Cozaar®

Losartan Potassium

Angiotensin II Receptor Antagonist

Merck Frosst

http://www.merck.com/

Cozaar Monograph PDF download here.

 

CPS:PIS_m143600

 

 

 

Pharmacology

Losartan antagonizes angiotensin II by blocking the angiotensin type 1 (AT₁) receptor.

     Angiotensin II is the primary vasoactive hormone of the renin-angiotensin system. Its effects include vasoconstriction and the stimulation of aldosterone secretion by the adrenal cortex.

     Losartan and its active metabolite, E-3174, block the vasoconstrictor and aldosterone-secreting effects of angiotensin II by selectively blocking the binding of angiotensin II to AT₁ receptors found in many tissues, including vascular smooth muscle. A second type of angiotensin II receptor has been identified as the AT₂ receptor, but it plays no known role in cardiovascular homeostasis to date. Both losartan and its active metabolite do not exhibit any agonist activity at the AT₁ receptor, and have much greater affinity, in the order of 1 000-fold, for the AT₁ receptor than for the AT₂ receptor. In vitro binding studies indicate that losartan itself is a reversible, competitive antagonist at the AT₁ receptor, while the active metabolite is 10 to 40 times more potent than losartan, and is a reversible, non-competitive antagonist of the AT₁ receptor.

     Neither losartan nor its active metabolite inhibits angiotensin converting enzyme (ACE), also known as kininase II, the enzyme that converts angiotensin I to angiotensin II and degrades bradykinin, nor do they bind to or block other hormone receptors or ion channels known to be important in cardiovascular regulation.

 

Pharmacokinetics

Losartan is an orally active agent that undergoes substantial first-pass metabolism by cytochrome P₄₅₀ enzymes. It is converted, in part, to an active carboxylic acid metabolite, E-3174, that is responsible for most of the angiotensin II receptor antagonism that follows oral losartan administration.

     The terminal half-life of losartan itself is about 2 hours, and that of the active metabolite, about 6 to 9 hours. The pharmacokinetics of losartan and this metabolite are linear with oral losartan doses up to 200 mg and do not change over time. Neither losartan nor its metabolite accumulate in plasma upon repeated once-daily administration.

     Following oral administration, losartan is well absorbed, with systemic bioavailability of losartan approximately 33%. About 14% of an orally-administered dose of losartan is converted to the active metabolite, although about 1% of subjects did not convert losartan efficiently to the active metabolite.

     Mean peak concentrations of losartan occur at about 1 hour, and that of its active metabolite at about 3 to 4 hours. Although maximum plasma concentrations of losartan and its active metabolite are approximately equal, the AUC of the metabolite is about 4 times greater than that of losartan.

     Both losartan and its active metabolite are highly bound to plasma proteins, primarily albumin, with plasma free fractions of 1.3% and 0.2% respectively. Plasma protein binding is constant over the concentration range achieved with recommended doses. Studies in rats indicate that losartan crosses the blood-brain barrier poorly, if at all.

     Various losartan metabolites have been identified in human plasma and urine. In addition to the active carboxylic acid metabolite, E-3174, several inactive metabolites are formed. In vitro studies indicate that the cytochrome P₄₅₀ isoenzymes 2C9 and 3A4 are involved in the biotransformation of losartan to its metabolites.

     The volume of distribution of losartan is about 34 L, and that of the active metabolite is about 12 L.

     Total plasma clearance of losartan is about 600 mL/min, with about 75 mL/min accounted for by renal clearance. Total plasma clearance of the active metabolite is about 50 mL/min, with about 25 mL/min accounted for by renal clearance. Both biliary and urinary excretion contribute substantially to the elimination of losartan and its metabolites.

     Following oral ¹⁴C-labeled losartan, about 35% of radioactivity is recovered in the urine and about 60% in the feces. Following an i.v. dose of ¹⁴C-labeled losartan, about 45% of radioactivity is recovered in the urine and 50% in the feces.

Pharmacodynamics

Losartan inhibits the pressor effect of angiotensin II. A dose of 100 mg inhibits this effect by about 85% at peak, with 25 to 40% inhibition persisting for 24 hours. Removal of the negative feedback of angiotensin II causes a 2 to 3 fold rise in plasma renin activity, and a consequent rise in angiotensin II plasma concentration, in hypertensive patients.

     Maximum blood pressure lowering, following oral administration of a single dose of losartan, as seen in hypertensive patients, occurs at about 6 hours.

     In losartan-treated patients during controlled trials, there was no meaningful change in heart rate.

     There is no apparent rebound effect after abrupt withdrawal of losartan therapy.

     Black hypertensive patients show a smaller average blood pressure response to losartan monotherapy than other hypertensive patients.

Clinical Trials

The Reduction of Endpoints in Non-Insulin Dependent Diabetes Mellitus (NIDDM) with the Angiotensin II Receptor Antagonist Losartan (RENAAL) study was a large, multicenter, randomized, placebo-controlled, double-blind study conducted worldwide in 1513 hypertensive patients with type 2 diabetes and  proteinuria (751 patients entered treatment with losartan).  The goal of the study was to demonstrate the renal protective effects of losartan over and above the benefits of blood pressure control alone.  To meet this objective the study was designed to achieve equal blood pressure control in both treatment groups.  Patients with proteinuria and serum creatinine of 1.3-3.0 mg/dL were randomized to receive losartan 50 mg once daily titrated according to blood pressure response, or placebo, on a background of conventional antihypertensive therapy excluding ACE inhibitors and angiotensin II antagonists.  Investigators were instructed to titrate study drug to 100 mg once daily as appropriate; 72% of patients were taking the 100 mg daily dose the majority of the time they were on study drug.  Other antihypertensive agents (diuretics, calcium-channel blockers, alpha- or beta-blockers, and centrally acting agents) could be added as needed in both groups.  Patients were followed for approximately 5 years (mean of 3.4 years).

     Important inclusion criteria of the RENAAL study included: type 2 diabetes defined as:  (1) diabetes diagnosed after the age of 30; (2) insulin not required within the first 6 months of diagnosis; and (3) no history of diabetic ketoacidosis; ages of 31  to 70; serum creatinine between 1.3 (1.5 for males >60 kg) and 3.0 mg/dL; and first morning urinary albumin/creatinine ratio (UA/Cr) of ≥ 300 mg/g (or a 24-hour urine total protein of >500 mg/day).  Patients could have been normotensive or hypertensive.

     Important exclusion criteria of the RENAAL study included: type 1 diabetes; history of heart failure; history of myocardial infarction or coronary artery bypass graft surgery within 1 month prior to study start, cerebral vascular accident or percutaneous transluminal coronary angioplasty within 6 months prior to study start, and history of transient ischemic attacks (TIA) within the year prior to study start; known history or current diagnosis of nondiabetic renal disease such as chronic glomerulonephritis or polycystic kidney disease; and uncontrolled diabetes, i.e., HBA1c >12%.

     The primary endpoint of the study was the composite endpoint of doubling of serum creatinine, end-stage renal disease (need for dialysis or transplantation), or death.  The results showed that treatment with losartan (327 events, 43.5%) as compared with placebo (359 events, 47.1%) resulted in a 16.1% risk reduction (p=0.022) for patients reaching the primary composite endpoint. For the following individual components of the primary endpoint, the results also showed significant risk reduction in the group treated with losartan as compared to placebo: 25.3% risk reduction in doubling of serum creatinine (21.6% vs 26.0%), (p=0.006); 28.6% risk reduction in end-stage renal disease (19.6% vs 25.5%), (p=0.002).  The rate of the all-cause deaths component was not significantly different between losartan and placebo group, 21.0% and 20.3%, respectively.

     The secondary endpoints of the study were: change in proteinuria; the rate of progression of renal disease; and the composite of morbidity and mortality from cardiovascular causes (hospitalization for heart failure, myocardial infarction, revascularization, stroke, hospitalization for unstable angina, or cardiovascular death).  For the secondary endpoint of change in proteinuria, the results showed an average reduction of 34.3% in the level of proteinuria in the group treated with losartan (p<0.001) over the mean of 3.4 years.  For the secondary endpoint of rate of progression of renal disease, treatment with losartan reduced the rate of decline in renal function during the chronic phase of the study by 13.9%, (p=0.01) as measured by the reciprocal of the serum creatinine concentration.

     In this study, losartan was generally well tolerated as evidenced by a similar incidence of discontinuations due to side effects compared to placebo. A tertiary endpoint in the study was assessment of quality of life. The results of this analysis suggest that there is no difference in the change of quality of life between treatment arms.

 

Indications

Treatment of essential hypertension.

     Losartan may be used alone or concomitantly with thiazide diuretics.

     A great majority of patients with severe hypertension in controlled clinical trials required combination therapy. Losartan has been used concomitantly with beta-blockers and calcium channel blockers, but the data on such use are limited.

     The safety and efficacy of concurrent use with angiotensin converting enzyme inhibitors have not been established.

Type 2 Diabetic Patients with Proteinuria and Hypertension: Losartan is also indicated to delay the progression of renal disease as measured by the occurrence of doubling of serum creatinine, and end stage renal disease,  and to reduce proteinuria (see Pharmacology, Clinical Trials).

 

Contraindications

In patients who are hypersensitive to any component of this product.

 

Warnings

Pregnancy

Drugs that act directly on the renin-angiotensin system can cause fetal and neonatal morbidity and death when administered to pregnant women. When pregnancy is detected, losartan should be discontinued as soon as possible.

     The use of drugs that act directly on the renin-angiotensin system during the second and third trimesters of pregnancy has been associated with fetal and neonatal injury, including hypotension, neonatal skull hypoplasia, anuria, reversible or irreversible renal failure and death. Oligohydramnios has also been reported, presumably resulting from decreased fetal renal function; oligohydramnios in this setting has been associated with fetal limb contractures, craniofacial deformation, and hypoplastic lung development. Prematurity, intrauterine growth retardation, and patent ductus arteriosus have also been reported, although it is not clear whether these occurrences were due to exposure to the drug. These adverse effects do not appear to have resulted from intrauterine drug exposure that has been limited to the first trimester.

     Mothers whose embryos and fetuses are exposed to an angiotensin II receptor antagonist only during the first trimester should be so informed. Nonetheless, when patients become pregnant, physicians should have the patient discontinue the use of losartan as soon as possible.

     Rarely (probably less often than once in every thousand pregnancies), no alternative to an angiotensin II receptor antagonist will be found. In these rare cases, the mothers should be apprised of the potential hazards to their fetuses, and serial ultrasound examinations should be performed to assess the intra-amniotic environment.

     If oligohydramnios is observed, losartan should be discontinued unless it is considered life-saving for the mother. Contraction stress testing (CST), a non-stress test (NST), or biophysical profiling (BPP) may be appropriate, depending upon the week of pregnancy. Patients and physicians should be aware, however, that oligohydramnios may not appear until after the fetus has sustained irreversible injury.

     Infants with histories of in utero exposure to an angiotensin II receptor antagonist should be closely observed for hypotension, oliguria, and hyperkalemia. If oliguria occurs, attention should be directed toward support of blood pressure and renal perfusion. Exchange transfusion may be required as means of reversing hypotension and/or substituting for impaired renal function. Neither losartan nor the active metabolite can be removed by hemodialysis.

Animal Data: Losartan has been shown to produce adverse effects in rat fetuses and neonates, which include decreased body weight, mortality and/or renal toxicity. Significant levels of losartan and its active metabolite were shown to be present in rat milk. Based on pharmacokinetic assessments, these findings are attributed to drug exposure in late gestation and during lactation.

Hypotension

Occasionally, symptomatic hypotension has occurred after administration of losartan, in some cases after the first dose. It is more likely to occur in patients who are volume-depleted by diuretic therapy, dietary salt restriction, dialysis, diarrhea or vomiting. In these patients, because of the potential fall in blood pressure, therapy should be started under close medical supervision. Similar considerations apply to patients with ischemic heart or cerebrovascular disease, in whom an excessive fall in blood pressure could result in myocardial infarction or cerebrovascular accident.

 

Precautions

Hypersensitivity: Angioedema (see Adverse Effects).

Renal Impairment: As a consequence of inhibiting the renin-angiotensin-aldosterone system, changes in renal function have been reported in susceptible individuals. In patients whose renal function may depend on the activity of the renin-angiotensin-aldosterone system, such as patients with bilateral renal artery stenosis, unilateral renal artery stenosis to a solitary kidney, or severe congestive heart failure, treatment with agents that inhibit this system has been associated with oliguria, progressive azotemia, and rarely, acute renal failure and/or death. In susceptible patients, concomitant diuretic use may further increase risk.

     Use of losartan should include appropriate assessment of renal function.

Hyperkalemia: In a clinical study conducted in patients with type 2 diabetes  with proteinuria and hypertension, the incidence of hyperkalemia was higher in the group treated with losartan (9.9%) as compared to the placebo group (3.4%), however, few patients discontinued therapy due to hyperkalemia. Careful monitoring of serum potassium is recommended (see Pharmacology, Clinical Trials and Adverse Effects, Laboratory Test Findings, Hyperkalemia).

Hepatic Impairment: Based on pharmacokinetic data which demonstrate significantly increased plasma concentrations of losartan and its active metabolite in cirrhotic patients after administration of losartan, a lower dose should be considered for patients with hepatic impairment, or a history of hepatic impairment (see Dosage).

Valvular Stenosis: There is concern on theoretical grounds that patients with aortic stenosis might be at particular risk of decreased coronary perfusion when treated with vasodilators because they do not develop as much afterload reduction.

 

Lactation

It is not known whether losartan or its active metabolite are excreted in human milk, however significant levels of both of these compounds have been shown to be present in the milk of lactating rats. Because many drugs are excreted in human milk, and because of their potential for affecting the nursing infant adversely, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.

 

Children

Safety and effectiveness have not been established.

Geriatrics

No overall differences in safety were observed between elderly and younger patients, but appropriate caution should nevertheless be used when prescribing to elderly, as increased vulnerability to drug effect is possible in this patient population. This conclusion is based on 391 of 2085 (19%) patients, 65 years and over who received losartan monotherapy in controlled trials for hypertension. This was also the finding in a controlled clinical study in type 2 diabetic patients with proteinuria and hypertension with 248 (33%) of patients over 65 years of age (see Pharmacology, Clinical Trials).

 

Drug Interactions

Antihypertensive effect of losartan may be attenuated by the NSAID indomethacin.

Diuretics: Patients on diuretics, and especially those in whom diuretic therapy was recently instituted, may occasionally experience an excessive reduction of blood pressure after initiation of therapy with losartan. The possibility of symptomatic hypotension with the use of losartan can be minimized by discontinuing the diuretic prior to initiation of treatment and/or lowering the initial dose of losartan (see Warnings, Hypotension and Dosage). No drug interaction of clinical significance has been identified with thiazide diuretics.

Agents Increasing Serum Potassium: Concomitant use of potassium-sparing diuretics (e.g., spironolactone, triamterene, amiloride), potassium supplements, or salt substitutes containing potassium may lead to increases in serum potassium.

     Since losartan decreases the production of aldosterone, potassium-sparing diuretics or potassium supplements should be given only for documented hypokalemia and with frequent monitoring of serum potassium. Potassium-containing salt substitutes should also be used with caution.

Lithium Salts: As with other drugs which eliminate sodium, lithium clearance may be reduced. Therefore, serum lithium levels should be monitored carefully if lithium salts are to be administered.

Digitalis: In 9 healthy volunteers, when a single oral dose of 0.5 mg digoxin was administered to patients receiving losartan for 11 days, digoxin AUC and digoxin C_max ratios, relative to placebo, were found to be 1.06 (90% C.I. 0.98 to 1.14) and 1.12 (90% C.I. 0.97 to 1.28), respectively. The effect of losartan on steady-state pharmacokinetics of cardiac glycosides is not known.

Warfarin: Losartan administered for 7 days did not affect the pharmacokinetics or pharmacodynamic activity of a single dose of warfarin. The effect of losartan on steady-state pharmacokinetics of warfarin is not known.

Drugs Affecting Cytochrome P450 System: Rifampin, an inducer of drug metabolism, decreases the concentrations of the active metabolite of losartan. In humans, 2 inhibitors of P450 3A4 have been studied. Ketoconazole did not affect the conversion of losartan to the active metabolite after i.v. administration of losartan, and erythromycin had no clinically significant effect after oral losartan administration. Fluconazole, an inhibitor of P450 2C9, decreased active metabolite concentration. The pharmacodynamic consequences of concomitant use of losartan and inhibitors of P450 2C9 have not been examined.

     When losartan was administered to 10 healthy male volunteers as a single dose in steady-state conditions of phenobarbital, a cytochrome P450 inducer, losartan AUC, relative to baseline, was 0.80 (90% C.I. 0.72 to 0.88), while AUC of the active metabolite, E-3174, was 0.80 (90% C.I. 0.78 to 0.82).

     When losartan was administered to 8 healthy male volunteers as a single dose in steady-state conditions of cimetidine, a cytochrome P450 inhibitor, losartan AUC, relative to baseline, was 1.18 (90% C.I. 1.10 to 1.27), while AUC of the active metabolite, E-3174, was 1.00 (90% C.I. 0.92 to 1.08).

 

Adverse Effects

Losartan has been evaluated for safety in more than 3300 patients treated for essential hypertension. Of these, 2085 were treated with losartan monotherapy in controlled clinical trials.

     In open studies, over 1200 patients were treated with losartan for more than 6 months, and over 800 for more than 1 year.

     In controlled clinical trials, discontinuation of therapy due to clinical adverse experiences occurred in 2.3% and 3.7% of patients treated with losartan and placebo, respectively.

     The following potentially serious adverse reactions have been reported rarely with losartan in controlled clinical trials: syncope and hypotension.

     In these double-blind controlled clinical trials, the following adverse reactions reported with losartan occurred in ≥ 1% of patients, regardless of drug relationship: see  Table 1.

CPS:Cozaar_t1Click here for Table 1

Table 1: Cozaar

Adverse Reactions that Occurred in ≥ 1% of Patients

 

	Cozaar % (n=2085)	Placebo % (n=535)
Body as a Whole
Asthenia/Fatigue	3.8	3.9
Edema/Swelling	1.7	1.9
Abdominal Pain	1.7	1.7
Chest Pain	1.1	2.6
Cardiovascular
Palpitation	1.0	0.4
Tachycardia	1.0	1.7
Digestive
Diarrhea	1.9	1.9
Dyspepsia	1.1	1.5
Nausea	1.8	2.8
Musculoskeletal
Back Pain	1.6	1.1
Muscle Cramps	1.0	1.1
Nervous/Psychiatric
Dizziness	4.1	2.4
Headache	14.1	17.2
Insomnia	1.1	0.7
Respiratory
Cough	3.1	2.6
Nasal Congestion	1.3	1.1
Pharyngitis	1.5	2.6
Sinus Disorder	1.0	1.3
Upper Respiratory Infection	6.5	5.6

 

     In these controlled clinical trials, dizziness was the only adverse experience, occurring in more than 1% of cases, that was reported as drug-related, and that occurred at a greater incidence in losartan-treated (2.4%) than placebo-treated (1.3%) patients.

     In double-blind, controlled clinical trials, the following adverse reactions were reported with losartan at an occurrence rate of less than 1%, regardless of drug relationship: orthostatic effects, somnolence, vertigo, epistaxis, tinnitus, constipation, malaise and rash.

     Losartan was generally well tolerated in a controlled clinical trial in type 2 diabetic patients with proteinuria and hypertension.  The most common drug-related side effects were asthenia/fatigue, dizziness, hypotension and hyperkalemia (see Precautions, Hyperkalemia).

Postmarketing Experience: Other adverse reactions reported rarely in open-label studies or postmarketing use, regardless of drug relationship, include anemia, hepatitis, liver function test abnormalities, drug-induced cough, asthenia, diarrhea, migraine, myalgia, pruritus, taste disorder and urticaria.

     Anaphylactic reactions, angioedema (involving swelling of the larynx and glottis causing airway obstruction and/or swelling of the face, lips, and/or tongue and pharynx, requiring intubation/tracheotomy in some cases) have been reported rarely in patients treated with losartan; some of these patients previously experienced angioedema with ACE inhibitors. Vasculitis, including Henoch-Schoenlien purpura, have been reported rarely.

Laboratory Test Findings: In controlled clinical trials, clinically important changes in standard laboratory parameters were rarely associated with administration of losartan.

Liver Function Tests: In double-blind hypertensive trials, elevations of AST and ALT occurred in 1.1% and 1.9% of patients treated with losartan monotherapy and in 0.8% and 1.3% of patients treated with placebo, respectively. When AST or ALT elevations ≥ 2X upper limit of normal were compared, the frequency was similar to that seen in placebo.

Hyperkalemia: In controlled hypertensive trials with losartan, elevation of serum potassium over 5.5 mEq/L occurred in 1.5% of patients.

     In a clinical study conducted in type 2 diabetic patients with proteinuria and hypertension, 9.9% of patients treated with losartan and 3.4% of patients treated with placebo developed hyperkalemia (see Precautions, Hyperkalemia).

Creatinine, Blood Urea Nitrogen: Minor increases in BUN or serum creatinine were observed in less than 0.1% of patients with essential hypertension treated with losartan alone. No patient discontinued taking losartan alone due to increased BUN or serum creatinine.

Hemoglobin and Hematocrit: Small decreases in hemoglobin and hematocrit (mean decreases of approximately 0.11 g % and 0.09 volume %, respectively) occurred frequently in patients treated with losartan alone, but were rarely of clinical importance. In controlled clinical trials no patients were discontinued due to anemia. Discontinuation of losartan treatment due to anemia was reported with postmarketing use of losartan.

     In clinical trials, the following were noted to occur with an incidence of <1%, regardless of drug relationship: thrombocytopenia, eosinophilia.

 

Overdose

 

 

Symptoms

Limited data are available in regard to overdosage with losartan in humans. The most likely manifestation of overdosage would be hypotension and/or tachycardia.

 

 

Treatment

If symptomatic hypotension should occur, supportive treatment should be instituted.

     Neither losartan nor the active metabolite can be removed by hemodialysis.

 

Dosage

Losartan may be administered with or without food, however it should be taken consistently with respect to food intake at about the same time every day.

Hypertension: The dosage of losartan must be individualized.

     Initiation of therapy requires consideration of recent antihypertensive drug treatment, the extent of blood pressure elevation, salt restriction, and other pertinent clinical factors. The dosage of other antihypertensive agents used with losartan may need to be adjusted.

Monotherapy: The usual starting dose of losartan is 50 mg once daily.

     Dosage should be adjusted according to blood pressure response. The maximal antihypertensive effect is attained 3 to 6 weeks after initiation of therapy.

     The usual dose range for losartan is 50 to 100 mg once daily. A dose of 100 mg daily should not be exceeded, as no additional antihypertensive effect is obtained with higher doses.

     In most patients taking losartan 50 mg once daily, the antihypertensive effect is maintained. In some patients treated once daily, the antihypertensive effect may diminish toward the end of the dosing interval. This can be evaluated by measuring the blood pressure just prior to dosing to determine whether satisfactory control is being maintained for 24 hours. If it is not, either twice daily administration with the same total daily dosage, or an increase in the dose should be considered. If blood pressure is not adequately controlled with losartan alone, a non-potassium-sparing diuretic may be administered concomitantly.

     For patients with volume depletion, a starting dose of 25 mg once daily should be considered (see Warnings, Hypotension and Precautions, Drug Interactions).

Concomitant Diuretic Therapy: In patients receiving diuretics, losartan therapy should be initiated with caution, since these patients may be volume depleted and thus more likely to experience hypotension following initiation of additional antihypertensive therapy. Whenever possible, all diuretics should be discontinued 2 to 3 days prior to the administration of losartan, to reduce the likelihood of hypotension (see Warnings, Hypotension and Precautions, Drug Interactions). If this is not possible because of the patient's condition, losartan should be administered with caution and the blood pressure monitored closely. Thereafter, the dosage should be adjusted according to the individual response of the patient.

Type 2 Diabetic Patients with Proteinuria and Hypertension: The usual starting dose is 50 mg once daily.  The dose may be increased to 100 mg once daily based on blood pressure response. Losartan may be administered with other antihypertensive agents (e.g., diuretics, calcium channel blockers, alpha- or beta-blockers, and centrally acting agents) as well as with insulin and other commonly used hypoglycemic agents (e.g., sulfonylureas, glitazones and glucosidase inhibitors).

 

Geriatrics

No initial dosage adjustment is necessary for most elderly patients. However, appropriate monitoring of these patients is recommended.

Renal Impairment: No initial dosage adjustment is usually necessary for patients with renal impairment, including those requiring hemodialysis. However, appropriate monitoring of these patients is recommended.

Hepatic Impairment: An initial dosage of 25 mg should be considered for patients with hepatic impairment or a history of hepatic impairment (see Precautions, Hepatic Impairment and Pharmacology).

 

Supplied

25 mg

Each light green, teardrop shaped, unscored, film-coated tablet, with code 951 on one side and MRK on the other, contains: losartan potassium 25 mg. Nonmedicinal ingredients: coloring agents (D&C Yellow No. 10 aluminum lake, FD&C Blue No. 2 aluminum lake, and titanium dioxide), cornstarch, hydroxypropyl cellulose, hydroxypropyl methylcellulose, lactose, magnesium stearate and microcrystalline cellulose. Potassium: 2.12 mg (<1 mmol). Blister packages of 30.

50 mg

Each green, teardrop shaped, unscored, film-coated tablet, with code MRK 952 on one side and COZAAR on the other, contains: losartan potassium 50 mg. Nonmedicinal ingredients: coloring agents (D&C Yellow No. 10 aluminum lake, FD&C Blue No. 2 aluminum lake, and titanium dioxide), cornstarch, hydroxypropyl cellulose, hydroxypropyl methylcellulose, lactose, magnesium stearate and microcrystalline cellulose. Potassium: 4.24 mg (<1 mmol). Blister packages of 30.

100 mg

Each dark green, teardrop shaped, unscored, film-coated tablet, with code 960 on one side and MRK on the other, contains: losartan potassium 100 mg. Nonmedicinal ingredients: coloring agents (D&C Yellow No. 10 aluminum lake, FD&C Blue No. 2 aluminum lake, and titanium dioxide), cornstarch, hydroxypropyl cellulose, hydroxypropyl methylcellulose, lactose, magnesium stearate and microcrystalline cellulose. Potassium: 8.48 mg (<1 mmol). Blister packages of 30.

     Store at room temperature (15 to 30°C). Protect from light.