Aprovel

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 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 widens blood vessels and reduces vascular resistance, which leads to lower blood pressure. It may also help reduce the strain on the kidneys and protect them from damage associated with hypertension and diabetes.

Indications Aprovelz

• Hypertension: Aprovel is used to lower high blood pressure in adult patients. It 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 with microalbuminuria (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 (ACE inhibitors) or if ACE inhibitors are not effective enough.

Release form

Aprovel is often produced in tablet form for oral administration. Tablets come in different dosages, allowing the optimal dose to be selected depending on the individual patient's needs.

Pharmacodynamics

• Angiotensin II receptor blocking: Irbesartan binds to angiotensin II receptors in vascular tissue and other organs, interfering with the effects of this hormone. Angiotensin II normally 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 causes vasodilation and a decrease in blood pressure.
• Decreased 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 to reduce blood pressure.
• Reducing the workload on the heart: By reducing blood pressure and vascular resistance, irbesartan reduces the 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 mellitus, 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, mainly 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 via the kidneys, and the remainder via the faeces. The plasma half-life of irbesartan is about 11-15 hours.
• Food effect: Food has no clinically significant effect on the absorption of irbesartan, so the drug can be taken with or without food.

Dosing and administration

1. Hypertension:

   • The starting dose for adults is usually 150 mg once daily.
   • If further reduction in blood pressure is required, 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 then up to 300 mg per day depending on the response to treatment.

Irbesartan is usually taken once daily, with or without food. The tablet should be swallowed whole with water.

Use Aprovelz during pregnancy

• Fetotoxicity:

  • Studies have shown that angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor antagonists may cause fetotoxicity when administered during 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 looking at the use of angiotensin II receptor antagonists during pregnancy found that long-term use of these drugs was associated with a high risk of adverse pregnancy outcomes, including limb developmental delay and spontaneous abortion (Velázquez-Armenta et al., 2007).

• Effect on the fetus:

  • Use of irbesartan before conception and in early pregnancy may result in fetal growth restriction 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, swelling of the face or difficulty breathing.
• Pregnancy: The use of Aprovel is contraindicated during pregnancy, especially in the second and third trimesters, as it may lead to the development of severe abnormalities in the fetus, such as decreased renal function, hypoplasia of the skull and posterior brain area.
• Lactation: Aprovel is excreted in breast milk, so its use is contraindicated during breastfeeding.
• Blood coagulation: 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 if there is concomitant renal impairment.
• Combination with Alskept (alpha-lisinopril): Combined use of Aprovel and Alskept is contraindicated due to the risk of hypotensive effects.

Side effects Aprovelz

• Decreased blood pressure: This is one of the typical actions of the drug. In rare cases, it can cause hypotension (a severe decrease in blood pressure), especially in patients with severe hypovolemia (low fluid content in the body), which can lead to dizziness or fainting.
• Headache: Some patients may experience headache 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 high levels of potassium in the blood, which can be dangerous, especially in patients with impaired kidney function or when taking other medications that can also increase potassium levels.
• Allergic reactions: These may include skin rash, itching, hives, swelling of the face, or difficulty breathing. If any signs of allergy occur, stop taking Aprovel and consult a doctor.
• Increased blood urea and creatinine levels: This may occur in some patients, especially those with impaired renal function.
• Muscle or joint pain: This may also be a side effect of Aprovel.

Overdose

• A sharp decrease in blood pressure, which can lead to dizziness and fainting.
• Drowsiness, sleepiness and a general feeling of weakness.
• Cardiac arrhythmias or respiratory problems are also possible.

Interactions with other drugs

• Drugs that increase the risk of hyperkalemia: Aprovel may increase the increase in 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: Combined use of Aprovel with other antihypertensive drugs, such as diuretics, angiotensin-converting enzyme inhibitors (ACEI), calcium antagonists or beta-blockers, may lead to an increased hypotensive effect.
• Drugs that increase the risk of hypotension: Combined use of Aprovel with alcohol, antidepressants, sedatives or hypnotics may enhance the hypotensive effect and increase the risk of orthostatic hypotension (a decrease in blood pressure when changing body position).
• Lithium: Irbesartan may decrease the clearance of lithium, which may lead to increased lithium blood levels and toxic effects.
• Nephrotoxic drugs: Irbesartan may enhance the nephrotoxicity of some drugs, especially nonsteroidal anti-inflammatory drugs (NSAIDs) and drugs metabolized in the kidney.