No

Angiotensin II Antagonists

Treatment of hypertension with or without concurrent use of thiazide diuretics

C/D (2nd and 3rd trimesters)

Breast-feeding/lactation: Avoid use in the nursing mother, if possible, since it is postulated that losartan is excreted in breast milk

Hypersensitivity to losartan or any component; hypersensitivity to other A-II receptor antagonists; primary hyperaldosteronism; bilateral renal artery stenosis; pregnancy (2nd and 3rd trimesters)

Avoid use or use a smaller dose in patients who are volume depleted; correct depletion first. Deterioration in renal function can occur with initiation. Use with caution in unilateral renal artery stenosis and pre-existing renal insufficiency; significant aortic/mitral stenosis.

1% to 10%:

Central nervous system: Dizziness (3.5%), insomnia (1.4%)

Cardiovascular: First dose hypotension (dose-related; 0.5% with 50 mg, 2.2% with 100 mg)

Gastrointestinal: Diarrhea (2.4%), dyspepsia (1.3%), abdominal pain (1.6%), Nausea (1.5%)

Neuromuscular & skeletal: Back pain (1.8%), muscle cramps (1.1%), myalgia (1%), leg pain (1%)

Upper respiratory infection (7.9%), cough (3.4% versus 3.3% in placebo), nasal congestion (2%), sinus disorder (1.2%), sinusitis (1%)

>1% but frequency less than or equal to placebo: Asthenia, fatigue, edema, abdominal pain, chest pain, nausea, headache, pharyngitis

<1% (Limited to important or life-threatening symptoms): Angioedema,anaphylactic reactions, hepatitis, hyperkalemia, hyponatremia, facial edema, fever, orthostatic effects, syncope, angina, AV block (second degree), CVA, hypotension, myocardial infarction, arrhythmias, palpitations, bradycardia, tachycardia, ventricular arrhythmias, anorexia, constipation, dental pain, xerostomia, flatulence, gastritis, vomiting, anemia, gout, arm pain, hip pain, joint swelling, arthralgia, arthritis, muscle weakness, anxiety, ataxia, confusion, depression, hypesthesia, decreased libido, memory impairment, migraine, nervousness, paresthesia, peripheral neuropathy, sleep disorder, somnolence, tremor, vertigo, dyspnea, bronchitis, pharyngitis, epistaxis, rhinitis, alopecia, dermatitis, dry skin, ecchymosis, erythema, flushing, photosensitivity, pruritus, rash, sweating, urticaria, blurred vision, conjunctivitis, taste perversion, tinnitus, decreased visual acuity, impotence, nocturia, urinary frequency, increased serum creatinine, increased BUN, decreased hemoglobin, decreased hematocrit, increased transaminases, increased bilirubin. May be associated with worsening of renal function in patients dependent on renin-angiotensin-aldosterone system, panic disorder

Case reports: Henoch-Schönlein purpura, anemia, acute psychosis with paranoid delusions, pancreatitis, dysgeusia, ageusia, maculopapular rash

Symptoms may occur with very significant overdosages including hypotension and tachycardia

Treatment should be supportive

CYP2C9 substrate and CYP3A3/4 substrate

Fluconazole (and possibly other azoles) decreases the plasma level of losartan's active metabolite; monitor for decreased efficacy.

Lithium: Risk of toxicity may be increased by losartan; monitor lithium levels.

Potassium-sparing diuretics (amiloride, potassium, spironolactone, triamterene): Increased risk of hyperkalemia.

Potassium supplements may increase the risk of hyperkalemia.

Rifampin may reduce antihypertensive efficacy of losartan.

Trimethoprim (high dose) may increase the risk of hyperkalemia.

As a selective and competitive, nonpeptide angiotensin II receptor antagonist, losartan blocks the vasoconstrictor and aldosterone-secreting effects of angiotensin II; losartan interacts reversibly at the AT1 and AT2 receptors of many tissues and has slow dissociation kinetics; its affinity for the AT1 receptor is 1000 times greater than the AT2 receptor. Angiotensin II receptor antagonists may induce a more complete inhibition of the renin-angiotensin system than ACE inhibitors, they do not affect the response to bradykinin, and are less likely to be associated with nonrenin-angiotensin effects (eg, cough and angioedema). Losartan increases urinary flow rate and in addition to being natriuretic and kaliuretic, increases excretion of chloride, magnesium, uric acid, calcium, and phosphate.

Onset of effect: 6 hours

Distribution: Does not cross the blood brain barrier; V_d: Losartan: 34 L; E-3174: 12 L

Protein binding: Highly bound to plasma proteins

Metabolism: 14% of an orally administered dose is metabolized by cytochrome P-450 enzymes to an active metabolite E-3174 (40 times more potent than losartan); undergoes substantial first-pass metabolism

Bioavailability: 25% to 33%; AUC of E-3174 is 4 times greater than that of losartan

Half-life: Losartan: 1.5-2 hours; E-3174: 6-9 hours

Time to peak: Peak serum levels of losartan: 1 hour; metabolite, E-3174: 3-4 hours

Elimination: 3% to 8% excreted in urine as unchanged parent or as E-3174; ~35% of a dose is recovered in urine and 60% in feces; total plasma clearance of losartan: 600 mL/minute: its active metabolite: 50 mL/minute

Oral: The usual starting dose is 50 mg once daily. Can be administered once or twice daily with total daily doses ranging from 25 mg to 100 mg.

Usual initial doses in patients receiving diuretics or those with intravascular volume depletion: 25 mg

Patients not receiving diuretics: 50 mg

Dosing adjustment in renal impairment: None necessary

Dosing adjustment in hepatic impairment or geriatric patients: Reduce the initial dose to 25 mg; divide dosage intervals into two.

Not removed via hemodialysis

Supine blood pressure, electrolytes, serum creatinine, BUN, urinalysis, symptomatic hypotension and tachycardia, CBC

The angiotensin II receptor antagonists appear to have similar indications as the ACE inhibitors. While these drugs have been shown to be effective in treating hypertension, their efficacy in heart failure is being vigorously evaluated. In the ELITE study comparing losartan to captopril in elderly patients with symptomatic heart failure, losartan was better tolerated and was accompanied by decreased mortality and fewer hospitalizations than captopril. These preliminary findings were not supported in a follow-up study (ELITE II) which showed similar cardiovascular outcomes between patients randomized to captopril or losartan. The angiotensin II antagonists are especially useful in providing an alternative therapy in those patients who have intractable cough in response to ACE-inhibitor therapy. Similar to ACE inhibitors, pre-existing volume depletion caused by diuretic therapy may potentiate hypotension in response to angiotensin II antagonists.

May cause dizziness or insomnia; may rarely cause anxiety, confusion, depression, and sleep disorders

Barbiturates may decrease the effects of losartan

No information available to require special precautions

No effects or complications reported

Take exactly as directed; do not discontinue without consulting prescriber. Take first dose at bedtime. This drug does not eliminate need for diet or exercise regimen as recommended by prescriber. May cause dizziness, fainting, lightheadedness (use caution when driving or engaging in tasks that require alertness until response to drug is known); diarrhea (buttermilk, boiled milk, yogurt may help). Report chest pain or palpitations; unrelenting headache; swelling of extremities, face, or tongue; difficulty in breathing or unusual cough; flu-like symptoms; or other persistent adverse reactions Pregnancy/breast-feeding precautions: Do not get pregnant while taking this medication; use appropriate barrier contraceptive measures. If you are, or plan to be pregnant, notify your prescriber at once. Do not breast-feed.

Observe for symptomatic hypotension and tachycardia especially in patients with CHF; hyponatremia, high-dose diuretics, or severe volume depletion

Tablet, film coated, as potassium: 25 mg, 50 mg

Brunner HR, Christen Y, Munafo A, et al, "Clinical Experience With Angiotensin II Receptor Antagonists," Am J Hypertens, 1992, 5(12 Pt 2):243S-246S.

Gansevoort RT, de Zeeuw D, Shahinfar S, et al, "Effects of the Angiotensin II Antagonist Losartan in Hypertensive Patients With Renal Disease," J Hypertens Suppl, 1994, 12(2):S37-S42.

Munger MA and Furniss SM, "Angiotensin II Receptor Blockers: Novel Therapy for Heart Failure?" Pharmacotherapy, 1996, 16(2 Pt 2):59S-68S.

Shaw W, Keane W, Sica D, et al, "Safety and Antihypertensive Effects of Losartan (MK-954; DUP753); A New Angiotensin II Receptor Antagonist in Patients With Hypertension and Renal Disease," Clin Pharmacol Ther, 1993, 53:140.