] Ezetimibe and Simvastatin Tablets Drug Interactions Associated With Increased Risk of Myopathy/Rhabdomyolysis ( 2.3 , 2.4 , 4 , 5.1 , 7.1 , 7.2 , 7.3 , 7.8 , 12.3 ) Interacting Agents Prescribing Recommendations Strong CYP3A4 Inhibitors, (e.g., itraconazole, ketoconazole, posaconazole, voriconazole, erythromycin, clarithromycin, telithromycin, HIV protease inhibitors, boceprevir, telaprevir, nefazodone, cobicistat-containing products), gemfibrozil, cyclosporine, danazol Contraindicated with ezetimibe and simvastatin tablets Niacin (≥1 g/day) For Chinese patients, not recommended with ezetimibe and simvastatin tablets Verapamil, diltiazem, dronedarone Do not exceed 10 mg/10 mg ezetimibe and simvastatin tablets, daily Amiodarone, amlodipine, ranolazine Do not exceed 10 mg/20 mg ezetimibe and simvastatin tablets, daily Lomitapide For patients with HoFH, do not exceed 10 mg/20 mg ezetimibe and simvastatin tablets 1 Daptomycin Temporally suspend ezetimibe and simvastatin tablets Grapefruit juice Avoid grapefruit juice 1. 7.3 Amiodarone, Dronedarone, Ranolazine, or Calcium Channel Blockers The risk of myopathy, including rhabdomyolysis, is increased by concomitant administration of amiodarone, dronedarone, ranolazine, or calcium channel blockers such as verapamil, diltiazem or amlodipine [ see Dosage and Administration ( 2.3 ) and Warnings and Precautions ( 5.1 ) and Table 6 in Clinical Pharmacology ( 12.3 ) ].
Source: FDA drug label - ezetimibe and simvastatin
7 DRUG INTERACTIONS NSAIDS: Increased risk of renal impairment and loss of antihypertensive effect (7) If simvastatin is co-administered with amlodipine, do not exceed doses greater than 20 mg daily of simvastatin (7) Do not co-administer aliskiren with telmisartan and amlodipine tablets in patients with diabetes (7.2) 7.1 Drug Interactions with Telmisartan and Amlodipine Tablets The pharmacokinetics of amlodipine and telmisartan are not altered when the drugs are co-administered. No drug interaction studies have been conducted with telmisartan and amlodipine tablets and other drugs, although studies have been conducted with the individual amlodipine and telmisartan components of telmisartan and amlodipine tablets, as described below: 7.2 Drug Interactions with Telmisartan Aliskiren: Do not co-administer aliskiren with telmisartan and amlodipine tablets in patients with diabetes. Avoid use of aliskiren with telmisartan and amlodipine tablets in patients with renal impairment (GFR <60 mL/min).
Source: FDA drug label - telmisartan and amlodipine
7 DRUG INTERACTIONS Potassium supplements/potassium-sparing diuretics: hyperkalemia ( 7.1 ) Lithium: Increased serum lithium levels; toxicity symptoms ( 7.1 ) Injectable gold: facial flushing, nausea, vomiting, hypotension ( 7.1 ) Nonsteroidal Anti-Inflammatory Drugs (NSAIDs): Risk of renal dysfunction, loss of antihypertensive effect (7.1) Do not exceed doses greater than 20 mg daily of simvastatin (7.1) mTOR inhibitors: increased risk of angioedema ( 7.1 ) Dual inhibition of the RAS: Increased risk of renal impairment, hypotension, and hyperkalemia (7.1) Neprilysin inhibitors: increased risk of angioedema ( 7.1 ) 7.1 Drug/Drug Interactions Amlodipine Simvastatin : Coadministration of simvastatin with amlodipine increases the systemic exposure of simvastatin. Limit the dose of simvastatin in patients on amlodipine to 20 mg daily. CYP3A4 Inhibitors : Coadministration with CYP3A inhibitors (moderate and strong) results in increased systemic exposure to amlodipine and may require dose reduction.
Source: FDA drug label - amlodipine besylate and benazepril hydrochloride
Examples: • Amlodipine, clevidipine, felodipine, isradipine, nicardipine, nifedipine, nimodipine, and nisoldipine Drugs that May Induce Magnesium Loss Clinical Impact: • Reduced magnesium concentrations may impact efficacy Intervention: • Monitor magnesium concentrations frequently and adjust the Magnesium Sulfate in 5% Dextrose Injection dosage to maintain concentrations in the target range [see Dosage and Administration (2) ] .
Source: FDA drug label - magnesium sulfate in dextrose
Amlodipine Impact of Other Drugs on Amlodipine CYP3A Inhibitors Coadministration with CYP3A inhibitors (moderate and strong) results in increased systemic exposure to amlodipine and may require dose reduction. Monitor for symptoms of hypotension and edema when amlodipine is coadministered with CYP3A inhibitors to determine the need for dose adjustment [see Clinical Pharmacology (12.3)] . CYP3A Inducers No information is available on the quantitative effects of CYP3A inducers on amlodipine.
Source: FDA drug label - amlodipine valsartan and hydrochlorothiazide
7 DRUG INTERACTIONS Data from a drug-drug interaction study involving 10 mg of amlodipine and 80 mg of atorvastatin in healthy subjects indicate that the pharmacokinetics of amlodipine are not altered when the drugs are co-administered. The effect of amlodipine on the pharmacokinetics of atorvastatin showed no effect on the C max : 91% (90% confidence interval: 80 to 103%), but the AUC of atorvastatin increased by 18% (90% confidence interval: 109 to 127%) in the presence of amlodipine, which is not clinically meaningful. No drug interaction studies have been conducted with amlodipine and atorvastatin and other drugs, although studies have been conducted in the individual amlodipine and atorvastatin components, as described below: Amlodipine See full prescribing information for details regarding concomitant use of amlodipine and atorvastatin tablets with other drugs or grapefruit juice that increase the risk of myopathy and rhabdomyolysis (2.5, 7.3 ).
Source: FDA drug label - amlodipine and atorvastatin
7 DRUG INTERACTIONS 7.1 In Vitro Data In vitro data indicate that amlodipine has no effect on the human plasma protein binding of digoxin, phenytoin, warfarin, and indomethacin. 7.2 Cimetidine Co-administration of amlodipine with cimetidine did not alter the pharmacokinetics of amlodipine. 7.3 Grapefruit Juice Co-administration of 240 mL of grapefruit juice with a single oral dose of amlodipine 10 mg in 20 healthy volunteers had no significant effect on the pharmacokinetics of amlodipine.
Source: FDA drug label - amlodipine besylate
7 DRUG INTERACTIONS Amlodipine ( 7.1 ): If simvastatin is co-administered with amlodipine, do not exceed 20 mg daily of simvastatin. Increased exposure of amlodipine when coadministered with CYP3A inhibitors. 7.1 Drug Interactions with Amlodipine Simvastatin: Co-administration of simvastatin with amlodipine increases the systemic exposure of simvastatin.
Source: FDA drug label - amlodipine besylate and olmesartan medoxomil
Amlodipine Diltiazem Amlodipine, Diltiazem: [See Warnings and Precautions ( 5.4 )] Nifedipine Nifedipine: Nifedipine is a substrate for CYP3A.
Source: FDA drug label - clarithromycin
Calcium Channel Blockers : amlodipine, diltiazem, felodipine, nicardipine, nifedipine, verapamil ↑ calcium channel blockers Clinical monitoring of patients is recommended.
Source: FDA drug label - darunavir
amlodipine, diltiazem, felodipine, nifedipine, verapamil ↑ calcium channel blockers Clinical monitoring is recommended for co-administration with calcium channel blockers metabolized by CYP3A.
Source: FDA drug label - darunavir ethanolate and cobicistat
These include colchicine toxicity with colchicine; rhabdomyolysis with simvastatin, lovastatin and atorvastatin; and hypotension with calcium channel blockers metabolized by CYP3A4 (e.g., verapamil, amlodipine, diltiazem) (see PRECAUTIONS - Drug Interactions ).
Source: FDA drug label - erythromycin
Calcium channel blockers : Certain calcium channel antagonists (nifedipine, isradipine, amlodipine, verapamil, and felodipine) are metabolized by CYP3A4.
Source: FDA drug label - fluconazole
7.3 Amlodipine When sildenafil tablets 100 mg were co-administered with amlodipine (5 mg or 10 mg) to hypertensive patients, the mean additional reduction on supine blood pressure was 8 mmHg systolic and 7 mmHg diastolic [ see Warnings and Precautions ( 5.5 ), Clinical Pharmacology ( 12.2 ) ].
Source: FDA drug label - sildenafil
7.3 Amlodipine When sildenafil 100 mg was co-administered with amlodipine (5 mg or 10 mg) to hypertensive patients, the mean additional reduction on supine blood pressure was 8 mmHg systolic and 7 mmHg diastolic [ see Warnings and Precautions (5.5) , Clinical Pharmacology (12.2) ].
Source: FDA drug label - sildenafil citrate
For patients taking amiodarone, amlodipine, or ranolazine, do not exceed simvastatin 20 mg daily [see DOSAGE AND ADMINISTRATION ( 2.5 )] .
Source: FDA drug label - simvastatin
Clinical pharmacology studies were conducted to assess the effect of tadalafil on the potentiation of the blood-pressure-lowering effects of selected antihypertensive medications (amlodipine, angiotensin II receptor blockers, bendrofluazide, enalapril, and metoprolol).
Source: FDA drug label - tadalafil
Amlodipine Diltiazem Nifedipine Ergot Alkaloids Clinical Effect Clarithromycin is a strong CYP3A inhibitor.
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