Lovastatin is an oral antilipemic agent produced by fermentation of Aspergillus terreus. Lovastatin represents the first HMG-CoA reductase inhibitor to be introduced. Lovastatin was developed as a prodrug to concentrate active drug in the liver during first-pass circulation. Simvastatin is also a prodrug, but pravastatin and fluvastatin are not. Lovastatin (Mevacor) doses of 10-80 mg/day, given in 1-2 divided doses, result in mean LDL reductions ranging from 21-42%. Lovastatin (Mevacor) was approved by the FDA for the treatment of hypercholesterolemia in August 1987. Since that time, its indications have been expanded to include slowing the progression of coronary atherosclerosis, primary prevention (myocardial infarction prophylaxis), and stroke prophylaxis. In the AFCAPS/TexCAPS primary prevention study, lovastatin reduced the risk for the first acute major coronary event in adult men and women with average total and LDL cholesterol levels and below average HDL cholesterol levels. After an average of 5.2 years, lovastatin reduced the incidence of first acute major coronary event by 37%, fatal or nonfatal myocardial infarction by 40%, unstable angina by 32%, and coronary revascularization procedures by 33%, respectively. Additionally, a large retrospective study demonstrated that continuation of statin therapy provides an ongoing reduction in all-cause mortality in patients with and without known coronary heart disease (CHD), with the greatest risk reduction among patients with a baseline LDL-C >= 190 mg/dl and patients initiated on higher efficacy statins (i.e., simvastatin, pravastatin, or lovastatin 80 mg/day; atorvastatin >= 20 mg/day; rosuvastatin >= 10 mg/day). Among patients with a proportion of days covered (PDC) of >= 90%, determined by the number of statin prescriptions dispensed during the time between the first statin prescription and the end of follow up, there was a 45% and 51% lower mortality risk in the primary (patients without known CHD) and secondary (patients with known CHD) prevention groups, respectively, compared to patients with a PDC <= 10%. The mean length of follow up was 4 and 5 years in the primary and secondary prevention groups, respectively, with a maximum length of follow up of 9.5 years. Several generic equivalents for Mevacor were approved in December, 2001. Advicor (see separate monograph), a combination product for lovastatin and niacin, was approved by the FDA in December, 2001. The FDA approved an extended-release formulation of lovastatin, Altocor, on June 26, 2002. The proprietary name for Altocor lovastatin extended-release tablets was changed to Aloprev by the FDA on July 21, 2004. An FDA advisory committee voted 20 to 3 against marketing lovastatin 20 mg as an OTC product during January 2005. Although favorable results were reported by the manufacturer-sponsored CUSTOM study in regard to OTC lovastatin use , the FDA advisory committee raised concerns of inappropriate self-selection (self-diagnosis) by the study participants. In December 2007, an FDA advisory panel again voted 10 to 2 against the OTC marketing of lovastatin citing concern that patients would not be able to properly follow instructions to safely use lovastatin without a prescription.
General Administration Information
NOTE: Patients receiving lovastatin therapy should also be placed on a standard cholesterol-lowering diet, and this diet should be continued throughout therapy. Serum lipoprotein concentrations should be determined periodically and dosage adjusted according to individual response and established NCEP treatment guidelines.
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Oral Administration
-Avoid administration with grapefruit juice to avoid potential increases in drug serum concentrations. Evening dosing of lovastatin is preferable to optimize cholesterol-lowering effects.
Oral Solid Formulations:
-Immediate-release tablets: Administer with the evening meal to maximize oral bioavailability.
-Extended-release tablets: Administer Altoprev tablets in the evening at bedtime, preferably without food. Food decreases the absorption of Altoprev. Tablets should be swallowed whole; do not crush or chew.
Amyotrophic lateral sclerosis (ALS, Lou Gehrig's Disease) has been reported to the FDA in a higher than expected number of patients taking statins like lovastatin. ALS is a progressive motor neuron disorder with symptoms such as difficulty walking or standing, difficulty with fine motor skills, atrophy of tongue and hand muscles, dysphagia, dysarthria, and muscle paralysis. Due to the seriousness of ALS and the extensive use of statins, FDA further examined data from 41 long-term controlled clinical trials. The results of the review showed no increased incidence of ALS in patients treated with a statin compared with placebo. Specifically, 9 of approximately 64,000 patients treated with a statin (4.2 cases per 100,000 patient-years) and 10 of approximately 56,000 patients treated with placebo (5 case per 100,000 patient-years) were diagnosed with ALS. FDA is examining the feasibility of performing additional epidemiologic studies to further examine the incidence and clinical course of ALS in patients taking statins.
Thyroid function abnormalities and elevations in bilirubin have been reported with HMG-CoA reductase inhibitors although this effect is not necessarily associated with lovastatin use.
Toxicity to the skeletal muscle occurs infrequently but can be a serious adverse reaction to lovastatin therapy. Statin-induced myopathy is generally dose-related. In general, rhabdomyolysis is a rare (less than 1/100,000 prescriptions) complication of HMG-CoA reductase inhibitor ('statin') therapy. Myopathy, rhabdomyolysis, and acute renal failure (unspecified) (due to renal tubular obstruction, myoglobinuria) have been reported rarely with the use of lovastatin, but the risk is increased when lovastatin is used in combination with drugs known to interact with HMG-Co-A reductase inhibitors. Rhabdomyolysis may occur anytime during drug treatment and the risk may be increased by a number of confounding factors including age, concomitant drug therapy, renal dysfunction, and concomitant disease states. Many cases result in hospitalization and a need for dialysis for treatment. Vigilant clinical monitoring during prescribing can help limit serious adverse events. Patients should be monitored for symptoms of myopathy or rhabdomyolysis (unexplained myalgia, drowsiness/lethargy, fatigue, asthenia/weakness, fever, and/or myasthenia) and CPK serum concentrations. Elevations of creatinine phosphokinase (CPK) of at least twice the normal on 1 or more occasions occur in approximately 11% of patients. During clinical trials, myalgia has been reported in 1.8 to 3% of patients, muscle cramps have been reported in 0.6 to 1.1% of patients, and asthenia has been reported in 1.2 to 3% of patients. The risk of myopathy is dose-related. In the EXCEL study, one case of myopathy occurred among 4933 patients receiving 20 to 40 mg/day lovastatin; whereas 4 of 1649 patients experienced myopathy at the 80 mg/day dosage. The myopathy risk is greater if lovastatin is administered with gemfibrozil, lipid-lowering doses of nicotinic acid (1 g/day or greater), CYP3A4 inhibitors, or cyclosporine. Myopathy or myositis can reverse if therapy is discontinued. A study of lovastatin therapy in more than 3,300 women revealed that myopathy occurred too infrequently to accurately apply statistical analysis. Lovastatin should be discontinued immediately in any patient who develops myopathy or elevations in CPK.
Adverse GI effects occur with lovastatin use but are usually mild. They include nausea (1.9-2.5%), dyspepsia (1-1.6%), constipation (2-3.5%), diarrhea (2-3%), flatulence (3.7-4.5%), and abdominal pain (2-2.5%). Gastroesophageal reflux, xerostomia, and vomiting also have been reported in 0.5-1% of patients in clinical trials of immediate release lovastatin. Anorexia has been reported with HMG-CoA reductase inhibitors.
Immune-mediated necrotizing myopathy (IMNM), an autoimmune myopathy, has occurred rarely (1 to 3 of every 100,000 patients) with HMG-CoA reductase inhibitors, such as lovastatin. Recurrence of IMNM has been reported following administration of the same or a different statin. IMNM is characterized by myalgia with symmetrical and proximal muscle weakness and elevated serum creatine phosphokinase, which persist despite discontinuation of HMG-CoA reductase inhibitor treatment. Some cases have occurred months to years after starting HMG-CoA reductase therapy and the myopathy progressed following therapy discontinuation. Other characteristics include positive anti-HMG-CoA reductase antibody, muscle biopsy showing necrotizing myopathy, and improvement with immunosuppressive agents. Dysphagia and respiratory failure have also been reported in patients with IMNM. Reported serum creatine phosphokinase levels have ranged from 576 to 35,000 International Units/L. Patients who develop IMNM may require additional neuromuscular and serologic testing. If IMNM develops, HMG-CoA reductase inhibitor therapy should be discontinued and treatment with immunosuppressants, such as high dose corticosteroids, intravenous immune globulin (IVIG), or other immunosuppressive agents, may be needed.
Although rare, severe hepatotoxicity may occur during HMG-CoA reductase inhibitor therapy. Hepatitis, fatty changes of the liver, cholestasis with jaundice, pancreatitis, and rarely, cirrhosis, fulminant hepatic necrosis, hepatic failure, and hepatoma have been reported during therapy with HMG-CoA reductase inhibitors. Lovastatin therapy has been associated with elevated hepatic enzymes. Liver function tests (LFTs) should be performed prior to initiation of therapy with lovastatin and then repeated as clinically indicated. If serious liver injury with clinical symptoms and/or hyperbilirubinemia or jaundice occurs during treatment with lovastatin, promptly interrupt therapy. If an alternate etiology is not found, do not restart lovastatin. Persistent elevations of serum transaminases (to more than 3 times upper limit of normal) were reported in 1.9% of patients receiving lovastatin for >= 1 year during early clinical trials; enzyme elevations decrease to pretreatment concentrations after drug discontinuation. This increase in serum transaminases usually occurred 3-12 months after initiation of therapy and was not associated with jaundice or other symptoms of liver disease. In one study, the incidence of persistent increases in serum transaminases over 48 weeks was 0.1% for placebo, 0.1% for 20 mg/day, 0.9% for 40 mg/day, and 1.5% for 80 mg/day. In another study with a median of 5.1 years of follow-up, persistent increases in serum transaminases were seen in 0.7% of patients taking 20 mg/day and 0.4% of patients taking 40 mg/day of lovastatin.
Headache is the most common central nervous system effect associated with lovastatin use, occurring in 2.1-8% of patients taking immediate-release and extended-release formulations (placebo 2.7-6%). Dizziness has also been reported in 0.5-2% of lovastatin-treated patients (0.7-6% placebo). Insomnia and paresthesias also have been reported during lovastatin therapy (0.5-1%). Rare cases of cognitive impairment (e.g., memory loss, forgetfulness, amnesia, memory impairment, confusion) have been associated with the use of statins. A review of available data by the FDA did not find an association between the event and a specific statin, statin dose, concomitant medication, or age of the patient. In general, post-marketing reports described patients over the age of 50 years who experienced notable, but ill-defined memory loss or impairment that was reversible upon statin discontinuation. The cases did not appear to be associated with progressive or fixed dementia. The time to symptom onset (1 day to years) and resolution (median 3 weeks) is variable. Other neurological effects reported with HMG-CoA reductase inhibitors and not necessarily associated with lovastatin use include dysgeusia, impairment of extra-ocular movement, facial paresis, tremor, vertigo, peripheral nerve palsy, psychic disturbances, anxiety, and depression.
Arthralgia has been reported during therapy with lovastatin. During clinical trials of immediate-release lovastatin, arthralgia was reported in 0.5-1% of patients receiving lovastatin. In controlled trials of extended-release lovastatin (e.g., vs. placebo and vs. lovastatin immediate-release), arthralgia was reported in 6% of patients taking immediate-release lovastatin, 5% of patients receiving extended-release lovastatin and 6% of those taking placebo.
Allergic reactions can occur with lovastatin therapy. Rash (unspecified) occurs in 0.8-1.3% of patients receiving lovastatin therapy vs. 0.7% for placebo. A variety of general skin changes (i.e., nodules, discoloration, dryness of mucous membranes, changes to hair/nails) have been reported during HMG-CoA reductase inhibitor therapy. Alopecia and pruritus have been reported in 0.5-1% of patients receiving lovastatin. An apparent hypersensitivity syndrome has been reported rarely with HMG-CoA reductase inhibitors which has included one or more of the following features or anaphylactoid reactions: anaphylaxis, angioedema, lupus-like symptoms, polymyalgia rheumatica, dermatomyositis, vasculitis, purpura, thrombocytopenia, leukopenia, hemolytic anemia, positive ANA, ESR increase, eosinophilia, arthritis, arthralgia, urticaria, asthenia, photosensitivity, fever, chills, flushing, malaise, dyspnea, toxic epidermal necrolysis, erythema multiforme, and Stevens-Johnson syndrome.
Blurred vision has been reported in 0.9-1.2% of lovastatin-treated patients (vs. 0.8% placebo). Ocular irritation has been reported in 0.5-1% of patients in lovastatin clinical trials. Other ocular effects reported with HMG-CoA reductase inhibitors and not necessarily associated with lovastatin use include progression of cataracts (lens opacities), and ophthalmoplegia.
An association between HMG-CoA reductase inhibitors (statins), including lovastatin, and peripheral neuropathy has been reported in the literature (case series, case-control studies, cohort studies). In a nested case-control study of a Danish population, the odds ratio for idiopathic peripheral neuropathy in 166 patients that ever or were currently taking a statin, was 3.7 (95% CI 1.8-7.6); similar results have been found in other population based studies, although the number of patients studied was significantly smaller. Case reports and series indicate that the onset of neuropathy is typically > 1 year after drug initiation and is reversible with drug discontinuation. However, cases describing irreversible neuropathy are also reported. The adverse effect appears to be a class effect because in all cases, when a patient is either rechallenged or treated with a different statin, the symptoms of neuropathy return. While the data appear to support an association between HMG-CoA reductase inhibitors and peripheral neuropathy, the incidence is rare and estimated to be approximately 1 per 14,000 person-years. Furthermore, a causal relationship cannot be definitively established based on the observational nature of the available data. The benefits of statin therapy far outweigh any risk of peripheral neuropathy; however, until more information is available, health care providers should be aware of this adverse effect.
Increased hemoglobin A1c and fasting serum glucose (hyperglycemia) have been reported during therapy with HMG-CoA reductase inhibitors. A meta-analysis of 13 statin trials with 91,140 participants showed a 9% increase in the likelihood of the development of diabetes (OR 1.09; 95% CI 1.02-1.17). The incidence of diabetes was higher in high-risk patients (i.e., age 70-82 years with or at high risk of cardiovascular disease, myocardial infarction within the last 6 months, or heart failure) compared to patients with low diabetes risk (i.e., low BMI). Additionally, an analysis of the data from the Women's Health Initiative (WHI) trial found that statin use in postmenopausal women is associated with an increased risk of new-onset diabetes mellitus (multivariate-adjusted HR 1.48; 95% CI 1.38-1.59). No difference in the risk for diabetes between statins was detected in either analysis. Because the use of statins has been associated with significant benefit for cardiovascular risk reduction and all-cause mortality at comparable rates in diabetic and non-diabetic patients , no changes to clinical practice guidelines have been recommended in either population. However, the increased risk of diabetes should be considered when initiating lovastatin therapy in patients at low risk for cardiovascular events and in patient groups where the cardiovascular benefit of statin therapy has not been established.
During clinical studies, infection was reported in 11% of patients taking extended-release lovastatin and 16% of those taking immediate-release lovastatin (placebo = 9%). Sinusitis was reported in 4% and 6%, respectively (placebo = 3%), and urinary tract infection was reported in 2% and 3%, respectively (placebo = 6%). Influenza (reported as flu-syndrome) was reported in 5% of patients taking either formulation (placebo = 3%).
During clinical studies, pain was reported in 3% of patients taking extended-release lovastatin and 5% of those taking immediate-release lovastatin (placebo = 0%). Back pain was reported in 5% of patients taking either formulation (placebo = 3%). Leg pain and shoulder pain were reported in 0.5-1% of patients during clinical trials of immediate-release lovastatin. Accidental injury was reported in 6% of patients receiving extended-release lovastatin and in 4% of those taking immediate-release lovastatin (placebo = 9%).
During clinical trials of lovastatin, chest pain (unspecified) was reported in 0.5-1% of patients.
The following reproductive effects have been reported with HMG-CoA reductase inhibitors and are not necessarily associated with lovastatin use gynecomastia, libido decrease, impotence (erectile dysfunction).
HMG-CoA reductase inhibitors (statins), such as lovastatin, inhibit the synthesis of mevalonate and decrease Co-Enzyme Q-10 concentrations, which may lead to Co-Enzyme Q-10 deficiency. Supplementation with vitamin Co-Enzyme Q-10 may limit potential adverse reactions.
Exacerbation and induction of myasthenia gravis has been reported during treatment with statins, including lovastatin. In a review of adult patients enrolled at a neuromuscular disease clinic over a 4-year time period, 6 of 54 myasthenia gravis patients (11%) receiving statin therapy experienced worsening myasthenia gravis. In a disproportionality analysis of the World Health Organization's VigiBase pharmacovigilance database, 169 of 3,967 (4.2%) of adverse reactions with the term 'myasthenia gravis and related conditions' were related to statin therapy. The reporting odds ratio (ROR) of myasthenia gravis relative to all other adverse reactions was 2.66 [95% CI: 2.28, 3.1] for statin therapy. In addition, the ROR was greater than 1 and statistically significant for all individual statins except lovastatin. The onset of symptoms following initiation of statin therapy has ranged from 1 week to 4 months for exacerbation and 6 months to 6 years for induction of myasthenia gravis. Partial or complete recovery has been reported following discontinuation of statin therapy; however, some patients have required treatment with pyridostigmine or immunosuppressive agents. Though this appears to be a rare adverse reaction, clinicians should closely monitor patients with myasthenia gravis for disease exacerbation and encourage them to report any muscle-related symptoms.
Lovastatin is contraindicated in any patient with lovastatin hypersensitivity or hypersensitive to any component of the medication.
Lovastatin is contraindicated in patients with active hepatic disease (e.g., cholestasis, hepatic encephalopathy, hepatitis, jaundice) or unexplained persistent elevations in serum aminotransferase concentrations. Assess liver enzymes prior to initiation of lovastatin therapy and repeat as clinically indicated. After extensive data review, the FDA concluded that the risk of serious liver injury is very low and routine periodic monitoring of liver enzymes has not been effective in detection or prevention of serious hepatic injury. Patients should minimize alcohol intake while receiving lovastatin therapy, and lovastatin should be avoided in patients with alcoholism. Instruct patients to promptly report any symptoms of hepatic injury (e.g., fatigue, anorexia, right upper abdominal discomfort, dark urine or jaundice). If serious hepatic injury with clinical symptoms and/or hyperbilirubinemia or jaundice occurs during treatment with lovastatin, therapy should be interrupted. If an alternate etiology is not found, do not restart lovastatin. Prior to initiating lovastatin therapy, secondary causes for hypercholesterolemia, such as dysproteinemias, obstructive liver disease, and alcoholism, should be excluded.
All patients should be advised to report promptly any unexplained muscle pain, tenderness or weakness that may indicate myopathy, particularly if accompanied by malaise or fever. Myopathy sometimes takes the form of rhabdomyolysis with or without acute renal failure secondary to myoglobinuria, and rare fatalities have occurred. Discontinue lovastatin immediately if myopathy is diagnosed or suspected. In most cases, muscle symptoms, and creatine kinase (CK) increases resolve when treatment is promptly discontinued. The risk of myopathy and/or rhabdomyolysis is dose-related and may occur when initiating therapy or during dose increases. Predisposing risk factors for myopathy include advanced age, females, renal disease or renal insufficiency, hypotension, acute infection, endocrine disease such as hypothyroidism, electrolyte imbalance, uncontrolled seizure disorder, major surgery, and trauma. Lovastatin may need to be temporarily withheld in patients experiencing these conditions acutely. The risk of developing myopathy or rhabdomyolysis is increased when HMG-CoA reductase inhibitors are used in combination with certain other drugs. Several drugs are known to decrease lovastatin metabolism and increase the risk of myopathy and rhabdomyolysis; some drugs are contraindicated for use with lovastatin. Rhabdomyolysis has been associated with lovastatin therapy alone, when combined with immunosuppressive therapy including cyclosporine in transplant patients, and when combined in non-transplant patients with either gemfibrozil, lipid-lowering doses of nicotinic acid, or with the antifungal agent itraconazole. Because renal failure is possible if lovastatin-induced rhabdomyolysis occurs, lovastatin may be contraindicated in conditions that can cause decreased renal perfusion. Lovastatin should also be used with caution in patients with pre-existing renal impairment (renal disease, renal failure) and dosage adjustments are recommended in patients with creatinine clearance (CrCl) less than 30 mL/minute. In patients with severe renal impairment (CrCl 10 to 30 mL/minute), the plasma concentrations of total inhibitors after a single dose of lovastatin are approximately 2-fold higher than those in healthy volunteers. Lovastatin should be discontinued immediately in any patient who develops myopathy or elevations in CPK. The usual recommended starting dose of lovastatin extended-release should be limited to 20 mg/day PO in patients with complicated medical conditions including renal insufficiency; higher doses should be used only after careful consideration of the potential risks and benefits. Prior to initiating lovastatin therapy, secondary causes for hypercholesterolemia, such as nephrotic syndrome or hypothyroidism, should be excluded.
Prior to initiating therapy with lovastatin, secondary causes for hypercholesterolemia (e.g., uncontrolled diabetes mellitus) should be excluded. The usual starting dose of lovastatin extended-release should be limited to 20 mg/day PO in patients with complicated medical conditions (e.g., diabetes); higher doses should be used only after careful consideration of the potential risks and benefits. If lovastatin is initiated in a patient with diabetes mellitus, increased monitoring of blood glucose control may be warranted. Increased A1C, hyperglycemia, and worsening glycemic control have been reported during therapy with HMG-CoA reductase inhibitors. Because the use of statins has been associated with significant benefit for cardiovascular risk reduction and all-cause mortality at comparable rates in diabetic and non-diabetic patients , no changes to clinical practice guidelines have been recommended in either population. However, the increased risk of diabetes mellitus should be considered when initiating lovastatin therapy in patients at low risk for cardiovascular events and in patient groups where the cardiovascular benefit of statin therapy has not been established. Although an analysis of participants from the JUPITER trial found an increased incidence of developing diabetes in patients allocated to rosuvastatin compared to placebo (270 reports of diabetes vs. 216 in the placebo group; HR 1.25, 95% CI 1.05 to 1.49, p = 0.01), the cardiovascular and mortality benefits of statin therapy exceeded the diabetes hazard even in patients at high risk for developing diabetes (i.e., patients with one or more major diabetes risk factor: metabolic syndrome, impaired fasting glucose, BMI 30 kg/m2 or greater, or A1C over 6%). In patients at high risk for developing diabetes, treatment with rosuvastatin was associated with a 39% reduction in the primary endpoint (composite of non-fatal myocardial infarction, non-fatal stroke, unstable angina or revascularization, and cardiovascular death) (HR 0.61, 95% CI 0.47 to 0.79, p = 0.0001), nonsignificant reductions in venous thromboembolism (VTE) (HR 0.64, CI 0.39 to 1.06, p = 0.08) and total mortality (HR 83, CI 0.64 to 1.07, p = 0.15), and a 28% increase in diabetes (HR 1.28, CI 1.07 to 1.54, p = 0.01). In patients with no major diabetes risk factor, treatment with rosuvastatin was associated with a 52% reduction in the primary endpoint (HR 0.48, 95% CI 0.33 to 0.68, p = 0.0001), nonsignificant reductions in VTE (HR 0.47, CI 0.21 to 1.03, p = 0.05) and total mortality (HR 0.78, CI 0.59 to 1.03, p = 0.08), and no increase in diabetes (HR 0.99, CI 0.45 to 2.21, p = 0.99). For those at high risk for developing diabetes, 134 total cardiovascular events or deaths were avoided for every 54 new cases of diabetes diagnosed. In those without major risk factors, 86 total cardiovascular events or deaths were avoided with no excess new cases of diabetes diagnosed.
Immune-mediated necrotizing myopathy (IMNM), an autoimmune myopathy, has occurred rarely (1 to 3 of every 100,000 patients) with HMG-CoA reductase inhibitors, such as lovastatin. Recurrence of IMNM has been reported following administration of the same or a different statin. IMNM is characterized by myalgia with symmetrical and proximal muscle weakness and elevated serum creatine phosphokinase, which persist despite discontinuation of HMG-CoA reductase inhibitor treatment. Some cases have occurred months to years after starting HMG-CoA reductase therapy and the myopathy progressed following therapy discontinuation. Other characteristics include positive anti-HMG-CoA reductase antibody, muscle biopsy showing necrotizing myopathy, and improvement with immunosuppressive agents. Dysphagia and respiratory failure have also been reported in patients with IMNM. Reported serum creatine phosphokinase levels have ranged from 576 to 35,000 International Units/L. Patients who develop IMNM may require additional neuromuscular and serologic testing. If IMNM develops, HMG-CoA reductase inhibitor therapy should be discontinued and treatment with immunosuppressants, such as high dose corticosteroids, intravenous immune globulin (IVIG), or other immunosuppressive agents, may be needed.
Because advanced age (65 years or more) is a predisposing factor for myopathy, including rhabdomyolysis, lovastatin should be prescribed with caution in the geriatric patient. Geriatric patients receiving immediate-release lovastatin have been reported to have 45% higher mean plasma levels of HMG-CoA reductase inhibitory activity compared to younger adults. During clinical trials, no overall differences in safety or efficacy have been observed between older and younger patients receiving lovastatin. However, it is possible that some elderly patients may have an increased cholesterol-lowering response to lovastatin, consistent with other HMG-CoA reductase inhibitors. The manufacturer for extended-release lovastatin recommends initiating dosage at 20 mg/day for elderly patients; higher doses may be considered after carefully weighing the risks and benefits of therapy. The federal Omnibus Budget Reconciliation Act (OBRA) regulates medication use in residents of long-term care facilities (LTCFs). According to OBRA, HMG-CoA reductase inhibitors may impair liver function, and liver function monitoring should occur consistent with individual manufacturer recommendations (e.g., baseline, 12 weeks after initiation, after any dose increase, and periodically thereafter). HMG-CoA reductase inhibitors may cause myalgia, myopathy, and rhabdomyolysis that can precipitate kidney failure, particularly in combination with other cholesterol-lowering medications.
Lovastatin is contraindicated for use in pregnancy because of the potential effects of HMG-CoA reductase inhibitors on cholesterol pathways and the potential for fetal harm. Cholesterol and other products of the cholesterol biosynthesis pathway are essential components for fetal development, including synthesis of steroids and cell membranes. Treatment should be immediately discontinued as soon as pregnancy is recognized. Lovastatin has been shown to cause malformations of vertebrae and ribs in fetal rats when given at doses 50 times the maximum recommended human dose, based on body surface area. In a prospective review of about 100 pregnancies in women exposed to simvastatin or another structurally related HMG-CoA reductase inhibitor, the incidence of congenital anomalies, spontaneous abortions, and fetal deaths/stillbirths did not exceed what would be expected in the general population. However, atherosclerosis is a chronic process and the discontinuation of lipid-lowering drugs during pregnancy should have little impact on the outcome of long-term therapy of primary hypercholesterolemia. If the patient becomes pregnant while taking this drug, lovastatin should be discontinued immediately and the patient should be apprised of the potential hazard to the fetus. Lovastatin should only be administered to females of child-bearing potential, including adolescents at least 1 year post-menarche, when such patients are highly unlikely to conceive and have been informed of the potential hazards. Contraception requirements are advised; females should be counseled regarding appropriate methods of contraception while on therapy. The effects of statins on spermatogenesis and fertility have not been studied in adequate numbers of patients. The effects, if any, of lovastatin on the pituitary-gonadal axis in pre-menopausal females are unknown. Patients treated with lovastatin who display clinical evidence of endocrine dysfunction should be evaluated appropriately.
According to the manufacturer, lovastatin is contraindicated for use in breast-feeding women. Many HMG-CoA reductase inhibitors are known to be excreted into breast milk. Cholesterol and other products of the cholesterol biosynthesis pathway are essential components for infant growth and development, including synthesis of steroids and cell membranes. HMG-CoA reductase inhibitors to decrease the synthesis of cholesterol and possibly other products of the cholesterol biosynthesis pathway. The importance of continued lovastatin therapy to the mother should be considered in making the decision whether to discontinue breast-feeding or discontinue the medication. If pharmacotherapy is necessary in the nursing mother, a nonabsorbable resin such as cholestyramine, colesevelam, or colestipol should be considered. These agents do not enter the bloodstream and thusly will not be excreted during lactation. However, resins bind fat-soluble vitamins and prolonged use may result in deficiencies of these vitamins in the mother and her nursing infant. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.
Safety and efficacy of lovastatin have not been established in infants and children younger than 10 years of age. Because cholesterol plays a crucial role in growth and development, the clinical implications of using pharmacologic therapy to alter the normal production of cholesterol in young children is not clear. Because of these potential safety concerns and lack of safety data, most experts generally recommend delaying cholesterol-lowering medications until the child is at least 8 to 10 years old. In some cases of severe familial hypercholesterolemia, however, HMG-CoA reductase inhibitors have been used in younger children with careful monitoring of growth and development.
Exacerbation and induction of myasthenia gravis have been reported during treatment with statins, including lovastatin. The onset of symptoms following initiation of statin therapy has ranged from 1 week to 4 months for exacerbation and 6 months to 6 years for induction of myasthenia gravis. Partial or complete recovery has been reported following discontinuation of statin therapy; however, some patients have required treatment with pyridostigmine or immunosuppressive agents. Though this appears to be a rare adverse reaction, clinicians should closely monitor patients with myasthenia gravis for disease exacerbation and encourage them to report any muscle-related symptoms.
-Lovastatin 40 to 80 mg once daily is considered to be a moderate-intensity statin (expected to lower low-density lipoprotein cholesterol (LDL-C) by 30% to 49%), while lovastatin 20 mg once daily is considered low-intensity (expected to lower LDL-C by less than 30%).
-Choice of moderate- or low-intensity statin therapy is dependent on patient age, baseline LDL-C, ASCVD risk factors, and concomitant diseases. High-intensity therapy provides greatest LDL-C reductions and is associated with a significantly greater reduction in ASCVD events vs. moderate- or low-intensity therapy.
-Guidelines recommend assessment of liver function at baseline and if signs or symptoms of hepatic injury occur.
-Monitor lipid concentrations at 4 to 12 weeks after initiation or dose adjustment, and then every 3 to 12 months as necessary.
For general dosing information in persons requiring moderate-intensity statin therapy:
Oral dosage (immediate-release):
Adults: 40 or 80 mg PO once daily.
For general dosing information in persons requiring low-intensity statin therapy:
Oral dosage (immediate-release):
Adults: 20 mg PO once daily.
For the treatment of hypercholesterolemia, including hyperlipidemia, hyperlipoproteinemia, or hypertriglyceridemia, as an adjunct to dietary control:
Oral dosage (immediate-release tablets):
Adults: Initially, 10 to 20 mg PO once daily with the evening meal. Patients requiring LDL reductions of 20% or more to achieve their goal may begin with 20 mg PO once daily, while patients requiring lower reductions may begin with 10 mg PO once daily. The recommended dosing range is 10 to 80 mg/day PO in single or 2 divided doses. The maximum daily dose is 80 mg/day PO. At a dosage range of 10 to 80 mg/day, the mean LDL reduction range is 21% to 42%. Dividing the daily dosage into 2 doses is slightly more effective than once daily dosing. Dosage adjustments should be made at intervals of four weeks or more to attain desired cholesterol reduction. Geriatric patients may have greater LDL reductions at the usual dose compared to younger adults. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.
Adolescents and Children 10 years and older including girls who are at least 1 year post-menarche: Initially, 10 to 20 mg PO once daily with the evening meal. Patients requiring reductions in LDL cholesterol of 20% or more to achieve their goal can be started at 20 mg PO once daily, while patients requiring lower reductions may begin with 10 mg PO once daily. Maximum dosage is 40 mg/day PO. Dosage adjustments should be made at intervals of 4 weeks or more to attain desired cholesterol reduction. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. NOTE: Lovastatin may be used as an adjunct to diet in adolescents and children 10 years and older (including girls at least 1 year post-menarche) when either: 1) the LDL remains 190 mg/dL or higher or 2) the LDL remains higher than 160 mg/dL and there is an increased risk for cardiovascular disease (e.g., positive family history of premature cardiovascular disease or 2 or more other risk factors are present).
Oral dosage (lovastatin extended-release tablets; Altoprev):
Adults: Initially, 20 to 60 mg PO once daily (mean LDL reduction range: 30% to 41%), given in the evening at bedtime. Food reduces absorption of the extended-release tablets. For patients requiring smaller LDL reductions, lovastatin extended-release is not recommended; immediate-release lovastatin should be considered. Dosage adjustments should be made at intervals of 4 weeks or more to attain desired cholesterol reduction. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.
Geriatric or Patients with complicated medical conditions (e.g., renal insufficiency, diabetes): The manufacturer recommends 20 mg PO once daily, given in the evening at bedtime. Higher doses should be used only after careful consideration of the potential risks and benefits. For patients requiring smaller cholesterol reductions, the extended-release dosage form is not recommended; immediate-release lovastatin should be considered. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.
For slowing the progression of coronary atherosclerosis:
Oral dosage (immediate-release tablets):
Adults: Initially, 20 mg PO once daily with the evening meal. The recommended dosing range is 10 to 80 mg/day PO in single or two divided doses. The maximum daily dose is 80 mg/day PO. At the usual dosage range of 20 to 80 mg/day PO, the mean LDL reduction range is 27% to 42%. Dosage adjustments should be made at intervals of 4 weeks or more to attain desired cholesterol reduction. In patients with coronary artery disease, a study of lovastatin 80 mg/day significantly reduced coronary artery stenosis. Geriatric patients may have greater LDL reductions at the usual dose compared to younger adults. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.
Oral dosage (lovastatin extended-release tablets; Altoprev):
Adults: Initially, 20 to 60 mg PO once daily (mean LDL reduction range: 30% to 41%), given in the evening at bedtime. Food reduces absorption of the extended-release tablets. For patients requiring smaller LDL reductions, lovastatin extended-release tablets are not recommended; immediate-release lovastatin should be considered. Dosage adjustments should be made at intervals of four weeks or more to attain desired cholesterol reduction. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.
Geriatric or Patients with complicated medical conditions (e.g., renal insufficiency, diabetes): Initially, 20 mg PO once daily given in the evening at bedtime. Higher doses should be used only after careful consideration of the potential risks and benefits. For patients requiring smaller cholesterol reductions, the extended-release dosage form is not recommended; immediate-release lovastatin should be considered. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.
For myocardial infarction prophylaxis (primary prevention):
Oral dosage (immediate-release tablets):
Adults: Initially, 20 to 40 mg PO once daily with the evening meal. The recommended dosing range is 10 to 80 mg/day PO in single or two divided doses. The maximum daily dose is 80 mg/day PO. At the usual dosage range of 20 to 80 mg/day PO, the mean LDL reduction range is 27% to 42%. Dosage adjustments should be made at intervals of four weeks or more to attain desired cholesterol reduction. In the AFCAPS/TexCAPS primary prevention study, lovastatin reduced the risk for the first acute major coronary event in adult men and women with average total and LDL cholesterol levels and below average HDL cholesterol levels. After an average of 5.2 years, lovastatin reduced the incidence of first acute major coronary event by 37%, fatal or nonfatal myocardial infarction by 40%, unstable angina by 32%, and coronary revascularization procedures by 33%, respectively. Geriatric patients may have greater LDL reductions at usual doses compared to younger adults. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.
Oral dosage (lovastatin extended-release tablets; Altoprev):
Adults: Initially, 20 to 60 mg PO once daily (mean LDL reduction range: 30% to 41%), given in the evening at bedtime. Food reduces absorption of the extended-release tablets. For patients requiring smaller cholesterol reductions, the extended-release dosage form is not recommended; immediate-release lovastatin should be considered. Dosage adjustments should be made at intervals of 4 weeks or more to attain desired cholesterol reduction. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.
Geriatric or Patients with complicated medical conditions (e.g., renal insufficiency, diabetes): 20 mg PO once daily given in the evening at bedtime. Higher doses up to 60 mg/day should be used only after careful consideration of the potential risks and benefits. For patients requiring smaller cholesterol reductions, the extended-release dosage form is not recommended; immediate-release lovastatin should be considered. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.
For slowing the progression of atherosclerosis in patients with carotid artery disease (i.e., stroke prophylaxis*):
Oral dosage (immediate-release tablets):
Adults: Initially, 20 mg PO once daily with the evening meal. The recommended dosing range is 10 to 80 mg/day PO in single or 2 divided doses. The maximum daily dose is 80 mg/day PO. At the usual dosage range of 20 to 80 mg/day PO, the mean LDL reduction range is 27% to 42%. Dosage adjustments should be made at intervals of 4 weeks or more to attain desired cholesterol reduction. Lovastatin, in doses of 20 to 40 mg PO per day, was compared with low-dose warfarin in patients with early carotid disease. Lovastatin was shown to significantly reduce cardiovascular events which included coronary heart disease death, stroke, and non-fatal myocardial infarction. Although these cardiovascular events were analyzed collectively and therefore no direct conclusions can be drawn regarding stroke prophylaxis specifically, this study focused on patients with documented carotid disease and the resulting change in mean carotid artery intimal-medial thickness in the carotid artery. All patients were encouraged to take aspirin daily. Geriatric patients may have greater LDL reductions at usual doses compared to younger adults. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.
Oral dosage (lovastatin extended-release tablets; Altoprev):
Adults: Initially, 20 to 60 mg PO once daily (mean LDL reduction range: 30% to 41%), given in the evening at bedtime. Food reduces absorption of the extended-release tablets. For patients requiring smaller LDL reductions, lovastatin extended-release is not recommended; immediate-release lovastatin should be considered. Dosage adjustments should be made at intervals of 4 weeks or more to attain desired cholesterol reduction. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.
Geriatric or Patients with complicated medical conditions (e.g., renal insufficiency, diabetes): 20 mg PO once daily given in the evening at bedtime. Higher doses should be used only after careful consideration of the potential risks and benefits. For patients requiring smaller cholesterol reductions, the extended-release dosage form is not recommended; immediate-release lovastatin should be considered. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.
Maximum Dosage Limits:
-Adults
80 mg/day PO immediate-release tablets (e.g., Mevacor); 60 mg/day PO extended-release tablets (Altoprev). Max 20 mg/day PO immediate-release or extended-release lovastatin if taking fibrates, niacin, danazol, or cyclosporine; max 40 mg/day PO immediate-release lovastatin if taking amiodarone or verapamil; max 20 mg/day PO extended-release lovastatin if taking amiodarone or verapamil.
-Geriatric
80 mg/day PO immediate-release tablets (e.g., Mevacor); 60 mg/day PO extended-release tablets (Altoprev). Max 20 mg/day PO immediate-release or extended-release lovastatin if taking fibrates, niacin, danazol, or cyclosporine; max 40 mg/day PO immediate-release lovastatin if taking amiodarone or verapamil; max 20 mg/day PO extended-release lovastatin if taking amiodarone or verapamil.
-Adolescents
40 mg/day PO immediate-release tablets (e.g., Mevacor). Safety and efficacy have not been established for extended-release tablets (e.g., Altoprev).
-Children
10 years and older: 40 mg/day PO immediate-release tablets (e.g., Mevacor). Safety and efficacy have not been established for extended-release tablets (e.g., Altoprev).
Less than 10 years: Safety and efficacy have not been established.
Patients with Hepatic Impairment Dosing
Not recommended in patients with hepatic disease (see Contraindications).
Patients with Renal Impairment Dosing
CrCl >= 30 ml/min: No dosage adjustment needed.
CrCl < 30 ml/min: Using dosages > 20 mg/day should be carefully considered.
Intermittent hemodialysis
The dialyzability of lovastatin and its metabolites is unknown.
*non-FDA-approved indication
Abrocitinib: (Moderate) Monitor for an increase in lovastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with abrocitinib is necessary. Concomitant use may increase lovastatin exposure. Lovastatin is a P-gp substrate; abrocitinib is a P-gp inhibitor.
Adagrasib: (Contraindicated) Coadministration of lovastatin and adagrasib is contraindicated due to the risk of elevated plasma concentrations of lovastatin leading to myopathy and rhabdomyolysis. Lovastatin is a sensitive CYP3A and P-gp substrate and adagrasib is a strong CYP3A and P-gp inhibitor. Coadministration with another strong CYP3A inhibitor increased lovastatin exposure by 11 to 36-fold.
Amiodarone: (Major) In general, in patients taking amiodarone, the lovastatin adult dose should not exceed 40 mg/day PO. Lovastatin doses greater than 40 mg/day should only be used in patients taking amiodarone in whom the benefit is expected to outweigh the increased risk of myopathy. Amiodarone may inhibit lovastatin metabolism via hepatic CYP3A4 isoenzymes. Monitor for signs and symptoms of myopathy in patients receiving amiodarone concurrently with any dose of lovastatin.
Amlodipine: (Moderate) Carefully weigh the benefits of combined use of amlodipine and lovastatin against the potential risks. Lovastatin exposure may increase resulting in increased risk of myopathy/rhabdomyolysis. Although FDA-approved labeling for amlodipine or lovastatin do not suggest dose adjustments, guidelines recommend limiting the dose of lovastatin to 20 mg/day if combined with amlodipine. Lovastatin is a CYP3A4 substrate; amlodipine is a weak CYP3A4 inhibitor.
Amlodipine; Atorvastatin: (Moderate) Carefully weigh the benefits of combined use of amlodipine and lovastatin against the potential risks. Lovastatin exposure may increase resulting in increased risk of myopathy/rhabdomyolysis. Although FDA-approved labeling for amlodipine or lovastatin do not suggest dose adjustments, guidelines recommend limiting the dose of lovastatin to 20 mg/day if combined with amlodipine. Lovastatin is a CYP3A4 substrate; amlodipine is a weak CYP3A4 inhibitor.
Amlodipine; Benazepril: (Moderate) Carefully weigh the benefits of combined use of amlodipine and lovastatin against the potential risks. Lovastatin exposure may increase resulting in increased risk of myopathy/rhabdomyolysis. Although FDA-approved labeling for amlodipine or lovastatin do not suggest dose adjustments, guidelines recommend limiting the dose of lovastatin to 20 mg/day if combined with amlodipine. Lovastatin is a CYP3A4 substrate; amlodipine is a weak CYP3A4 inhibitor.
Amlodipine; Celecoxib: (Moderate) Carefully weigh the benefits of combined use of amlodipine and lovastatin against the potential risks. Lovastatin exposure may increase resulting in increased risk of myopathy/rhabdomyolysis. Although FDA-approved labeling for amlodipine or lovastatin do not suggest dose adjustments, guidelines recommend limiting the dose of lovastatin to 20 mg/day if combined with amlodipine. Lovastatin is a CYP3A4 substrate; amlodipine is a weak CYP3A4 inhibitor.
Amlodipine; Olmesartan: (Moderate) Carefully weigh the benefits of combined use of amlodipine and lovastatin against the potential risks. Lovastatin exposure may increase resulting in increased risk of myopathy/rhabdomyolysis. Although FDA-approved labeling for amlodipine or lovastatin do not suggest dose adjustments, guidelines recommend limiting the dose of lovastatin to 20 mg/day if combined with amlodipine. Lovastatin is a CYP3A4 substrate; amlodipine is a weak CYP3A4 inhibitor.
Amlodipine; Valsartan: (Moderate) Carefully weigh the benefits of combined use of amlodipine and lovastatin against the potential risks. Lovastatin exposure may increase resulting in increased risk of myopathy/rhabdomyolysis. Although FDA-approved labeling for amlodipine or lovastatin do not suggest dose adjustments, guidelines recommend limiting the dose of lovastatin to 20 mg/day if combined with amlodipine. Lovastatin is a CYP3A4 substrate; amlodipine is a weak CYP3A4 inhibitor.
Amlodipine; Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) Carefully weigh the benefits of combined use of amlodipine and lovastatin against the potential risks. Lovastatin exposure may increase resulting in increased risk of myopathy/rhabdomyolysis. Although FDA-approved labeling for amlodipine or lovastatin do not suggest dose adjustments, guidelines recommend limiting the dose of lovastatin to 20 mg/day if combined with amlodipine. Lovastatin is a CYP3A4 substrate; amlodipine is a weak CYP3A4 inhibitor.
Amoxicillin; Clarithromycin; Omeprazole: (Contraindicated) The concurrent use of lovastatin and clarithromycin is contraindicated due to the risk of myopathy and rhabdomyolysis. If no alternative to a short course of treatment with clarithromycin therapy is available, lovastatin use must be suspended during clarithromycin treatment. Lovastatin is metabolized by CYP3A4, and clarithromycin is a strong inhibitor of CYP3A4.
Aprepitant, Fosaprepitant: (Moderate) Use caution if lovastatin and aprepitant, fosaprepitant are used concurrently and monitor for an increase in lovastatin-related adverse effects, including myopathy and rhabdomyolysis, for several days after administration of a multi-day aprepitant regimen. Lovastatin is a CYP3A4 substrate. Aprepitant, when administered as a 3-day oral regimen (125 mg/80 mg/80 mg), is a moderate CYP3A4 inhibitor and inducer and may increase plasma concentrations of lovastatin. For example, a 5-day oral aprepitant regimen increased the AUC of another CYP3A4 substrate, midazolam (single dose), by 2.3-fold on day 1 and by 3.3-fold on day 5. After a 3-day oral aprepitant regimen, the AUC of midazolam (given on days 1, 4, 8, and 15) increased by 25% on day 4, and then decreased by 19% and 4% on days 8 and 15, respectively. As a single 125 mg or 40 mg oral dose, the inhibitory effect of aprepitant on CYP3A4 is weak, with the AUC of midazolam increased by 1.5-fold and 1.2-fold, respectively. After administration, fosaprepitant is rapidly converted to aprepitant and shares many of the same drug interactions. However, as a single 150 mg intravenous dose, fosaprepitant only weakly inhibits CYP3A4 for a duration of 2 days; there is no evidence of CYP3A4 induction. Fosaprepitant 150 mg IV as a single dose increased the AUC of midazolam (given on days 1 and 4) by approximately 1.8-fold on day 1; there was no effect on day 4. Less than a 2-fold increase in the midazolam AUC is not considered clinically important.
Atazanavir: (Contraindicated) Concurrent use of lovastatin and anti-retroviral protease inhibitors is contraindicated. The risk of developing myopathy, rhabdomyolysis, and acute renal failure is substantially increased if lovastatin is administered concomitantly with anti-retroviral protease inhibitors. Lovastatin is a substrate of CYP3A4 and anti-retroviral protease inhibitors are strong inhibitors of CYP3A4; therefore, coadministration may result in substantial increases in plasma concentrations of lovastatin.
Atazanavir; Cobicistat: (Contraindicated) Concomitant use of lovastatin with cobicistat is contraindicated due to the potential for myopathy, including rhabdomyolysis. Coadministration is expected to significantly increase lovastatin plasma concentrations. Lovastatin is a substrate for CYP3A4; cobicistat is a strong inhibitor of CYP3A. Coadministration with another strong CYP3A4 inhibitor increased lovastatin exposure by 11 to 36-fold. (Contraindicated) Concurrent use of lovastatin and anti-retroviral protease inhibitors is contraindicated. The risk of developing myopathy, rhabdomyolysis, and acute renal failure is substantially increased if lovastatin is administered concomitantly with anti-retroviral protease inhibitors. Lovastatin is a substrate of CYP3A4 and anti-retroviral protease inhibitors are strong inhibitors of CYP3A4; therefore, coadministration may result in substantial increases in plasma concentrations of lovastatin.
Barbiturates: (Moderate) Barbiturates are significant hepatic CYP3A4 inducers. Monitor for potential reduced cholesterol-lowering efficacy when barbiturates are co-administered with HMG-CoA reductase inhibitors metabolized by CYP3A4 including lovastatin.
Berotralstat: (Moderate) Monitor for an increase in lovastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with berotralstat is necessary. Coadministration may increase the exposure of lovastatin. Lovastatin is a sensitive substrate of CYP3A4 and berotralstat is a moderate CYP3A4 inhibitor.
Bortezomib: (Minor) Monitor patients for the development of peripheral neuropathy when receiving bortezomib in combination with other drugs that can cause peripheral neuropathy like HMG-CoA reductase inhibitors; the risk of peripheral neuropathy may be additive.
Bosentan: (Moderate) Co-administration of bosentan may decrease the plasma concentrations of lovastatin, a CYP3A4 substrate. The possibility of reduced anti-lipemic efficacy should be considered. Patients receiving CYP3A4 metabolized statins should have cholesterol levels monitored after adding bosentan therapy to evaluate the need for anti-lipemic dosage adjustment.
Cannabidiol: (Moderate) Monitor for an increase in lovastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with cannabidiol is necessary. Concomitant use may increase lovastatin exposure. Lovastatin is a P-gp substrate; cannabidiol is a P-gp inhibitor.
Capmatinib: (Moderate) Monitor for an increase in lovastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with capmatinib is necessary. Concomitant use may increase lovastatin exposure. Lovastatin is a substrate of P-gp; capmatinib is an inhibitor of P-gp.
Carbamazepine: (Minor) Carbamazepine, which is a CYP3A4 inducer, may decrease the efficacy of HMG-Co-A reductase inhibitors which are CYP3A4 substrates, such as lovastatin. Monitor for potential reduced cholesterol-lowering efficacy when these drugs are co-administered with HMG-CoA reductase inhibitors which are metabolized by CYP3A4.
Ceritinib: (Contraindicated) Coadministration of lovastatin and ceritinib is contraindicated due to the risk of elevated plasma concentrations of lovastatin leading to myopathy and rhabdomyolysis. Lovastatin is a sensitive CYP3A4 substrate and ceritinib is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased lovastatin exposure by 11 to 36-fold.
Cilostazol: (Moderate) Cilostazol may interact with lovastatin, but it is not clear if the interaction could be clinically significant. In healthy volunteers, peak plasma concentrations of lovastatin did not change with co-administration of cilostazol. However, peak plasma concentrations and the AUC of lovastatin's active metabolite did increase. Also, the peak plasma concentrations and AUC of cilostazol were decreased by roughly 15% when lovastatin was co-administered.
Cimetidine: (Moderate) Use HMG-CoA reductase inhibitors with caution with concomitant drugs that may decrease the levels or activity of endogenous steroids, such as cimetidine. Evaluate patients with signs and symptoms of endocrine dysfunction appropriately. HMG-CoA reductase inhibitors interfere with cholesterol synthesis and theoretically might blunt adrenal and/or gonadal steroid production.
Clarithromycin: (Contraindicated) The concurrent use of lovastatin and clarithromycin is contraindicated due to the risk of myopathy and rhabdomyolysis. If no alternative to a short course of treatment with clarithromycin therapy is available, lovastatin use must be suspended during clarithromycin treatment. Lovastatin is metabolized by CYP3A4, and clarithromycin is a strong inhibitor of CYP3A4.
Cobicistat: (Contraindicated) Concomitant use of lovastatin with cobicistat is contraindicated due to the potential for myopathy, including rhabdomyolysis. Coadministration is expected to significantly increase lovastatin plasma concentrations. Lovastatin is a substrate for CYP3A4; cobicistat is a strong inhibitor of CYP3A. Coadministration with another strong CYP3A4 inhibitor increased lovastatin exposure by 11 to 36-fold.
Colchicine: (Major) Use caution and the lowest HMG-CoA reductase inhibitor dose necessary if coadministration with colchicine is necessary due to an increased risk of myopathy and rhabdomyolysis. Carefully weigh the potential benefits and risk of combined therapy. Closely monitor patients for signs and symptoms of muscle pain, tenderness, or weakness especially during the initial months of therapy and during upward titration of either drug. There is no assurance that period monitoring of creatinine phosphokinase (CPK) will prevent the occurrence of myopathy. Case reports exist describing the development of myotoxicity with the concurrent administration of colchicine and HMG-CoA reductase inhibitors (e.g., simvastatin, atorvastatin, fluvastatin, lovastatin, pravastatin).
Conivaptan: (Moderate) Monitor for an increase in lovastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with conivaptan is necessary. Coadministration may increase the exposure of lovastatin. Lovastatin is a CYP3A and P-gp substrate and conivaptan is a moderate CYP3A and P-gp inhibitor.
Crizotinib: (Moderate) Monitor for an increase in lovastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with crizotinib is necessary. Lovastatin is a sensitive substrate of CYP3A4 and crizotinib is a moderate CYP3A inhibitor.
Cyclosporine: (Major) Avoid the concurrent use of cyclosporine and lovastatin. Cyclosporine may increase the risk of myopathy, rhabdomyolysis and acute renal failure in patients taking lovastatin. In uncontrolled clinical studies of lovastatin, myopathy was reported more frequently in patients receiving concomitant therapy with cyclosporine. Cyclosporine may reduce the clearance of the HMG-CoA reductase inhibitors (statins), Cyclosporine has been shown to increase the AUC of HMG-CoA reductase inhibitors, presumably due to CYP3A4 inhibition.
Dabigatran: (Moderate) Consider a statin other than lovastatin or simvastatin if HMG-CoA reductase inhibition is necessary for a patient receiving dabigatran. Increased serum concentrations of dabigatran are possible when coadministered with lovastatin. If use together is medically necessary, patients should be monitored for increased adverse effects of dabigatran and an increased risk for bleeding. A mechanism for this interaction may be the inhibition of P-gp by lovastatin; dabigatran is a P-gp substrate. In one clinical trial, patients receiving dabigatran with lovastatin or simvastatin experienced a higher risk of major hemorrhage relative to the use of other statins that are not P-gp inhibitors. P-gp inhibition and renal impairment are the major independent factors that result in increased exposure to dabigatran.
Dabrafenib: (Major) The concomitant use of dabrafenib and lovastatin may lead to decreased lovastatin concentrations and loss of efficacy. Use of an alternative agent is recommended. If concomitant use of these agents together is unavoidable, monitor patients for loss of lovastatin efficacy. Dabrafenib is a moderate CYP3A4 inducer and lovastatin is a sensitive CYP3A4 substrate. Concomitant use of dabrafenib with a single dose of another sensitive CYP3A4 substrate decreased the AUC value of the sensitive CYP3A4 substrate by 65%.
Daclatasvir: (Moderate) Caution and close monitoring is advised if daclatasvir is administered with HMG-CoA reductase inhibitors (Statins). Use of these drugs together may result in elevated Statin serum concentrations, potentially resulting in adverse effects such as myopathy and rhabdomyolysis.
Danazol: (Major) The risk of myopathy and rhabdomyolysis is increased if danazol is used with lovastatin. In adult patients taking danazol, the initial lovastatin dose should not exceed 10 mg/day PO, and the total lovastatin dose should not exceed 20 mg/day PO. A single case report has documented the onset of myositis which progressed to rhabdomyolysis with myoglobinuria after danazol was added to a regimen containing lovastatin. Although other drugs were in use concurrently, a drug interaction between danazol and lovastatin is suspected since danazol (CYP3A4 inhibitor) is known to inhibit lovastatin metabolism. If concurrent use of lovastatin and danazol is desired, carefully weigh the benefit of lovastatin against the risk of myopathy and rhabdomyolysis.
Daptomycin: (Major) Temporarily suspend HMG-CoA reductase inhibitors in patients taking daptomycin as cases of rhabdomyolysis have been reported with concomitant use. Both agents can cause myopathy and rhabdomyolysis when given alone and the risk may be increased when given together.
Darunavir: (Contraindicated) Concurrent use of lovastatin and anti-retroviral protease inhibitors is contraindicated. The risk of developing myopathy, rhabdomyolysis, and acute renal failure is substantially increased if lovastatin is administered concomitantly with anti-retroviral protease inhibitors. Lovastatin is a substrate of CYP3A4 and anti-retroviral protease inhibitors are strong inhibitors of CYP3A4; therefore, coadministration may result in substantial increases in plasma concentrations of lovastatin.
Darunavir; Cobicistat: (Contraindicated) Concomitant use of lovastatin with cobicistat is contraindicated due to the potential for myopathy, including rhabdomyolysis. Coadministration is expected to significantly increase lovastatin plasma concentrations. Lovastatin is a substrate for CYP3A4; cobicistat is a strong inhibitor of CYP3A. Coadministration with another strong CYP3A4 inhibitor increased lovastatin exposure by 11 to 36-fold. (Contraindicated) Concurrent use of lovastatin and anti-retroviral protease inhibitors is contraindicated. The risk of developing myopathy, rhabdomyolysis, and acute renal failure is substantially increased if lovastatin is administered concomitantly with anti-retroviral protease inhibitors. Lovastatin is a substrate of CYP3A4 and anti-retroviral protease inhibitors are strong inhibitors of CYP3A4; therefore, coadministration may result in substantial increases in plasma concentrations of lovastatin.
Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Contraindicated) Concomitant use of lovastatin with cobicistat is contraindicated due to the potential for myopathy, including rhabdomyolysis. Coadministration is expected to significantly increase lovastatin plasma concentrations. Lovastatin is a substrate for CYP3A4; cobicistat is a strong inhibitor of CYP3A. Coadministration with another strong CYP3A4 inhibitor increased lovastatin exposure by 11 to 36-fold. (Contraindicated) Concurrent use of lovastatin and anti-retroviral protease inhibitors is contraindicated. The risk of developing myopathy, rhabdomyolysis, and acute renal failure is substantially increased if lovastatin is administered concomitantly with anti-retroviral protease inhibitors. Lovastatin is a substrate of CYP3A4 and anti-retroviral protease inhibitors are strong inhibitors of CYP3A4; therefore, coadministration may result in substantial increases in plasma concentrations of lovastatin.
Delavirdine: (Contraindicated) The risk of myopathy, including rhabdomyolysis, may be increased when delavirdine is given in combination with HMG-CoA reductase inhibitors. Concomitant use of delavirdine and the CYP3A4 substrate lovastatin is not recommended. If treatment with an HMG-CoA reductase inhibitor is necessary, pravastatin should also be considered, since it is not significantly metabolized by CYP3A4 or CYP2C9 isoenzymes.
Diltiazem: (Major) Coadministration of diltiazem and lovastatin increases the risk for myopathy/rhabdomyolysis particularly with higher doses of lovastatin. In adult patients taking diltiazem, the initial lovastatin dose should not exceed 10 mg/day PO, and the total lovastatin dose should not exceed 20 mg/day PO. The benefits of the use of lovastatin in patients taking diltiazem should be carefully weighed against the risks of this combination.
Dronedarone: (Major) Although FDA-approved labeling for lovastatin recommends limiting the dose of lovastatin to 20 mg/day if combined with dronedarone, guidelines recommend limiting the lovastatin dose to 10 mg/day during concurrent use. Lovastatin exposure may increase resulting in increased risk of myopathy/rhabdomyolysis. Lovastatin is a CYP3A4 substrate; dronedarone is a moderate CYP3A4 inhibitor.
Duvelisib: (Moderate) Monitor for an increase in lovastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with duvelisib is necessary. Coadministration may increase the exposure of lovastatin. Lovastatin is a sensitive substrate of CYP3A4 and duvelisib is a moderate CYP3A4 inhibitor.
Efavirenz: (Minor) Efavirenz has potential to induce CYP3A4 isoenzymes which may decrease the efficacy of lovastatin.
Efavirenz; Emtricitabine; Tenofovir Disoproxil Fumarate: (Minor) Efavirenz has potential to induce CYP3A4 isoenzymes which may decrease the efficacy of lovastatin.
Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Minor) Efavirenz has potential to induce CYP3A4 isoenzymes which may decrease the efficacy of lovastatin.
Elacestrant: (Moderate) Monitor for an increase in lovastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with elacestrant is necessary. Concomitant use may increase lovastatin exposure. Lovastatin is a P-gp substrate; elacestrant is a P-gp inhibitor.
Elbasvir; Grazoprevir: (Moderate) The manufacturer of elbasvir; grazoprevir recommends caution during concurrent administration with lovastatin. Although this interaction has not been studied, use of these drugs together may result in elevated lovastatin plasma concentrations. Use the lowest effective lovastatin dose and monitor patients for statin-related adverse events (such as myopathy). Lovastatin is a substrate for the hepatic enzymes CYP3A; grazoprevir is a weak CYP3A inhibitor.
Elexacaftor; tezacaftor; ivacaftor: (Moderate) Monitor for lovastatin-related adverse reactions (i.e., myopathy/rhabdomyolysis) during coadministration of elexacaftor; tezacaftor; ivacaftor as concurrent use may increase exposure of lovastatin. Lovastatin is a substrate for the transporter OATP1B1; elexacaftor; tezacaftor; ivacaftor may inhibit uptake of OATP1B1. (Moderate) Monitoring for lovastatin-related adverse events (i.e., myopathy, rhabdomyolysis) is recommended if administered concurrently with ivacaftor. Coadministration can increase lovastatin exposure leading to increased or prolonged therapeutic effects and adverse events. Lovastatin is a CYP3A4 substrate; ivacaftor is a weak CYP3A4 inhibitor.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Contraindicated) Concomitant use of lovastatin with cobicistat is contraindicated due to the potential for myopathy, including rhabdomyolysis. Coadministration is expected to significantly increase lovastatin plasma concentrations. Lovastatin is a substrate for CYP3A4; cobicistat is a strong inhibitor of CYP3A. Coadministration with another strong CYP3A4 inhibitor increased lovastatin exposure by 11 to 36-fold.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Contraindicated) Concomitant use of lovastatin with cobicistat is contraindicated due to the potential for myopathy, including rhabdomyolysis. Coadministration is expected to significantly increase lovastatin plasma concentrations. Lovastatin is a substrate for CYP3A4; cobicistat is a strong inhibitor of CYP3A. Coadministration with another strong CYP3A4 inhibitor increased lovastatin exposure by 11 to 36-fold.
Enasidenib: (Moderate) Monitor for an increase in lovastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with enasidenib is necessary. Concomitant use may increase lovastatin exposure. Lovastatin is a substrate of P-gp; enasidenib is an inhibitor of P-gp.
Encorafenib: (Moderate) Coadministration of encorafenib with lovastatin may result in increased toxicity or decreased efficacy of lovastatin. Lovastatin is a sensitive CYP3A4 substrate. In vitro studies with encorafenib showed time-dependent inhibition of CYP3A4 and induction of CYP3A4. The clinical relevance of the in vivo effect of encorafenib on CYP3A4 is not established.
Erythromycin: (Contraindicated) Concurrent use of lovastatin and erythromycin is contraindicated. The risk of developing myopathy, rhabdomyolysis, and acute renal failure is substantially increased if lovastatin is administered concomitantly with strong CYP3A4 inhibitors including erythromycin. If no alternative to a short course of treatment with erythromycin is available, a brief suspension of lovastatin therapy during such treatment can be considered as there are no known adverse consequences to brief interruptions of long-term cholesterol-lowering therapy.
Eslicarbazepine: (Minor) In vivo studies suggest eslicarbazepine is an inducer of CYP3A4. Coadministration of CYP3A4 substrates, such as lovastatin, may result in decreased serum concentrations of the substrate. Monitor for decreased efficacy of lovastatin if coadministered with eslicarbazepine. Adjust the dose of lovastatin if clinically significant alterations in serum lipds are noted.
Etravirine: (Moderate) The risk of myopathy, including rhabdomyolysis, may be increased when antiretrovirals are given in combination with HMG-CoA reductase inhibitors. Concomitant use of etravirine and lovastatin (CYP3A4 substrate) may result in lower plasma concentrations of the HMG-CoA reductase inhibitor; dose adjustments may be necessary.
Fedratinib: (Moderate) Monitor for an increase in lovastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with fedratinib is necessary. Coadministration may increase the exposure of lovastatin. Lovastatin is a sensitive substrate of CYP3A4 and fedratinib is a moderate CYP3A4 inhibitor.
Fenofibrate: (Moderate) Concurrent use of fenofibrate and lovastatin may increase the risk of myopathy, rhabdomyolysis, and acute renal failure. The serious risk of myopathy and rhabdomyolysis should be weighed carefully against the benefit of further alteration in lipid concentrations by the combined use of fenofibrate or fenofibric acid and lovastatin.
Fenofibric Acid: (Moderate) Concurrent use of fenofibric acid and lovastatin may increase the risk of myopathy, rhabdomyolysis, and acute renal failure. The serious risk of myopathy and rhabdomyolysis should be weighed carefully against the benefit of further alteration in lipid concentrations by the combined use of fenofibric acid and lovastatin.
Fluconazole: (Moderate) Monitor for an increase in lovastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with fluconazole is necessary. Concomitant use may increase lovastatin exposure. Lovastatin is a sensitive substrate of CYP3A and fluconazole is a moderate CYP3A inhibitor.
Fosamprenavir: (Contraindicated) Concurrent use of lovastatin and anti-retroviral protease inhibitors is contraindicated. The risk of developing myopathy, rhabdomyolysis, and acute renal failure is substantially increased if lovastatin is administered concomitantly with anti-retroviral protease inhibitors. Lovastatin is a substrate of CYP3A4 and anti-retroviral protease inhibitors are strong inhibitors of CYP3A4; therefore, coadministration may result in substantial increases in plasma concentrations of lovastatin.
Fosphenytoin: (Moderate) Monitor for a decrease in lovastatin efficacy if concomitant use with phenytoin/fosphenytoin is necessary. Concomitant use may decrease lovastatin exposure. Lovastatin is a CYP3A substrate and phenytoin/fosphenytoin is a strong CYP3A inducer.
Fostemsavir: (Moderate) Monitor for lovastatin-related adverse reactions (i.e., myopathy/rhabdomyolysis) during concomitant use of fostemsavir as concurrent use may increase exposure of lovastatin. Lovastatin is a substrate for the transporter OATP1B1 and fostemsavir is an inhibitor of OATP1B1.
Futibatinib: (Moderate) Monitor for an increase in lovastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with futibatinib is necessary. Concomitant use may increase lovastatin exposure. Lovastatin is a P-gp substrate; futibatinib is a P-gp inhibitor.
Gemfibrozil: (Major) Avoid the concurrent use of gemfibrozil and lovastatin. The risk of myopathy and rhabdomyolysis is increased with combined gemfibrozil and HMG-CoA reductase inhibitor ("statin") therapy. Myopathy or rhabdomyolysis with or without acute renal failure have been reported as early as 3 weeks after initiation of combined therapy or after several months. There is no assurance that periodic monitoring of creatine kinase will prevent the occurrence of severe myopathy and kidney damage. In uncontrolled clinical studies of lovastatin, myopathy was reported more frequently in patients receiving concomitant therapy with gemfibrozil. Gemfibrozil may increase the risk of myopathy, rhabdomyolysis and acute renal failure in patients taking lovastatin. Data suggest that the addition of gemfibrozil to lovastatin therapy does not result in greater reductions in LDL-C than that achieved with lovastatin alone.
Gilteritinib: (Moderate) Monitor for an increase in lovastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with gilteritinib is necessary. Concomitant use may increase lovastatin exposure. Lovastatin is a P-gp substrate; gilteritinib is a P-gp inhibitor.
Glecaprevir; Pibrentasvir: (Major) Coadministration of glecaprevir with lovastatin is not recommended due to an increased risk of myopathy, including rhabdomyolysis. Coadministration may increase the plasma concentrations of lovastatin. Lovastatin is a substrate of the drug transporter OATP1B1; glecaprevir is an inhibitor of this transporter. In drug interaction studies, coadministration of lovastatin with glecaprevir; pibrentasvir resulted in 70% increase in the AUC of lovastatin. (Major) Coadministration of pibrentasvir with lovastatin is not recommended due to an increased risk of myopathy, including rhabdomyolysis. Coadministration may increase the plasma concentrations of lovastatin. Lovastatin is a substrate of the drug transporter OATP1B1; pibrentasvir is an inhibitor of this transporter. In drug interaction studies, coadministration of lovastatin with glecaprevir; pibrentasvir resulted in 70% increase in the AUC of lovastatin.
Grapefruit juice: (Major) Large quantities of grapefruit juice (>1 quart daily) should be avoided during lovastatin therapy due to the increased risk of myopathy. Grapefruit juice contains compounds that inhibit the CYP3A4 isozyme in the gut wall. Coadministration with grapefruit juice increases the plasma concentrations and AUC of lovastatin (and its beta-hydroxy acid metabolite) and may have a similar effect on the serum concentrations of simvastatin, atorvastatin, and cerivastatin, which are CYP3A4 substrates. Grapefruit juice should be avoided or minimized in patients taking these agents to avoid the potential for drug accumulation and toxicity (ie. myopathy and rhabdomyolysis).
Idelalisib: (Contraindicated) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with lovastatin, a CYP3A substrate, as lovastatin toxicities, such as myopathy, may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib. Consider an alternative to lovastatin. A single dose of 10 mg of rosuvastatin was administered alone and after idelailsib 150 mg for 12 doses in healthy subjects and no changes in exposure to rosuvastatin were observed.
Imatinib: (Major) Imatinib, STI-571 is a potent inhibitor of the cytochrome P450 3A4 isoenzyme. Concurrent use of lovastatin and imatinib may result in increased levels of lovastatin and potential toxicity. Concurrent use of simvastatin and imatinib resulted in 2- and 3.5-fold increases in simvastatin Cmax and AUC values, respectively.
Indinavir: (Contraindicated) Concurrent use of lovastatin and anti-retroviral protease inhibitors is contraindicated. The risk of developing myopathy, rhabdomyolysis, and acute renal failure is substantially increased if lovastatin is administered concomitantly with anti-retroviral protease inhibitors. Lovastatin is a substrate of CYP3A4 and anti-retroviral protease inhibitors are strong inhibitors of CYP3A4; therefore, coadministration may result in substantial increases in plasma concentrations of lovastatin.
Isavuconazonium: (Moderate) Concomitant use of isavuconazonium with lovastatin may result in increased serum concentrations of lovastatin. Lovastatin is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is an inhibitor of CYP3A4. Caution and close monitoring are advised if these drugs are used together.
Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Moderate) Rifampin has been reported to significantly increase the plasma clearance and decrease the serum concentrations of atorvastatin, simvastatin and fluvastatin, with the potential for reduced antilipemic efficacy. Although not studied, a similar interaction can be expected between other rifamycins (e.g., rifabutin, rifapentine) and other HMG-CoA reductase inhibitors (Statins). To evaluate this interaction, monitor serum lipid concentrations during coadministration of rifamycins with HMG-CoA reductase inhibitors.
Isoniazid, INH; Rifampin: (Moderate) Rifampin has been reported to significantly increase the plasma clearance and decrease the serum concentrations of atorvastatin, simvastatin and fluvastatin, with the potential for reduced antilipemic efficacy. Although not studied, a similar interaction can be expected between other rifamycins (e.g., rifabutin, rifapentine) and other HMG-CoA reductase inhibitors (Statins). To evaluate this interaction, monitor serum lipid concentrations during coadministration of rifamycins with HMG-CoA reductase inhibitors.
Isradipine: (Minor) Isradipine has been shown to increase the clearance of lovastatin. Lovastatin serum concentrations were correspondingly lower during isradipine administration. Lovastatin did not have any effect on isradipine pharmacokinetics. The clinical significance of this drug interaction is unclear at this time.
Itraconazole: (Contraindicated) Lovastatin is contraindicated for use during and for 2 weeks after itraconazole therapy due to the substantial increased risk of developing myopathy, rhabdomyolysis, and acute renal failure. In a small, double-blind study in healthy volunteers, lovastatin mean peak concentrations and lovastatin AUC increased by more than 20-fold when subjects were pretreated with itraconazole. Although side effects were not reported, one patient experienced a 10-fold increase in creatine kinase. One other case is noted of a patient who developed rhabdomyolysis when itraconazole was added to a stable regimen of lovastatin and niacin. Because pravastatin does not significantly rely on the CYP3A4 isoenzyme for metabolism, it is less likely to exhibit an interaction with the azole antifungals. Compared to a 19 to 20-fold increase in lovastatin AUC with concurrent itraconazole, the AUC of pravastatin is increased 1.7-fold when coadministered with itraconazole. The relatively small increase in pravastatin AUC during itraconazole therapy is postulated by the manufacturer to be due to inhibition of P-glycoprotein transport.
Ivacaftor: (Moderate) Monitoring for lovastatin-related adverse events (i.e., myopathy, rhabdomyolysis) is recommended if administered concurrently with ivacaftor. Coadministration can increase lovastatin exposure leading to increased or prolonged therapeutic effects and adverse events. Lovastatin is a CYP3A4 substrate; ivacaftor is a weak CYP3A4 inhibitor.
Ivosidenib: (Moderate) Monitor for loss of efficacy of lovastatin during coadministration of ivosidenib; a lovastatin dose adjustment may be necessary. Lovastatin is a sensitive substrate of CYP3A4; ivosidenib induces CYP3A4 and may lead to decreased lovastatin concentrations.
Ketoconazole: (Contraindicated) Concurrent use of lovastatin and ketoconazole is contraindicated. The risk of developing myopathy, rhabdomyolysis, and acute renal failure is substantially increased if lovastatin is administered concomitantly with strong CYP3A4 inhibitors including ketoconazole. If no alternative to a short course of treatment with ketoconazole is available, a brief suspension of lovastatin therapy during such treatment can be considered as there are no known adverse consequences to brief interruptions of long-term cholesterol-lowering therapy.
Lansoprazole; Amoxicillin; Clarithromycin: (Contraindicated) The concurrent use of lovastatin and clarithromycin is contraindicated due to the risk of myopathy and rhabdomyolysis. If no alternative to a short course of treatment with clarithromycin therapy is available, lovastatin use must be suspended during clarithromycin treatment. Lovastatin is metabolized by CYP3A4, and clarithromycin is a strong inhibitor of CYP3A4.
Lanthanum Carbonate: (Major) To limit absorption problems, HMG-CoA reductase inhibitors ("statins") should not be taken within 2 hours of dosing with lanthanum carbonate. Oral drugs known to interact with cationic antacids, like statin cholesterol treatments, may also be bound by lanthanum carbonate. Separate the times of administration appropriately. Monitor the patient's lipid profile to ensure the appropriate response to statin therapy is obtained.
Lasmiditan: (Moderate) Monitor for an increase in lovastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with lasmiditan is necessary. Concomitant use may increase lovastatin exposure. Lovastatin is a P-gp substrate; lasmiditan is a P-gp inhibitor.
Lefamulin: (Moderate) Monitor for an increase in lovastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with oral lefamulin is necessary. Coadministration may increase the exposure of lovastatin. Lovastatin is a sensitive substrate of CYP3A4 and oral lefamulin is a moderate CYP3A4 inhibitor; an interaction is not expected with intravenous lefamulin.
Leflunomide: (Major) Consider reducing the dose of HMG-CoA reductase inhibitors ("Statins" including atorvastatin, fluvastatin, lovastatin, pitavastatin, pravastatin, rosuvastatin, or simvastatin) during use of leflunomide and monitor patients closely for signs and symptoms of myopathy. For a patient taking leflunomide, the dose of rosuvastatin should not exceed 10 mg once daily. Patients should be advised to report promptly unexplained muscle pain, tenderness, or weakness, particularly if accompanied by malaise or fever. Following oral administration, leflunomide is metabolized to an active metabolite, teriflunomide, which is responsible for essentially all of leflunomide's in vivo activity. Teriflunomide is an inhibitor of the organic anion transporting polypeptide OATP1B1, and some statins are substrates for the OATP transporters. Teriflunomide may increase the exposure (AUC) of these statins. Increased concentrations of the statins increases the risk for myopathy and other statin-related side effects.
Lenacapavir: (Moderate) Monitor for an increase in lovastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with lenacapavir is necessary. Concomitant use may increase lovastatin exposure. Lovastatin is a CYP3A and P-gp substrate and lenacapavir is a moderate CYP3A and P-gp inhibitor.
Letermovir: (Major) Close monitoring for lovastatin-related adverse events (i.e., myopathy, rhabdomyolysis) and consideration of a lovastatin dose reduction is recommended if administered concurrently with letermovir. Concurrent use is contraindicated if the patient is also receiving cyclosporine. A clinically relevant increase in the plasma concentration of lovastatin may occur during concurrent administration with letermovir. The magnitude of this interaction may be increased in patients who are also receiving cyclosporine. Lovastatin is a sensitive substrate of CYP3A4 and the organic anion-transporting polypeptide (OATP1B1). Both letermovir and cyclosporine are moderate CYP3A4 inhibitors and inhibitors of OATP1B1. The combined effect of letermovir and cyclosporine on CYP3A4 substrates may be similar to a strong CYP3A4 inhibitor.
Levamlodipine: (Moderate) Carefully weigh the benefits of combined use of amlodipine and lovastatin against the potential risks. Lovastatin exposure may increase resulting in increased risk of myopathy/rhabdomyolysis. Although FDA-approved labeling for amlodipine or lovastatin do not suggest dose adjustments, guidelines recommend limiting the dose of lovastatin to 20 mg/day if combined with amlodipine. Lovastatin is a CYP3A4 substrate; amlodipine is a weak CYP3A4 inhibitor.
Levoketoconazole: (Contraindicated) Concurrent use of lovastatin and ketoconazole is contraindicated. The risk of developing myopathy, rhabdomyolysis, and acute renal failure is substantially increased if lovastatin is administered concomitantly with strong CYP3A4 inhibitors including ketoconazole. If no alternative to a short course of treatment with ketoconazole is available, a brief suspension of lovastatin therapy during such treatment can be considered as there are no known adverse consequences to brief interruptions of long-term cholesterol-lowering therapy.
Lomitapide: (Major) The risk of developing myopathy, including rhabdomyolysis may be increased if lovastatin is administered concomitantly with lomitapide. Consider reducing the dose of lovastatin when initiating lomitapide. Although the interaction between lovastatin and lomitapide has not been studied, coadministration of lomitapide and simvastatin approximately doubles the exposure to simvastatin. Because the metabolizing enzymes and transporters responsible for the disposition of lovastatin and simvastatin are similar, increased exposure to lovastatin should also be expected.
Lonafarnib: (Contraindicated) Coadministration of lovastatin and lonafarnib is contraindicated due to the risk of elevated plasma concentrations of lovastatin leading to myopathy and rhabdomyolysis. Lovastatin is a P-gp substrate and sensitive CYP3A4 substrate; lonafarnib is a P-gp inhibitor and strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased lovastatin exposure by 11 to 36-fold.
Lopinavir; Ritonavir: (Contraindicated) Concurrent use of lovastatin and anti-retroviral protease inhibitors is contraindicated. The risk of developing myopathy, rhabdomyolysis, and acute renal failure is substantially increased if lovastatin is administered concomitantly with anti-retroviral protease inhibitors. Lovastatin is a substrate of CYP3A4 and anti-retroviral protease inhibitors are strong inhibitors of CYP3A4; therefore, coadministration may result in substantial increases in plasma concentrations of lovastatin.
Lovastatin; Niacin: (Major) There is no clear indication for routine use of niacin in combination with lovastatin. The addition of niacin to a statin has not been shown to reduce cardiovascular morbidity or mortality. In addition, lipid-modifying doses (1 g/day or more) of niacin increase the risk of myopathy and rhabdomyolysis when combined with lovastatin. If coadministered, consider lower starting and maintenance does of lovastatin. Monitor patients closely for myopathy or rhabdomyolysis, particularly in the early months of treatment or after upward dose titration of either drug. Consider monitoring serum creatinine phosphokinase (CPK) and potassium periodically in such situations. Discontinue lovastatin immediately if myopathy is diagnosed or suspected.
Lumacaftor; Ivacaftor: (Moderate) Lumacaftor; ivacaftor may decrease the systemic exposure of lovastatin; if used together, monitor serum lipid concentrations. Lovastatin is a substrate of CYP3A4. Lumacaftor is a strong CYP3A inducer.
Lumacaftor; Ivacaftor: (Moderate) Monitoring for lovastatin-related adverse events (i.e., myopathy, rhabdomyolysis) is recommended if administered concurrently with ivacaftor. Coadministration can increase lovastatin exposure leading to increased or prolonged therapeutic effects and adverse events. Lovastatin is a CYP3A4 substrate; ivacaftor is a weak CYP3A4 inhibitor.
Maralixibat: (Minor) Maralixibat may reduce the oral absorption of HMG-CoA reductase inhibitors, also known as statins, which may reduce their efficacy. This risk is greatest with maralixibat doses greater than 4.75 mg. Monitor statin therapy and adjust the dose as needed based on clinical response. Maralixibat is a OATP2B1 inhibitor and statins are OATP2B1 substrates.
Maribavir: (Moderate) Monitor for an increase in lovastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with maribavir is necessary. Concomitant use may increase lovastatin exposure. Lovastatin is a P-gp substrate; maribavir is a P-gp inhibitor.
Mefenamic Acid: (Moderate) Mefenamic acid is a substrate for CYP2C9. Inhibitors of this enzyme, such as lovastatin, may lead to increased serum concentrations of mefenamic acid. If these drugs are administered concurrently, monitor for NSAID related side effects, such as fluid retention or GI irritation, or renal dysfunction and adjust the mefenamic acid dose, if needed.
Mifepristone: (Contraindicated) When mifepristone is used in the treatment of Cushing's syndrome, coadministration is contraindicated based on studies demonstrating significant lovastatin exposure increases which may lead to an increased risk of myopathy and rhabdomyolysis. Consider interruption of lovastatin therapy during use of mifepristone for pregnancy termination. Mifepristone inhibits CYP3A4; lovastatin is a CYP3A4 substrate. Coadministration of mifepristone increases serum levels drugs metabolized via CYP3A4 with narrow therapeutic indexes, such as lovastatin. Due to the slow elimination of mifepristone from the body, such interactions may be observed for a prolonged period after administration.
Mitapivat: (Moderate) Monitor for an increase in lovastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with mitapivat is necessary. Concomitant use may increase lovastatin exposure. Lovastatin is a P-gp substrate; mitapivat is a P-gp inhibitor.
Mitotane: (Major) Use caution if mitotane and lovastatin are used concomitantly, and monitor for decreased efficacy of lovastatin and a possible change in dosage requirements. Mitotane is a strong CYP3A4 inducer and lovastatin is a CYP3A4 substrate; coadministration may result in decreased plasma concentrations of lovastatin.
Nanoparticle Albumin-Bound Sirolimus: (Major) Guidelines recommend avoiding coadministration of lovastatin with sirolimus due to the potential for increased risk of myopathy/rhabdomyolysis. Consider use of an alternative statin such as atorvastatin, fluvastatin, pravastatin, or rosuvastatin with dose limitations in patients receiving sirolimus.
Nefazodone: (Contraindicated) Concurrent use of lovastatin and nefazodone is contraindicated. The risk of developing myopathy, rhabdomyolysis, and acute renal failure is substantially increased if lovastatin is administered concomitantly with nefazodone. Lovastatin is a substrate of CYP3A4 and nefazodone is a strong inhibitor of CYP3A4; therefore, coadministration may result in substantial increases in plasma concentrations of lovastatin.
Nelfinavir: (Contraindicated) Concurrent use of lovastatin and anti-retroviral protease inhibitors is contraindicated. The risk of developing myopathy, rhabdomyolysis, and acute renal failure is substantially increased if lovastatin is administered concomitantly with anti-retroviral protease inhibitors. Lovastatin is a substrate of CYP3A4 and anti-retroviral protease inhibitors are strong inhibitors of CYP3A4; therefore, coadministration may result in substantial increases in plasma concentrations of lovastatin.
Neratinib: (Moderate) Monitor for an increase in lovastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with neratinib is necessary. Concomitant use may increase lovastatin exposure. Lovastatin is a substrate of P-gp; neratinib is an inhibitor of P-gp.
Nevirapine: (Moderate) Monitor for reduced cholesterol-lowering efficacy of lovastatin if coadministration with nevirapine is necessary; a dose adjustment may be needed. Concomitant use may decrease lovastatin exposure. Lovastatin is a CYP3A substrate and nevirapine is a weak CYP3A inducer.
Niacin, Niacinamide: (Major) There is no clear indication for routine use of niacin in combination with lovastatin. The addition of niacin to a statin has not been shown to reduce cardiovascular morbidity or mortality. In addition, lipid-modifying doses (1 g/day or more) of niacin increase the risk of myopathy and rhabdomyolysis when combined with lovastatin. If coadministered, consider lower starting and maintenance does of lovastatin. Monitor patients closely for myopathy or rhabdomyolysis, particularly in the early months of treatment or after upward dose titration of either drug. Consider monitoring serum creatinine phosphokinase (CPK) and potassium periodically in such situations. Discontinue lovastatin immediately if myopathy is diagnosed or suspected.
Niacin; Simvastatin: (Major) There is no clear indication for routine use of niacin in combination with lovastatin. The addition of niacin to a statin has not been shown to reduce cardiovascular morbidity or mortality. In addition, lipid-modifying doses (1 g/day or more) of niacin increase the risk of myopathy and rhabdomyolysis when combined with lovastatin. If coadministered, consider lower starting and maintenance does of lovastatin. Monitor patients closely for myopathy or rhabdomyolysis, particularly in the early months of treatment or after upward dose titration of either drug. Consider monitoring serum creatinine phosphokinase (CPK) and potassium periodically in such situations. Discontinue lovastatin immediately if myopathy is diagnosed or suspected.
Nicardipine: (Moderate) Nicardipine is an inhibitor of CYP3A4 isoenzymes. Co-administration with nicardipine may lead to an increase in serum levels of drugs that are CYP3A4 substrates including lovastatin.
Nilotinib: (Moderate) Concomitant use of nilotinib and lovastatin may result in increased lovastatin levels. A lovastatin dose reduction may be necessary if these drugs are used together. Be alert for symptoms of statin-induced myopathy. Lovastatin is a CYP3A4 substrate; nilotinib is a moderate CYP3A4 inhibitor.
Nirmatrelvir; Ritonavir: (Contraindicated) Concomitant use of ritonavir-boosted nirmatrelvir and lovastatin is contraindicated. Discontinue use of lovastatin at least 12 hours before, during, and 5 days after treatment with ritonavir-boosted nirmatrelvir. Coadministration may increase lovastatin exposure resulting in increased toxicity. Lovastatin is a CYP3A substrate and nirmatrelvir is a CYP3A inhibitor. (Contraindicated) Concurrent use of lovastatin and anti-retroviral protease inhibitors is contraindicated. The risk of developing myopathy, rhabdomyolysis, and acute renal failure is substantially increased if lovastatin is administered concomitantly with anti-retroviral protease inhibitors. Lovastatin is a substrate of CYP3A4 and anti-retroviral protease inhibitors are strong inhibitors of CYP3A4; therefore, coadministration may result in substantial increases in plasma concentrations of lovastatin.
Olmesartan; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) Carefully weigh the benefits of combined use of amlodipine and lovastatin against the potential risks. Lovastatin exposure may increase resulting in increased risk of myopathy/rhabdomyolysis. Although FDA-approved labeling for amlodipine or lovastatin do not suggest dose adjustments, guidelines recommend limiting the dose of lovastatin to 20 mg/day if combined with amlodipine. Lovastatin is a CYP3A4 substrate; amlodipine is a weak CYP3A4 inhibitor.
Omeprazole; Amoxicillin; Rifabutin: (Minor) Rifampin has been reported to significantly increase the plasma clearance and decrease the serum concentrations of atorvastatin, simvastatin and fluvastatin, with the potential for reduced antilipemic efficacy. Although not studied, a similar interaction can be expected between other rifamycins (e.g., rifabutin, rifapentine) and other HMG-CoA reductase inhibitors (Statins). To evaluate this interaction, monitor serum lipid concentrations during coadministration of rifamycins with HMG-CoA reductase inhibitors.
Oritavancin: (Moderate) Lovastatin is metabolized by CYP3A4; oritavancin is a weak CYP3A4 inducer. Plasma concentrations and efficacy of lovastatin may be reduced if these drugs are administered concurrently.
Oxcarbazepine: (Minor) Oxcarbazepine, which is a CYP3A4 inducer, may decrease the efficacy of HMG-Co-A reductase inhibitors which are CYP3A4 substrates including lovastatin. Monitor for potential reduced cholesterol-lowering efficacy when these drugs are co-administered with HMG-CoA reductase inhibitors which are metabolized by CYP3A4.
Pacritinib: (Moderate) Monitor for an increase in lovastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with pacritinib is necessary. Concomitant use may increase lovastatin exposure. Lovastatin is a P-gp substrate; pacritinib is a P-gp inhibitor.
Pazopanib: (Moderate) Pazopanib is a weak inhibitor of CYP3A4. Coadministration of pazopanib and lovastatin, a CYP3A4 substrate, may cause an increase in systemic concentrations of lovastatin. Use caution when administering these drugs concomitantly.
Perindopril; Amlodipine: (Moderate) Carefully weigh the benefits of combined use of amlodipine and lovastatin against the potential risks. Lovastatin exposure may increase resulting in increased risk of myopathy/rhabdomyolysis. Although FDA-approved labeling for amlodipine or lovastatin do not suggest dose adjustments, guidelines recommend limiting the dose of lovastatin to 20 mg/day if combined with amlodipine. Lovastatin is a CYP3A4 substrate; amlodipine is a weak CYP3A4 inhibitor.
Phenytoin: (Moderate) Monitor for a decrease in lovastatin efficacy if concomitant use with phenytoin is necessary. Concomitant use may decrease lovastatin exposure. Lovastatin is a CYP3A substrate and phenytoin is a strong CYP3A inducer.
Pirtobrutinib: (Moderate) Monitor for an increase in lovastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with pirtobrutinib is necessary. Concomitant use may increase lovastatin exposure. Lovastatin is a P-gp substrate; pirtobrutinib is a P-gp inhibitor.
Posaconazole: (Contraindicated) Concurrent use of lovastatin and posaconazole is contraindicated. The risk of developing myopathy, rhabdomyolysis, and acute renal failure is substantially increased if lovastatin is administered concomitantly with strong CYP3A4 inhibitors including posaconazole. If no alternative to a short course of treatment with posaconazole is available, a brief suspension of lovastatin therapy during such treatment can be considered as there are no known adverse consequences to brief interruptions of long-term cholesterol-lowering therapy.
Pretomanid: (Moderate) Monitor for an increase in lovastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with pretomanid is necessary. Concomitant use may increase lovastatin exposure. Lovastatin is a P-gp substrate; pretomanid is a P-gp inhibitor.
Probenecid; Colchicine: (Major) Use caution and the lowest HMG-CoA reductase inhibitor dose necessary if coadministration with colchicine is necessary due to an increased risk of myopathy and rhabdomyolysis. Carefully weigh the potential benefits and risk of combined therapy. Closely monitor patients for signs and symptoms of muscle pain, tenderness, or weakness especially during the initial months of therapy and during upward titration of either drug. There is no assurance that period monitoring of creatinine phosphokinase (CPK) will prevent the occurrence of myopathy. Case reports exist describing the development of myotoxicity with the concurrent administration of colchicine and HMG-CoA reductase inhibitors (e.g., simvastatin, atorvastatin, fluvastatin, lovastatin, pravastatin).
Protease inhibitors: (Contraindicated) Concurrent use of lovastatin and anti-retroviral protease inhibitors is contraindicated. The risk of developing myopathy, rhabdomyolysis, and acute renal failure is substantially increased if lovastatin is administered concomitantly with anti-retroviral protease inhibitors. Lovastatin is a substrate of CYP3A4 and anti-retroviral protease inhibitors are strong inhibitors of CYP3A4; therefore, coadministration may result in substantial increases in plasma concentrations of lovastatin.
Quetiapine: (Moderate) In a published case, it has been hypothesized that the combination of lovastatin and quetiapine resulted in prolongation of the QTc interval. The suggested mechanism is competitive inhibition of the CYP3A4 isoenzyme leading to elevated quetiapine plasma concentrations. Both lovastatin and quetiapine are CYP3A4 substrates. The QTc interval returned to baseline when the lovastatin dose was reduced. The clinical significance and reproducibility of this interaction is unknown.
Quinine: (Moderate) Lovastatin is a CYP3A4 substrate; therefore, quinine has the potential to inhibit the metabolism of lovastatin leading to an increased potential of rhabdomyolysis. Patients receiving concomitant lovastatin and quinine should be monitored closely for muscle pain or weakness. Lower starting doses of lovastatin should be considered while patients are receiving quinine.
Raltegravir: (Moderate) Raltegravir use has been associated with elevated creatinine kinase concentrations; myopathy and rhabdomyolysis have been reported. Use raltegravir cautiously with drugs that increase the risk of myopathy or rhabdomyolysis such as HMG-CoA reductase inhibitors (Statins).
Ranolazine: (Moderate) Carefully weigh the benefits of combined use of ranolazine and lovastatin against the potential risks. Lovastatin exposure may increase resulting in increased risk of myopathy/rhabdomyolysis. Although FDA-approved labeling for ranolazine and lovastatin do not provide specific dose adjustments, guidelines recommend limiting the dose of lovastatin to 20 mg/day if combined with ranolazine. Lovastatin is a CYP3A4 substrate; ranolazine is a weak CYP3A4 inhibitor.
Red Yeast Rice: (Contraindicated) Since compounds in red yeast rice claim to have HMG-CoA reductase inhibitor activity, red yeast rice should not be used in combination with HMG-CoA reductase inhibitors. The administration of more than one HMG-CoA reductase inhibitor at one time would be duplicative therapy and perhaps increase the risk of drug-related toxicity including myopathy and rhabdomyolysis.
Ribociclib: (Contraindicated) Coadministration of lovastatin and ribociclib is contraindicated due to the risk of elevated plasma concentrations of lovastatin leading to myopathy and rhabdomyolysis. Lovastatin is a sensitive CYP3A4 substrate and ribociclib is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased lovastatin exposure by 11 to 36-fold.
Ribociclib; Letrozole: (Contraindicated) Coadministration of lovastatin and ribociclib is contraindicated due to the risk of elevated plasma concentrations of lovastatin leading to myopathy and rhabdomyolysis. Lovastatin is a sensitive CYP3A4 substrate and ribociclib is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased lovastatin exposure by 11 to 36-fold.
Rifabutin: (Minor) Rifampin has been reported to significantly increase the plasma clearance and decrease the serum concentrations of atorvastatin, simvastatin and fluvastatin, with the potential for reduced antilipemic efficacy. Although not studied, a similar interaction can be expected between other rifamycins (e.g., rifabutin, rifapentine) and other HMG-CoA reductase inhibitors (Statins). To evaluate this interaction, monitor serum lipid concentrations during coadministration of rifamycins with HMG-CoA reductase inhibitors.
Rifampin: (Moderate) Rifampin has been reported to significantly increase the plasma clearance and decrease the serum concentrations of atorvastatin, simvastatin and fluvastatin, with the potential for reduced antilipemic efficacy. Although not studied, a similar interaction can be expected between other rifamycins (e.g., rifabutin, rifapentine) and other HMG-CoA reductase inhibitors (Statins). To evaluate this interaction, monitor serum lipid concentrations during coadministration of rifamycins with HMG-CoA reductase inhibitors.
Ritlecitinib: (Moderate) Monitor for an increase in lovastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with ritlecitinib is necessary. Concomitant use may increase lovastatin exposure. Lovastatin is a sensitive substrate of CYP3A and ritlecitinib is a moderate CYP3A inhibitor.
Ritonavir: (Contraindicated) Concurrent use of lovastatin and anti-retroviral protease inhibitors is contraindicated. The risk of developing myopathy, rhabdomyolysis, and acute renal failure is substantially increased if lovastatin is administered concomitantly with anti-retroviral protease inhibitors. Lovastatin is a substrate of CYP3A4 and anti-retroviral protease inhibitors are strong inhibitors of CYP3A4; therefore, coadministration may result in substantial increases in plasma concentrations of lovastatin.
Saquinavir: (Contraindicated) Concurrent use of lovastatin and anti-retroviral protease inhibitors is contraindicated. The risk of developing myopathy, rhabdomyolysis, and acute renal failure is substantially increased if lovastatin is administered concomitantly with anti-retroviral protease inhibitors. Lovastatin is a substrate of CYP3A4 and anti-retroviral protease inhibitors are strong inhibitors of CYP3A4; therefore, coadministration may result in substantial increases in plasma concentrations of lovastatin.
Sarilumab: (Moderate) Utilize caution with concomitant use of sarilumab and CYP3A4 substrate drugs, such as lovastatin, where a decrease in effectiveness is undesirable. Monitor lipid panels and adjust therapy as indicated. Inhibition of IL-6 signaling by sarilumab may restore CYP450 activities to higher levels leading to increased metabolism of drugs that are CYP450 substrates as compared to metabolism prior to treatment. This effect on CYP450 enzyme activity may persist for several weeks after stopping sarilumab. A 45% decrease in exposure to another "statin" was noted in a drug interaction study. In vitro, sarilumab has the potential to affect expression of multiple CYP enzymes, including CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, and CYP3A4. Lovastatin is a CYP3A4 substrate.
Selpercatinib: (Moderate) Monitor for an increase in lovastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with selpercatinib is necessary. Concomitant use may increase lovastatin exposure. Lovastatin is a P-gp substrate; selpercatinib is a P-gp inhibitor.
Siltuximab: (Moderate) Caution is warranted in patients receiving siltuximab who are taking CYP3A4 substrates, such as lovastatin, in which a decreased effect would be undesirable. Monitor the patient's lipid profile as clinically indicated and adjust treatment as necessary. Cytochrome P450s in the liver are down regulated by infection and inflammation stimuli, including cytokines such as interleukin-6 (IL-6). Inhibition of IL-6 signaling by siltuximab may restore CYP450 activities to higher levels leading to increased metabolism of drugs that are CYP450 substrates as compared to metabolism prior to treatment. The effect of siltuximab on CYP450 enzyme activity can persist for several weeks after stopping therapy.
Sirolimus: (Major) Guidelines recommend avoiding coadministration of lovastatin with sirolimus due to the potential for increased risk of myopathy/rhabdomyolysis. Consider use of an alternative statin such as atorvastatin, fluvastatin, pravastatin, or rosuvastatin with dose limitations in patients receiving sirolimus.
Sodium Phenylbutyrate; Taurursodiol: (Moderate) Monitor for an increase in lovastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with taurursodiol is necessary. Concomitant use may increase lovastatin exposure. Lovastatin is a P-gp substrate; taurursodiol is a P-gp inhibitor.
Sotorasib: (Moderate) Monitor for an increase in lovastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with sotorasib is necessary. Concomitant use may increase lovastatin exposure. Lovastatin is a substrate of P-gp; sotorasib is an inhibitor of P-gp.
Sparsentan: (Moderate) Monitor for an increase in lovastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with sparsentan is necessary. Concomitant use may increase lovastatin exposure. Lovastatin is a P-gp substrate; sparsentan is a P-gp inhibitor.
St. John's Wort, Hypericum perforatum: (Moderate) St. John's Wort appears to induce several isoenzymes of the hepatic cytochrome P450 enzyme system. Co-administration of St. John's Wort could decrease the efficacy of some medications metabolized by these enzymes including lovastatin.
Stiripentol: (Moderate) Consider a dose adjustment of lovastatin when coadministered with stiripentol. Coadministration may alter plasma concentrations of lovastatin resulting in an increased risk of adverse reactions and/or decreased efficacy. Lovastatin is a sensitive CYP3A4 substrate. In vitro data predicts inhibition or induction of CYP3A4 by stiripentol potentially resulting in clinically significant interactions.
Tacrolimus: (Major) Guidelines recommend avoiding coadministration of lovastatin with tacrolimus due to the potential for increased risk of myopathy/rhabdomyolysis. Consider use of an alternative statin such as atorvastatin, fluvastatin, pravastatin, or rosuvastatin with dose limitations in patients receiving tacrolimus.
Telmisartan; Amlodipine: (Moderate) Carefully weigh the benefits of combined use of amlodipine and lovastatin against the potential risks. Lovastatin exposure may increase resulting in increased risk of myopathy/rhabdomyolysis. Although FDA-approved labeling for amlodipine or lovastatin do not suggest dose adjustments, guidelines recommend limiting the dose of lovastatin to 20 mg/day if combined with amlodipine. Lovastatin is a CYP3A4 substrate; amlodipine is a weak CYP3A4 inhibitor.
Tepotinib: (Moderate) Monitor for an increase in lovastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with tepotinib is necessary. Concomitant use may increase lovastatin exposure. Lovastatin is a substrate of P-gp; tepotinib is an inhibitor of P-gp.
Teriflunomide: (Major) Consider reducing the dose of HMG-CoA reductase inhibitors ("Statins" including atorvastatin, fluvastatin, lovastatin, pitavastatin, pravastatin, rosuvastatin, or simvastatin) during use of teriflunomide and monitor patients closely for signs and symptoms of myopathy. For a patient taking teriflunomide, the dose of rosuvastatin should not exceed 10 mg once daily. Patients should be advised to report promptly unexplained muscle pain, tenderness, or weakness, particularly if accompanied by malaise or fever. Teriflunomide is an inhibitor of the organic anion transporting polypeptide OATP1B1, and some statins are substrates for the OATP transporters. Teriflunomide may increase the exposure (AUC) of these statins. Increased concentrations of the statins increases the risk for myopathy and other statin-related side effects.
Tezacaftor; Ivacaftor: (Moderate) Monitoring for lovastatin-related adverse events (i.e., myopathy, rhabdomyolysis) is recommended if administered concurrently with ivacaftor. Coadministration can increase lovastatin exposure leading to increased or prolonged therapeutic effects and adverse events. Lovastatin is a CYP3A4 substrate; ivacaftor is a weak CYP3A4 inhibitor.
Ticagrelor: (Major) Avoid lovastatin doses higher than 40 mg/day when used concomitantly with ticagrelor as concomitant use will result in higher serum concentrations of lovastatin. Lovastatin is metabolized by CYP3A4 and ticagrelor is an inhibitor of CYP3A4.
Tipranavir: (Contraindicated) Concurrent use of lovastatin and anti-retroviral protease inhibitors is contraindicated. The risk of developing myopathy, rhabdomyolysis, and acute renal failure is substantially increased if lovastatin is administered concomitantly with anti-retroviral protease inhibitors. Lovastatin is a substrate of CYP3A4 and anti-retroviral protease inhibitors are strong inhibitors of CYP3A4; therefore, coadministration may result in substantial increases in plasma concentrations of lovastatin.
Tocilizumab: (Moderate) Utilize caution with concomitant use of tocilizumab and CYP3A4 substrate drugs, such as lovastatin, where a decrease in effectiveness is undesirable. Monitor lipid panels and adjust therapy as indicated. Inhibition of IL-6 signaling by tocilizumab may restore CYP450 activities to higher levels leading to increased metabolism of drugs that are CYP450 substrates as compared to metabolism prior to treatment. This effect on CYP450 enzyme activity may persist for several weeks after stopping tocilizumab. A 57% decrease in the exposure of another "statin" was noted 1 week after a single tocilizumab dose. In vitro, tocilizumab has the potential to affect expression of multiple CYP enzymes, including CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, and CYP3A4. Lovastatin is a CYP3A4 substrate.
Trandolapril; Verapamil: (Major) Coadministration of verapamil and lovastatin increases the risk for myopathy/rhabdomyolysis, particularly with higher doses of lovastatin. In patients taking verapamil, the initial lovastatin dose should not exceed 10 mg/day PO. While the FDA-approved product labeling for lovastatin products recommends a maximum lovastatin dosage of 20 mg/day when these agents are used together, the product labeling for verapamil suggests a maximum lovastatin dosage of 40 mg/day. The benefits of the use of lovastatin in patients taking verapamil should be carefully weighed against the risks of this combination. Specific dosage recommendations for pediatric patients receiving this combination are not available.
Tucatinib: (Contraindicated) Coadministration of lovastatin and tucatinib is contraindicated due to the risk of elevated plasma concentrations of lovastatin leading to myopathy and rhabdomyolysis. Lovastatin is a sensitive CYP3A4 substrate and tucatinib is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased lovastatin exposure by 11 to 36-fold.
Verapamil: (Major) Coadministration of verapamil and lovastatin increases the risk for myopathy/rhabdomyolysis, particularly with higher doses of lovastatin. In patients taking verapamil, the initial lovastatin dose should not exceed 10 mg/day PO. While the FDA-approved product labeling for lovastatin products recommends a maximum lovastatin dosage of 20 mg/day when these agents are used together, the product labeling for verapamil suggests a maximum lovastatin dosage of 40 mg/day. The benefits of the use of lovastatin in patients taking verapamil should be carefully weighed against the risks of this combination. Specific dosage recommendations for pediatric patients receiving this combination are not available.
Voclosporin: (Moderate) Monitor for an increase in lovastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with voclosporin is necessary. Concomitant use may increase lovastatin exposure. Lovastatin is a substrate of P-gp; voclosporin is an inhibitor of P-gp.
Vonoprazan; Amoxicillin; Clarithromycin: (Contraindicated) The concurrent use of lovastatin and clarithromycin is contraindicated due to the risk of myopathy and rhabdomyolysis. If no alternative to a short course of treatment with clarithromycin therapy is available, lovastatin use must be suspended during clarithromycin treatment. Lovastatin is metabolized by CYP3A4, and clarithromycin is a strong inhibitor of CYP3A4.
Voriconazole: (Contraindicated) Coadministration of lovastatin and voriconazole is contraindicated due to the risk of elevated plasma concentrations of lovastatin leading to myopathy and rhabdomyolysis. Lovastatin is a sensitive CYP3A4 substrate and voriconazole is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased lovastatin exposure by 11 to 36-fold.
Voxelotor: (Moderate) Monitor for an increase in lovastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with voxelotor is necessary. Concomitant use may increase lovastatin exposure. Lovastatin is a sensitive substrate of CYP3A and voxelotor is a moderate CYP3A inhibitor.
Warfarin: (Moderate) Monitor INR carefully in patients taking warfarin when lovastatin is initiated or a lovastatin dosage adjustment is made. Lovastatin's influence on warfarin's clinical effects is unclear. Bleeding and/or prolonged prothrombin time have been reported in a few patients when lovastatin was taken concurrently with coumarin anticoagulants. However, one small clinical trial found no effect on prothrombin time when lovastatin was given to patients receiving warfarin. Another HMG-CoA reductase inhibitor was found to increase the INR by < 2 seconds in healthy subjects taking low doses of warfarin. Alternatively, it appears that pravastatin and atorvastatin may be less likely to significantly interact with warfarin based on drug interaction studies.
Zafirlukast: (Minor) Zafirlukast inhibits the CYP3A4 isoenzymes and should be used cautiously in patients stabilized on drugs metabolized by CYP3A4, such as lovastatin.
Lovastatin is a prodrug with little or no inherent activity but is hydrolyzed in vivo to mevinolinic acid. Mevinolinic acid, one of lovastatin's several active metabolites, is structurally similar to HMG-CoA (hydroxymethylglutaryl CoA). Once hydrolyzed, lovastatin competes with HMG-CoA for HMG-CoA reductase, a hepatic microsomal enzyme. Interference with the activity of this enzyme reduces the quantity of mevalonic acid, a precursor of cholesterol. This process occurs within the hepatocyte and is one of two mechanisms that generate cholesterol. Cholesterol also can be taken up from LDL by endocytosis. Since de novo synthesis of cholesterol is impaired by lovastatin, the second mechanism is augmented. Thus, lovastatin also enhances clearance of LDL. Lovastatin exerts its effects mainly on total cholesterol and LDL, with minor effects seen on HDL and triglycerides. Because peak cholesterol synthesis occurs in the early morning hours, evening dosing for lovastatin is preferable.
HMG-CoA reductase inhibitors have been reported to decrease endogenous CoQ10 serum concentrations; the clinical significance of these effects is unknown.
Lovastatin is administered orally. Both lovastatin and its beta-hydroxyacid metabolite are highly bound to plasma proteins (more than 95%). Lovastatin crosses the blood-brain barrier and the placental barrier, and may be distributed into human milk. Lovastatin is a prodrug that is hydrolyzed to mevinolinic acid and metabolized to several other active derivatives via hepatic CYP3A4 isoenzymes. The major active metabolites present in human plasma are the beta-hydroxyacid (lovastatin acid), its 6'-hydroxy derivative, and two additional metabolites. The plasma half-life of mevinolinic acid is about 1.1 to 1.7 hours. Following a single dose of immediate-release lovastatin to adults with hypercholesterolemia, 83% is excreted in the feces as both active and inactive metabolites. Drug eliminated via the stool represents both unabsorbed drug and drug and metabolites secreted in the bile. Only 10% of a dose is eliminated renally.
Affected cytochrome P450 isoenzymes and drug transporters: CYP3A4
Lovastatin is a substrate of CYP3A4 hepatic metabolism, but does not affect the metabolism of CYP3A4 substrates. It has multiple significant drug interactions with CYP3A4 inhibitors, which may result in increased HMG-CoA reductase inhibition and toxicity including myopathy and rhabdomyolysis. There is evidence suggesting that lovastatin may be a P-gp substrate and inhibitor; however, the clinical relevance of this on drug-drug interactions has not been established.
-Route-Specific Pharmacokinetics
Oral Route
Lovastatin is incompletely absorbed from the GI tract and undergoes extensive first-pass extraction in the liver. Lovastatin was purposely developed as a prodrug to concentrate active inhibitors in the liver during first-pass circulation. Only fewer than 5% (with considerable inter-individual variation) of active inhibitors reaches the systemic circulation following immediate-release lovastatin. Peak concentrations of active and total HMG Co-A reductase inhibitors occur within 2 to 4 hours after oral administration of immediate-release lovastatin. The presence of food in the GI tract enhances oral absorption. Lovastatin absorption appears to be increased by at least 30% by grapefruit juice; however, the effect is dependent on the amount of grapefruit juice consumed and the interval between grapefruit juice and lovastatin ingestion. When compared to 40 mg of immediate-release lovastatin, Altoprev 40 mg (extended-release lovastatin) produces a 3.9% greater LDL-reduction. At the same dosage (40 mg), Altoprev is also associated with greater lovastatin (prodrug) bioavailability, a lower lovastatin Cmax, prolonged absorption (increased Tmax), comparable exposure to the lovastatin acid metabolite, and similar exposure to active and total inhibitors of HMG-CoA reductase. Food decreases the bioavailability of Altoprev. When Altoprev is given with a meal, plasma concentrations of lovastatin and lovastatin acid are about 0.5 to 0.6 times those observed when administered in the fasting state. Diurnal variation in cholesterol synthesis has been documented; single daily doses of lovastatin (immediate-release or extended-release formulations) are most effective when given in the evening.
-Special Populations
Renal Impairment
In patients with severe renal impairment (CrCl 10 to 30 mL/minute), the plasma concentrations of total inhibitors after a single dose of lovastatin are approximately two-fold higher than those in healthy volunteers. The dialyzability of lovastatin or its metabolites is unknown.
Geriatric
Elderly patients receiving immediate-release lovastatin have been reported to have 45% higher mean plasma levels of HMG-CoA reductase inhibitory activity vs. younger patients.
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