Lovastatin

Lipid-modifying agents HMG-CoA reductase inhibitors: lovastatin, simvastatin ↑ lovastatin ↑ simvastatin Coadministration of REYATAZ with lovastatin or simvastatin is contraindicated.

HMG-CoA reductase inhibitors : lovastatin simvastatin ↑lovastatin ↑simvastatin Coadministration with lovastatin or simvastatin is contraindicated due to the potential for serious reactions such as myopathy, including rhabdomyolysis [see Contraindications (4) ] .

Lipid-modifying agents HMG-CoA reductase inhibitors: lovastatin, simvastatin ↑ lovastatin ↑ simvastatin Coadministration of atazanavir with lovastatin or simvastatin is contraindicated.

Strong CYP3A4 inhibitor increases risk of myopathy by reducing lovastatin elimination.

Gastroprokinetic Agents: Cisapride Contraindicated Cisapride : [See Contraindications (4.2) ] Lipid-lowering agents: Lomitapide Lovastatin Simvastatin Atorvastatin Pravastatin Fluvastatin Contraindicated Use With Caution No Dose Adjustment Lomitapide, Lovastatin, Simvastatin: Clarithromycin may increase the exposure of these drugs by inhibition of CYP3A metabolism, thereby increasing the risk of toxicities from these drugs [see Contraindications (4.5) and Warnings and Precautions (5.4) ] Atorvastatin, Pravastatin, Fluvastatin: [See Warnings and Precautions (5.4) ] Hypoglycemic Agents: Nateglinide Pioglitazone Repaglinide Rosiglitazone Insulin Use With Caution Nateglinide, Pioglitazone, Repaglinide, Rosiglitazone : [See Warnings and Precautions (5.4) and Adverse Reactions (6.2) ] Insulin : [See Warnings and Precautions (5.4) and Adverse Reactions (6.2) ] Immunosuppressants: Cyclosporine Tacrolimus Use With Caution Cyclosporine : There have been spontaneous or published reports of CYP3A based interactions of clarithromycin with cyclosporine.

Lipid-modifying Agents: HMG-CoA reductase inhibitors: lovastatin simvastatin ↑ lovastatin ↑ simvastatin Coadministration with lovastatin or simvastatin is contraindicated due to potential for serious reactions such as myopathy including rhabdomyolysis.

Lipid Modifying Agents: HMG-CoA reductase inhibitors: lovastatin, simvastatin ↑ lovastatin ↑ simvastatin Co-administration is contraindicated due to potential for serious reactions such as myopathy including rhabdomyolysis.

Lipid Modifying Agents: HMG-CoA reductase inhibitors : lovastatin, simvastatin atorvastatin, pravastatin, rosuvastatin Other lipid modifying agents: lomitapide ↑ lovastatin ↑ simvastatin ↑ HMG-CoA reductase inhibitors ↑ lomitapide Co-administration is contraindicated due to potential for serious reactions such as myopathy including rhabdomyolysis.

Lipid Modifying Agents HMG-CoA reductase inhibitors: lovastatin, simvastatin ↑ lovastatin ↑ simvastatin Co-administration is contraindicated due to potential for serious reactions such as myopathy including rhabdomyolysis.

Lipid modifying agents: HMG-CoA reductase inhibitors: lovastatin, simvastatin ↑ lovastatin ↑ simvastatin Co-administration is contraindicated due to potential for serious reactions such as myopathy including rhabdomyolysis.

Lipid-modifying Agents: HMG-CoA Reductase Inhibitors: lovastatin simvastatin ↑ lovastatin ↑ simvastatin Coadministration with lovastatin or simvastatin is contraindicated due to potential for serious reactions such as myopathy including rhabdomyolysis.

Lipid-modifying Agents: HMG-CoA Reductase Inhibitors: lovastatin simvastatin ↑ lovastatin ↑ simvastatin Coadministration with lovastatin or simvastatin is contraindicated due to potential for serious reactions such as myopathy including rhabdomyolysis.

Strong CYP3A4 inhibitor increases risk of myopathy by reducing lovastatin elimination.

Increased risk of myopathy, including rhabdomyolysis when used with erythromycin due to CYP3A4 metabolism inhibition.

Lipid Modifying Agents: HMG-CoA reductase inhibitors : Atorvastatin a Lovastatin, simvastatin Other lipid modifying agents : Lomitapide ↑Atorvastatin ↑Lovastatin ↑Simvastatin ↑Lomitapide Titrate atorvastatin dose carefully and use the lowest necessary dose; do not exceed atorvastatin 20 mg/day. Coadministration with lovastatin or simvastatin is contraindicated due to potential for serious reactions such as risk of myopathy including rhabdomyolysis [see Contraindications (4)] .

CYP3A4 inhibitor increases risk of myopathy by reducing lovastatin elimination.

Lipid-Lowering Drugs Lomitapide Lovastatin a Simvastatin a Contraindicated during and 2 weeks after itraconazole treatment.

(See PRECAUTIONS: DRUG INTERACTIONS .) Additionally, the following other drugs are contraindicated with ketoconazole tablets: methadone, disopyramide, dronedarone, ergot alkaloids such as dihydroergotamine, ergometrine, ergotamine, methylergometrine, irinotecan, lurasidone, oral midazolam, alprazolam, triazolam, felodipine, nisoldipine, ranolazine, tolvaptan, eplerenone, lovastatin, simvastatin and colchicine. (See PRECAUTIONS: DRUG INTERACTIONS .) Myopathy Coadministration of CYP3A4 metabolized HMG-CoA reductase inhibitors such as simvastatin, and lovastatin is contraindicated with ketoconazole tablets.

HMG-CoA Reductase Inhibitors: Lovastatin Simvastatin Contraindicated Lovastatin, Simvastatin, Atorvastatin, Pravastatin, Fluvastatin : (see CONTRAINDICATIONS , WARNINGS ).

Prevention or Management HMG CoA reductase inhibitors (“Statins”) Coadministration of ZOKINVY with lovastatin, simvastatin, or atorvastatin is contraindicated [see Contraindications ( 4 )] . As noted above, use with lovastatin, simvastatin, or atorvastatin, and midazolam is contraindicated [see Contraindications ( 4 )] ).

Lipid-modifying agents HMG-CoA Reductase Inhibitors: lovastatin simvastatin atorvastatin rosuvastatin Microsomal triglyceride transfer protein (MTTP) Inhibitor: lomitapide ↑ lovastatin ↑ simvastatin ↑ atorvastatin ↑ rosuvastatin ↑ lomitapide Contraindicated due to potential for myopathy including rhabdomyolysis [see Contraindications (4)].

Concomitant use of simvastatin or lovastatin is contraindicated because of the increased risk of myopathy and rhabdomyolysis.

Strong CYP3A4 inhibitor increases risk of myopathy by reducing lovastatin elimination.

HMG-CoA reductase inhibitors lovastatin, simvastatin ↑ lovastatin ↑ simvastatin Co-administration contraindicated due to potential for myopathy including rhabdomyolysis [see Contraindications (4) ] . If treatment with PAXLOVID is considered medically necessary, discontinue use of lovastatin and simvastatin at least 12 hours prior to initiation of PAXLOVID, during the 5 days of PAXLOVID treatment, and for 5 days after completing PAXLOVID.

Prevention or Management Atorvastatin, Lovastatin, Simvastatin Concomitant use with posaconazole is contraindicated.

Strong CYP3A4 inhibitors increase risk of myopathy by reducing lovastatin elimination.

Lipid-modifying agents HMG-CoA Reductase Inhibitor: lovastatin simvastatin atorvastatin rosuvastatin Microsomal triglyceride transfer protein (MTTP) Inhibitor: lomitapide ↑ lovastatin ↑ simvastatin ↑ atorvastatin ↑ rosuvastatin ↑ lomitapide Contraindicated due to potential for myopathy including rhabdomyolysis [see Contraindications (4) ].

Lipid-modifying agents HMG-CoA Reductase Inhibitor: lovastatin simvastatin atorvastatin rosuvastatin Microsomal triglyceride transfer protein (MTTP) Inhibitor: lomitapide ↑ lovastatin ↑ simvastatin ↑ atorvastatin ↑ rosuvastatin ↑ lomitapide Contraindicated due to potential for myopathy including rhabdomyolysis [see Contraindications ( 4 )] .

Strong CYP3A4 inhibitor increases risk of myopathy by reducing lovastatin elimination.

Strong CYP3A4 inhibitor increases risk of myopathy by reducing lovastatin elimination.

Strong CYP3A4 inhibitor increases risk of myopathy by reducing lovastatin elimination.

Increases risk of myopathy/rhabdomyolysis when used with HMG-CoA reductase inhibitors like lovastatin.

Increases plasma concentration of HMG-CoA reductase inhibitor. Limit dose to 40 mg.

Other Potentially Significant Drug Interactions Concomitant Drug Class or Food Noted or Anticipated Outcome Clinical Comment HMG-CoA Reductase Inhibitors: atorvastatin, fluvastatin, lovastatin, pravastatin, simvastatin Pharmacokinetic and/or pharmacodynamic interaction: the addition of one drug to a stable long-term regimen of the other has resulted in myopathy and rhabdomyolysis (including a fatality) Weigh the potential benefits and risks and carefully monitor patients for any signs or symptoms of muscle pain, tenderness, or weakness, particularly during initial therapy; monitoring CPK (creatine phosphokinase) will not necessarily prevent the occurrence of severe myopathy.

Concomitant use increases risk of myopathy and rhabdomyolysis.

Increases risk of myopathy/rhabdomyolysis, particularly with higher doses of lovastatin.

While there are no adequate and well-controlled studies in pregnant women, there has been one report of severe congenital bony deformity, tracheoesophageal fistula, and anal atresia (VATER association) in a baby born to a woman who took dextroamphetamine sulfate with lovastatin during the first trimester of pregnancy.

There has been one report of severe congenital bony deformity, tracheo-esophageal fistula, and anal atresia (vater association) in a baby born to a woman who took dextroamphetamine sulfate with lovastatin during the first trimester of pregnancy.

Increases risk of myopathy/rhabdomyolysis, particularly with higher doses of lovastatin.

Increases risk of myopathy/rhabdomyolysis, particularly with higher doses of lovastatin.

Erythromycin has been reported to increase concentrations of lovastatin, an HMG-CoA reductase inhibitor.

Lipid-lowering drugs that increase risk of myopathy when given with lovastatin.

Lipid-lowering drug that can cause myopathy alone; increases risk of myopathy when given with lovastatin.

Risk of myopathy including rhabdomyolysis is increased when combined with lomitapide. Dose reduction recommended due to increased lovastatin exposure.

Nicotinic acid at doses ≥1 g/day increases risk of myopathy when given with lovastatin.

Increases risk of myopathy, including rhabdomyolysis, when used with lovastatin.

( 7.3) • Patients receiving more than 40 mg per day of simvastatin or lovastatin may be at increased risk of statin-related adverse effects. 7.4 Simvastatin, Lovastatin , Rosuvastatin Ticagrelor increases serum concentrations of simvastatin and lovastatin because these drugs are metabolized by CYP3A4. Avoid simvastatin and lovastatin doses greater than 40 mg [see Clinical Pharmacology ( 12.3 )].

Increases risk of myopathy/rhabdomyolysis, particularly with higher doses of lovastatin.

CYP3A4 substrate combination associated with myopathy/rhabdomyolysis. Limit lovastatin dose to 40 mg daily.

Closely monitor patients for signs of reduced effectiveness when deferasirox is administered with drugs metabolized by CYP3A4 (e.g., alfentanil, aprepitant, budesonide, buspirone, conivaptan, cyclosporine, darifenacin, darunavir, dasatinib, dihydroergotamine, dronedarone, eletriptan, eplerenone, ergotamine, everolimus, felodipine, fentanyl, hormonal contraceptive agents, indinavir, fluticasone, lopinavir, lovastatin, lurasidone, maraviroc, midazolam, nisoldipine, pimozide, quetiapine, quinidine, saquinavir, sildenafil, simvastatin, sirolimus, tacrolimus, tolvaptan, tipranavir, triazolam, ticagrelor, and vardenafil) [ see Clinical Pharmacology (12.3)].

Eslicarbazepine acetate can induce CYP3A4, decreasing plasma concentrations of lovastatin. Dose adjustment may be needed if clinically significant change in lipids is noted.

7.2 Pharmacokinetic Drug Interactions Table 3: Effect of Fexinidazole on other Drugs Drugs Metabolized by Cytochrome P450 (CYP) 3A4/5 Examples (not fully inclusive): Lovastatin, simvastatin, nisoldipine, saquinavir, midazolam, certain hormonal contraceptives (e.g., birth control pills, skin patches, implant) Clinical Impact Fexinidazole is considered a moderate CYP3A4/5 inducer [see Clinical Pharmacology (12.3) ] .

There have been rare reports of rhabdomyolysis involving patients receiving the combination of nefazodone and either simvastatin or lovastatin, also a substrate of CYP3A4 (see ADVERSE REACTIONS , Postintroduction Clinical Experience ). Caution should be used if nefazodone is administered in combination with HMG-CoA reductase inhibitors that are metabolized by CYP3A4, such as simvastatin, atorvastatin, and lovastatin, and dosage adjustments of these HMG-CoA reductase inhibitors are recommended.

Caution should be exercised when paclitaxel is concomitantly administered with known substrates (e.g., midazolam, buspirone, felodipine, lovastatin, eletriptan, sildenafil, simvastatin, and triazolam), inhibitors (e.g., atazanavir, clarithromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, and telithromycin), and inducers (e.g., rifampin and carbamazepine) of CYP3A4.

Exercise caution when co-administering KEVZARA with CYP3A4 substrate drugs where decrease in effectiveness is undesirable, e.g., oral contraceptives, lovastatin, atorvastatin, etc.

Exercise caution when SYLVANT is co-administered with CYP3A4 substrate drugs where a decrease in effectiveness would be undesirable (e.g., oral contraceptives, lovastatin, atorvastatin).

Exercise caution when coadministering TOFIDENCE with CYP3A4 substrate drugs where decrease in effectiveness is undesirable, e.g., oral contraceptives, lovastatin, atorvastatin, etc.

Exercise caution when coadministering TYENNE with CYP3A4 substrate drugs where decrease in effectiveness is undesirable, e.g., oral contraceptives, lovastatin, atorvastatin, etc.

Lovastatin Simvastatin Atorvastatin Use VOQUEZNA TRIPLE PAK with caution.

Coumarin anticoagulant; bleeding and increased prothrombin time reported with lovastatin. Requires monitoring.

Additionally, no dosage adjustment for substrates of CYP2D6 (e.g., dextromethorphan), CYP3A4 (e.g., lovastatin), CYP2B6 (e.g., bupropion), BCRP (e.g., rosuvastatin), or P-gp (e.g., fexofenadine) is required when administered concomitantly with REXULTI.

Oral Hypoglycemic Agents In pharmacokinetic studies of lovastatin in hypercholesterolemic non-insulin dependent diabetic patients, there was no drug interaction with glipizide or with chlorpropamide (see CLINICAL PHARMACOLOGY , Clinical Studies in Adults ).

In a ten-subject randomized, open-label, 4-way crossover study, coadministration of diltiazem (120 mg BID diltiazem SR for 2 weeks) with a single 20 mg dose of lovastatin resulted in 3- to 4-fold increase in mean lovastatin AUC and C max versus lovastatin alone. Diltiazem plasma levels were not significantly affected by lovastatin or pravastatin.

Fluvastatin Lovastatin Simvastatin ↑ fluvastatin ↑ lovastatin ↑ simvastatin Statin-associated adverse events such as myopathy should be closely monitored.

Lovastatin simvastatin fluvastatin pitavastatin ↓ lovastatin ↓ simvastatin ↑ fluvastatin ↑ pitavastatin Lovastatin and simvastatin are CYP3A substrates and co-administration with etravirine tablets may result in lower plasma concentrations of the HMG-CoA reductase inhibitor. Lovastatin simvastatin fluvastatin pitavastatin ↓ lovastatin ↓ simvastatin ↑ fluvastatin ↑ pitavastatin Lovastatin and simvastatin are CYP3A substrates and co-administration with etravirine tablets may result in lower plasma concentrations of the HMG-CoA reductase inhibitor.

7.7 Simvastatin and Lovastatin Due to an interaction with cyclosporine, clinical studies of everolimus with cyclosporine conducted in kidney transplant patients strongly discouraged patients with receiving HMG-CoA reductase inhibitors such as simvastatin and lovastatin [see Warnings and Precautions ( 5.11 )] .

7.7 Simvastatin and Lovastatin Due to an interaction with cyclosporine, clinical studies of everolimus with cyclosporine conducted in kidney transplant patients strongly discouraged patients with receiving HMG-CoA reductase inhibitors such as simvastatin and lovastatin [see Warnings and Precautions (5.11) ] .

HMG-CoA Reductase Inhibitors: Atorvastatin Lovastatin Simvastatin ↑ atorvastatin ↑ lovastatin ↑ simvastatin Coadministration may increase the concentration of atorvastatin, lovastatin, and simvastatin.

HMG-CoA Reductase Inhibitors: lovastatin simvastatin ↑ lovastatin ↑ simvastatin Initiate lovastatin and simvastatin with the lowest starting dose and titrate carefully while monitoring for safety (e.g., myopathy).

fluvastatin, lovastatin, pravastatin, rosuvastatin ↑ HMG-CoA reductase inhibitors When PREVYMIS is co-administered with these statins, a statin dosage reduction may be necessary . When PREVYMIS is co-administered with cyclosporine, use of lovastatin is not recommended.

Examples Alfentanil, avanafil, buspirone, conivaptan b , dabigatran etexilate, darifenacin, darunavir, digoxin, ebastine, everolimus, fexofenadine, ibrutinib, lomitapide, lovastatin, lurasidone, midazolam, naloxegol, nisoldipine, saquinavir, simvastatin, sirolimus, tacrolimus, tipranavir b , triazolam, and vardenafil.

Chloral Hydrate Diazepam Ethionamide Lovastatin Metoclopramide 6-Mercaptopurine Nitroprusside Para-aminosalicylate sodium Perphenazine Resorcinol (excessive topical use) Thiazide Diuretics These agents have been associated with thyroid hormone and/or TSH level alterations by various mechanisms.

Limit the daily dose of lovastatin to 40 mg.

Propranolol In normal volunteers, there was no clinically significant pharmacokinetic or pharmacodynamic interaction with concomitant administration of single doses of lovastatin and propranolol.

Co-administration of propranolol with lovastatin or pravastatin, decreased 18% to 23% the AUC of both, but did not alter their pharmacodynamics. Co-administration of propranolol with lovastatin or pravastatin, decreased 18% to 23% the AUC of both, but did not alter their pharmacodynamics. Co-administration of propranolol with lovastatin or pravastatin, decreased 18% to 23% the AUC of both, but did not alter their pharmacodynamics.

Thus, clinicians considering combined therapy of quinine sulfate with atorvastatin or other HMG-CoA reductase inhibitors (“statins”) that are CYP3A4 substrates (e.g., simvastatin, lovastatin) should carefully weigh the potential benefits and risks of each medication.

Thus, clinicians considering combined therapy of quinine sulfate with atorvastatin or other HMG-CoA reductase inhibitors ("statins") that are CYP3A4 substrates (e.g., simvastatin, lovastatin) should carefully weigh the potential benefits and risks of each medication.

atorvastatin fluvastatin lovastatin simvastatin ↑ atorvastatin ↑ fluvastatin ↑ lovastatin ↑ simvastatin Coadministration with VOSEVI may increase the concentrations of atorvastatin, fluvastatin, lovastatin, and simvastatin.

Midazolam or Lovastatin) — Tadalafil had no significant effect on exposure (AUC) to midazolam or lovastatin.

However, clinical studies have shown that lovastatin does not reduce basal plasma cortisol concentration or impair adrenal reserve, and does not reduce basal plasma testosterone concentration. Another HMG-CoA reductase inhibitor has been shown to reduce the plasma testosterone response to HCG. In the same study, the mean testosterone response to HCG was slightly but not significantly reduced after treatment with lovastatin 40 mg daily for 16 weeks in 21 men.

Limit the daily dose of lovastatin to 40 mg.