What is the recommended dose and frequency of Losartan (angiotensin II receptor antagonist) for treating hypertension and diabetic nephropathy?

From the Guidelines

The recommended dose of losartan for treating hypertension and diabetic nephropathy is 50-100 mg once daily, with a starting dose of 50 mg once daily, which can be titrated up to 100 mg once daily based on blood pressure response and proteinuria reduction. For patients with diabetic nephropathy, the recommended dose is 50 mg once daily, which can be titrated up to 100 mg once daily depending on proteinuria reduction and blood pressure control 1. Losartan works by blocking angiotensin II receptors, preventing the hormone from binding and causing blood vessel constriction, thereby lowering blood pressure. This mechanism also reduces proteinuria and slows kidney disease progression in diabetic patients. The medication is typically taken at the same time each day to maintain consistent blood levels, and patients should be monitored for hypotension, hyperkalemia, and changes in kidney function, especially when starting therapy or adjusting doses. Full therapeutic effects may take 3-6 weeks to develop, though some blood pressure reduction is usually seen within the first week of treatment.

Some key points to consider when prescribing losartan include:

• Lower starting doses of 25 mg daily are advised for patients who are volume-depleted (such as those on diuretics) or those with hepatic impairment.
• Losartan should be titrated to the maximal tolerated dose, with close monitoring of serum potassium and serum creatinine levels within 2 to 4 weeks of initiation of or change in dose.
• Combination therapy with ACE inhibitors and ARBs is harmful and should be avoided in patients with diabetes and CKD.
• Mineralocorticoid receptor antagonists, such as spironolactone and eplerenone, are effective for resistant hypertension, but studies examining the long-term risks and benefits of adding a mineralocorticoid receptor antagonist to concomitant use of ACE inhibitors or ARBs are due to be reported soon.

It's also important to note that the 2020 KDIGO clinical practice guideline recommends the use of RAS inhibitors, such as losartan, in patients with diabetes, hypertension, and albuminuria, and that these medications should be titrated to the maximal tolerated dose, with close monitoring of serum potassium and serum creatinine levels 1.

From the FDA Drug Label

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 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 The usual starting dose is 50 mg once daily. The dose should be increased to 100 mg once daily based on blood pressure response Usual adult dose: 50 mg once daily. Usual dose: 50 mg once daily. Increase dose to 100 mg once daily if further blood pressure response is needed.

The recommended dose and frequency of Losartan for treating hypertension and diabetic nephropathy is:

• 50 mg once daily as the usual starting dose
• The dose can be increased to 100 mg once daily as needed to control blood pressure
• For hypertensive patients with left ventricular hypertrophy, the usual starting dose is 50 mg once daily, with the option to add hydrochlorothiazide 12.5 mg daily and/or increase the dose of losartan potassium tablets to 100 mg once daily
• For nephropathy in type 2 diabetic patients, the usual dose is 50 mg once daily, with the option to increase the dose to 100 mg once daily if further blood pressure response is needed 2, 2, 2.

From the Research

Losartan Dose and Frequency

The recommended dose and frequency of Losartan for treating hypertension and diabetic nephropathy are as follows:

• The optimal dose of Losartan is 100 mg daily for renoprotection and blood pressure reduction in type 1 diabetic patients with diabetic nephropathy 3.
• Losartan 50 mg/day can be administered without regard to food, and the maximum recommended daily dose is 100mg, which can be given as a once-daily dose or by splitting the same total daily dose into two doses 4.
• For patients with type 2 diabetes and nephropathy, Losartan 50 to 100 mg once daily is effective in reducing the incidence of a doubling of serum creatinine, end-stage renal disease, or death 5, 6.

Administration and Pharmacokinetics

• Losartan is rapidly absorbed, reaching maximum concentrations 1-2 hours post-administration, and its pharmacokinetics are linear, dose-proportional, and do not substantially change with repetitive administration 4.
• The major metabolic pathway for Losartan is by the cytochrome P450 (CYP) 3A4, 2C9, and 2C10 isoenzymes, and it has a favorable drug-drug interaction profile 4.
• Losartan does not have a significant effect on renal function in patients with or without renal insufficiency, and it is well tolerated in clinical trials 4, 7.

Clinical Efficacy

• Losartan is effective in reducing blood pressure and proteinuria in patients with hypertension and diabetic nephropathy 3, 5, 6.
• It has a similar effect to enalapril on kidney function and is well tolerated in clinical trials 6, 7.
• Losartan also reduces the incidence of cardiovascular morbidity and mortality, particularly in patients with heart failure 5.