Amlodipine + Enalapril

Usage

• Amlodipine + Enalapril is prescribed for the treatment of hypertension (high blood pressure). It may also be used for other conditions as determined by a physician.
• Pharmacological Classification: Antihypertensive (combination of a calcium channel blocker and an ACE inhibitor).
• Mechanism of Action: Amlodipine blocks calcium influx into vascular smooth muscle and cardiac muscle, causing vasodilation and reducing cardiac workload. Enalapril inhibits the angiotensin-converting enzyme (ACE), preventing the formation of angiotensin II, a potent vasoconstrictor. This leads to vasodilation and decreased aldosterone secretion, reducing blood volume and further lowering blood pressure.

Alternate Names

• No widely recognized alternate generic names.
• Brand Names: Amace, Amlogen-EL, Amlovin-E, Amtas-E, Amzel-EL, Dilvas-Am, Entp-A, Hytrol-Am, Klodip Ace (India). Brand names may vary by region.

How It Works

• Pharmacodynamics: Amlodipine reduces systemic vascular resistance and blood pressure through vasodilation. It has minimal negative inotropic effects. Enalapril reduces peripheral vascular resistance, blood volume, and cardiac afterload.
• Pharmacokinetics:
  • Absorption: Amlodipine is well absorbed orally, with peak plasma concentrations reached in 6-12 hours. Enalapril is rapidly absorbed, with peak concentrations of enalaprilat (the active metabolite) occurring in 3-4 hours. Food does not significantly affect the absorption of either drug.
  • Metabolism: Amlodipine is extensively metabolized by the liver. Enalapril is hydrolyzed to enalaprilat.
  • Elimination: Amlodipine is excreted primarily in the urine and feces as metabolites. Enalaprilat is primarily excreted by the kidneys.
• Mode of Action:
  • Amlodipine: Inhibits calcium influx through L-type calcium channels in vascular smooth muscle and cardiac muscle, leading to vasodilation.
  • Enalapril: Inhibits ACE, preventing conversion of angiotensin I to angiotensin II.
• Receptor Binding/Enzyme Inhibition/Neurotransmitter Modulation:
  • Amlodipine: L-type calcium channel blocker.
  • Enalapril: ACE inhibitor.
• Elimination Pathways:
  • Amlodipine: Hepatic metabolism, renal and fecal excretion.
  • Enalapril: Renal excretion of enalaprilat.

Dosage

Standard Dosage

Adults:

• Initial dose: Amlodipine 5 mg + Enalapril 10 mg once daily.
• Maintenance dose: May be increased to a maximum of Amlodipine 10 mg + Enalapril 20 mg per day as needed to control blood pressure.

Children:

• Use is generally not recommended in children under 6 years of age. For children older than 6 years, dosing must be determined by a doctor based on weight and medical condition.

Special Cases:

• Elderly Patients: Start with a lower dose and titrate cautiously.
• Patients with Renal Impairment: Reduce the dose based on the degree of impairment.
• Patients with Hepatic Dysfunction: Start with a lower dose and titrate cautiously.
• Patients with Comorbid Conditions: Dosage adjustment may be required depending on the specific comorbidity.

Clinical Use Cases

Dosing in these settings should be individualized based on patient needs and clinical status under the guidance of a specialist:

• Intubation: Maintain usual antihypertensive regimen unless contraindicated.
• Surgical Procedures: Continue medication as directed by anesthesiologist and surgeon.
• Mechanical Ventilation: Continue as directed by critical care team.
• Intensive Care Unit (ICU) Use: Monitor and adjust dose based on patient status.
• Emergency Situations: Dosage adjustment may be necessary; consult specialist.

Dosage Adjustments

• Renal/hepatic dysfunction: Reduce dose.
• Metabolic disorders: Adjust dose as needed.
• Genetic polymorphisms: Consider if impacting drug metabolism.

Side Effects

Common Side Effects

• Dizziness, headache, fatigue, peripheral edema, cough.

Rare but Serious Side Effects

• Angioedema, hypotension, syncope, renal failure, hyperkalemia.

Long-Term Effects

• Renal impairment (with prolonged use of enalapril), electrolyte imbalances.

Adverse Drug Reactions (ADR)

• Angioedema, severe hypotension, acute renal failure.

Contraindications

• Hypersensitivity to amlodipine, enalapril, or other ACE inhibitors.
• History of angioedema related to ACE inhibitor use.
• Pregnancy (especially second and third trimesters).

Drug Interactions

• Aliskiren, lithium, potassium supplements, potassium-sparing diuretics, NSAIDs, some statins, certain antidiabetic agents.
• CYP3A4 inhibitors (e.g., ketoconazole, itraconazole) may increase amlodipine levels.
• Alcohol may enhance the hypotensive effects.

Pregnancy and Breastfeeding

• Pregnancy: Contraindicated, especially during the second and third trimesters, due to the risk of fetal harm.
• Breastfeeding: Amlodipine passes into breast milk, enalapril in minimal amounts; use with caution and monitor infant for hypotension.

Drug Profile Summary

• Mechanism of Action: Amlodipine: calcium channel blocker, vasodilator. Enalapril: ACE inhibitor, vasodilator.
• Side Effects: Dizziness, headache, edema, cough, angioedema (rare).
• Contraindications: Hypersensitivity, angioedema history, pregnancy.
• Drug Interactions: Aliskiren, potassium supplements, NSAIDs, some statins.
• Pregnancy & Breastfeeding: Avoid in pregnancy. Use with caution during breastfeeding.
• Dosage: Adults: initially 5/10 mg once daily, up to 10/20 mg.
• Monitoring Parameters: Blood pressure, potassium levels, renal function.

Popular Combinations

• Often used as a single-pill combination for synergistic antihypertensive effects.

Precautions

• General Precautions: Monitor renal function, potassium levels, blood pressure.

• Specific Populations:

  • Pregnant Women: Contraindicated.
  • Breastfeeding Mothers: Use with caution.
  • Children & Elderly: Dosage adjustments may be required.

• Lifestyle Considerations: Limit alcohol intake; advise against driving or operating machinery until effects are known.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Amlodipine + Enalapril?

A: Initial dose is typically Amlodipine 5 mg + Enalapril 10 mg once daily, adjustable up to a maximum of Amlodipine 10 mg + Enalapril 20 mg per day.

Q2: Can this combination be used in patients with diabetes?

A: Yes, but caution is advised due to the potential for hyperkalemia. Monitor potassium levels closely.

Q3: What are the most serious side effects to watch out for?

A: Angioedema, severe hypotension, and acute renal failure.

Q4: Can this combination be used during pregnancy?

A: No, it is contraindicated, particularly in the second and third trimesters due to the risk of fetal harm.

Q5: What if a patient misses a dose?

A: Take the missed dose as soon as remembered, unless it is almost time for the next dose. Do not double the dose.

Q6: How should I counsel patients about lifestyle modifications?

A: Encourage lifestyle modifications such as sodium restriction, regular exercise, weight loss, and stress reduction to enhance blood pressure control.

Q7: Are there any specific monitoring requirements for this combination?

A: Yes, monitor blood pressure, potassium levels, and renal function regularly.

Q8: What should I do if a patient develops angioedema?

A: Discontinue the medication immediately and seek urgent medical attention.

Q9: Can this combination be used in patients with renal impairment?

A: Yes, but the dose needs to be reduced based on the level of renal function.

Q10: What other medications should be avoided while taking this combination?

A: Aliskiren, potassium supplements, potassium-sparing diuretics, lithium, certain NSAIDs, and certain antidiabetic agents. Discuss all medications with a physician before starting this combination.