Usage
- This medication is prescribed for the treatment of hypertension (high blood pressure) and stable coronary artery disease. It may also be used as initial therapy for hypertension in patients likely requiring multiple medications to achieve blood pressure goals.
- Pharmacological Classification: This is a combination drug belonging to the class of antihypertensives, specifically combining an ACE inhibitor (perindopril) and a calcium channel blocker (amlodipine).
- Mechanism of Action: Amlodipine works by relaxing and widening blood vessels, improving blood flow and reducing the heart’s workload. Perindopril, an angiotensin-converting enzyme (ACE) inhibitor, further widens blood vessels and prevents the body from retaining water. This combined action effectively lowers blood pressure.
Alternate Names
- While “Amlodipine + Perindopril erbumine” represents the generic name, regional or international variations may exist.
- Brand Names: Prestalia, Coveram, Amaday PL.
How It Works
- Pharmacodynamics: This combination causes vasodilation, reducing peripheral vascular resistance and lowering blood pressure. It also improves myocardial oxygen supply in stable coronary artery disease.
- Pharmacokinetics: Amlodipine is well-absorbed orally, reaching peak plasma concentrations in 6 to 12 hours. It is extensively metabolized by the liver and primarily excreted in the urine. Perindopril is converted to its active metabolite, perindoprilat, by hydrolysis in the liver. Perindoprilat is eliminated primarily through renal excretion.
- Mode of Action: Amlodipine blocks calcium influx into vascular smooth muscle cells and cardiac muscle, causing vasodilation. Perindopril inhibits ACE, reducing the formation of angiotensin II, a potent vasoconstrictor, and preventing the breakdown of bradykinin, a vasodilator. This leads to vasodilation and reduced blood pressure.
- Receptor Binding/Enzyme Inhibition: Amlodipine acts on L-type calcium channels. Perindopril inhibits ACE.
- Elimination Pathways: Amlodipine is primarily hepatically metabolized and excreted in the urine and feces. Perindopril is converted to perindoprilat in the liver and excreted mainly by the kidneys.
Dosage
Standard Dosage
Adults:
- Initial dose: One tablet of Amlodipine 2.5 mg + Perindopril 3.5 mg orally once daily.
- Maintenance dose: Titrated up to a maximum of Amlodipine 10 mg + Perindopril 14 mg once daily as needed to achieve blood pressure control. Dosage adjustments should occur every 7-14 days.
- Administration: Tablets should be taken orally, preferably in the morning before a meal.
Children:
- This combination is not recommended for use in children and adolescents. Safety and efficacy have not been established in this population.
Special Cases:
- Elderly Patients: Start at a lower dose of Amlodipine (2.5 mg) and titrate cautiously as needed. Close monitoring is recommended, especially in patients over 65.
- Patients with Renal Impairment: For mild to moderate renal impairment (creatinine clearance 30-80 mL/min), the maximum dose is Amlodipine 5 mg + Perindopril 7 mg. Not recommended for severe renal impairment (CrCl <30 mL/min).
- Patients with Hepatic Dysfunction: Administer with caution. Dosage recommendations have not been established for patients with hepatic impairment. Start at the lower end of the dosing range.
- Patients with Comorbid Conditions: Use with caution in patients with heart failure, severe obstructive coronary artery disease, or cerebrovascular disease. Close monitoring is essential.
Clinical Use Cases
- The specific dosage recommendations for clinical settings such as intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations may vary depending on individual patient circumstances and concomitant medications. Dosage adjustments should be based on clinical judgment.
Dosage Adjustments
- Dose adjustments are based on blood pressure response and patient tolerance. Consider renal function, hepatic function, and other comorbidities.
Side Effects
Common Side Effects:
- Peripheral edema, dizziness, lightheadedness, headache, cough, flushing, nausea.
Rare but Serious Side Effects:
- Angioedema (swelling of the face, lips, tongue, or throat), hypotension, hyperkalemia, acute renal failure, hepatic dysfunction.
Long-Term Effects:
- Chronic kidney disease, electrolyte imbalances.
Adverse Drug Reactions (ADR):
- Angioedema, severe hypotension, syncope, hepatotoxicity.
Contraindications
- Hypersensitivity to amlodipine, perindopril, or any ACE inhibitor.
- History of angioedema related to ACE inhibitor therapy.
- Pregnancy (second and third trimesters).
- Severe hypotension, shock.
- Left ventricular outflow tract obstruction (e.g., aortic stenosis).
- Hemodynamically unstable heart failure after acute myocardial infarction.
- Concomitant use with aliskiren in patients with diabetes or renal impairment.
- Bilateral renal artery stenosis.
Drug Interactions
- Other antihypertensive medications (additive hypotensive effect).
- Potassium supplements or potassium-sparing diuretics (risk of hyperkalemia).
- Lithium (increased lithium levels).
- NSAIDs (reduced antihypertensive effect, risk of renal impairment).
- Grapefruit juice (increased amlodipine levels).
- CYP3A4 inhibitors (increased amlodipine levels).
Pregnancy and Breastfeeding
- Pregnancy Safety Category: Contraindicated during the second and third trimesters. Not recommended during the first trimester. ACE inhibitors can cause fetal harm.
- Breastfeeding: Not recommended. Amlodipine passes into breast milk, and the effects of perindopril on nursing infants are unknown.
Drug Profile Summary
- Mechanism of Action: Calcium channel blocker and ACE inhibitor combination, causing vasodilation and lowering blood pressure.
- Side Effects: Peripheral edema, cough, dizziness, hypotension.
- Contraindications: Angioedema history, pregnancy, severe hypotension, bilateral renal artery stenosis.
- Drug Interactions: Other antihypertensives, potassium supplements, lithium, NSAIDs.
- Pregnancy & Breastfeeding: Contraindicated in the second and third trimesters of pregnancy; not recommended during breastfeeding.
- Dosage: Starting dose 2.5/3.5 mg once daily, up to 10/14 mg.
- Monitoring Parameters: Blood pressure, renal function, serum potassium, electrolytes.
Popular Combinations
- Often used in combination with a thiazide diuretic, such as hydrochlorothiazide, for enhanced blood pressure control.
Precautions
- Monitor for hypotension, especially in patients with volume depletion or renal impairment.
- Monitor renal function and electrolytes, particularly potassium.
- Assess for signs of angioedema.
- Caution in patients with hepatic impairment.
- Avoid alcohol and potassium supplements unless specifically directed by a physician.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Amlodipine + Perindopril erbumine?
A: The initial dose is typically 2.5/3.5 mg once daily, titratable up to a maximum of 10/14 mg once daily depending on individual patient needs and tolerability.
Q2: What are the common side effects?
A: Common side effects include peripheral edema, dizziness, headache, and cough.
Q3: Is this medication safe during pregnancy?
A: No. This combination is contraindicated during the second and third trimesters of pregnancy and not recommended during the first trimester.
Q4: Can patients with kidney problems take this drug?
A: It can be used with caution and dose adjustment in patients with mild to moderate renal impairment. It is not recommended for patients with severe renal impairment.
Q5: What are the serious side effects to watch out for?
A: Angioedema, severe hypotension, and hyperkalemia are serious side effects that warrant immediate medical attention.
Q6: Does this medication interact with other drugs?
A: Yes, it can interact with other antihypertensives, potassium supplements, lithium, and NSAIDs, among others. Always review a patient’s medication list for potential interactions.
Q7: How does this combination lower blood pressure?
A: It combines two mechanisms: calcium channel blockade (amlodipine) and ACE inhibition (perindopril) to relax and widen blood vessels and reduce blood volume.
Q8: Are there any dietary restrictions while on this medication?
A: Patients should avoid grapefruit and grapefruit juice, as they can increase amlodipine levels. Potassium intake should be monitored, and salt substitutes should be used cautiously.
Q9: Can I take this medication if I am breastfeeding?
A: This combination is generally not recommended during breastfeeding due to the potential for infant exposure to amlodipine and the unknown effects of perindopril.
Q10: How long does it take for this medicine to start working?
A: Patients may notice some blood pressure lowering effect within a few days, but it may take several weeks to reach maximum effectiveness.
