AVALIDE- irbesartan and hydrochlorothiazide tablet, film coated
sanofi-aventis U.S. LLC
WARNING: FETAL TOXICITY
When pregnancy is detected, discontinue AVALIDE as soon as possible.Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus.
DESCRIPTION
AVALIDE (irbesartan-hydrochlorothiazide) tablets are combination of an angiotensin II receptor antagonist (AT1 subtype), irbesartan, and thiazide diuretic, hydrochlorothiazide (HCTZ).
Irbesartan is non-peptide compound, chemically described as 2-butyl-3-[p -(o -1H -tetrazol-5-ylphenyl)benzyl]-1,3-diazaspiro[4.4]non-1-en-4-one. Its empirical formula is C25 H28 N6 O
Irbesartan is white to off-white crystalline powder with molecular weight of 428.5. It is nonpolar compound with partition coefficient (octanol/water) of 10.1 at pH of 7.4. Irbesartan is slightly soluble in alcohol and methylene chloride and practically insoluble in water.
Hydrochlorothiazide is 6-chloro-3,4-dihydro-2H -1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide. Its empirical formula is C7 H8 ClN3 O4 S2
AVALIDE is available for oral administration in film-coated tablets containing either 150 mg or 300 mg of irbesartan combined with 12.5 mg of hydrochlorothiazide. All dosage strengths contain the following inactive ingredients: lactose monohydrate, microcrystalline cellulose, croscarmellose sodium, hypromellose, magnesium stearate, silicon dioxide, ferric oxide red, ferric oxide yellow, polyethylene glycol, titanium dioxide, and carnauba wax.
Mechanism of Action
Irbesartan
Angiotensin II is potent vasoconstrictor formed from angiotensin in reaction catalyzed by angiotensin-converting enzyme (ACE, kininase II). Angiotensin II is the principal pressor agent of the RAS and also stimulates aldosterone synthesis and secretion by adrenal cortex, cardiac contraction, renal resorption of sodium, activity of the sympathetic nervous system, and smooth muscle cell growth. Irbesartan blocks the vasoconstrictor and aldosterone-secreting effects of angiotensin II by selectively binding to the AT1 angiotensin II receptor. There is also an AT2 receptor in many tissues, but it is not involved in cardiovascular homeostasis.
Hydrochlorothiazide
Hydrochlorothiazide is thiazide diuretic. Thiazides affect the renal tubular mechanisms of electrolyte reabsorption, directly increasing excretion of sodium and chloride in approximately equivalent amounts. Indirectly, the diuretic action of hydrochlorothiazide reduces plasma volume, with consequent increases in plasma renin activity, increases in aldosterone secretion, increases in urinary potassium loss, and decreases in serum potassium. The renin-aldosterone link is mediated by angiotensin II, so coadministration of an angiotensin II receptor antagonist tends to reverse the potassium loss associated with these diuretics.
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 (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 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 combination compared with monotherapy.
DOSAGE AND ADMINISTRATION
2.1 General Considerations
The side effects of irbesartan are generally rare and apparently independent of dose; those of hydrochlorothiazide are mixture of dose-dependent (primarily hypokalemia) and dose-independent phenomena (e.g., pancreatitis), the former much more common than the latter. [See Adverse Reactions .]
Maximum antihypertensive effects are attained within to weeks after 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
Initial Therapy
The usual starting dose is AVALIDE 150/12.5 mg once daily. The dosage can be increased after to weeks of therapy to maximum of 300/25 mg once daily as needed to control blood pressure
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 heart debossed on one side and ?2875? or ?2876? on the reverse side, respectively.
4 CONTRAINDICATIONS
AVALIDE is contraindicated in patients who are hypersensitive to any component of this product.
Because of the hydrochlorothiazide component, this product is contraindicated in patients with anuria or hypersensitivity to other sulfonamide-derived drugs.
Do not coadminister aliskiren with AVALIDE in patients with diabetes [see Drug Interactions ].
5 WARNINGS AND PRECAUTIONS
5.1 Fetal Toxicity
Pregnancy Category D
Hypotension in Volume- or Salt-Depleted Patients
DRUG INTERACTIONS
7.1 Non-Steroidal Anti-Inflammatory Agents Including Selective Cyclooxygenase-2 Inhibitors (COX-2 Inhibitors)
Irbesartan
In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, coadministration of NSAIDs, including selective COX-2 inhibitors, with angiotensin II receptor antagonists, including irbesartan, may result in deterioration of renal function, including possible acute renal failure. These effects are usually reversible. Therefore, monitor renal function and blood pressure periodically in patients receiving irbesartan and NSAID therapy.
Hydrochlorothiazide
Administration of non-steroidal anti-inflammatory agent, including selective COX-2 inhibitor can reduce the diuretic, natriuretic, and antihypertensive effects of loop, potassium-sparing, and thiazide diuretics. Therefore, when AVALIDE (irbesartan-hydrochlorothiazide) tablets and non-steroidal anti-inflammatory agents are used concomitantly, the patient should be observed closely to determine if the desired effect of the diuretic is obtained.
Dual Blockade of the Renin-Angiotensin System (RAS)
Agents Increasing Serum Potassium
Antidiabetic Drugs (oral agents and insulin)
Cholestyramine and Colestipol Resins
Lithium
Carbamazepine
PATIENT COUNSELING info.
Pregnancy
Tell female patients of childbearing age about the consequences of exposure to AVALIDE during pregnancy. Discuss treatment options with women planning to become pregnant. Ask patients to report pregnancies to their physician as soon as possible.
Symptomatic Hypotension
Tell patients using AVALIDE that they may feel lightheaded, especially during the first days of use. Tell patients to inform their physician if they feel lightheaded or faint. Tell the patient, if fainting occurs, stop using AVALIDE and contact the prescribing doctor.
Tell patients using AVALIDE that getting dehydrated can lower their blood pressure too much and lead to lightheadedness and possible fainting. Dehydration may occur with excessive sweating, diarrhea, or vomiting and with not drinking enough liquids.
Potassium Supplements
Advise patients not to use potassium supplements or salt substitutes containing potassium without consulting their healthcare provider.
Acute myopia and secondary angle-closure glaucoma
Advise patients to discontinue AVALIDE and seek immediate medical attention if they experience symptoms of Acute Myopia or Secondary Angle-Closure Glaucoma
