Dosing must be individualized. The usual starting dose of losartan is 50 mg once daily, with 25 mg recommended for patients with intravascular volume depletion (e.g., patients treated with diuretics) (see WARNINGS, Hypotension — Volume-Depleted Patients) and patients with a history of hepatic impairment (see WARNINGS, Impaired Hepatic Function). Losartan can be administered once or twice daily at total daily doses of 25 to 100 mg. If the antihypertensive effect measured at trough using once-a-day dosing is inadequate, a twice-a-day regimen at the same total daily dose or an increase in dose may give a more satisfactory response.

Hydrochlorothiazide is effective in doses of 12.5 to 50 mg once daily and can be given at doses of 12.5 to 25 mg as HYZAAR.

To minimize dose-independent side effects, it is usually appropriate to begin combination therapy only after a patient has failed to achieve the desired effect with monotherapy.

The side effects (see WARNINGS) of losartan are generally rare and apparently independent of dose; those of hydrochlorothiazide are a mixture of dose-dependent (primarily hypokalemia) and dose-independent phenomena (e.g., pancreatitis), the former much more common than the latter. Therapy with any combination of losartan and hydrochlorothiazide will be associated with both sets of dose-independent side effects.

Replacement Therapy: The combination may be substituted for the titrated components.

Dose Titration by Clinical Effect: A patient whose blood pressure is not adequately controlled with losartan monotherapy (see above) or hydrochlorothiazide alone may be switched to HYZAAR 50/12.5 (losartan 50 mg/hydrochlorothiazide 12.5 mg) once daily. If blood pressure remains uncontrolled after about 3 weeks of therapy, the dose may be increased to two tablets of HYZAAR 50/12.5 once daily or one tablet of HYZAAR 100/25 (losartan 100 mg/hydrochlorothiazide 25 mg) once daily. A patient whose blood pressure is not adequately controlled with losartan 100 mg monotherapy (see above) may be switched to HYZAAR 100/12.5 once daily. If blood pressure remains uncontrolled after about 3 weeks of therapy, the dose may be increased to two tablets of HYZAAR 50/12.5 once daily or one tablet of HYZAAR 100/25 (losartan 100 mg/hydrochlorothiazide 25 mg) once daily.

A patient whose blood pressure is inadequately controlled by 25 mg once daily of hydrochlorothiazide, or is controlled but who experiences hypokalemia with this regimen, may be switched to HYZAAR 50/12.5 (losartan 50 mg/hydrochlorothiazide 12.5 mg) once daily, reducing the dose of hydrochlorothiazide without reducing the overall expected antihypertensive response. The clinical response to HYZAAR 50/12.5 should be subsequently evaluated, and if blood pressure remains uncontrolled after about 3 weeks of therapy, the dose may be increased to two tablets of HYZAAR 50/12.5 once daily or one tablet of HYZAAR 100/25 (losartan 100 mg/hydrochlorothiazide 25 mg) once daily.

The usual dose of HYZAAR is one tablet of HYZAAR 50/12.5 once daily. More than two tablets of HYZAAR 50/12.5 once daily or more than one tablet of HYZAAR 100/25 once daily is not recommended. The maximal antihypertensive effect is attained about 3 weeks after initiation of therapy.

Use in Patients with Renal Impairment: The usual regimens of therapy with HYZAAR may be followed as long as the patient's creatinine clearance is >30 mL/min. In patients with more severe renal impairment, loop diuretics are preferred to thiazides, so HYZAAR is not recommended.

Patients with Hepatic Impairment: HYZAAR is not recommended for titration in patients with hepatic impairment (see WARNINGS, Impaired Hepatic Function) because the appropriate 25 mg starting dose of losartan cannot be given.