Avalide (Irbesartan / Hydrochlorothiazide) - Indications and Dosage

INDICATIONS AND USAGE

AVALIDE^® (irbesartan-hydrochlorothiazide) Tablets are indicated for the treatment of hypertension.

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

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

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

Patients with stage 2 (moderate or severe) hypertension are at 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 may be shaped by considerations such as the baseline blood pressure, the target goal, and the incremental likelihood of achieving goal with a combination compared with monotherapy.

Data from Studies V and VI [see Clinical Studies ] provide estimates of the probability of reaching a blood pressure goal with AVALIDE compared to irbesartan or HCTZ monotherapy. The relationship between baseline blood pressure and achievement of a SeSBP <140 or <130 mmHg or SeDBP <90 or <80 mmHg in patients treated with AVALIDE compared to patients treated with irbesartan or HCTZ monotherapy are shown in Figures 1a through 2b.

*For all probability curves, patients without blood pressure measurements at Week 7 (Study VI) and Week 8 (Study V) were counted as not reaching goal (intent-to-treat analysis).
Figure 1a: Probability of Achieving SBP <140 mmHg in Patients from Initial Therapy Studies V (Week 8) and VI (Week 7)*		Figure 1b: Probability of Achieving SBP <130 mmHg in Patients from Initial Therapy Studies V (Week 8) and VI (Week 7)*
Figure 2a: Probability of Achieving DBP <90 mmHg in Patients from Initial Therapy Studies V (Week 8) and VI (Week 7)*		Figure 2b: Probability of Achieving DBP <80 mmHg in Patients from Initial Therapy Studies V (Week 8) and VI (Week 7)*

The above graphs provide a rough approximation of the likelihood of reaching a targeted blood pressure goal (e.g., Week 8 sitting systolic blood pressure ≤140 mmHg) for the treatment groups. The curve of each treatment group in each study was estimated by logistic regression modeling from all available data of that treatment group. The estimated likelihood at the right tail of each curve is less reliable due to small numbers of subjects with high baseline blood pressures.

For example, a patient with a blood pressure of 180/105 mmHg has about a 25% likelihood of achieving a goal of <140 mmHg (systolic) and 50% likelihood of achieving <90 mmHg (diastolic) on irbesartan alone (and lower still likelihoods on HCTZ alone).

The likelihood of achieving these goals on AVALIDE rises to about 40% (systolic) or 70% (diastolic).

DOSAGE AND ADMINISTRATION

General Considerations

The side effects of irbesartan 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. [See Adverse Reactions (6) .]

Maximum antihypertensive effects are attained within 2 to 4 weeks after a change in dose.

AVALIDE may be administered with or without food.

AVALIDE may be administered with other antihypertensive agents.

Renal impairment. The usual regimens of therapy with AVALIDE 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 AVALIDE is not recommended.

Hepatic impairment. No dosage adjustment is necessary in patients with hepatic impairment.

Add-On Therapy

In patients not controlled on monotherapy with irbesartan or hydrochlorothiazide, the recommended doses of AVALIDE, in order of increasing mean effect, are (irbesartan-hydrochlorothiazide) 150/12.5 mg, 300/12.5 mg, and 300/25 mg. The largest incremental effect will likely be in the transition from monotherapy to 150/12.5 mg. [See Clinical Studies .]

Replacement Therapy

AVALIDE may be substituted for the titrated components.

Initial Therapy

The usual starting dose is AVALIDE 150/12.5 mg once daily. The dosage can be increased after 1 to 2 weeks of therapy to a maximum of 300/25 mg once daily as needed to control blood pressure [see Clinical Studies ]. AVALIDE is not recommended as initial therapy in patients with intravascular volume depletion [see Warnings and Precautions ].

DOSAGE FORMS AND STRENGTHS

AVALIDE^® (irbesartan-hydrochlorothiazide) 150/12.5 mg and 300/12.5 mg film-coated tablets are peach, biconvex, and oval with a heart debossed on one side and "2875" or "2876" on the reverse side, respectively.

HOW SUPPLIED/STORAGE AND HANDLING

How Supplied

AVALIDE^® (irbesartan-hydrochlorothiazide) film-coated tablets have markings on both sides and are available in the strengths and packages listed in the following table:

Tablet Strength (irbesartan and hydrochlorothiazide)	Film-Coated Tablet Color/Shape	Tablet Markings	Package Size	NDC Code
150 mg/12.5 mg	peach, biconvex, oval-shaped	heart debossed on one side and “2875” on the reverse	Bottles of 30 Bottles of 90	0087-2875-31 0087-2875-32
300 mg/12.5 mg	peach, biconvex, oval-shaped	heart debossed on one side and “2876” on the reverse	Bottles of 30 Bottles of 90	0087-2876-31 0087-2876-32

Storage

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