Approved

Aprovel is the trade name of a drug whose main active ingredient is irbesartan. Irbesartan belongs to a class of drugs known as angiotensin II receptor antagonists (ARA II) or angiotensin receptor blockers. It is used to treat hypertension (high blood pressure) and to protect the kidneys in patients with type 2 diabetes mellitus accompanied by protein in the urine (microalbuminuria) to prevent the progression of chronic kidney disease.

Irbesartan works by blocking the action of angiotensin II, which is a powerful vasoconstrictor hormone. By blocking angiotensin receptors, irbesartan dilates blood vessels and reduces vascular resistance, which leads to a decrease in blood pressure. It may also help reduce stress on the kidneys and protect them from damage associated with hypertension and diabetes.

Indications Approved

• Hypertension: Aprovel is used to reduce high blood pressure in adult patients. This may help prevent complications associated with high blood pressure, such as stroke, heart attack, and kidney damage.
• Chronic kidney disease in patients with type 2 diabetes: Aprovel may be prescribed to protect the kidneys and reduce the progression of chronic kidney disease in patients with type 2 diabetes, especially those who have microalbuminuria (the presence of protein in the urine).
• Heart failure: In some cases, Aprovel may be used to treat heart failure in patients, especially if they cannot tolerate angiotensin-converting enzyme inhibitors (ACEIs) or if ACEIs are not effective enough.

Release form

Aprovel is often produced in the form of tablets for oral administration. Tablets can have different dosages, which allows you to select the optimal dose depending on the individual needs of the patient.

Pharmacodynamics

• Angiotensin II receptor blocking: Irbesartan binds to angiotensin II receptors in vascular tissues and other organs, interfering with the effects of this hormone. Angiotensin II generally causes vasoconstriction, increasing blood pressure, and also stimulates the release of aldosterone, which leads to sodium and water retention. Blocking angiotensin II receptors with irbesartan leads to vasodilation and a decrease in blood pressure.
• Reduced peripheral vascular resistance: Since irbesartan blocks the vasoconstrictor effects of angiotensin II, this leads to a decrease in peripheral vascular resistance, which in turn helps lower blood pressure.
• Reducing workload on the heart: By reducing blood pressure and peripheral vascular resistance, irbesartan reduces workload on the heart, which may be beneficial for patients with heart failure.
• Kidney protection: Irbesartan may have a protective effect on the kidneys, especially in patients with diabetes, by preventing the progression of proteins in the urine (microalbuminuria) and preserving kidney function.

Pharmacokinetics

• Absorption: Irbesartan is generally well absorbed from the gastrointestinal tract after oral administration. Peak blood concentrations are usually reached 1-2 hours after administration.
• Bioavailability: The bioavailability of irbesartan after oral administration is approximately 60-80% of the dose.
• Metabolism: Irbesartan undergoes extensive metabolism in the liver, where it undergoes oxidation and glucuronidation. The main metabolites are irbesartan-2-O-glucuronide and irbesartan-3-carboxymethyl ether.
• Protein binding: Approximately 90-95% of irbesartan is bound to plasma proteins, primarily albumin.
• Distribution: The volume of distribution of irbesartan is approximately 53-93 liters. It penetrates well into tissues, including the kidneys, liver and heart.
• Excretion: About 20% of the dose is excreted unchanged through the kidneys, and the rest through the intestines. The half-life of irbesartan from plasma is about 11-15 hours.
• Effect of food: Food does not have a clinically significant effect on the absorption of irbesartan, so the drug can be taken regardless of meals.

Dosing and administration

1. Hypertension:

   • The starting dose for adults is usually 150 mg once daily.
   • If additional blood pressure reduction is needed, the dose can be increased to the maximum, which is usually 300 mg once daily.
   • In patients with moderate to severe hypertension and diabetes mellitus, it is recommended to start with a dose of 300 mg.

2. Diabetes mellitus with microalbuminuria:

   • The starting dose for adults is usually 150 mg once daily.
   • If necessary, the dose can be increased to 300 mg per day.

3. Heart failure:

   • The starting dose for adults is usually 75 mg once daily.
   • If well tolerated, the dose can be increased to 150 mg and further to 300 mg per day depending on the response to treatment.

Irbesartan is usually taken once a day, regardless of meals. The tablet should be swallowed whole with water.

Use Approved during pregnancy

• Fetotoxicity:

  • Studies indicate that angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor antagonists may cause fetotoxicity when used in the second and third trimesters of pregnancy. Cases of exencephaly and unilateral renal agenesis have been reported in fetuses of women taking irbesartan during pregnancy (Boix et al., 2005).

• Negative pregnancy outcomes:

  • A study examining the use of angiotensin II receptor antagonists during pregnancy found that long-term use of these drugs is associated with a high risk of adverse pregnancy outcomes, including delayed limb development and spontaneous abortion (Velázquez-Armenta et al., 2007).

• Effect on the fetus:

  • Use of irbesartan before conception and early pregnancy may result in fetal growth retardation and an increased risk of adverse outcomes. In one case, a woman taking irbesartan was diagnosed with a fetus with Turner syndrome and delayed limb development (Velázquez-Armenta et al., 2007).

Contraindications

• Hypersensitivity: The drug is contraindicated in cases of known hypersensitivity to irbesartan or any of the components of the drug. This may manifest as allergic reactions, including skin rash, itching, facial swelling, or difficulty breathing.
• Pregnancy: The use of Aprovel is contraindicated during pregnancy, especially in the second and third trimesters, as this can lead to the development of severe disorders in the fetus, such as decreased renal function, hypoplasia of the skull and posterior region of the brain.
• Lactation: Aprovel is excreted into breast milk, so its use is contraindicated during breastfeeding.
• Blood clotting: The drug should be used with caution in patients with bleeding disorders or in patients receiving anticoagulants.
• Symptomatic hypotension: The drug should be used with caution in patients with severe hypotension, as irbesartan may cause a decrease in blood pressure.
• Heart failure: Aprovel should be used with caution in patients with heart failure, especially those with concomitant renal impairment.
• Combination with Alskept (alfa-lisinopril): The combined use of Aprovel and Alskept is contraindicated due to the risk of hypotensive effects.

Side effects Approved

• Lowering blood pressure: This is one of the typical effects of the medicine. In rare cases, this can cause hypotension (severe low blood pressure), especially in patients with severe hypovolemia (low body fluids), which can lead to dizziness or fainting.
• Headache: Some patients may experience headaches while taking Aprovel.
• Dizziness and drowsiness: This also applies to possible side effects, especially at the beginning of treatment or when changing the dosage.
• Hyperkalemia: In rare cases, Aprovel may cause an increase in potassium levels in the blood, which can be dangerous, especially in patients with impaired kidney function or when taking other medications that may also increase potassium levels.
• Allergic reactions: Include skin rash, itching, hives, facial swelling, or difficulty breathing. If any signs of allergy occur, you should stop taking Aprovel and consult a doctor.
• Elevated blood urea and creatinine levels: This may occur in some patients, especially those with impaired kidney function.
• Muscle or joint pain: This can also be a side effect of Aprovel.

Overdose

• Severe decrease in blood pressure, which can lead to dizziness and fainting.
• Drowsiness, drowsiness and general feeling of weakness.
• Cardiac arrhythmias or respiratory disorders are also possible.

Interactions with other drugs

• Drugs that increase the risk of hyperkalemia: Aprovel may increase blood potassium levels when taken concomitantly with potassium-sparing diuretics (eg, spironolactone, amiloride), potassium supplements, or other drugs that may also increase potassium levels.
• Other antihypertensive drugs: The combined use of Aprovel with other antihypertensive drugs, such as diuretics, angiotensin-converting enzyme inhibitors (ACEIs), calcium antagonists or beta-blockers, may lead to increased hypotensive effect.
• Drugs that increase the risk of hypotension: Combined use of Aprovel with alcohol, antidepressants, sedatives or hypnotics can enhance the hypotensive effect and increase the risk of orthostatic hypotension (a decrease in blood pressure with changes in body position).
• Lithium: Irbesartan may reduce the clearance of lithium, which may result in increased lithium blood levels and toxic effects.
• Nephrotoxic drugs: Irbesartan may increase the nephrotoxicity of some drugs, especially nonsteroidal anti-inflammatory drugs (NSAIDs) and drugs metabolized by the kidney.