ZILZOX 40 & 80
Composition AzilsartanMedoxomil 40mg & 80mg Tablets
Indication Zilzox (AzilsartanMedoxomil) is an angiotensin II receptor blocker (ARB) indicated for the treatment of mild to moderate essential hypertension.
Mechanism of Action

Azilsartanmedoxomil, a prodrug, is hydrolysed to Azilsartan during absorption from the gastrointestinal tract. Azilsartan is a selective AT1 subtype angiotensin II receptor blocker (ARB) Azilsartan blocks the vasoconstrictor and aldosterone-secreting effects of angiotensin II by selectively blocking the binding of angiotensin II to the AT1 receptor in many tissues, such as vascular smooth muscle and the adrenal gland. Its action is, therefore, independent of the pathway for angiotensin II synthesis.

An AT2 receptor is also found in many tissues, but this receptor is not known to be associated with cardiovascular homeostasis. Azilsartan has >10,000 fold greater affinity for the AT1 receptor than for the AT2 receptor. Because Azilsartan does not inhibit ACE (kinase II), it should not affect the response to bradykinin.

Pharmacokinetic's

Absorption

Azilsartanmedoxomil is hydrolyzed to Azilsartan, the active metabolite, in the gastrointestinal tract during absorption. Azilsartanmedoxomil is not detected in plasma after oral administration. Dose proportionality in exposure was established for Azilsartan in the Azilsartanmedoxomil dose range of 20 mg to 320 mg after single or multiple dosing.

The estimated absolute bioavailability of Azilsartan following administration of Azilsartanmedoxomil is approximately 60%. After oral administration of Azilsartanmedoxomil, 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 16 L. 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 rats, minimal Azilsartan-associated radioactivity crossed the blood-brain barrier. Azilsartan passed across the placental barrier in pregnant rats and was distributed to the foetus.

Metabolism and Elimination

Azilsartan is metabolized to two primary metabolites. The major metabolite in plasma is formed by Ode alkylation, 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 M-II do not contribute to the pharmacologic activity of Zilzox. The major enzyme responsible for Azilsartan metabolism is CYP2C9.

Following an oral dose of 14C-labeled Azilsartanmedoxomil, approximately 55% of radioactivity was recovered in faeces and approximately 42% in urine, with 15% of the dose excreted in urine as Azilsartan. 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 five days, and no accumulation in plasma occurs with repeated once-daily dosing.

Side effects

Common side effects of Azilsartanmedoxomil include:

Nausea,

Diarrhoea,

Fatigue,

Muscle spasm,

Cough,

Dizziness,

Weakness, and

Tired feeling.

Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure

Precaution

Fetal Toxicity

Use of drugs that act on the renin-angiotensin system during the second and third trimesters of pregnancy reduces foetal renal function and increases foetal and neonatal morbidity and death. Resulting oligohydramnios can be associated with foetal lung hypoplasia and skeletal deformations. Potential neonatal adverse effects include skull hypoplasia, anuria, hypotension, renal failure, and death. When pregnancy is detected, discontinue Zilzox as soon as possible

Hypotension In Volume-Or Salt-Depleted Patients

In patients with an activated renin-angiotensin system, such as volume-and/or salt-depleted patients (e.g., those being treated with high doses of diuretics), symptomatic hypotension may occur after initiation of treatment with Zilzox. Correct volume or salt depletion prior to administration of Zilzox, or start treatment at 40 mg. If hypotension does occur, the patient should be placed in the supine position and, if necessary, given an intravenous infusion of normal saline. A transient hypotensive response is not a contraindication to further treatment, which usually can be continued without difficulty once the blood pressure has stabilized.

Impaired Renal Function

As a consequence of inhibiting the renin-angiotensin system, changes in renal function may be anticipated in susceptible individuals treated with Zilzox. In patients whose renal function may depend on the activity of the renin-angiotensin system (e.g., patients with severe congestive heart failure, renal artery stenosis, or volume depletion), treatment with angiotensin-converting enzyme inhibitors and angiotensin receptor blockers has been associated with oliguria or progressive azotemia and rarely with acute renal failure and death. Similar results may be anticipated in patients treated with Zilzox.

In studies of ACE inhibitors in patients with unilateral or bilateral renal artery stenosis, increases in serum creatinine or blood urea nitrogen have been reported. There has been no long-term use of Azilsartanmedoxomil in patients with unilateral or bilateral renal artery stenosis, but similar results may be expected.

Dosage

The recommended dose in adults is 80 mg taken orally once daily. Consider a starting dose of 40 mg for patients who are treated with high doses of diuretics.

If blood pressure is not controlled with Zilzox alone, additional blood pressure reduction can be achieved by taking Zilzox with other antihypertensive agents.