Azisan Plus Tablet

For the treatment of hypertension, to lower blood pressure:

• In patients not adequately controlled with ARB monotherapy
• As initial therapy in patients likely to need multiple drugs to help

To achieve blood pressure goals and to reduce the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions.

Azisan Plus contains an angiotensin II receptor blocker (ARB) and a thiazide-like diuretic and is indicated for the treatment of hypertension, to lower blood pressure. This may be used in patients whose blood pressure is not adequately controlled on monotherapy. This may be used as initial therapy if a patient is likely to need multiple drugs to achieve blood pressure goals. Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions. These benefts have been seen in controlled trials of antihypertensive drugs from a wide variety of pharmacologic classes including thiazide-like diuretics such as chlorthalidone and ARBs such as azilsartan medoxomil.

Azilsartan medoxomil is an angiotensin II receptor blocker (ARB). Azilsartan helps blood vessels to dilate. It also helps to excrete of Sodium and water from body. This combination also contains a diuretic. Chlorthalidone works in the kidneys to flush excess water and salt (sodium) from the body. Together, these 2 medicines work to help lower blood pressure in people who need more than 1 medicine to treat their high blood pressure (hypertension).

Absorption: Azilsartan medoxomil is rapidly hydrolyzed to azilsartan, the active metabolite, in the gastrointestinal tract during absorption. Azilsartan medoxomil is not detected in plasma after oral administration. The estimated absolute bioavailability of azilsartan following administration of azilsartan medoxomil is approximately 60%. After oral administration of azilsartan medoxomil, peak plasma concentrations (Cmax) of azilsartan are reached within 1.5 to 3 hours. Food does not affect the bioavailability of azilsartan.

Distribution: The volume of distribution of azilsartan is approximately 16L. Azilsartan is highly bound to human plasma proteins (>99%), mainly serum albumin. Protein binding is constant at azilsartan plasma concentrations well above the range achieved with recommended doses. In whole blood, chlorthalidone is predominantly bound to erythrocyte carbonic anhydrase. In the plasma, approximately 75% of chlorthalidone is bound to plasma proteins, 58% of the drug being bound to albumin.

Metabolism and Elimination: Azilsartan medoxomil: Azilsartan is metabolized to two primary metabolites. The major metabolite in plasma is formed by O-dealkylation, referred to as metabolite M II, and the minor metabolite is formed by decarboxylation, referred to as metabolite M-I. Systemic exposures to the major and minor metabolites in humans were approximately 50% and less than 1% of azilsartan, respectively. M-I and MII do not contribute to the pharmacologic activity of azilsartan medoxomil. The major enzyme responsible for azilsartan metabolism is CYP2C9. The elimination half-life of azilsartan is approximately 11 hours and renal clearance is approximately 2.3 mL/min. Steady-state levels of azilsartan are achieved within 5 days and no accumulation in plasma occurs with repeated once-daily dosing.

Chlorthalidone: The major portion of the drug is excreted unchanged by the kidneys. Nonrenal routes of elimination have yet to be clarified. Data are not available regarding the percentage of dose as unchanged drug and metabolites, the concentration of the drug in body fuids, degree of uptake by a particular organ or in the fetus, or passage across the blood-brain barrier.

The recommended starting dose is 40/12.5 mg taken orally once daily. Most of the antihypertensive effect is apparent within 1 to 2 weeks. This combination may be used to provide additional blood pressure lowering for patients not adequately controlled on ARB or diuretic monotherapy treatment. Patients not controlled with azilsartan medoxomil 80 mg may have an additional systolic/diastolic clinic blood pressure reduction of 13/6 mm Hg when switched to this combination 40/12.5 mg.

This combination may be used as initial therapy if a patient is likely to need multiple drugs to achieve blood pressure goals. Patients titrated to the individual components (azilsartan medoxomil and chlorthalidone) may instead receive the corresponding dose of this combination. This may be taken with or without food.

Renal clearance of lithium is reduced by diuretics, such as chlorthalidone increasing the risk of lithium toxicity. NSAIDs increase risk of renal dysfunction and interfere with antihypertensive effect

This is contraindicated in patients with anuria.

The following potential adverse reactions are-

• Fetal toxicity
• Hypotension in Volume- or Salt-Depleted Patients
• Impaired Renal Function
• Hypokalemia Hyperuricemia

Pregnancy Category D. Use of drugs that affect the renin-angiotensin system during the second and third trimesters of pregnancy reduces fetal renal function and increases fetal and neonatal morbidity and death.

• In patients with an activated renin-angiotensin-aldosterone system (RAAS), such as volume- and/or salt-depleted patients, Azisan Plus can cause excessive hypotension. Correct volume or salt depletion prior to administration of azilsartan and chlorthalidone.
• In patients with renal artery stenosis, Azisan Plus may cause renal failure.
• Monitor renal function in patients with renal impairment. Consider discontinuing Azisan Plus with progressive renal impairment.
• Heart rhythm problems (e.g., bradycardia, QT prolongation, ventricular tachycardia), liver problems, certain uncorrected mineral imbalances (low potassium/magnesium levels), severe kidney problems.

Combined antihypertensive preparations

Store in a cool & dry place, away from light and children.