Irbesartan - Uses, Mechanism of Action, Precautions, and Side Effects

Overview:

Irbesartan is an angiotensin receptor blocker (ARB) indicated in treating hypertension (elevated blood pressure) and diabetic nephropathy (a serious consequence of type 1 and type 2 diabetes that causes a decline in the functioning of kidneys). It can also be used with hydrochlorothiazide in people who do not respond to monotherapy. ARBs do not cause dry cough. Irbesartan was granted FDA (Food and Drug Administration) approval on the 30th of September 1997.

How Does Irbesartan Work?

High blood pressure can maximize the workload of the heart and arteries. If this prolongs for a long time, the functioning of the heart and arteries may be impaired. Lowering the blood pressure can minimize the risk of heart attacks and stroke.

Irbesartan works by preventing angiotensin ll from binding to the AT1 receptors in the tissues of the vascular smooth muscles and the adrenal gland. Irbesartan and its active metabolite bind to the AT1 receptor with almost 8500 times more affinity than they bind to the AT2 receptors. This prevention causes vascular smooth muscle relaxation and prevents the secretion of aldosterone (a steroid hormone secreted by the adrenal glands), thus lowering the raised blood pressure. Angiotensin ll would otherwise bind to the AT1 receptor, causing vasoconstriction (constriction of blood vessels) and hypertension.

Uses of Irbesartan:

Irbesartan is indicated in:

• Hypertension.

• Diabetic nephropathy in type 2 diabetes.

Limitations:

Irbesartan should not be administered with the drug Aliskiren.

Dosage Restrictions:

1. Route of Administration: Oral.

2. Dosage Strengths:

• 75 mg.

• 150 mg.

• 300 mg.

3. Dosage Forms:

The drug is available as white to off-white, biconvex oval, film-coated tablet embossed with a heart on one side and ‘2871’, ‘2872’, and ‘2873’ for 75 mg, 150 mg, and 300 mg, respectively on the other side.

Special Considerations:

• Gender - No difference based on gender has been found in healthy elderly and young people. No gender-related dose adjustment is necessary.

• Geriatric - No adjustment of dose is necessary for the elderly.

• Renal Insufficiency - Irbesartan is not removed through hemodialysis. No dosage adjustment is required in individuals with mild to severe renal impairment unless the individual is volume depleted.

• Hepatic Insufficiency - No adjustment of dose is required in patients with mild to moderate hepatic (liver) insufficiency.

Warnings and Contraindications:

Irbesartan is not indicated in patients who are hypersensitive to any drug component. For example, Aliskiren, a renin inhibitor, should not be administered with Irbesartan in diabetic patients.

Warnings and Precautions:

1. Fetal Toxicity (Pregnancy Category D) -

The use of antihypertensive drugs in the second and third trimesters of pregnancy leads to a decrease in the renal function of the fetus, thereby increasing fetal and neonatal morbidity. In addition, Irbesartan has been found to cause a decrease in the amniotic fluid resulting in fetal lung hypoplasia and skeletal deformities. Other fetal adverse effects include skull hypoplasia, anuria, hypotension, renal failure, and death.

2. Hypotension in Volume (Salt-depleted Patients) -

Excessive hypotension has rarely been reported in patients with uncomplicated hypertension. However, antihypertensive therapy might cause hypotension in patients with intravascular volume or sodium depletion, such as patients on diuretics or dialysis.

3. Impaired Kidney Function -

For patients whose kidney functions depend on the activity of the renin-angiotensin-aldosterone system, like those with congestive heart failure, treatment with Irbesartan has been found to cause oliguria and progressive azotemia.

For Patients:

What Is Hypertension?

Hypertension (high blood pressure) is an increase in blood pressure above normal. In this condition, the blood force against the arterial walls is very high. The normal blood pressure range is 120/80 mm of Hg, and in hypertension, the blood pressure may peak to 140/90 mm of Hg or above. Hypertension is usually asymptomatic, but if left untreated, it can cause severe health conditions like heart disease and stroke.

Why Is Irbesartan Prescribed for Hypertension?

Irbesartan is used on its own or combined with other medicines to treat high blood pressure. It is from a class of medications called angiotensin ll receptor antagonists. It works by obstructing the action of certain substances that tighten the blood vessels, thereby enabling the blood to flow more smoothly and ensuring effective pumping of the heart.

Facts One Should Know About Irbesartan:

How Should One Take Irbesartan?

• Irbesartan comes in the form of a tablet and is to be taken orally. It is sold under the brand name Avapro in the United States and as Irovel 150 mg in India.

• It should be taken once daily with or without food.

• It should be taken around the same time every day.

What Should One Discuss With The Doctor Before Beginning Irbesartan?

Before taking the medication, the doctor should be informed of the following:

• Whether one is allergic to Irbesartan or any other medication.

• Whether one has diabetes or taking the medication Aliskiren.

• Whether one is taking other prescription or non-prescription medications, such as vitamins and nutritional supplements.

• If one is taking medications such as Benazepril, Captopril, Enalapril, Fosinopril, Lisinopril, Moexipril, Perindopril, Quinapril, Ramipril, and Trandolapril; Aspirin, and other nonsteroidal anti-inflammatory medications (NSAIDs) such as Ibuprofen, Naproxen, and selective COX-2 inhibitors such as Celecoxib; diuretics, and potassium supplements.

• If one ever had heart failure or kidney disease.

• If one is breastfeeding.

Is Irbesartan Safe?

Irbesartan is a safe blood pressure medicine, with fewer side effects, especially for people with diabetes.

Is Irbesartan Effective?

Irbesartan controls blood pressure but does not cure it. It takes around two weeks for the drug to act fully.

What Side Effects Can One Expect With Irbesartan?

The following side effects can be expected:

• Diarrhea.

• Heartburn.

• Excessive fatigue.

Serious side effects include:

• Swelling of the face, throat, tongue, lips, eyes, hands, feet, ankles, or lower legs.

• Sore throat or hoarseness of voice.

• Difficulty breathing.

The use of Irbesartan is not usually linked with an increased incidence of dry cough.

Can One Stop Taking Irbesartan Without the Doctor’s Approval?

One must not stop the medication without the doctor’s consent.

Are There Any Dietary Restrictions to Consider When Taking Irbesartan?

While taking Irbesartan, avoid taking salt substitutes that contain potassium without consulting the doctor. If the doctor prescribes a low-salt or low-sodium diet, follow the instructions carefully.

How Should One Store Irbesartan?

• The medicine should be kept in a tightly closed container, out of kids’ reach.

• It should be stored at normal temperature, away from heat and moisture.

How Should One Dispose off Irbesartan?

• The unused medications should be disposed off in such a way that pets, kids, or any other person cannot take them.

• The drug should not be flushed into the toilet.

• The medicine should be disposed off through the medicine take-back programs of the community.

What To Do in Case of Overdose?

In case of an overdose, if the patient is showing symptoms such as dizziness, fainting, and a fast or slow heartbeat, contact poison control or the emergency services as soon as possible.

For Doctors:

Indications -

Irbesartan is indicated in the following conditions:

• Hypertension: Irbesartan can be used alone or in combination with other antihypertensive drugs.

• Nephropathy in Type 2 Diabetes: Irbesartan decreases the rate of progression of nephropathy.

What Is the Pharmacology of Anastrozole?

Description:

Irbesartan is an angiotensin ll receptor antagonist. It is a non-peptide compound with an empirical formula of C25H28N60. Irbesartan is a white to off-white colored crystalline powder. The molecular weight is 428.5, and the pH is 7.4. The medicine is slightly soluble in alcohol and methylene chloride but is insoluble in water.

Components -

1. Active Ingredients -

Irbesartan.

2. Inactive Ingredients -

• Lactose monohydrate.

• Microcrystalline cellulose.

• Croscarmellose sodium.

• Hypromellose.

• Silicon dioxide.

• Magnesium stearate.

• Titanium dioxide.

• Polyethylene glycol 3000.

Clinical Pharmacology:

Mechanism of Action -

Angiotensin ll is a vasoconstrictor derived from angiotensin l in a reaction catalyzed by an angiotensin-converting enzyme (ACE, kinase ll). Angiotensin ll is the primary pressor agent of the renin-angiotensin system (RAS) and also stimulates the synthesis and secretion of aldosterone by the adrenal cortex, and is involved in cardiac contraction, absorption of sodium by the kidneys, sympathetic nervous system activity, and the growth of smooth muscle cells.

Irbesartan blocks the vasoconstriction and aldosterone secretion of angiotensin ll by binding to the AT1 angiotensin ll receptor. Blockage of the AT1 receptor removes the negative feedback of angiotensin ll on the secretion of renin but the increased plasma renin activity and circulating angiotensin ll do not overcome its effect on blood pressure. In addition, Irbesartan does not inhibit ACE or renin or affect other hormone receptors and ion channels that are involved in the cardiovascular regulation of blood pressure.

Pharmacodynamics -

Irbesartan is an angiotensin receptor blocker and is used in the treatment of hypertension and diabetic nephropathy. It has a long period of action and is taken once a day. It has a broad therapeutic index with a low dose of 150 mg daily to a dose of 900 mg per day and is tolerated well in healthy individuals.

Pharmacokinetics -

Mean Cmax -

60% to 80%.

Median Tmax -

1.5 to 2 hours.

[Cmax- Maximum concentration achieved by a drug in the blood, cerebrospinal fluid, or target organ after administration of a dose].

[Tmax- Time taken for a drug to reach maximum concentration after administration of a dose].

Pharmacokinetic Changes -

Irbesartan shows linear pharmacokinetics over the therapeutic range of dosage (over the dose range of 10 to 600 mg). The half-life of elimination is around 11 to 15 hours.

A. Distribution-

Steady-state Plasma Levels -

There is a limited accumulation of Irbesartan (less than 20 %) in the plasma after repeated daily dosing. The absorption of Irbesartan is slightly delayed by food.

Time to Approach Steady-state Levels -

Steady-state concentration is achieved within three days.

Binding to Plasma Proteins - 90 %.

B. Metabolism -

Irbesartan is metabolized through glucuronide conjugation and oxidation. After oral or intravenous administration of 14C-labeled Irbesartan, more than 80 % of the plasma radioactivity is accountable to the unchanged form of Irbesartan. The primary metabolite of Irbesartan is the inactive Irbesartan glucuronide conjugate.

C. Excretion -

Recovery of Anastrozole -

Irbesartan and its metabolites are excreted through the renal and biliary routes. About 20 % of the radioactivity is recovered in the urine, and the remaining 80 % is recovered in the feces.

D. Elimination -

• Renal clearance is 3 to 3.5 mL/min.

• Total body clearance is 157 to 176 mL/min.

Special Considerations:

1. Renal Insufficiency -

In patients with kidney impairment or patients on hemodialysis, the pharmacokinetics of Irbesartan does not change. Irbesartan is not removed after hemodialysis. So dose adjustment is needed in individuals with mild to severe renal impairment unless they are volume depleted.

2. Hepatic Insufficiency -

The drug's pharmacokinetics were not affected in those with mild to moderate cirrhosis of the liver who were on repeated oral administration of Irbesartan. Therefore, no dosage adjustment is required in such cases.

3. Pregnancy -

Irbesartan can cause harm to the fetus if administered to a pregnant woman, especially in the second and third trimesters of pregnancy. Therefore, the drug therapy should be discontinued once the woman is pregnant.

4. Lactation -

There is no information on the presence of Irbesartan in human milk, its effect on milk production, or its effects on a breastfed infant.

Drug Interactions -

• Aliskiren - The risk of hyperkalemia increases when Aliskiren is used along with Irbesartan.

• Amphetamine - Amphetamine might decrease the antihypertensive activity of Irbesartan.

• Benazepril - The severity of renal failure, hypotension, and hyperkalemia increases when Benazepril is used along with Irbesartan.

What Have Clinical Trials Shown With Regard to Irbesartan?

Clinical Overview of Irbesartan: Expanding the Therapeutic Window in Hypertension -

Irbesartan is a new angiotensin ll receptor antagonist and has been found to reduce high blood pressure when compared to other antihypertensive drugs of other classes. The effect of Irbesartan has been shown in a clinical trial comprising 1691 Irbesartan-treated patients and 539 placebo-treated patients. In addition, active-drug-controlled trials with beta-blockers, angiotensin-converting enzyme inhibitors, calcium antagonists, and diuretics have confirmed positive results with Irbesartan.

Results -

The edge of Irbesartan over other antihypertensive agents of various classes is its capability to widen the therapeutic window in treating hypertension. In addition, Irbesartan has also been found to clear dose-related responses with no dose-related effects on adverse events. This might help a significant number of patients to achieve long-term blood pressure control without worrying about the side effects.

Patient Counseling Information:

Administration Instructions -

• The medicine should be taken orally as directed by the doctor.

• It should be taken once daily with or without food.

• It should be used regularly, preferably at the same time to get the maximum benefit.

• In case the condition does not improve or worsens, then inform the doctor.

• In case of a missed dose, the dose should be taken immediately after remembering unless it is time for the next dose. Do not take two tablets simultaneously.

Complications or Side Effects -

Common side effects include:

• Heartburn.

• Tiredness.

• Diarrhea.

• Dizziness.

• Joint and muscle pain.

• Upper respiratory tract infection.

• Orthostatic hypotension.

Serious side effects include:

• Hyperkalemia - An increase in the levels of potassium in the blood.

• Chest pain.

• Severe headache.

• Anemia.

• Hypoglycemia in diabetic patients.

• The whites of the eyes and skin turn yellow.

• Hepatitis.

• Irregular heartbeat.

• Muscle cramps.

• High fever.

• Impaired kidney function.

Allergic Reactions -

• Swelling of the face, tongue, throat, lips, eyes, hands, and feet.

• Difficulty breathing.

• Sore throat or hoarseness of voice.

• Skin rashes or hives.

• Wheezing.