Losartan

Brand names: COZAAR, HYZAAR, Losartan Potassium, Losartan Potassium and Hydrochlorothiazide, Losartan potassium, Losartan potassium and hydrochlorothiazide, losartan potassium and hydrochlorothiazide

Boxed warning

WARNING: FETAL TOXICITY When pregnancy is detected, discontinue losartan potassium tablets as soon as possible. Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus. [see Warnings and Precautions (5.1) ]. WARNING: FETAL TOXICITY See full prescribing information for complete boxed warning. When pregnancy is detected, discontinue losartan potassium tablets as soon as possible. Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus. ( 5.1 )

Warnings

BOXED WARNING: BOXED WARNING - Fetal Toxicity: "When pregnancy is detected, discontinue losartan potassium tablets as soon as possible." Drugs affecting the renin-angiotensin system cause fetal injury and death, particularly during the second and third trimesters, resulting in oligohydramnios, lung hypoplasia, and skeletal deformations. Additional Warnings: - Symptomatic hypotension may occur in volume-depleted patients; correct conditions before administration or use lower starting doses - Impaired renal function changes reported in susceptible individuals - Hyperkalemia risk, particularly in diabetic patients with renal impairment

Contraindications

4 CONTRAINDICATIONS Losartan potassium tablets, are contraindicated: • In patients who are hypersensitive to any component of this product. • For coadministration with aliskiren in patients with diabetes. • Hypersensitivity to any component. ( 4 ) • Coadministration with aliskiren in patients with diabetes. ( 4 )

Overdose

10 OVERDOSAGE Significant lethality was observed in mice and rats after oral administration of 1000 mg/kg and 2000 mg/kg, respectively, about 44 and 170 times the maximum recommended human dose on a mg/m 2 basis. Limited data are available in regard to overdosage in humans. The most likely manifestation of overdosage would be hypotension and tachycardia; bradycardia could occur from parasympathetic (vagal) stimulation. If symptomatic hypotension should occur, supportive treatment should be instituted. Neither losartan nor its active metabolite can be removed by hemodialysis.

Drug interactions

7 DRUG INTERACTIONS • Agents increasing Serum Potassium: Risk of hyperkalemia. ( 7.1 ) • Lithium: Risk of lithium toxicity. ( 7.2 ) • NSAIDs: Increased risk of renal impairment and reduced diuretic, natriuretic, and antihypertensive effects. ( 7.3 ) • Dual inhibition of the Renin-Angiotensin System: Increased risk of renal impairment, hypotension, syncope, and hyperkalemia. ( 7.4 ) 7.1 Agents Increasing Serum Potassium Coadministration of losartan with other drugs that raise serum potassium levels may result in hyperkalemia. Monitor serum potassium in such patients. 7.2 Lithium Increases in serum lithium concentrations and lithium toxicity have been reported during concomitant administration of lithium with angiotensin II receptor antagonists. Monitor serum lithium levels during concomitant use. 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. These effects are usually reversible. Monitor renal function periodically in patients receiving losartan and NSAID therapy. The antihypertensive effect of angiotensin II receptor antagonists, including losartan, may be attenuated by NSAIDs, including selective COX-2 inhibitors. 7.4 Dual Blockade of the Renin-Angiotensin System (RAS) Dual blockade of the RAS with angiotensin receptor blockers, ACE inhibitors, or aliskiren is associated with increased risks of hypotension, syncope, hyperkalemia, and changes in renal function (including acute renal failure) compared to monotherapy. The Veterans Affairs Nephropathy in Diabetes (VA NEPHRON-D) trial enrolled 1448 patients with type 2 diabetes, elevated urinary-albumin-to-creatinine ratio, and decreased estimated glomerular filtration rate (GFR 30 to 89.9 mL/min), randomized them to lisinopril or placebo on a background of losartan therapy and followed them for a median of 2.2 years. Patients receiving the combination of losartan and lisinopril did not obtain any additional benefit compared to monotherapy for the combined endpoint of decline in GFR, end stage renal disease, or death, but experienced an increased incidence of hyperkalemia and acute kidney injury compared with the monotherapy group. In most patients no benefit has been associated with using two RAS inhibitors concomitantly. In general, avoid combined use of RAS inhibitors. Closely monitor blood pressure, renal function, and electrolytes in patients on losartan potassium tablets and other agents that affect the RAS. Do not coadminister aliskiren with losartan potassium tablets in patients with diabetes. Avoid use of aliskiren with losartan potassium tablets in patients with renal impairment (GFR <60 mL/min).

Uses

Losartan potassium tablets treat hypertension alone or combined with other antihypertensive agents. The medication also addresses diabetic nephropathy with elevated serum creatinine and proteinuria in type 2 diabetes patients with hypertension history, reducing nephropathy progression rates.

Dosage forms & strengths

Tablet Tablet, Film Coated TABLET

LOSARTAN POTASSIUM 100 mg HYDROCHLOROTHIAZIDE 25 mg LOSARTAN POTASSIUM 25 mg LOSARTAN POTASSIUM 50 mg HYDROCHLOROTHIAZIDE 12.5 mg losartan potassium 100 mg hydrochlorothiazide 12.5 mg hydrochlorothiazide 25 mg losartan potassium 25 mg losartan potassium 50 mg LOSARTAN POTASSIUM 50 mg/1 LOSARTAN POTASSIUM 25 mg/1 LOSARTAN POTASSIUM 100 mg/1

2 DOSAGE AND ADMINISTRATION Hypertension • Usual adult dose: 50 mg once daily. ( 2.1 ) • Usual pediatric starting dose: 0.7 mg per kg once daily (up to 50 mg). ( 2.1 ) Hypertensive Patients with Left Ventricular Hypertrophy • Usual starting dose: 50 mg once daily. ( 2.2 ) • Add hydrochlorothiazide 12.5 mg and/or increase losartan potassium tablets to 100 mg followed by an increase to hydrochlorothiazide 25 mg if further blood pressure response is needed. ( 2.2 , 14.2 ) Nephropathy in Type 2 Diabetic Patients • Usual dose: 50 mg once daily. ( 2.3 ) • Increase dose to 100 mg once daily if further blood pressure response is needed. ( 2.3 ) 2.1 Hypertension Adult Hypertension The usual starting dose of losartan potassium tablet is 50 mg once daily. The dosage can be increased to a maximum dose of 100 mg once daily as needed to control blood pressure [see Clinical Studies (14.1) ] . A starting dose of 25 mg is recommended for patients with possible intravascular depletion (e.g., on diuretic therapy). Pediatric Hypertension The usual recommended starting dose is 0.7 mg per kg once daily (up to 50 mg total) administered as a tablet or a suspension [see Dosage and Administration (2.5) ]. Dosage should be adjusted according to blood pressure response. Doses above 1.4 mg per kg (or in excess of 100 mg) daily have not been studied in pediatric patients [see Clinical Pharmacology (12.3) , Clinical Studies (14.1) , and Warnings and Precautions (5.2) ] . Losartan potassium tablets are not recommended in pediatric patients less than 6 years of age or in pediatric patients with estimated glomerular filtration rate less than 30 mL/min/1.73 m 2 [see Use in Specific Populations (8.4) , Clinical Pharmacology (12.3) , and Clinical Studies (14) ]. 2.2 Hypertensive Patients with Left Ventricular Hypertrophy The usual starting dose is 50 mg of losartan potassium tablet once daily. Hydrochlorothiazide 12.5 mg daily should be added and/or the dose of losartan potassium tablets should be increased to 100 mg once daily followed by an increase in hydrochlorothiazide to 25 mg once daily based on blood pressure response [see Clinical Studies (14.2) ] . 2.3 Nephropathy in Type 2 Diabetic Patients The usual starting dose is 50 mg once daily. The dose should be increased to 100 mg once daily based on blood pressure response [see Clinical Studies (14.3) ] . 2.4 Dosage Modifications in Patients with Hepatic Impairment In patients with mild-to-moderate hepatic impairment the recommended starting dose of losartan potassium tablet is 25 mg once daily. Losartan potassium tablets have not been studied in patients with severe hepatic impairment [see Use in Specific Populations (8.8) and Clinical Pharmacology (12.3) ] . 2.5 Preparation of Suspension (for 200 mL of a 2.5 mg/mL suspension) Add 10 mL of Purified Water USP to an 8 ounce (240 mL) amber polyethylene terephthalate (PET) bottle containing ten 50 mg losartan potassium tablets. Immediately shake for at least 2 minutes. Let the concentrate stand for 1 hour and then shake for 1 minute to disperse the tablet contents. Separately prepare a 50/50 volumetric mixture of Ora-Plus TM and Ora-Sweet SF TM . Add 190 mL of the 50/50 Ora-Plus TM /Ora- Sweet SF TM mixture to the tablet and water slurry in the PET bottle and shake for 1 minute to disperse the ingredients. The suspension should be refrigerated at 2 to 8°C (36 to 46°F) and can be stored for up to 4 weeks. Shake the suspension prior to each use and return promptly to the refrigerator.