LosartanPA study guide

Mechanism

Losartan and its active metabolite block angiotensin II from binding the AT1 receptor in blood vessels and the adrenal gland. This prevents angiotensin II from constricting vessels and releasing aldosterone. Unlike ACE inhibitors, it does not inhibit ACE, so bradykinin is not built up.

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Why they happen and how to manage them

Hyperkalemia

Blocking angiotensin II lowers aldosterone, so the kidney excretes less potassium. Management: Check potassium periodically; avoid potassium supplements and salt substitutes; lower the dose or stop if needed.

Acute kidney injury

Angiotensin II keeps glomerular filtration up by constricting the efferent arteriole; blocking it drops filtration pressure, especially with renal artery stenosis, volume depletion, or NSAIDs. Management: Check creatinine after starting; correct volume depletion; hold if renal function drops significantly.

First-dose hypotension

Volume- or salt-depleted patients rely on an activated renin-angiotensin system to hold blood pressure. Management: Correct volume first and start at 25 mg in patients on diuretics.

Less cough than ACE inhibitors

ARBs do not block ACE, so bradykinin does not accumulate. Management: A reasonable switch for patients with ACE inhibitor cough.

Fetal toxicity

The fetal kidney depends on the renin-angiotensin system for perfusion and urine output. Management: Stop as soon as pregnancy is detected; counsel women of childbearing potential.

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Common and serious

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Narrow therapeutic index

The label does not describe a narrow therapeutic index or direct dosing by measured blood levels of the drug.

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Blood pressure

Why

Response and hypotension

When

After starting and during titration, especially with diuretics

Act on

Correct volume or salt depletion; start at 25 mg if volume depleted

Normal

Below 120/80 mm Hg.

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Potassium

Why

Hyperkalemia

When

Periodically, and when other potassium-raising drugs are used

Act on

Hyperkalemia may require a dose cut or stopping losartan

Normal

3.7 to 5.2 mEq/L.

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Serum creatinine

Why

Renal function decline

When

Periodically in at-risk patients such as renal artery stenosis, CKD, severe heart failure, volume depletion, or NSAID use

Act on

Consider holding or stopping with a clinically significant drop in renal function

Normal

0.7 to 1.3 mg/dL in men and 0.5 to 0.95 mg/dL in women.

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Adult dose

Hypertension

50 mg once daily to start; may increase to a maximum of 100 mg once daily. Start at 25 mg if volume depleted.

Hypertension with left ventricular hypertrophy

50 mg once daily. Add hydrochlorothiazide 12.5 mg and/or raise losartan to 100 mg, then raise hydrochlorothiazide to 25 mg, based on blood pressure response.

Diabetic nephropathy (type 2 diabetes)

50 mg once daily; increase to 100 mg once daily based on blood pressure response.

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Renal adjustment

No dose change needed for renal impairment unless the patient is also volume depleted. Monitor renal function in patients whose kidneys depend on the renin-angiotensin system, such as renal artery stenosis or severe heart failure.

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Hepatic adjustment

Mild to moderate hepatic impairment: start at 25 mg once daily, since levels of losartan and its metabolite rise. Not studied in severe hepatic impairment.

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Boxed warning

Fetal toxicity. Drugs acting on the renin-angiotensin system can injure or kill the developing fetus. Stop losartan as soon as pregnancy is detected.

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Contraindications

• Hypersensitivity to any product component
• Use with aliskiren in patients with diabetes

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Key interactions

Potassium supplements, potassium salt substitutes, or other drugs that raise potassium

Hyperkalemia. Check potassium.

Lithium

Higher lithium levels and toxicity. Monitor lithium levels.

NSAIDs, including COX-2 inhibitors

Can worsen renal function, mainly in older, volume-depleted, or renally impaired patients, and can blunt the blood pressure effect.

ACE inhibitors, other ARBs, or aliskiren (dual RAS blockade)

More hypotension, syncope, hyperkalemia, and kidney injury without added benefit. Generally avoid; never combine with aliskiren in diabetes.

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Antidote or reversal

No antidote. Overdose most likely causes hypotension and tachycardia, or bradycardia from vagal stimulation. Give supportive care for symptomatic hypotension. Hemodialysis does not remove losartan or its active metabolite.

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Pregnancy

Can cause fetal harm. Use in the second and third trimesters reduces fetal kidney function, causing oligohydramnios, lung hypoplasia, skull and skeletal defects, and death. Stop as soon as pregnancy is detected. Watch exposed newborns for hypotension, oliguria, and hyperkalemia.

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Lactation

Unknown if it passes into human milk; significant levels were found in rat milk. Decide whether to stop breastfeeding or stop the drug.

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Pediatric

Hypertension from age 6: start 0.7 mg/kg once daily, up to 50 mg, adjusted to blood pressure. Doses above 1.4 mg/kg or 100 mg daily are unstudied. Not recommended under age 6 or with GFR below 30 mL/min/1.73 m2.

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Geriatric

No overall differences in safety or effectiveness compared with younger patients, though greater sensitivity in some older adults cannot be ruled out.

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