an or hydrochlorothiazide monotherapy. The figures below provide estimates of the likelihood of achieving systolic or diastolic blood pressure control with DiovanHCT 320/25mg, based upon baseline systolic or diastolic blood pressure. The curve of each treatment group was estimated by logistic regression modeling. The estimated likelihood at the right tail of each curve is less reliable due to small numbers of subjects with high baseline blood pressures.
Figure 1: Probability of Achieving Systolic Blood Pressure <140 mmHg at Week 8
Figure 2: Probability of Achieving Diastolic Blood Pressure<90 mmHg at Week 8
Figure 3: Probability of Achieving Systolic Blood Pressure <130 mmHg at Week 8
Figure 4: Probability of Achieving Diastolic Blood Pressure<80 mmHg at Week 8
For example, a patient with a baseline blood pressure of 160/100 mmHg has about a 41% likelihood of achieving a goal of <140 mmHg (systolic) and 60% likelihood of achieving <90 mmHg (diastolic) on valsartan alone and the likelihood of achieving these goals on HCTZ alone is about 50% (systolic) or 57% (diastolic). The likelihood of achieving these goals on Diovan HCT rises to about 84% (systolic) or 80% (diastolic). The likelihood of achieving these goals on placebo is about 23% (systolic) or 36% (diastolic).
2DOSAGE AND ADMINISTRATION
2.1General Considerations
The side effects of valsartan are generally rare and appear 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 [see Adverse Reactions (6)].
Dose once-daily. Maximum antihypertensive effects are attained within 2 to 4 weeks after a change in dose.
DiovanHCT may be administered with or without food.
DiovanHCT may be administered with other antihypertensive agents.
Elderly patients:No initial dosage adjustment is required for elderly patients.
Renal impairment:The usual regimens of therapy with DiovanHCT may be followed as long as the patient’s creatinine clearance is >30mL/min. In patients with more severe renal impairment, loop diuretics are preferred to thiazides, so DiovanHCT is not recommended.
Hepatic impairment:Care should be exercised with dosing of DiovanHCT in patients with hepatic impairment. Start with a low dose and titrate slowly in patients with hepatic impairment [see Warnings and Precautions (5.3)].
2.2Add-On Therapy
A patient whose blood pressure is not adequately controlled with valsartan (or another ARB) alone or hydrochlorothiazide alone may be switched to combination therapy with DiovanHCT.
A patient who experiences dose-limiting adverse reactions on either component alone may be switched to Diovan HCT containing a lower dose of that component in combination with the other to achieve similar blood pressure reductions. The clinical response to Diovan HCT should be subsequently eva luated and if blood pressure remains uncontrolled after 3 to 4 weeks of therapy, the dose may be titrated up to a maximum of320/25 mg.
2.3Replacement Therapy
DiovanHCT may be substituted for the titrated components.
2.4Initial Therapy
The usual starting dose is DiovanHCT 160/12.5mg once daily. The dosage can be increased after 1 to 2 weeks of therapy to a maximum of one 320/25mg tablet once daily as needed to control blood pressure [see Clinical Studies (14.2)]. DiovanHCT is
