Usage
- Amlodipine + Irbesartan is prescribed for the treatment of essential hypertension (high blood pressure) in adults. It is specifically indicated for patients whose blood pressure is not adequately controlled by monotherapy with either amlodipine or irbesartan.
- Pharmacological Classification: Antihypertensive, combining a calcium channel blocker (amlodipine) and an angiotensin II receptor blocker (ARB) (irbesartan).
- Mechanism of Action: This combination therapy lowers blood pressure through two distinct mechanisms. Amlodipine inhibits calcium influx into vascular smooth muscle cells, leading to vasodilation. Irbesartan blocks the action of angiotensin II, a hormone that causes vasoconstriction, further promoting vasodilation and reducing blood pressure.
Alternate Names
- This fixed-dose combination is often referred to as amlodipine/irbesartan.
- Brand Names: Aprovasc, Co-Aprovel
How It Works
- Pharmacodynamics: Amlodipine exerts its antihypertensive effect by inhibiting the influx of calcium ions into vascular smooth muscle and cardiac muscle, resulting in vasodilation and decreased peripheral vascular resistance. Irbesartan 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. These complementary actions result in a synergistic reduction in blood pressure.
- Pharmacokinetics: Both amlodipine and irbesartan are orally active. Amlodipine is well absorbed, with peak plasma concentrations occurring in 6 to 12 hours. Irbesartan is also well absorbed, with peak plasma concentrations reached in 1.5 to 2 hours. The concurrent administration of these drugs does not significantly affect the pharmacokinetics of each component. Both drugs are extensively metabolized by the liver, primarily by CYP3A4 (amlodipine) and CYP2C9 (irbesartan). Elimination is primarily via hepatic and renal routes for both components.
- Mode of Action: Amlodipine: Blocks L-type calcium channels. Irbesartan: Blocks angiotensin II AT1 receptors.
- Receptor Binding, Enzyme Inhibition, or Neurotransmitter Modulation: Irbesartan binds to the AT1 receptor of Angiotensin II, blocking Angiotensin II binding and its downstream effects. Amlodipine blocks calcium channels, primarily impacting vascular smooth muscle.
- Elimination Pathways: Primarily hepatic metabolism for both drugs, with subsequent renal and biliary excretion.
Dosage
Standard Dosage
Adults:
- Initial dose: One tablet of amlodipine/irbesartan (150 mg irbesartan/5 mg amlodipine or 150 mg irbesartan/10 mg amlodipine) once daily.
- Maintenance dose: Can be increased to a maximum of 300 mg irbesartan/10 mg amlodipine per day, based on individual blood pressure response.
Children:
- Safety and efficacy not established in children.
Special Cases:
- Elderly Patients: No dosage adjustment is generally required. However, start with the lowest dose and monitor closely.
- Patients with Renal Impairment: No dosage adjustment is generally needed unless the patient is also volume-depleted.
- Patients with Hepatic Dysfunction: Amlodipine should be used with caution in patients with hepatic impairment. Initiate at the lowest dose and titrate slowly.
- Patients with Comorbid Conditions: Use with caution in patients with heart failure. For patients with diabetic nephropathy, the combination should not be used with ACE inhibitors.
Clinical Use Cases
- Amlodipine/irbesartan’s primary use is in the chronic management of hypertension. It is not specifically indicated for acute situations like intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations such as cardiac arrest.
Dosage Adjustments
- Adjust dosage based on blood pressure response.
- Consider renal function and hepatic function when adjusting dosage.
Side Effects
Common Side Effects
- Dizziness, lightheadedness, edema (swelling of ankles or feet), flushing, fatigue.
Rare but Serious Side Effects
- Allergic reactions (angioedema), hypotension, worsening angina, liver dysfunction, increased potassium levels (hyperkalemia).
Long-Term Effects
- Potential long-term effects include electrolyte imbalances, kidney problems, and cardiovascular events if blood pressure remains uncontrolled.
Adverse Drug Reactions (ADR)
- Angioedema, severe hypotension, acute renal failure, hepatotoxicity.
Contraindications
- Hypersensitivity to irbesartan, amlodipine, or dihydropyridines.
- Pregnancy and breastfeeding.
- Cardiogenic shock, obstruction of the left ventricular outflow tract (e.g., aortic stenosis), unstable angina.
- Concomitant use of aliskiren in patients with diabetes or moderate to severe renal impairment.
- Concomitant use of ACE inhibitors in patients with diabetic nephropathy.
Drug Interactions
- Aliskiren (contraindicated in patients with diabetes or renal impairment).
- ACE inhibitors (contraindicated in patients with diabetic nephropathy).
- Potassium-sparing diuretics or potassium supplements (risk of hyperkalemia).
- Lithium (increased lithium levels).
- Non-steroidal anti-inflammatory drugs (NSAIDs) (may reduce the antihypertensive effect).
- CYP3A4 inhibitors or inducers (may affect amlodipine levels).
- CYP2C9 inhibitors (may affect irbesartan levels).
- Grapefruit juice (may increase amlodipine levels).
Pregnancy and Breastfeeding
- Pregnancy Safety Category: D (irbesartan), C (amlodipine). Contraindicated in pregnancy.
- Irbesartan can cause fetal harm or death.
- Amlodipine’s safety in pregnancy has not been established.
- Both drugs are contraindicated during breastfeeding.
Drug Profile Summary
- Mechanism of Action: Calcium channel blockade (amlodipine) and angiotensin II receptor blockade (irbesartan).
- Side Effects: Dizziness, edema, flushing, fatigue, hypotension, hyperkalemia.
- Contraindications: Pregnancy, breastfeeding, hypersensitivity, certain cardiovascular conditions, concomitant use with aliskiren or ACE inhibitors in specific populations.
- Drug Interactions: Aliskiren, ACE inhibitors, potassium supplements, lithium, NSAIDs, CYP3A4 and CYP2C9 inhibitors/inducers.
- Pregnancy & Breastfeeding: Contraindicated.
- Dosage: One tablet daily, adjustable up to 300 mg/10 mg.
- Monitoring Parameters: Blood pressure, renal function (in certain patients), potassium levels (in certain patients).
Popular Combinations
- This product is a popular combination of irbesartan and amlodipine. It is sometimes used in conjunction with hydrochlorothiazide, another antihypertensive.
Precautions
- General Precautions: Assess for volume depletion, renal function, and hepatic function. Monitor blood pressure and potassium levels.
- Specific Populations: Use with caution in elderly patients and those with hepatic impairment. Contraindicated in pregnancy and breastfeeding. Not established in children.
- Lifestyle Considerations: Patients should limit alcohol intake and avoid potassium-rich salt substitutes.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Amlodipine + Irbesartan?
A: The usual starting dose is one tablet (150mg irbesartan/5mg amlodipine or 150mg irbesartan/10mg amlodipine) once daily. The maximum dose is 300mg irbesartan/10mg amlodipine per day.
Q2: Can Amlodipine + Irbesartan be used in patients with renal impairment?
A: Generally, no dosage adjustment is necessary for patients with renal impairment unless the patient is volume-depleted.
Q3: Is Amlodipine + Irbesartan safe during pregnancy?
A: No. Amlodipine + Irbesartan is contraindicated in pregnancy. It can cause fetal harm or death.
Q4: What are the most common side effects of Amlodipine + Irbesartan?
A: Common side effects include dizziness, lightheadedness, edema (swelling of the ankles or feet), flushing, and fatigue.
Q5: Can Amlodipine + Irbesartan be used with other blood pressure medications?
A: It can be used with other antihypertensives but with caution. Co-administration with aliskiren or ACE inhibitors is contraindicated in certain patient populations (see Contraindications). Concomitant use with potassium-sparing diuretics or potassium supplements can increase the risk of hyperkalemia.
Q6: What should I do if I miss a dose of Amlodipine + Irbesartan?
A: Take the missed dose as soon as you remember, unless it is almost time for the next dose. Do not double the dose to catch up.
Q7: How does Amlodipine + Irbesartan interact with grapefruit juice?
A: Grapefruit juice can increase the levels of amlodipine in the blood. It is best to avoid grapefruit juice while taking this medication.
Q8: Can Amlodipine + Irbesartan be crushed or chewed?
A: No. Swallow the tablet whole with water.
Q9: What are the signs of an allergic reaction to Amlodipine + Irbesartan?
A: Signs of an allergic reaction can include swelling of the face, lips, tongue, or throat; difficulty breathing; rash; itching; or hives. Seek immediate medical attention if these occur.
Q10: How often should I monitor my blood pressure while taking Amlodipine + Irbesartan?
A: Regular blood pressure monitoring is important. The frequency of monitoring will depend on the individual patient’s condition and the judgment of the healthcare provider.
