Azisan40 mg

Azisan is an angiotensin II receptor blocker (ARB) that is FDA-approved for the following use:

• Hypertension (established/approved use): Treatment of high blood pressure in adults, to lower blood pressure. Lowering blood pressure reduces the risk of fatal and non-fatal cardiovascular events, primarily strokes and myocardial infarctions.
• Combination therapy: Azisan may be used alone or in combination with other antihypertensive agents (such as a thiazide diuretic or a calcium channel blocker) when blood pressure is not adequately controlled on a single agent.

Azisan is not approved for use in children, and it is not indicated for heart failure or diabetic nephropathy, although other drugs in the ARB class are used for those conditions.

Azisan is a prodrug that is rapidly converted to its active form, azilsartan, during absorption from the gastrointestinal tract. It belongs to the angiotensin II receptor blocker (ARB) class of antihypertensive medicines. Azisan works by selectively blocking the binding of angiotensin II to the AT1 receptor found in vascular smooth muscle and other tissues, which prevents the vasoconstriction and aldosterone-releasing effects of angiotensin II, resulting in lowered blood pressure.

Azisan is used as a once-daily oral tablet for long-term management of hypertension and is generally well tolerated, with a lower incidence of dry cough compared to ACE inhibitors.

Azisan belongs to the therapeutic class of Angiotensin II Receptor Blockers (ARBs), a group of antihypertensive agents also known as "sartans". This class works by blocking the angiotensin II type 1 (AT1) receptor rather than inhibiting the angiotensin-converting enzyme (ACE), which distinguishes Azisan and related ARBs from ACE inhibitors.

Azilsartan Medoxomil is a prodrug that is hydrolyzed during gastrointestinal absorption to azilsartan, the pharmacologically active moiety. Azilsartan selectively and competitively blocks the binding of angiotensin II to the AT1 receptor in vascular smooth muscle and the adrenal gland, blocking the vasoconstrictive and aldosterone-secreting effects of angiotensin II.

Pharmacokinetics of Azilsartan Medoxomil

• Absorption: Peak plasma concentrations of azilsartan are reached approximately 1.5 to 3 hours after oral administration of Azilsartan Medoxomil; absolute bioavailability is about 60%.
• Distribution: Azilsartan is greater than 99% bound to plasma proteins.
• Metabolism: Azilsartan is metabolized mainly by CYP2C9 to inactive metabolites.
• Elimination: The elimination half-life is approximately 11 hours; azilsartan is eliminated in feces (via bile) and urine.

The onset of blood pressure-lowering effect with Azilsartan Medoxomil occurs within 2 weeks, with maximal effect typically seen by 4 weeks of continued therapy.

Azisan has the following clinically significant drug interactions:

• NSAIDs (e.g., ibuprofen, indomethacin): Concomitant use may reduce the antihypertensive effect of Azisan and may worsen renal function, particularly in elderly or volume-depleted patients; renal function should be monitored.
• Potassium-sparing diuretics, potassium supplements, or salt substitutes containing potassium: May increase the risk of hyperkalemia when used with Azisan.
• Lithium: Concomitant use with Azisan can increase serum lithium concentrations and lithium toxicity; monitor lithium levels closely.
• Aliskiren: Combination with Azisan is contraindicated in patients with diabetes due to increased risk of hyperkalemia, hypotension, and renal impairment (see Contraindications).
• Other antihypertensive agents (ACE inhibitors, other ARBs, diuretics): Additive blood pressure-lowering effect and increased risk of hypotension when combined with Azisan.

Most patients tolerate Azisan well. Reported side effects include:

Common Side Effects

• Diarrhea (reported somewhat more often than with placebo or some other ARBs, especially at the 80 mg dose)
• Dizziness
• Fatigue
• Muscle spasms
• Cough

Less Common but Clinically Important Effects

• Hyperkalemia (elevated blood potassium)
• Hypotension (low blood pressure), particularly in volume-depleted patients
• Increase in blood creatinine/worsening renal function

Rare/Postmarketing Reports

• Angioedema (swelling of face, lips, tongue, or throat) - seek emergency care immediately if this occurs
• Rash and pruritus (itching)
• Acute kidney injury

Azisan is associated with a low incidence of dry cough compared with ACE inhibitors.

Pregnancy

Azisan is contraindicated in pregnancy. Drugs that act directly on the renin-angiotensin system, including Azisan, can cause fetal injury and death when used during the second and third trimesters, including oligohydramnios, fetal lung and skeletal abnormalities, hypotension, and neonatal renal failure. If pregnancy is detected, Azisan should be discontinued as soon as possible, and an alternative antihypertensive should be used under physician guidance.

Lactation

It is not known whether Azisan is excreted in human breast milk, but it has been detected in the milk of lactating rats. Because of the potential for serious adverse effects in a nursing infant, a decision should be made to discontinue breastfeeding or discontinue Azisan, taking into account the importance of the drug to the mother; consult a physician before use while breastfeeding.

Important warnings for Azisan:

• Fetal toxicity (boxed warning level concern): Azisan can cause serious injury or death to a developing fetus; discontinue immediately if pregnancy is detected (see Pregnancy and Lactation, and Contraindications).
• Hypotension in volume- or salt-depleted patients: Correct volume or salt depletion prior to starting Azisan, or begin with a lower starting dose, to reduce the risk of symptomatic hypotension.
• Impaired renal function: As a consequence of inhibiting the renin-angiotensin system, changes in renal function, including acute renal failure, can occur in susceptible individuals treated with Azisan, particularly those whose renal function depends on the activity of this system (e.g., severe congestive heart failure, renal artery stenosis). Monitor renal function periodically.
• Hyperkalemia: Monitor serum potassium periodically, especially in patients with renal impairment, diabetes, or those taking potassium supplements or potassium-sparing diuretics along with Azisan.
• Dual blockade of the renin-angiotensin system: Avoid combining Azisan with an ACE inhibitor or aliskiren unless clearly necessary and under close medical supervision.

Limited human data are available on overdose with Azisan. The most likely manifestation of overdose is hypotension; bradycardia may also occur from parasympathetic (vagal) stimulation. If an overdose of Azisan is suspected, seek immediate medical attention or contact a poison control center/emergency services. Treatment is supportive, and may include intravenous fluid replacement and close monitoring of blood pressure and vital signs. It is not known whether Azisan can be removed by hemodialysis.

Pediatric Use

Safety and efficacy of Azisan in patients younger than 18 years have not been established; it is not recommended for use in children.

Geriatric Use

No overall differences in safety or effectiveness of Azisan have been observed between elderly and younger patients, but greater sensitivity in some older individuals cannot be ruled out; monitor renal function periodically, particularly in patients aged 75 years and older.

Renal Impairment

No initial dose adjustment of Azisan is required in mild-to-moderate renal impairment; use with caution and monitor renal function in patients with severe renal impairment.

Hepatic Impairment

Use Azisan with caution in patients with moderate-to-severe hepatic impairment, as clinical experience is limited.

Pregnancy and Lactation

See Pregnancy and Lactation section - Azisan is contraindicated in pregnancy.

Angiotensin II Receptor Blocker (ARB); Antihypertensive agent.

Azilsartan Medoxomil is a prodrug that is converted to azilsartan after oral absorption. Azilsartan selectively blocks the binding of angiotensin II to the AT1 receptor in vascular smooth muscle and the adrenal gland. Angiotensin II is a potent vasoconstrictor that also stimulates aldosterone synthesis and release. By blocking AT1 receptors, Azilsartan Medoxomil blocks the vasoconstrictor and aldosterone-secreting effects of angiotensin II, which results in decreased peripheral vascular resistance and lowered blood pressure, without affecting the breakdown of bradykinin (unlike ACE inhibitors).

D

Azisan is not approved for use in pediatric patients. Safety and efficacy in patients younger than 18 years of age have not been established, and there is insufficient data on appropriate dosing, effectiveness, or long-term safety of Azisan in children. It should not be used in this age group outside of specific physician guidance in exceptional circumstances.