Diovan HCT (Valsartan / Hydrochlorothiazide) - Indications and Dosage

INDICATIONS AND USAGE

Diovan HCT (valsartan and hydrochlorothiazide, USP) is indicated for the treatment of hypertension.

Diovan HCT may be used in patients whose blood pressure is not adequately controlled on monotherapy.

Diovan HCT may be used as initial therapy in patients who are likely to need multiple drugs to achieve blood pressure goals.

The choice of Diovan HCT as initial therapy for hypertension should be based on an assessment of potential benefits and risks.

Patients with stage 2 hypertension are at a relatively high risk for cardiovascular events (such as strokes, heart attacks, and heart failure), kidney failure, and vision problems, so prompt treatment is clinically relevant. The decision to use a combination as initial therapy should be individualized and should be shaped by considerations such as baseline blood pressure, the target goal and the incremental likelihood of achieving goal with a combination compared to monotherapy. Individual blood pressure goals may vary based upon the patient’s risk.

Data from the high dose multifactorial trial [see Clinical Studies] provides estimates of the probability of reaching a target blood pressure with Diovan HCT compared to valsartan or hydrochlorothiazide monotherapy. The figures below provide estimates of the likelihood of achieving systolic or diastolic blood pressure control with Diovan HCT 320/25 mg, 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).

D OSAGE AND ADMINISTRATION

General 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.

Diovan HCT may be administered with or without food.

Diovan HCT 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 Diovan HCT 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 Diovan HCT is not recommended.

Hepatic impairment : Care should be exercised with dosing of Diovan HCT in patients with hepatic impairment. Start with a low dose and titrate slowly in patients with hepatic impairment [s ee Warnings and Precautions (5.3)].

Add-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 Diovan HCT.

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 evaluated and if blood pressure remains uncontrolled after 3 to 4 weeks of therapy, the dose may be titrated up to a maximum of 320/25 mg.

Replacement Therapy

Diovan HCT may be substituted for the titrated components.

Initial Therapy

The usual starting dose is Diovan HCT 160/12.5 mg once daily. The dosage can be increased after 1 to 2 weeks of therapy to a maximum of one 320/25 mg tablet once daily as needed to control blood pressure [see Clinical Studies]. Diovan HCT is not recommended as initial therapy in patients with intravascular volume depletion [see Warnings and Precautions  (5.2)].

DOSAGE FORMS AND STRENGTHS

80/12.5 mg tablets, imprinted CG/HGH (Side 1/Side 2)

160/12.5 mg tablets, imprinted CG/HHH

160/25 mg tablets, imprinted NVR/HXH

320/12.5 mg tablets, imprinted NVR/HIL

320/25 mg tablets, imprinted NVR/CTI

HOW SUPPLIED/STORAGE AND HANDLING

Diovan HCT (valsartan and hydrochlorothiazide, USP) is available as non-scored tablets containing valsartan/hydrochlorothiazide 80/12.5 mg, 160/12.5 mg, 160/25 mg, 320/12.5 mg and 320/25 mg. Strengths are available as follows.

80/12.5 mg Tablet - Light orange, ovaloid with slightly convex faces debossed CG on one side and HGH on the other side.

      Bottles of 90       NDC 0078-0314-34

      Bottles of 14,000       NDC 0078-0314-33

      Unit Dose (blister pack)       NDC 0078-0314-06

      Box of 100 (strips of 10)

160/12.5 mg Tablet - Dark red, ovaloid with slightly convex faces debossed CG on one side and HHH on the other side.

      Bottles of 90       NDC 0078-0315-34

      Bottles of 7,000       NDC 0078-0315-17

      Unit Dose (blister pack)       NDC 0078-0315-06

      Box of 100 (strips of 10)

      Unit Dose (blister pack of 30)       NDC 0078-0315-15

160/25 mg Tablet - Brown orange, ovaloid with slightly convex faces debossed NVR on one side and HXH on the other side.

      Bottles of 90       NDC 0078-0383-34

      Bottles of 7,000       NDC 0078-0383-17

      Unit Dose (blister pack)       NDC 0078-0383-06

      Box of 100 (strips of 10)

      Unit Dose (blister pack of 30)       NDC 0078-0383-15

320/12.5 mg Tablet - Pink, ovaloid with beveled edge, debossed NVR on one side and HIL on the other side.

      Bottles of 90       NDC 0078-0471-34

      Bottles of 3,500       NDC 0078-0471-11

      Unit Dose (blister pack)       NDC 0078-0471-06

      Box of 100 (strips of 10)

      Unit Dose (blister pack of 30)       NDC 0078-0471-15

320/25 mg Tablet - Yellow, ovaloid with beveled edge, debossed NVR on one side and CTI on the other side.

      Bottles of 90       NDC 0078-0472-34

      Bottles of 3,500       NDC 0078-0472-11

      Unit Dose (blister pack)       NDC 0078-0472-06

      Box of 100 (strips of 10)

      Unit Dose (blister pack of 30)       NDC 0078-0472-15

Store at 25ºC (77ºF); excursions permitted to 15-30ºC (59-86ºF) [see USP Controlled Room Temperature].

Protect from moisture.

Dispense in tight container (USP).