Usage
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Amlodipine + Benazepril is prescribed for the treatment of hypertension (high blood pressure). It may be used alone or in combination with other antihypertensive medications when blood pressure is not adequately controlled by monotherapy. It is generally not recommended for initial therapy and is typically initiated after inadequate response to either component alone.
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Pharmacological Classification: This medication is a combination of two drugs:
- Amlodipine: Dihydropyridine Calcium Channel Blocker (CCB)
- Benazepril: Angiotensin-Converting Enzyme (ACE) inhibitor.
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Mechanism of Action: Amlodipine works by relaxing the smooth muscles of blood vessels, allowing them to dilate and reducing peripheral vascular resistance, thus lowering blood pressure. Benazepril inhibits the conversion of angiotensin I to angiotensin II, a potent vasoconstrictor. This action also reduces blood pressure and can have beneficial effects on the heart and kidneys in patients with hypertension.
Alternate Names
- There is no internationally recognized non-proprietary name for the combination product.
- Brand Name: Lotrel
How It Works
- Pharmacodynamics: Amlodipine primarily affects the peripheral arterioles, causing vasodilation and a reduction in systemic vascular resistance. Benazepril, by blocking the renin-angiotensin-aldosterone system (RAAS), reduces vasoconstriction, sodium and water retention, and sympathetic nervous system activity, contributing to a decrease in blood pressure. The combination of these two agents provides synergistic antihypertensive effects.
- Pharmacokinetics: Both drugs are orally administered and well-absorbed. Amlodipine has a long half-life (30-50 hours), allowing for once-daily dosing. It is extensively metabolized by the liver and primarily excreted in the feces. Benazepril is a prodrug converted to its active metabolite, benazeprilat, in the liver. Benazeprilat has a half-life of approximately 10-11 hours and is primarily excreted by the kidneys.
- Mode of Action: Amlodipine blocks the influx of calcium ions into vascular smooth muscle cells, preventing muscle contraction and promoting vasodilation. Benazepril inhibits ACE, preventing the formation of angiotensin II and blocking its vasoconstricting effects.
- Receptor Binding/Enzyme Inhibition: Amlodipine binds to L-type calcium channels in vascular smooth muscle. Benazepril inhibits the angiotensin-converting enzyme.
- Elimination Pathways: Amlodipine is hepatically metabolized and excreted mainly in the feces. Benazepril is metabolized to benazeprilat in the liver, and benazeprilat is primarily excreted in the urine.
Dosage
Standard Dosage
Adults:
- Initial dose: 2.5 mg amlodipine / 10 mg benazepril once daily.
- Maintenance dose: The dose may be titrated up to a maximum of 10 mg amlodipine / 40 mg benazepril once daily, based on the individual patient’s blood pressure response and tolerability. Dose adjustments are typically made at intervals of 7-14 days.
Children:
- The safety and efficacy of amlodipine + benazepril have not been established in pediatric patients.
Special Cases:
- Elderly Patients: An initial dose of 2.5 mg amlodipine is recommended in elderly patients due to increased sensitivity to the drug’s effects. Subsequent dose adjustments should be made cautiously.
- Patients with Renal Impairment: For patients with creatinine clearance (CrCl) less than 30 mL/min, a lower initial dose of benazepril is recommended, and dose titration should be done with careful monitoring of renal function.
- Patients with Hepatic Dysfunction: For patients with severe hepatic impairment, a lower initial dose of amlodipine (2.5 mg) is recommended, and dose titration should be done cautiously.
- Patients with Comorbid Conditions: Patients with heart failure should be closely monitored for hypotension. In patients with diabetes, co-administration with aliskiren is contraindicated.
Clinical Use Cases
Amlodipine + Benazepril is primarily indicated for chronic hypertension management. It is not typically used in acute clinical situations like intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations like cardiac arrest. In such cases, other medications with more rapid onset and direct hemodynamic effects are preferred.
Dosage Adjustments
Dose adjustments should be individualized based on patient factors such as age, renal and hepatic function, concomitant medications, and response to therapy.
Side Effects
Common Side Effects:
- Cough
- Dizziness
- Headache
- Peripheral edema (swelling of feet and ankles)
Rare but Serious Side Effects:
- Angioedema (swelling of face, lips, tongue, or throat)
- Hypotension (low blood pressure)
- Syncope (fainting)
- Acute renal failure
- Hyperkalemia (high potassium levels)
- Liver dysfunction
Long-Term Effects:
- Chronic cough (with benazepril)
- Electrolyte imbalances
Adverse Drug Reactions (ADR):
- Angioedema
- Severe hypotension
- Hyperkalemia
- Hepatotoxicity
Contraindications
- History of angioedema related to ACE inhibitor therapy.
- Hypersensitivity to amlodipine, benazepril, or any other ACE inhibitor.
- Pregnancy (Category D/X - contraindicated)
- Concomitant use with sacubitril/valsartan or other neprilysin inhibitors.
- Bilateral renal artery stenosis.
Drug Interactions
- Aliskiren (especially in patients with diabetes)
- Potassium supplements or potassium-sparing diuretics
- Lithium
- NSAIDs (can reduce antihypertensive effect and increase risk of renal impairment)
- Simvastatin (increased risk of myopathy)
- Other antihypertensive medications (additive effects)
- CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, erythromycin) can increase amlodipine levels.
Pregnancy and Breastfeeding
- Pregnancy: Amlodipine + Benazepril is contraindicated during pregnancy. ACE inhibitors can cause fetal harm, including renal failure, hypotension, and growth retardation.
- Breastfeeding: It is unknown if amlodipine or benazepril are excreted in human milk. Due to the potential for adverse effects on the nursing infant, the use of amlodipine + benazepril during breastfeeding is not recommended.
Drug Profile Summary
- Mechanism of Action: Combines calcium channel blockade and ACE inhibition to lower blood pressure.
- Side Effects: Cough, dizziness, headache, peripheral edema. Rare but serious: angioedema, hypotension, renal failure, hyperkalemia.
- Contraindications: Angioedema history, hypersensitivity, pregnancy, concomitant use with sacubitril/valsartan.
- Drug Interactions: Aliskiren, potassium supplements, lithium, NSAIDs, simvastatin.
- Pregnancy & Breastfeeding: Contraindicated in pregnancy; use with caution during breastfeeding.
- Dosage: Adults: 2.5 mg/10 mg once daily initially, titrated to a maximum of 10 mg/40 mg once daily.
- Monitoring Parameters: Blood pressure, renal function (BUN, creatinine, electrolytes), potassium levels.
Popular Combinations
Amlodipine + Benazepril is often used in combination with hydrochlorothiazide when dual therapy is not sufficient to control blood pressure.
Precautions
- General Precautions: Monitor renal function, potassium levels, and blood pressure regularly. Assess for signs and symptoms of angioedema.
- Specific Populations:
- Pregnant Women: Contraindicated.
- Breastfeeding Mothers: Not recommended.
- Children & Elderly: Safety and efficacy not established in children; start with a low dose in elderly patients.
- Lifestyle Considerations: Patients should be advised to follow lifestyle modifications, including diet, exercise, and smoking cessation, to optimize blood pressure control.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Amlodipine + Benazepril?
A: The initial dose is typically 2.5 mg amlodipine / 10 mg benazepril once daily. The dose may be titrated up to a maximum of 10 mg amlodipine/40 mg benazepril based on individual response.
Q2: What are the most common side effects?
A: Common side effects include cough, dizziness, headache, and peripheral edema.
A: Angioedema, severe hypotension, hyperkalemia, signs of liver dysfunction, and acute renal failure are serious and require urgent medical attention.
Q4: Can Amlodipine + Benazepril be used in pregnant women?
A: No, Amlodipine + Benazepril is contraindicated during pregnancy due to the risk of fetal harm associated with ACE inhibitors.
Q5: How does Amlodipine + Benazepril interact with other medications?
A: It can interact with other antihypertensives (additive effects), potassium supplements (hyperkalemia), lithium, NSAIDs, and certain cholesterol-lowering drugs.
Q6: What should patients be monitored for during treatment?
A: Blood pressure, renal function, potassium levels, and signs of angioedema should be monitored regularly.
Q7: Can this combination be used in patients with renal or hepatic impairment?
A: It can be used but with careful dose adjustments and close monitoring. Lower initial doses are generally recommended in these patient populations.
Q8: Is Amlodipine + Benazepril used for initial therapy of hypertension?
A: No, this combination is generally not recommended for initial therapy. It is usually considered when monotherapy with either agent is not effective or well-tolerated.
Q9: What is the mechanism of action for this combination?
A: Amlodipine blocks calcium channels in vascular smooth muscle, leading to vasodilation. Benazepril inhibits the renin-angiotensin system, reducing vasoconstriction and sodium and water retention. These mechanisms work together to lower blood pressure.
Q10: What should patients be counseled about regarding lifestyle modifications?
A: Patients should be encouraged to adopt healthy lifestyle habits, such as maintaining a balanced diet, engaging in regular exercise, limiting alcohol consumption, and quitting smoking to optimize blood pressure control and overall cardiovascular health.
