficacy when clopidogrel is administered with lovastatin.
Cobicistat: (Severe) 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.
Cobicistat; Elvitegravir; Emtricitabine; Tenofovir Alafenamide: (Severe) 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.
Cobicistat; Elvitegravir; Emtricitabine; Tenofovir Disoproxil Fumarate: (Severe) 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.
Colchicine: (Moderate) Case reports exist describing the development of myotoxicity (i.e., muscle pain and weakness, rhabdomyolysis) with the concurrent administration of colchicine and HMG-CoA reductase inhibitors (Statins). Statins involved in the reported cases include simvastatin, atorvastatin, fluvastatin, lovastatin, and pravastatin. The pharmacokinetic and/or pharmacodynamic mechanism of this interaction is not clear; however, both colchicine and statins are associated with the development of myotoxicity and concurrent use may increase the risk of myotoxicity. Patients receiving these agents concurrently should be monitored for myotoxicity.
Conivaptan: (Major) Concomitant use of conivaptan, a potent CYP3A4 inhibitor and P-glycoprotein (P-gp) inhibitor, and lovastatin, a CYP3A4/P-gp substrate, should be avoided. Conivaptan 30 mg/day IV results in a 3-fold increase in the AUC of simvastatin, another CYP3A4 substrate. Theoretically, similar pharmacokinetic effects could be seen with lovastatin. In clinical trials of oral conivaptan, two cases of rhabdomyolysis occurred in patients who were also receiving HMG-CoA reductase inhibitors known to be metabolized by CYP3A4. According to the manufacturer, concomitant use of conivaptan with drugs that are primarily metabolized by CYP3A4, such as lovastatin, should be avoided. Subsequent treatment with CYP3A substrates, such as lovastatin, may be initiated no sooner than 1 week after completion of conivaptan therapy.
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 CYP3A4 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 74%.
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.
Dalfopristin; Quinupristin: (Moderate) Dalfopristin; quinupristin has been shown to inhibit CYP3A4 and may decrease the elimination of lovastatin, a CYP3A4 substrate.
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.
Dapagliflozin: (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin (nicotinic acid) is added or deleted to the medication regimen. Dosage adjustments may be necessary.
Dapagliflozin; Metformin: (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin (nicotinic acid) is added or deleted to the medication regimen. Dosage adjustments may be necessary. (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin (nicotinic acid) is added or deleted to the medication regimen. Dosage adjustments may be necessary.
Dapagliflozin; Saxagliptin: (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin (nicotinic acid) is added or deleted to the medication regimen. Dosage adjustments may be necessary.
Daptomycin: (Moderate) Daptomycin has been associated with elevated CPK in clinical trials. HMG-CoA reductase inhibitors are known to cause myopathy. Since data regarding co-administration of daptomycin with HMG-CoA reductase inhibitors are limited, temporary suspension of HMG-CoA reductase inhibitor therapy should be considered in patients receiving daptomycin.
Darunavir: (Severe) 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: (Severe) 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. (Severe) 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.
Dasabuvir; Ombitasvir; Paritaprevir; Ritonavir: (Severe) Concomitant use of dasabuvir; ombitasvir; paritaprevir; ritonavir or ombitasvir; paritaprevir; ritonavir with lovastatin is contraindicated due to the potential for severe adverse reactions, including myopathy and rhabdomyolysis. Coadministration may result in elevated lovastatin systemic concentrations. Lovastatin is a substrate of the hepatic isoenzyme CYP3A4; ritonavir is a potent inhibitor of this isoenzyme. In addition, lovastatin may inhibit P-glycoprotein (P-gp), a drug efflux transporter for which dasabuvir, ombitasvir, paritaprevir and ritonavir are substrates. (Severe) Concomitant use of dasabuvir; ombitasvir; paritaprevir; ritonavir with lovastatin is contraindicated due to the potential for severe adverse reactions, including myopathy and rhabdomyolysis. Coadministration may result in elevated lovastatin systemic concentrations. Lovastatin is a substrate of the hepatic isoenzyme CYP3A4; ritonavir is a potent inhibitor of this isoenzyme. In addition, lovastatin may inhibit P-glycoprotein (P-gp), a drug efflux transporter for which dasabuvir, ombitasvir, paritaprevir and ritonavir are substrates. (Severe) 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.
Dasatinib: (Moderate) Dasatinib is a time-dependent, weak inhibitor of CYP3A4. Therefore, caution is warranted when drugs that are metabolized by this enzyme like lovastatin are administered concurrently with dasatinib as increased adverse reactions may occur.
Delavirdine: (Severe) 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: (Moderate) Dronedarone is metabolized by CYP3A and is an inhibitor of CYP3A, CYP2D6, and P-gp. Lovastatin is a substrate for CYP3A4. Coadministration of dronedarone and simvastatin, a substrate for CYP2D6 and CYP3A4, resulted in an increase in simvastatin and simvastatin acid exposure by 4- and 2-fold, respectively. Monitor for signs and symptoms of myopathy in patients receiving dronedarone concurrently with lovastatin.
Dulaglutide: (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. When used at daily doses of 750 to 2,000 mg, niacin significantly lowers LDL cholesterol and triglycerides while increasing HDL cholesterol. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients on antidiabetic therapy for blood glucose control if niacin (nicotinic acid) is added or deleted to the medication regimen and adjust dosages as clinically warranted
Efavirenz: (Minor) Efavirenz has potential to induce CYP3A4 isoenzymes which may decrease the efficacy of lovastatin.
Efavirenz; Emtricitabine; Tenofovir: (Minor) Efavirenz has potential to induce CYP3A4 isoenzymes which may decrease the efficacy of lovastatin.
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.
Empagliflozin: (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin (nicotinic acid) is added or deleted to the medication regimen. Dosage adjustments may be necessary.
Empagliflozin; Linagliptin: (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin (nicotinic acid) is added or deleted to the medication regimen. Dosage adjustments may be necessary.
Empagliflozin; Metformin: (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin (nicotinic acid) is added or deleted to the medication regimen. Dosage adjustments may be necessary. (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin (nicotinic acid) is added or deleted to the medication regimen. Dosage adjustments may be necessary.
Eplerenone: (Moderate) Cutaneous vasodilation induced by niacin may become problematic if high-dose niacin is used concomitantly with other antihypertensive agents. This effect is of particular concern in the setting of acute myocardial infarction, unstable angina, or other acute hemodynamic compromise.
Epoprostenol: (Moderate) Cutaneous vasodilation induced by niacin may become problematic if high-dose niacin is used concomitantly with other antihypertensive agents, especially epoprostenol. This effect is of particular concern in the setting of acute myocardial infarction, unstable angina, or other acute hemodynamic compromise.
Erlotinib: (Moderate) Concomitant use of erlotinib and HMG-coA reductase inhibitors (statins) may increase the risk for statin-induced myopathy. Myopathy and rhabdomyolysis has been observed rarely with concurrent use of statins and erlotinib during post-market use. The mechanism for this interaction is not known. Use erlotinib and statins together with caution and monitor for signs or symptoms of statin-related adverse events including myopathy (e.g., muscle pain or weakness) and rhabdomyolysis (e.g., nausea/vomiting, dark colored urine).
Erythromycin: (Severe) 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.
Erythromycin; Sulfisoxazole: (Severe) 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.
Ethanol: (Moderate) Ethanol-containing beverages or hot beverages/foods can exacerbate cutaneous vasodilation caused by niacin and should be avoided around the time of niacin ingestion. In general, this interaction would not be harmful, but might decrease patient tolerance of niacin. Ethanol and niacin, particularly sustained-release niacin, are both potentially hepatotoxic. Although no data are available regarding enhanced hepatotoxicity, excessive ethanol use should be discouraged. (Moderate) Intake of ethanol should be avoided or minimized during lovastatin therapy to reduce the risk of hepatic injury. The manufacturer advises caution for use of lovastatin in patients who ingest substantial quantities of alcohol.
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.
Exenatide: (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. When used at daily doses of 750 to 2,000 mg, niacin significantly lowers LDL cholesterol and triglycerides while increasing HDL cholesterol. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients on antidiabetic therapy for blood glucose control if niacin (nicotinic acid) is added or deleted to the medication regimen and adjust dosages as clinically warranted
Ezetimibe; Simvastatin: (Moderate) The risk of myopathy increases when HMG-Co-A reductase inhibitors are administered concurrently with antilipemic doses of niacin (i.e., 1 g per day or more). Patients undergoing combined therapy should be carefully monitored for myopathy or rhabdomyolysis, particularly in the early months of treatment or during periods of upward dose titration of either drug. Chinese patients receiving concomitant lipid-altering doses of niacin-containing products should not receive the 80 mg dose of simvastatin due to increased risk of myopathy. When possible, avoid concurrent use of HMG-reductase inhibitors with drugs known to increase the risk of developing rhabdomyolysis or acute renal failure. The serious risk of myopathy or rhabdomyolysis should be weighed carefully versus the benefits of combined 'statin' and fibrate therapy; there is no assurance that periodic monitoring of CK will prevent the occurrence of severe myopathy and renal damage.
Fenofibrate: (Major) 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: (Major) 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: (Major) The risk of developing myopathy, rhabdomyolysis, and acute renal failure may be increased if lovastatin is administered concomitantly with fluconazole. Lovastatin is a sensative CYP3A4 substrate. Fluconazole also inhibits CYP3A4 isoenzymes, but to a lesser extent than ketoconazole and itraconazole.
Fluvastatin: (Moderate) The risk of myopathy increases when HMG-Co-A reductase inhibitors are administered concurrently with antilipemic doses of niacin (i.e., 1 g per day or more). Patients undergoing combined therapy should be carefully monitored for myopathy or rhabdomyolysis, particularly in the early months of treatment or during periods of upward dose titration of either drug. Chinese patients receiving concomitant lipid-altering doses of niacin-containing products should not receive the 80 mg dose of simvastatin due to increased risk of myopathy. When possible, avoid concurrent use of HMG-reductase inhibitors with drugs known to increase the risk of developing rhabdomyolysis or acute renal failure. The serious risk of myopathy or rhabdomyolysis should be weighed carefully versus the benefits of combined 'statin' and fibrate therapy; there is no assurance that periodic monitoring of CK will prevent the occurrence of severe myopathy and renal damage.
Food: (Moderate) Hot beverages and foods can exacerbate cutaneous vasodilation caused by niacin and should be avoided around the time of niacin ingestion. In general, this interaction would not be harmful, but might decrease patient tolerance of niacin.
Fosamprenavir: (Severe) 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) Fosphenytoin, a CYP3A4 inducer, may decrease the efficacy of lovastatin, a CYP3A4 substrate. One case study documented an increase in total serum cholesterol concentrations when phenytoin, the active metabolite of fosphenytoin, was administered concurrently with another HMG Co-A reductase inhibitor, atorvastatin. Total serum cholesterol concentrations then decreased when phenytoin was discontinued. Monitor for potential reduced cholesterol-lowering efficacy.
Gemfibrozil: (Major) Avoid the concurrent use of gemfibrozil and lovastatin. Gemfibrozil 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 gemfibrozil. Preliminary data suggests that the addition of gemfibrozil to lovastatin therapy does not result in greater reductions in LDL-C than that achieved with lovastatin alone.
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 transporters P-glycoprotein (P-gp) and OATP1B1; glecaprevir is an inhibitor of these transporters. In drug interaction studies, coadministration of lovastatin with glecaprevir; pibrentasvir resulted in 70% increase in the AUC of lovastatin. Additionally, glecaprevir is a P-gp substrate and lovastatin is a P-gp inhibitor; concentrations of glecaprevir may also be increased. (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 transporters P-glycoprotein (P-gp) and OATP1B1; pibrentasvir is an inhibitor of these transporters. In drug interaction studies, coadministration of lovastatin with glecaprevir; pibrentasvir resulted in 70% increase in the AUC of lovastatin. Additionally, pibrentasvir is a P-gp substrate and lovastatin is a P-gp inhibitor; concentrations of pibrentasvir may also be increased.
Glimepiride: (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin (nicotinic acid) is added or deleted to the medication regimen. Dosage adjustments may be necessary.
Glimepiride; Pioglitazone: (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin (nicotinic acid) is added or deleted to the medication regimen. Dosage adjustments may be necessary.
Glimepiride; Rosiglitazone: (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin (nicotinic acid) is added or deleted to the medication regimen. Dosage adjustments may be necessary.
Glipizide: (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin (nicotinic acid) is added or deleted to the medication regimen. Dosage adjustments may be necessary.
Glipizide; Metformin: (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin (nicotinic acid) is added or deleted to the medication regimen. Dosage adjustments may be necessary. (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin (nicotinic acid) is added or deleted to the medication regimen. Dosage adjustments may be necessary.
Glyburide: (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin (nicotinic acid) is added or deleted to the medication regimen. Dosage adjustments may be necessary.
Glyburide; Metformin: (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin (nicotinic acid) is added or deleted to the medication regimen. Dosage adjustments may be necessary. (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin (nicotinic acid) is added or deleted to the medication regimen. Dosage adjustments may be necessary.
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).
HMG-CoA reductase inhibitors: (Moderate) The risk of myopathy increases when HMG-Co-A reductase inhibitors are administered concurrently with antilipemic doses of niacin (i.e., 1 g per day or more). Patients undergoing combined therapy should be carefully monitored for myopathy or rhabdomyolysis, particularly in the early months of treatment or during periods of upward dose titration of either drug. Chinese patients receiving concomitant lipid-altering doses of niacin-containing products should not receive the 80 mg dose of simvastatin due to increased risk of myopathy. When possible, avoid concurrent use of HMG-reductase inhibitors with drugs known to increase the risk of developing rhabdomyolysis or acute renal failure. The serious risk of myopathy or rhabdomyolysis should be weighed carefully versus the benefits of combined 'statin' and fibrate therapy; there is no assurance that periodic monitoring of CK will prevent the occurrence of severe myopathy and renal damage.
Idelalisib: (Severe) 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.
Iloprost: (Moderate) Cutaneous vasodilation induced by niacin may become problematic if high-dose niacin is used concomitantly with other antihypertensive agents. This effect is of particular concern in the setting of acute myocardial infarction, unstable angina, or other acute hemodynamic compromise.
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.
Incretin Mimetics: (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. When used at daily doses of 750 to 2,000 mg, niacin significantly lowers LDL cholesterol and triglycerides while increasing HDL cholesterol. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients on antidiabetic therapy for blood glucose control if niacin (nicotinic acid) is added or deleted to the medication regimen and adjust dosages as clinically warranted
Indinavir: (Severe) 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.
Insulin Degludec; Liraglutide: (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. When used at daily doses of 750 to 2,000 mg, niacin significantly lowers LDL cholesterol and triglycerides while increasing HDL cholesterol. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients on antidiabetic therapy for blood glucose control if niacin (nicotinic acid) is added or deleted to the medication regimen and adjust dosages as clinically warranted
Insulin Glargine; Lixisenatide: (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. When used at daily doses of 750 to 2,000 mg, niacin significantly lowers LDL cholesterol and triglycerides while increasing HDL cholesterol. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients on antidiabetic therapy for blood glucose control if niacin (nicotinic acid) is added or deleted to the medication regimen and adjust dosages as clinically warranted
Insulins: (Moderate) Monitor patients receiving insulin closely for changes in diabetic control when niacin, niacinamide is instituted or discontinued. Dosage adjustments may be necessary. Niacin interferes with glucose metabolism and can result in hyperglycemia. When used at daily doses of 750 to 2000 mg, niacin significantly lowers LDL cholesterol and triglycerides while increasing HDL cholesterol. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy.
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: (Severe) 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) Use caution when administering ivacaftor and lovastatin concurrently. Ivacaftor is an inhibitor of CYP3A and P-glycoprotein (Pgp). Co-administration of ivacaftor with CYP3A and Pgp substrates, such as lovastatin, can increase lovastatin exposure leading to increased or prolonged therapeutic effects and adverse events.
Ixabepilone: (Minor) Ixabepilone is a weak inhibitor of P-glycoprotein (Pgp). Lovastatin is a Pgp substrate, and concomitant use of ixabepilone with a Pgp substrate may cause an increase in lovastatin concentrations. Use caution if ixabepilone is coadministered with a Pgp substrate.
Ketoconazole: (Severe) 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.
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.
Ledipasvir; Sofosbuvir: (Moderate) Caution and close monitoring of adverse reactions, such as myopathy and rhabdomyolysis, is advised with concomitant administration of lovastatin and ledipasvir; sofosbuvir. Both ledipasvir and lovastatin are substrates and inhibitors of the drug transporter P-glycoprotein (P-gp); sofosbuvir is a P-gp substrate. Taking these drugs together may increase plasma concentrations of all three drugs. According to the manufacturer, no dosage adjustments are required when ledipasvir; sofosbuvir is administered concurrently with P-gp inhibitors.
Letermovir: (Major) Close monitoring for lovastatin-related adverse events (i.e., myopathy, rhabd

omyolysis) 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.
Linagliptin: (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin (nicotinic acid) is added or deleted to the medication regimen. Dosage adjustments may be necessary.
Linagliptin; Metformin: (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin (nicotinic acid) is added or deleted to the medication regimen. Dosage adjustments may be necessary. (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin (nicotinic acid) is added or deleted to the medication regimen. Dosage adjustments may be necessary.
Liraglutide: (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. When used at daily doses of 750 to 2,000 mg, niacin significantly lowers LDL cholesterol and triglycerides while increasing HDL cholesterol. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients on antidiabetic therapy for blood glucose control if niacin (nicotinic acid) is added or deleted to the medication regimen and adjust dosages as clinically warranted
Lixisenatide: (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. When used at daily doses of 750 to 2,000 mg, niacin significantly lowers LDL cholesterol and triglycerides while increasing HDL cholesterol. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients on antidiabetic therapy for blood glucose control if niacin (nicotinic acid) is added or deleted to the medication regimen and adjust dosages as clinically warranted
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.
Loop diuretics: (Moderate) Cutaneous vasodilation induced by niacin may become problematic if high-dose niacin is used concomitantly with other antihypertensive agents. This effect is of particular concern in the setting of acute myocardial infarction, unstable angina, or other acute hemodynamic compromise.
Lopinavir; Ritonavir: (Severe) 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.
Lovastatin: (Moderate) The risk of myopathy increases when HMG-Co-A reductase inhibitors are administered concurrently with antilipemic doses of niacin (i.e., 1 g per day or more). Patients undergoing combined therapy should be carefully monitored for myopathy or rhabdomyolysis, particularly in the early months of treatment or during periods of upward dose titration of either drug. Chinese patients receiving concomitant lipid-altering doses of niacin-containing products should not receive the 80 mg dose of simvastatin due to increased risk of myopathy. When possible, avoid concurrent use of HMG-reductase inhibitors with drugs known to increase the risk of developing rhabdomyolysis or acute renal failure. The serious risk of myopathy or rhabdomyolysis should be weighed carefully versus the benefits of combined 'statin' and fibrate therapy; there is no assurance that periodic monitoring of CK will prevent the occurrence of severe myopathy and renal damage.
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) Use caution when administering ivacaftor and lovastatin concurrently. Ivacaftor is an inhibitor of CYP3A and P-glycoprotein (Pgp). Co-administration of ivacaftor with CYP3A and Pgp substrates, such as lovastatin, can increase lovastatin exposure leading to increased or prolonged therapeutic effects and adverse events.
Maraviroc: (Moderate) Use caution and closely monitor for increased adverse effects with the coadministration of maraviroc and lovastatin as increased maraviroc concentrations may occur. Maraviroc is a substrate of P-glycoprotein (P-gp); lovastatin is an inhibitor of P-gp. The effects of P-gp on the concentrations of maraviroc are unknown, although an increase in concentrations and thus, toxicity, are possible.
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.
Metformin: (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin (nicotinic acid) is added or deleted to the medication regimen. Dosage adjustments may be necessary.
Metformin; Pioglitazone: (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin (nicotinic acid) is added or deleted to the medication regimen. Dosage adjustments may be necessary.
Metformin; Repaglinide: (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin (nicotinic acid) is added or deleted to the medication regimen. Dosage adjustments may be necessary. (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin (nicotinic acid) is added or deleted to the medication regimen. Dosage adjustments may be necessary.
Metformin; Rosiglitazone: (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin (nicotinic acid) is added or deleted to the medication regimen. Dosage adjustments may be necessary.
Metformin; Saxagliptin: (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin (nicotinic acid) is added or deleted to the medication regimen. Dosage adjustments may be necessary. (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin (nicotinic acid) is added or deleted to the medication regimen. Dosage adjustments may be necessary.
Metformin; Sitagliptin: (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin (nicotinic acid) is added or deleted to the medication regimen. Dosage adjustments may be necessary. (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin (nicotinic acid) is added or deleted to the medication regimen. Dosage adjustments may be necessary.
Mifepristone, RU-486: (Severe) When used in the treatment of Cushing's syndrome, coadministration of mifepristone with lovastatin is contraindicated based on studies demonstrating significant drug exposure increases which may lead to an increased risk of myopathy and rhabdomyolysis. Mifepristone, RU-486 inhibits CYP3A4 in vitro. Coadministration of mifepristone may lead to an increase in serum levels drugs metabolized via CYP3A4, such as lovastatin. Due to the slow elimination of mifepristone from the body, such interactions may be observed for a prolonged period after mifepristone administration.
Miglitol: (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin (nicotinic acid) is added or deleted to the medication regimen. Dosage adjustments may be necessary.
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.
Nateglinide: (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin (nicotinic acid) is added or deleted to the medication regimen. Dosage adjustments may be necessary.
Nefazodone: (Severe) 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: (Severe) 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.
Nevirapine: (Minor) Nevirapine, 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
Niacin; Simvastatin: (Moderate) The risk of myopathy increases when HMG-Co-A reductase inhibitors are administered concurrently with antilipemic doses of niacin (i.e., 1 g per day or more). Patients undergoing combined therapy should be carefully monitored for myopathy or rhabdomyolysis, particularly in the early months of treatment or during periods of upward dose titration of either drug. Chinese patients receiving concomitant lipid-altering doses of niacin-containing products should not receive the 80 mg dose of simvastatin due to increased risk of myopathy. When possible, avoid concurrent use of HMG-reductase inhibitors with drugs known to increase the risk of developing rhabdomyolysis or acute renal failure. The serious risk of myopathy or rhabdomyolysis should be weighed carefully versus the benefits of combined 'statin' and fibrate therapy; there is no assurance that periodic monitoring of CK will prevent the occurrence of severe myopathy and renal damage.
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.
Ombitasvir; Paritaprevir; Ritonavir: (Severe) Concomitant use of dasabuvir; ombitasvir; paritaprevir; ritonavir or ombitasvir; paritaprevir; ritonavir with lovastatin is contraindicated due to the potential for severe adverse reactions, including myopathy and rhabdomyolysis. Coadministration may result in elevated lovastatin systemic concentrations. Lovastatin is a substrate of the hepatic isoenzyme CYP3A4; ritonavir is a potent inhibitor of this isoenzyme. In addition, lovastatin may inhibit P-glycoprotein (P-gp), a drug efflux transporter for which dasabuvir, ombitasvir, paritaprevir and ritonavir are substrates. (Severe) 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.
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.
Palbociclib: (Moderate) Monitor for an increase in lovastatin-related adverse reactions if coadministration with palbociclib is necessary. Palbociclib is a weak time-dependent inhibitor of CYP3A and lovastatin is a sensitive CYP3A4 substrate.
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.
Phenytoin: (Moderate) Phenytoin, a CYP3A4 inducer, may decrease the efficacy of lovastatin, a CYP3A4 substrate. One case study documented an increase in total serum cholesterol concentrations when phenytoin was administered concurrently with another HMG Co-A reductase inhibitor, atorvastatin. Total serum cholesterol concentrations then decreased when phenytoin was discontinued. Monitor for potential reduced cholesterol-lowering efficacy.
Posaconazole: (Severe) 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.
Potassium-sparing diuretics: (Moderate) Cutaneous vasodilation induced by niacin may become problematic if high-dose niacin is used concomitantly with other antihypertensive agents. This effect is of particular concern in the setting of acute myocardial infarction, unstable angina, or other acute hemodynamic compromise.
Pramlintide: (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin (nicotinic acid) is added or deleted to the medication regimen. Dosage adjustments may be necessary.
Pravastatin: (Moderate) The risk of myopathy increases when HMG-Co-A reductase inhibitors are administered concurrently with antilipemic doses of niacin (i.e., 1 g per day or more). Patients undergoing combined therapy should be carefully monitored for myopathy or rhabdomyolysis, particularly in the early months of treatment or during periods of upward dose titration of either drug. Chinese patients receiving concomitant lipid-altering doses of niacin-containing products should not receive the 80 mg dose of simvastatin due to increased risk of myopathy. When possible, avoid concurrent use of HMG-reductase inhibitors with drugs known to increase the risk of developing rhabdomyolysis or acute renal failure. The serious risk of myopathy or rhabdomyolysis should be weighed carefully versus the benefits of combined 'statin' and fibrate therapy; there is no assurance that periodic monitoring of CK will prevent the occurrence of severe myopathy and renal damage.
Protease inhibitors: (Severe) 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: (Major) The risk of myopathy and rhabdomyolysis may be increased in patients taking ranolazine and lovastatin concurrently; a lovastatin dosage adjustment may be considered. Ranolazine inhibits CYP3A isoenzymes and P-glycoprotein transport. Although not studied, ranolazine may theoretically increase plasma concentrations of CYP3A4 and/or P-glycoprotein substrates such as lovastatin. The plasma concentrations of simvastatin, a CYP3A4 substrate, and its active metabolite are each increased about 2-fold in healthy subjects receiving simvastatin (80 mg once daily) and ranolazine (1000 mg twice daily).The dose of simvastatin may have to be reduced when ranolazine is coadministered. Since lovastatin has a similar drug interaction profile relative to simvastatin, it is prudent to consider using lower doses of lovastatin during ranolazine therapy. Monitor serum lipid profile and for signs and symptoms of myopathy during coadministration.
Red Yeast Rice: (Severe) 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. (Major) Since compounds in red yeast rice are chemically similar to and possess actions similar to lovastatin, patients should avoid this dietary supplement if they currently take drugs known to increase the risk of myopathy when coadministered with HMG-CoA reductase inhibitors. Niacin (as nicotinic acid, vitamin B3 in antilipemic doses) directly increases the risk of myopathy.
Repaglinide: (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin (nicotinic acid) is added or deleted to the medication regimen. Dosage adjustments may be necessary.
Reserpine: (Moderate) Cutaneous vasodilation induced by niacin may become problematic if high-dose niacin is used concomitantly with other antihypertensive agents. This effect is of particular concern in the setting of acute myocardial infarction, unstable angina, or other acute hemodynamic compromise.
Ribociclib: (Moderate) Use caution if coadministration of ribociclib with lovastatin is necessary, as the systemic exposure of lovastatin may be increased resulting in increase in treatment-related adverse reactions. Ribociclib is a moderate CYP3A4 inhibitor and lovastatin is a CYP3A4 substrate.
Ribociclib; Letrozole: (Moderate) Use caution if coadministration of ribociclib with lovastatin is necessary, as the systemic exposure of lovastatin may be increased resulting in increase in treatment-related adverse reactions. Ribociclib is a moderate CYP3A4 inhibitor and lovastatin is a CYP3A4 substrate.
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.
Rifapentine: (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.
Ritonavir: (Severe) 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.
Rosuvastatin: (Moderate) The risk of myopathy increases when HMG-Co-A reductase inhibitors are administered concurrently with antilipemic doses of niacin (i.e., 1 g per day or more). Patients undergoing combined therapy should be carefully monitored for myopathy or rhabdomyolysis, particularly in the early months of treatment or during periods of upward dose titration of either drug. Chinese patients receiving concomitant lipid-altering doses of niacin-containing products should not receive the 80 mg dose of simvastatin due to increased risk of myopathy. When possible, avoid concurrent use of HMG-reductase inhibitors with drugs known to increase the risk of developing rhabdomyolysis or acute renal failure. The serious risk of myopathy or rhabdomyolysis should be weighed carefully versus the benefits of combined 'statin' and fibrate therapy; there is no assurance that periodic monitoring of CK will prevent the occurrence of severe myopathy and renal damage.
Saquinavir: (Severe) 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.
Sarilumab: (Moderate) In vitro, sarilumab has the potential to affect expression of multiple CYP enzymes, including CYP3A4. A 45% decrease in simvastatin exposure was noted 1 week after a single sarilumab dose; simvastatin is a CYP3A4 substrate. Utilize caution when using sarilumab with CYP3A4 substrate drugs where a decrease in effectiveness is undesirable such as lovastatin.
Saxagliptin: (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin (nicotinic acid) is added or deleted to the medication regimen. Dosage adjustments may be necessary.
Semaglutide: (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. When used at daily doses of 750 to 2,000 mg, niacin significantly lowers LDL cholesterol and triglycerides while increasing HDL cholesterol. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients on antidiabetic therapy for blood glucose control if niacin (nicotinic acid) is added or deleted to the medication regimen and adjust dosages as clinically warranted
Siltuximab: (Minor) Caution is warranted in patients with co-administered CYP3A4 substrates, such as lovastatin, in which a decreased effect would be undesirable. 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.
Simeprevir: (Moderate) Although coadministration of lovastatin with simeprevir has not been studied, use of these drugs together is expected to increase lovastatin exposure. If these drugs are given together, titrate the lovastatin dose carefully and use the lowest effective dose. Closely monitor for statin-associated adverse reactions, such as myopathy and rhabdomyolysis.
Simvastatin: (Moderate) The risk of myopathy increases when HMG-Co-A reductase inhibitors are administered concurrently with antilipemic doses of niacin (i.e., 1 g per day or more). Patients undergoing combined therapy should be carefully monitored for myopathy or rhabdomyolysis, particularly in the early months of treatment or during periods of upward dose titration of either drug. Chinese patients receiving concomitant lipid-altering doses of niacin-containing products should not receive the 80 mg dose of simvastatin due to increased risk of myopathy. When possible, avoid concurrent use of HMG-reductase inhibitors with drugs known to increase the risk of developing rhabdomyolysis or acute renal failure. The serious risk of myopathy or rhabdomyolysis should be weighed carefully versus the benefits of combined 'statin' and fibrate therapy; there is no assurance that periodic monitoring of CK will prevent the occurrence of severe myopathy and renal damage.
Simvastatin; Sitagliptin: (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin (nicotinic acid) is added or deleted to the medication regimen. Dosage adjustments may be necessary. (Moderate) The risk of myopathy increases when HMG-Co-A reductase inhibitors are administered concurrently with antilipemic doses of niacin (i.e., 1 g per day or more). Patients undergoing combined therapy should be carefully monitored for myopathy or rhabdomyolysis, particularly in the early months of treatment or during periods of upward dose titration of either drug. Chinese patients receiving concomitant lipid-altering doses of niacin-containing products should not receive the 80 mg dose of simvastatin due to increased risk of myopathy. When possible, avoid concurrent use of HMG-reductase inhibitors with drugs known to increase the risk of developing rhabdomyolysis or acute renal failure. The serious risk of myopathy or rhabdomyolysis should be weighed carefully versus the benefits of combined 'statin' and fibrate therapy; there is no assurance that periodic monitoring of CK will prevent the occurrence of severe myopathy and renal damage.
Sitagliptin: (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin (nicotinic acid) is added or deleted to the medication regimen. Dosage adjustments may be necessary.
Sofosbuvir; Velpatasvir: (Moderate) Use caution when administering velpatasvir with lovastatin. Taking these medications together may increase the plasma concentrations of both drugs, potentially resulting in adverse events. Both drugs are substrates and inhibitors of the drug transporter P-glycoprotein (P-gp).
Sofosbuvir; Velpatasvir; Voxilaprevir: (Moderate) Caution is advised when administering voxilaprevir with lovastatin. Taking these drugs together may increase lovastatin plasma concentrations; thereby increasing the risk for adverse events, such as myopathy or rhabdomyolysis. Initiate lovastatin at the lowest approved dose. If higher doses are needed, use the lowest necessary dose based on risk and benefit assessment. Lovastatin is a substrate of P-glycoprotein (P-gp). Voxilaprevir is an inhibitor of P-gp. (Moderate) Use caution when administering velpatasvir with lovastatin. Taking these medications together may increase the plasma concentrations of both drugs, potentially resulting in adverse events. Both drugs are substrates and inhibitors of the drug transporter P-glycoprotein (P-gp).
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.
Streptogramins: (Moderate) Dalfopristin; quinupristin has been shown to inhibit CYP3A4 and may decrease the elimination of lovastatin, a CYP3A4 substrate.
Sulfonylureas: (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin (nicotinic acid) is added or deleted to the medication regimen. Dosage adjustments may be necessary.
Tacrolimus: (Moderate) The risk of developing myopathy during therapy with HMG-CoA reductase inhibitors may be increased when used with tacrolimus.
Telaprevir: (Severe) The concurrent use of lovastatin and telaprevir is contraindicated due to the potential for serious/life-threatening reactions. Telaprevir is an inhibitor of CYP3A4, which is responsible lovastatin metabolism. Coadministration may result in large increases in lovastatin serum concentrations, which could cause adverse events such as myopathy and rhabdomyolysis.
Telbivudine: (Moderate) The risk of myopathy may be increased if an HMG-CoA reductase inhibitor is coadministered with telbivudine. Monitor patients for any signs or symptoms of unexplained muscle pain, tenderness, or weakness, particularly during periods of upward dosage titration. (Moderate) The risk of myopathy may be increased if niacin is coadministered with telbivudine. Physicians considering concomitant treatment should weigh carefully the potential benefits and risks; and should monitor patients for any signs or symptoms of unexplained muscle pain, tenderness, or weakness, particularly during periods of upward dosage titration.
Telithromycin: (Severe) Concurrent use of lovastatin and telithromycin 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 telithromycin. If no alternative to a short course of treatment with telithromycin 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.
Telotristat Ethyl: (Moderate) Use caution if coadministration of telotristat ethyl and lovastatin is necessary, as the systemic exposure of lovastatin may be decreased resulting in reduced efficacy; exposure to telotristat ethyl may also be increased. If these drugs are used together, monitor patients for suboptimal efficacy of lovastatin as well as an increase in adverse reactions related to telotristat ethyl. Consider increasing the dose of lovastatin if necessary. Lovastatin is a CYP3A4 substrate. The mean Cmax and AUC of another sensitive CYP3A4 substrate was decreased by 25% and 48%, respectively, when coadministered with telotristat ethyl; the mechanism of this interaction appears to be that telotristat ethyl increases the glucuronidation of the CYP3A4 substrate. Additionally, the active metabolite of telotristat ethyl, telotristat, is a substrate of P-glycoprotein (P-gp) and lovastatin is a P-gp inhibitor. Exposure to telotristat ethyl may increase.
Teriflunomide: (Moderate) Concurrent use of teriflunomide, an inhibitor of the hepatic uptake organic anion transporting polypeptide OATP1B1, with some HMG-CoA reductase inhibitors (Statins), including atorvastatin, lovastatin, pitavastatin, pravastatin, rosuvastatin, or simvastatin may increase the AUC of the statin. Administration of cyclosporine, another OATP1B1 inhibitor, increased the plasma AUC of pravastatin 9.9-fold. Additive hepatotoxicity may occur. Caution should also be exercised when using combination dosage forms, such as amlodipine; atorvastatin, ezetimibe; simvastatin, lovastatin; niacin, niacin; simvastatin, and simvastatin; sitagliptin. Monitor patients for signs of myopathy or hepatotoxicity.
Thiazide diuretics: (Moderate) Cutaneous vasodilation induced by niacin may become problematic if high-dose niacin is used concomitantly with other antihypertensive agents. This effect is of particular concern in the setting of acute myocardial infarction, unstable angina, or other acute hemodynamic compromise.
Thiazolidinediones: (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin (nicotinic acid) is added or deleted to the medication regimen. Dosage adjustments may be necessary.
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: (Severe) 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) In vitro, tocilizumab has the potential to affect expression of multiple CYP enzymes, including CYP3A4. A 57% decrease in simvastatin exposure was noted 1 week after a single tocilizumab dose; simvastatin is a CYP3A4 substrate. Utilize caution when using tocilizumab in combination with CYP3A4 substrate drugs where a decrease in effectiveness is undesirable such as lovastatin.
Tolazamide: (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin (nicotinic acid) is added or deleted to the medication regimen. Dosage adjustments may be necessary.
Tolbutamide: (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin (nicotinic acid) is added or deleted to the medication regimen. Dosage adjustments may be necessary.
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.
Treprostinil: (Moderate) Cutaneous vasodilation induced by niacin may become problematic if high-dose niacin is used concomitantly with other antihypertensive agents. This effect is of particular concern in the setting of acute myocardial infarction, unstable angina, or other acute hemodynamic compromise.
Vasodilators: (Moderate) Cutaneous vasodilation induced by niacin may become problematic if high-dose niacin is used concomitantly with other antihypertensive agents, especially peripheral vasodilators. This effect is of particular concern in the setting of acute myocardial infarction, unstable angina, or other acute hemodynamic compromise. The interaction is harmless unless niacin augments the hypotensive actions of clonidine.
Vemurafenib: (Moderate) Concomitant use of vemurafenib and lovastatin may result in altered concentrations of lovastatin and increased concentrations of vemurafenib. Vemurafenib is a substrate/inducer of CYP3A4 and a substrate/inhibitor of P-glycoprotein (PGP). Lovastatin is a substrate of CYP3A4 and a substrate/inhibitor of PGP. Use caution and monitor patients for toxicity and efficacy.
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.
Voriconazole: (Major) The risk of developing myopathy, rhabdomyolysis, and acute renal failure is substantially increased if lovastatin is administered concomitantly with CYP3A4 inhibitors (e.g., voriconazole). Although not studied clinically, voriconazole has been shown to inhibit lovastatin metabolism in vitro. Therefore, it is likely that coadministration of vorizonazole will result in increased plasma concentrations of lovastatin. According to the manufacturer, a dose reduction of lovastatin should be considered if the drugs are coadministered. Because pravastatin is not significantly metabolized, it is less likely to interact with the azole antifungals. A brief suspension of HMG-CoA reductase inhibitor therapy during such treatment can be considered as there are no known adverse consequences to brief interruptions of long-term cholesterol-lowering therapy; however, some manufacturers recommend dose adjustment of the statin. Administer voriconazole cautiously to patients receiving HMG-CoA reductase inhibitors.
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. (Moderate) Niacin (nicotinic acid) is occasionally associated with small but statistically significant increases (mean 4%) in prothrombin time. While rare, there is a possibility that an interaction would occur in some patients stabilized on warfarin. It appears prudent to monitor the INR periodically.
Zafirlukast: (Minor) Zafirlukast inhibits the CYP3A4 isoenzymes and should be used cautiously in patients stabilized on drugs metabolized by CYP3A4, such as lovastatin.
Zileuton: (Minor) Zileuton is metabolized by the cytochrome P450 isoenzyme 3A4 and could potentially compete with other CYP3A4 substrates including lovastatin.

Adults

40 mg/day PO lovastatin and 2000 mg/day PO niacin.

Elderly

40 mg/day PO lovastatin and 2000 mg/day PO niacin.

Adolescents

Safety and efficacy have not been established.

Children

Safety and efficacy have not been established.

Mechanism of Action: Advicor(TM) contains two antilipemic drugs, niacin extended-release and lovastatin. Lovastatin is an HMG-CoA reductase inhibitor, while niacin (nicotinic acid) is a B-complex vitamin.•Lovastatin: Lovastatin is produced by fermentation of Aspergillus terreus. 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.•Niacin: Niacin (nicotinic acid or 3-pyridinecarboxylic acid) is not directly converted into nicotinamide by the body; nicotinamide is only formed as a result of coenzyme metabolism. Nicotinic acid is incorporated into a coenzyme known as nicotinamide adenine dinucleotide (NAD) in erythrocytes and other tissues. A second coenzyme, nicotinamide adenine dinucleotide phosphate (NADP), is synthesized from NAD. These two coenzymes function in at least 200 different redox reactions in cellular metabolic pathways. Nicotinamide is released from NAD by hydrolysis in the liver and intestines and is transported to other tissues; these tissues use nicotinamide to produce more NAD as needed. Together with riboflavin and other micronutrients, the NAD and NADP coenzymes work to convert fats and proteins to glucose and assist in the oxidation of glucose.Nicotinic acid reduces total serum cholesterol, LDL, VLDL, and triglycerides, and increases HDL cholesterol. The mechanism of nicotinic acid's antilipemic effect is unknown but is unrelated to its biochemical role as a vitamin. One of nicotinic acid's primary actions is decreased hepatic synthesis of VLDL. Several mechanisms have been proposed, including inhibition of free fatty acid release from adipose tissue, increased lipoprotein lipase activity, decreased triglyceride synthesis, decreased VLDL-triglyceride transport, and an inhibition of lipolysis. This last mechanism may be due to niacin's inhibitory action on lipolytic hormones. Nicotinic acid possibly reduces LDL secondary to decreased VLDL production or enhanced hepatic clearance of LDL precursors. Nicotinic acid elevates total HDL by an unknown mechanism, but is associated with an increase in serum levels of Apo A-I and lipoprotein A-I, and a decrease in serum levels of Apo-B. Nicotinic acid is effective at elevating HDL even in patients whose only lipid abnormality is a low-HDL value. Niacin does not appear to affect the fecal excretion of fats, sterols, or bile acids. Clinical trial data suggest that women have a greater hypolipidemic response to niacin therapy than men at equivalent doses.Niacin, when used in antilipemic doses, acts on the peripheral circulation to produce dilation of cutaneous blood vessels and increase blood flow, mainly in the face, neck, and chest. This action produces the characteristic "niacin-flush". Niacin-induced vasodilation may be related to release of histamine and/or prostacyclin. Histamine secretion can increase gastric motility and acid secretion. Flushing may result in concurrent pruritus, headaches, or pain. The flushing effects of niacin appear to be related to the 3-carboxyl radical on its pyridine ring.

Lovastatin; niacin (Advicor) is administered orally.
Lovastatin: 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 of lovastatin (lovastatin acid), its 6'-hydroxy derivative, and two additional metabolites. The plasma half-life of mevinolinic acid is about 1.1—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. Approximately 10% of a dose is eliminated renally.
Niacin: Niacin is less than 20% bound to human serum proteins. Niacin is widely distributed throughout the body and it concentrates in the liver, spleen, and adipose tissue. Niacin undergoes rapid, extensive, and saturable first-pass metabolism via several pathways. Niacin is conjugated with glycine to form nicotinuric acid (NUA), which is then excreted in the urine. Some reversible metabolism from NUA back to niacin may occur in small amounts. The other pathway results in the formation of NAD. Roughly 12% of nicotinic acid is excreted unchanged in the urine with normal dosages. Greater proportions of niacin are renally excreted unchanged as dosages exceed 1000 mg/day and metabolic pathways become saturated.

Oral Route

In single-dose studies of Advicor, the rate and extent of niacin and lovastatin absorption were bioequivalent under fed conditions relative to Niaspan and Mevacor tablets, respectively.
Lovastatin: Lovastatin is incompletely absorbed from the GI tract and undergoes extensive first-pass extraction by the liver, its primary site of action. Less than 5% (with considerable inter-individual variation) of active drug reaches the systemic circulation. Peak concentrations of active and total HMG Co-A reductase inhibitors occur within 2—4 hours after immediate-release lovastatin administration. 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. Diurnal variation in cholesterol synthesis has been documented; single daily doses of lovastatin are most effective when given in the evening.
Niacin: Nicotinic acid is well-absorbed by the oral route. Following oral administration of extended-release Advicor, peak plasma concentrations are reached in 5 hours, and about 72% of the niacin dose is absorbed based on urinary excretion data. Administration with food maximizes bioavailability and minimizes GI intolerance. Peripheral vasodilation is seen within 20 minutes after administration of an immediate-release product and may last for up to 1 hour. The rate of onset of vasodilation is slower with sustained-release forms and may attenuate the severity of flushing.

Pregnancy

Lovastatin; niacin products are contraindicated during pregnancy; fetal harm is possible. Lovastatin has been shown to cause malformations of vertebrae and ribs in fetal rats when given in high doses. If the patient becomes pregnant while taking lovastatin; niacin, the drug should be discontinued immediately. Cholesterol and other products of the cholesterol biosynthesis pathway are essential components for fetal development, including synthesis of steroids and cell membranes. Lovastatin has been shown to cause malformations of vertebrae and ribs in fetal rats when given in high doses. 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; niacin should be discontinued immediately and the patient should be apprised of the potential hazard to the fetus. Lovastatin; niacin should only be administered to females of child-bearing potential 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; niacin who display clinical evidence of endocrine dysfunction should be evaluated appropriately.