Gastroprokinetic Agents: Cisapride Contraindicated Cisapride: [See Contraindications ( 4.2 )] Lipid-lowering agents: Lomitapide Lovastatin Simvastatin Contraindicated 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 )] Atorvastatin Pravastatin Use With Caution Fluvastatin No Dose Adjustment Hypoglycemic Agents: Nateglinide Pioglitazone Repaglinide Rosiglitazone Use With Caution Nateglinide, Pioglitazone, Repaglinide, Rosiglitazone: [See Warnings and Precautions ( 5.4 ) and Adverse Reactions ( 6.2 )] Insulin Insulin: [See Warnings and Precautions ( 5.4 ) and Adverse Reactions ( 6.2 )] Immunosuppressants: Cyclosporine Use With Caution Cyclosporine: There have been spontaneous or published reports of CYP3A based interactions of clarithromycin with cyclosporine.
Source: FDA drug label - clarithromycin
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.
Source: FDA drug label - colchicine
7.2 Transporters Use caution when concomitantly administering eltrombopag and drugs that are substrates of OATP1B1 (e.g., atorvastatin, bosentan, ezetimibe, fluvastatin, glyburide, olmesartan, pitavastatin, pravastatin, rosuvastatin, repaglinide, rifampin, simvastatin acid, SN-38 [active metabolite of irinotecan], valsartan) or breast cancer resistance protein (BCRP) (e.g., imatinib, irinotecan, lapatinib, methotrexate, mitoxantrone, rosuvastatin, sulfasalazine, topotecan).
Source: FDA drug label - eltrombopag
HMG-CoA reductase inhibitors (statins) Literature and postmarketing cases of myotoxicity, including muscle pain and weakness, myositis, and rhabdomyolysis, have been reported with concomitant administration of cyclosporine with lovastatin, simvastatin, atorvastatin, pravastatin, and, rarely fluvastatin.
Source: FDA drug label - cyclosporine
atorvastatin, fluvastatin, pitavastatin, pravastatin, rosuvastatin ↑ atorvastatin ↑ fluvastatin ↑ pravastatin ↑ rosuvastatin pitavastatin: effect unknown For atorvastatin, fluvastatin, pitavastatin, pravastatin, and rosuvastatin, start with the lowest recommended dose and titrate while monitoring for safety (e.g.
Source: FDA drug label - darunavir ethanolate and cobicistat
Fluvastatin Lovastatin Simvastatin ↑ fluvastatin ↑ lovastatin ↑ simvastatin Statin-associated adverse events such as myopathy should be closely monitored.
Source: FDA drug label - elbasvir and grazoprevir
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. Fluvastatin and pitavastatin are metabolized by CYP2C9 and co-administration with etravirine tablets may result in higher 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.
Source: FDA drug label - etravirine
Table 1: Drugs That Affect Phenytoin Concentrations Interacting Agent Examples Drugs that may increase phenytoin serum levels Antiepileptic drugs Ethosuximide, felbamate, oxcarbazepine, methsuximide, topiramate Azoles Fluconazole, ketoconazole, itraconazole, miconazole, voriconazole Antineoplastic agents Capecitabine, fluorouracil Antidepressants Fluoxetine, fluvoxamine, sertraline Gastric acid reducing agents H 2 antagonists (cimetidine), omeprazole Sulfonamides Sulfamethizole, sulfaphenazole, sulfadiazine, sulfamethoxazole trimethoprim Other Acute alcohol intake, amiodarone, chloramphenicol, chlordiazepoxide, disulfiram, estrogen, fluvastatin, isoniazid, methylphenidate, phenothiazines, salicylates, ticlopidine, tolbutamide, trazodone, warfarin Drugs that may decrease phenytoin serum levels Antineoplastic agents usually in combination Bleomycin, carboplatin, cisplatin, doxorubicin, methotrexate Antiviral agents Fosamprenavir, nelfinavir, ritonavir Antiepileptic drugs Carbamazepine, vigabatrin Other Chronic alcohol abuse, diazepam, diazoxide, folic acid, reserpine, rifampin, St. Warfarin Increased and decreased PT/INR responses have been reported when phenytoin is coadministered with warfarin Other Corticosteroids, doxycycline, estrogens, furosemide, oral contraceptives, paroxetine, quinidine, rifampin, sertraline, theophylline, and vitamin D Drugs whose level is decreased by phenytoin Antiepileptic drugs a Carbamazepine, felbamate, lamotrigine, topiramate, oxcarbazepine Antilipidemic agents Atorvastatin, fluvastatin, simvastatin Antiviral agents Efavirenz, lopinavir/ritonavir, indinavir, nelfinavir, ritonavir, saquinavir Fosamprenavir: phenytoin when given with fosamprenavir alone may decrease the concentration of amprenavir, the active metabolite.
Source: FDA drug label - extended phenytoin sodium
HMG-CoA reductase inhibitors : The risk of myopathy and rhabdomyolysis increases when fluconazole is coadministered with HMG-CoA reductase inhibitors metabolized through CYP3A4, such as atorvastatin and simvastatin, or through CYP2C9, such as fluvastatin.
Source: FDA drug label - fluconazole
(D) OATP1B1 substrates: Gemfibrozil is an inhibitor of OATP1B1 transporter and may increase exposure of drugs that are substrates of OATP1B1 (e.g., atrasentan, atorvastatin, bosentan, ezetimibe, fluvastatin, glyburide, SN-38 [active metabolite of irinotecan], rosuvastatin, pitavastatin, pravastatin, rifampin, valsartan, olmesartan).
Source: FDA drug label - gemfibrozil
Since metabolic interactions are unlikely between nefazodone and HMG-CoA reductase inhibitors that undergo little or no metabolism by the CYP3A4 isozyme, such as pravastatin or fluvastatin, dosage adjustments should not be necessary.
Source: FDA drug label - nefazodone hydrochloride
Table 2: Drugs That Affect Phenytoin Concentrations Interacting Agent Examples Drugs that may increase phenytoin serum levels Antiepileptic drugs Ethosuximide, felbamate, oxcarbazepine, methsuximide, topiramate Azoles Fluconazole, ketoconazole, itraconazole, miconazole, voriconazole Antineoplastic agents Capecitabine, fluorouracil Antidepressants Fluoxetine, fluvoxamine, sertraline Gastric acid reducing agents H 2 antagonists (cimetidine), omeprazole Sulfonamides Sulfamethizole, sulfaphenazole, sulfadiazine, sulfamethoxazole-trimethoprim Other Acute alcohol intake, amiodarone, chloramphenicol, chlordiazepoxide, disulfiram, estrogen, fluvastatin, isoniazid, methylphenidate, phenothiazines, salicylates, ticlopidine, tolbutamide, trazodone, warfarin Drugs that may decrease phenytoin serum levels Antacids Antacids may affect absorption of phenytoin. Warfarin Increased and decreased PT/INR responses have been reported when phenytoin is coadministered with warfarin Other Corticosteroids, doxycycline, estrogens, furosemide, oral contraceptives, paroxetine, quinidine, rifampin, sertraline, theophylline, and vitamin D Drugs whose level is decreased by phenytoin Anticoagulants Apixaban, dabigatran, edoxaban, rivaroxaban Antiepileptic drugs The effect of phenytoin on phenobarbital, valproic acid and sodium valproate serum levels is unpredictable Carbamazepine, felbamate, lacosamide, lamotrigine, topiramate, oxcarbazepine Antilipidemic agents Atorvastatin, fluvastatin, simvastatin Antiplatelets Ticagrelor Antiviral agents Efavirenz, lopinavir/ritonavir, indinavir, nelfinavir, ritonavir, saquinavir Fosamprenavir: phenytoin when given with fosamprenavir alone may decrease the concentration of amprenavir, the active metabolite.
Source: FDA drug label - phenytoin
Propranolol did not have an effect on the pharmacokinetics of fluvastatin. Propranolol did not have an effect on the pharmacokinetics of fluvastatin. Propranolol did not have an effect on the pharmacokinetics of fluvastatin.
Source: FDA drug label - propranolol hydrochloride
atorvastatin fluvastatin lovastatin simvastatin ↑ atorvastatin ↑ fluvastatin ↑ lovastatin ↑ simvastatin Coadministration with VOSEVI may increase the concentrations of atorvastatin, fluvastatin, lovastatin, and simvastatin.
Source: FDA drug label - sofosbuvir, velpatasvir, and voxilaprevir
In vitro studies with human liver microsomes showed that terbinafine does not inhibit the metabolism of tolbutamide, ethinylestradiol, ethoxycoumarin, cyclosporine, cisapride and fluvastatin.
Source: FDA drug label - terbinafine
In vitro studies with human liver microsomes showed that terbinafine does not inhibit the metabolism of tolbutamide, ethinylestradiol, ethoxycoumarin, cyclosporine, cisapride and fluvastatin.
Source: FDA drug label - terbinafine hydrochloride
Pravastatin Fluvastatin Use of a statin that is not dependent on CYP3A metabolism (e.g., fluvastatin) can be considered.
Source: FDA drug label - vonoprazan fumarate and amoxicillin
Table 2: Examples of CYP450 Interactions with Warfarin Enzyme Inhibitors Inducers CYP2C9 amiodarone, capecitabine, cotrimoxazole, etravirine, fluconazole, fluvastatin, fluvoxamine, metronidazole, miconazole, oxandrolone, sulfinpyrazone, tigecycline, voriconazole, zafirlukast aprepitant, bosentan, carbamazepine, phenobarbital, rifampin CYP1A2 acyclovir, allopurinol, caffeine, cimetidine, ciprofloxacin, disulfiram, enoxacin, famotidine, fluvoxamine, methoxsalen, mexiletine, norfloxacin, oral contraceptives, phenylpropanolamine, propafenone, propranolol, terbinafine, thiabendazole, ticlopidine, verapamil, zileuton montelukast, moricizine, omeprazole, phenobarbital, phenytoin, cigarette smoking CYP3A4 alprazolam, amiodarone, amlodipine, amprenavir, aprepitant, atorvastatin, atazanavir, bicalutamide, cilostazol, cimetidine, ciprofloxacin, clarithromycin, conivaptan, cyclosporine, darunavir/ritonavir, diltiazem, erythromycin, fluconazole, fluoxetine, fluvoxamine, fosamprenavir, imatinib, indinavir, isoniazid, itraconazole, ketoconazole, lopinavir/ritonavir, nefazodone, nelfinavir, nilotinib, oral contraceptives, posaconazole, ranitidine, ranolazine, ritonavir, saquinavir, telithromycin, tipranavir, voriconazole, zileuton armodafinil, amprenavir, aprepitant, bosentan, carbamazepine, efavirenz, etravirine, modafinil, nafcillin, phenytoin, pioglitazone, prednisone, rifampin, rufinamide 7.3 Drugs that Increase Bleeding Risk Examples of drugs known to increase the risk of bleeding are presented in Table 3 .
Source: FDA drug label - warfarin sodium