Losartan

Contraindicated in patients with diabetes. Should be avoided in patients with renal impairment (GFR <60 mL/min) due to increased risk of hypotension, syncope, hyperkalemia, and acute renal failure.

Avoid concomitant use of fluconazole with lemborexant Losartan: Fluconazole inhibits the metabolism of losartan to its active metabolite (E-31 74) which is responsible for most of the angiotensin II-receptor antagonism which occurs during treatment with losartan.

Dual blockade of renin-angiotensin system increases risks of hypotension, hyperkalemia, and acute kidney injury compared to monotherapy.

Combined losartan and lisinopril therapy resulted in increased incidence of hyperkalemia and acute kidney injury compared to monotherapy, without additional benefit.

Increases in serum lithium concentrations and lithium toxicity have been reported during concomitant administration. Monitor serum lithium levels during concomitant use.

May substantially increase steady-state plasma lithium levels, sometimes resulting in lithium toxicity.

May result in deterioration of renal function, including possible acute renal failure, especially in elderly, volume-depleted, or renal-impaired patients. Antihypertensive effect may be attenuated.

May result in deterioration of renal function, including possible acute renal failure, especially in elderly, volume-depleted, or renal-impaired patients. Antihypertensive effect may be attenuated.

NSAIDs may diminish antihypertensive effect. In elderly, volume-depleted, or renal-impaired patients, may result in deterioration of renal function including acute renal failure.

Indomethacin can reduce the antihypertensive effects of losartan. May result in further deterioration of renal function in patients with compromised renal function.

( 7.4 ) 7.1 Agents Increasing Serum Potassium Coadministration of losartan with other drugs that raise serum potassium levels may result in hyperkalemia. 7.3 Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) Including Selective Cyclooxygenase-2 Inhibitors (COX-2 Inhibitors) In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, coadministration of NSAIDs, including selective COX-2 inhibitors, with angiotensin II receptor antagonists (including losartan) may result in deterioration of renal function, including possible acute renal failure. Monitor renal function periodically in patients receiving losartan and NSAID therapy.

( 7.5 ) 7.1 Agents Increasing Serum Potassium Coadministration of losartan with other drugs that raise serum potassium levels may result in hyperkalemia. Monitor lithium levels in patients receiving losartan potassium and hydrochlorothiazide tablets and lithium. 7.3 Non-Steroidal Anti-Inflammatory Agents Including Selective Cyclooxygenase-2 Inhibitors Losartan Potassium In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, coadministration of NSAIDs, including selective COX-2 inhibitors, with angiotensin II receptor antagonists (including losartan) may result in deterioration of renal function, including possible acute renal failure.

In vivo testing showed no clinically significant changes in losartan exposure when co-administered with LOKELMA.

Since desogestrel is mainly metabolized by the cytochrome P450 2C9 enzyme (CYP 2C9) to form etonogestrel, the active progestin, there is a possibility of interaction with CYP 2C9 substrates or inhibitors (such as: ibuprofen, piroxicam, naproxen, phenytoin, fluconazole, diclofenac, tolbutamide, glipizide, celecoxib, sulfamethoxazole, isoniazid, torsemide, irbesartan, losartan, and valsartan).

7 DRUG INTERACTIONS Table 2: Oral drugs that can be administered concomitantly with ferric citrate Amlodipine Aspirin Atorvastatin Calcitriol Clopidogrel Digoxin Diltiazem Doxercalciferol Enalapril Fluvastatin Glimepiride Levofloxacin Losartan Metoprolol Pravastatin Propranolol Sitagliptin Warfarin Oral drugs that have to be separated from ferric citrate and meals Dosing Recommendations Doxycycline Take at least 1 hour before ferric citrate Ciprofloxacin Take at least 2 hours before or after ferric citrate Oral medications not listed in Table 2.

7.5 Drugs with No Observed Clinically Significant Interactions with MAVYRET No dose adjustment is required when MAVYRET is coadministered with the following medications: abacavir, amlodipine, caffeine, dextromethorphan, dolutegravir, elvitegravir/ cobicistat, emtricitabine, ethinyl estradiol of 20 mcg or less, felodipine, lamivudine, lamotrigine, losartan, midazolam, norethindrone or other progestin-only contraceptives, omeprazole, raltegravir, rilpivirine, sofosbuvir, tacrolimus, tenofovir alafenamide, tenofovir disoproxil fumarate, tolbutamide, and valsartan.

Table 3: No observed clinically important drug interactions of Veltassa Angiotensin-converting enzyme (ACE) inhibitors Benazepril, captopril, enalapril, fosinopril, lisinopril, perindopril, quinapril, ramipril, trandolapril Angiotensin II receptor blockers (ARB) Azilsartan, candesartan, irbesartan, losartan, olmesartan, valsartan β-adrenoceptor blockers (β-blocker) Metoprolol Loop diuretics Furosemide, bumetanide, torasemide Mineralocorticoid receptor antagonists (MRA) Eplerenone, finerenone, spironolactone Neprilysin inhibitors Sacubitril Sodium-glucose cotransporter-2 (SGLT-2) inhibitors Canagliflozin, dapagliflozin, empagliflozin Antibiotics Trimethoprim, amoxicillin, cephalexin Anticoagulants Warfarin, apixaban, rivaroxaban Anti-parathyroid agents and Thyroid preparations Cinacalcet Antithrombotic agents Clopidogrel, acetylsalicylic acid Blood glucose lowering drugs Glipizide Calcium channel blockers Amlodipine, verapamil Immunosuppressants Tacrolimus Others Lithium, allopurinol, atorvastatin, digoxin, phenytoin, riboflavin, sevelamer

Substitute non-enzyme inducing therapies at least 2 weeks prior to initiation of irinotecan therapy Decrease irinotecan and active metabolite exposure Levothyroxine Decrease exposure Losartan Parent Decrease AUC by 30% Active metabolite (E3174) Decrease AUC by 40% Methadone In patients well-stabilized on methadone, concomitant administration of rifampin resulted in a marked reduction in serum methadone levels and a concurrent appearance of withdrawal symptoms.

7 DRUG INTERACTIONS Table 1 Oral drugs that can be administered concomitantly with Velphoro Calcitriol Ciprofloxacin Digoxin Enalapril Furosemide HMG-CoA reductase inhibitors Hydrochlorothiazide Losartan Metoprolol Nifedipine Omeprazole Quinidine Warfarin Oral drugs that are to be separated from Velphoro Dosing Recommendations Doxycycline Acetylsalicylic acid Cephalexin Take at least 1 hour before Velphoro. Velphoro can be administered concomitantly with oral calcitriol, ciprofloxacin, digoxin, enalapril, furosemide, HMG‑CoA reductase inhibitors, hydrochlorothiazide, losartan, metoprolol, nifedipine, omeprazole, quinidine and warfarin.