Amlodipine + Losartan

Usage

• Amlodipine + Losartan is prescribed for the treatment of mild to moderate hypertension (high blood pressure), especially in patients whose blood pressure is not adequately controlled with monotherapy. It is also indicated in hypertension not responding to calcium channel blockers or angiotensin II receptor antagonists alone.
• Pharmacological Classification: Antihypertensive (a combination of a calcium channel blocker and an angiotensin II receptor antagonist).
• Mechanism of Action: This combination lowers blood pressure through two distinct mechanisms. Amlodipine, a calcium channel blocker, inhibits the influx of calcium ions into vascular smooth muscle cells, causing vasodilation. Losartan, an angiotensin II receptor blocker (ARB), inhibits the binding of angiotensin II to its receptors, preventing vasoconstriction and promoting vasodilation. The combined effect results in a synergistic reduction of blood pressure.

Alternate Names

• Amlodipine/Losartan
• Losartan/Amlodipine
• Brand Names: Amlozaar, Cozaar XQ, Amlife, Asomex-LT, and others.

How It Works

• Pharmacodynamics: Amlodipine + Losartan lowers blood pressure by decreasing peripheral vascular resistance. Amlodipine primarily affects arterial smooth muscle, while Losartan affects both arterial and venous tone. The combination provides a synergistic antihypertensive effect.

• Pharmacokinetics:

  • Absorption: Amlodipine is well absorbed orally, reaching peak plasma concentrations in 6-12 hours. Losartan is also well absorbed, with peak concentrations occurring in 1-2 hours. Losartan is metabolized to an active metabolite, EXP-3174, which contributes significantly to its antihypertensive effect.
  • Metabolism: Amlodipine is extensively metabolized by the liver, primarily by CYP3A4. Losartan is metabolized by CYP2C9 and CYP3A4 to its active metabolite.
  • Elimination: Amlodipine is primarily eliminated in the urine and feces, with a half-life of approximately 30-50 hours. Losartan and its active metabolite are eliminated primarily in the urine and bile.

• Mode of Action: Amlodipine blocks L-type calcium channels in vascular smooth muscle, reducing calcium influx and causing vasodilation. Losartan selectively blocks the AT1 subtype angiotensin II receptor, preventing angiotensin II-mediated vasoconstriction.

• Receptor Binding/Enzyme Inhibition: Losartan competitively binds to AT1 receptors, while Amlodipine blocks calcium channels.

• Elimination Pathways: Amlodipine is hepatically metabolized and excreted in urine and feces. Losartan is metabolized by CYP2C9 and CYP3A4, with both the parent drug and its active metabolite excreted renally and in the bile.

Dosage

Standard Dosage

Adults:

• Initial: One tablet of Amlodipine 5 mg + Losartan 50 mg once daily.
• If blood pressure remains uncontrolled after 1-2 weeks, the dose can be increased up to two tablets per day, or a 100mg Losartan + 5mg Amlodipine tablet once daily.

Children:

• The safety and efficacy in pediatric patients have not been established. Use with caution.

Special Cases:

• Elderly Patients: Start with a lower dose and titrate cautiously due to potential age-related decline in renal function and increased sensitivity to antihypertensive medications.
• Patients with Renal Impairment: Initiate therapy with caution. Close monitoring of renal function and potassium levels is necessary. Dose adjustment might be required.
• Patients with Hepatic Dysfunction: Use with caution, preferably at a lower dose. Amlodipine has a prolonged half-life in patients with hepatic impairment.
• Patients with Comorbid Conditions: Close monitoring is required in patients with heart failure, diabetes, and other cardiovascular conditions.

Clinical Use Cases

• Intubation, Surgical Procedures, Mechanical Ventilation, ICU Use, Emergency Situations: Dosage adjustments may be necessary depending on the patient’s hemodynamic status and other clinical factors. Consult with a specialist.

Dosage Adjustments

• Dose modification should be based on individual patient response and clinical status.
• Consider renal and hepatic function, other medications, and comorbid conditions.

Side Effects

Common Side Effects

• Dizziness, headache, fatigue, edema (swelling of ankles and feet), flushing, nausea, and cough.

Rare but Serious Side Effects

• Hypotension (low blood pressure), worsening angina, myocardial infarction (heart attack), angioedema (swelling of the face, lips, tongue, or throat), and allergic reactions.

Long-Term Effects

• Potential long-term effects include electrolyte imbalances (e.g., hyperkalemia), and worsening of renal function, particularly in patients with pre-existing renal disease.

Adverse Drug Reactions (ADR)

• Angioedema, severe hypotension, hepatotoxicity, and Stevens-Johnson syndrome are rare but serious ADRs requiring immediate attention.

Contraindications

• Hypersensitivity to amlodipine, losartan, or any component of the formulation.
• Pregnancy (especially second and third trimesters).
• Severe aortic stenosis, unstable angina, cardiogenic shock.

Drug Interactions

• Other antihypertensive medications (additive effects), potassium-sparing diuretics (increased risk of hyperkalemia), NSAIDs (may reduce antihypertensive effect), lithium (increased lithium levels), CYP3A4 inhibitors (may increase amlodipine levels), and grapefruit juice (may increase amlodipine and losartan levels).

Pregnancy and Breastfeeding

• Pregnancy: Contraindicated, especially in the second and third trimesters, due to the risk of fetal harm.
• Breastfeeding: Consult with a physician. Losartan is excreted in breast milk. Amlodipine’s safety during breastfeeding is not well established. Consider the risks and benefits.

Drug Profile Summary

• Mechanism of Action: Calcium channel blockade and angiotensin II receptor antagonism.
• Side Effects: Dizziness, headache, edema, fatigue, flushing, nausea, cough.
• Contraindications: Hypersensitivity, pregnancy, severe aortic stenosis.
• Drug Interactions: Other antihypertensives, potassium-sparing diuretics, NSAIDs, lithium, CYP3A4 inhibitors.
• Pregnancy & Breastfeeding: Contraindicated in pregnancy; caution advised during breastfeeding.
• Dosage: Initial: Amlodipine 5 mg + Losartan 50 mg once daily. Titrate as needed.
• Monitoring Parameters: Blood pressure, heart rate, renal function, electrolytes (especially potassium), and signs of edema.

Popular Combinations

• Hydrochlorothiazide is sometimes added to the combination for further blood pressure reduction in patients whose hypertension is not adequately controlled.

Precautions

• General Precautions: Monitor blood pressure, renal function, and electrolytes. Assess for signs and symptoms of hypotension, edema, and allergic reactions.

• Specific Populations:

  • Pregnant Women: Contraindicated.
  • Breastfeeding Mothers: Use with caution, if at all.
  • Children & Elderly: Start with lower doses and titrate cautiously.
  • Menstruating Individuals: No specific precautions typically needed.

• Lifestyle Considerations: Advise patients to avoid alcohol, which may exacerbate hypotension. Recommend lifestyle modifications, including weight loss, regular exercise, and a low-sodium diet. Avoid potassium supplements, and restrict high-potassium food intake.

FAQs (Frequently Asked Questions)

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

A: The usual initial dosage is one tablet of Amlodipine 5 mg + Losartan 50 mg once daily. The dose may be increased to two tablets per day or a 100 mg losartan + 5 mg amlodipine tablet once daily if blood pressure is not controlled after 1-2 weeks.

Q2: Can Amlodipine + Losartan be taken during pregnancy?

A: No, Amlodipine + Losartan is contraindicated during pregnancy, especially in the second and third trimesters, due to the risk of fetal harm.

Q3: What are the common side effects of Amlodipine + Losartan?

A: Common side effects include dizziness, headache, fatigue, edema (swelling of ankles and feet), flushing, nausea, and cough.

Q4: Are there any drug interactions I should be aware of with Amlodipine + Losartan?

A: Yes, significant drug interactions can occur with other antihypertensive medications, potassium-sparing diuretics, NSAIDs, lithium, CYP3A4 inhibitors, and grapefruit juice. Consult with a specialist for a detailed review of potential interactions.

Q5: How should I monitor patients taking Amlodipine + Losartan?

A: Monitor blood pressure, heart rate, renal function, electrolytes (especially potassium), and signs of edema. Regular follow-up is essential to assess treatment efficacy and detect any potential adverse effects.

Q6: Can Amlodipine + Losartan be used in patients with renal impairment?

A: Use with caution in patients with renal impairment, initiating therapy at a lower dose and titrating cautiously. Closely monitor renal function and electrolyte levels.

Q7: What should I do if my patient experiences dizziness while taking Amlodipine + Losartan?

A: Advise the patient to sit or lie down if they feel dizzy. Ensure adequate hydration. If dizziness is persistent or severe, consider reducing the dose or evaluating for other contributing factors. Consult a specialist.

Q8: Can Amlodipine + Losartan be taken with food?

A: Yes, this medication can be taken with or without food.

Q9: What is the mechanism of action of Amlodipine + Losartan?

A: Amlodipine blocks calcium channels in vascular smooth muscle, causing vasodilation. Losartan blocks angiotensin II receptors, preventing vasoconstriction. This combined action leads to a synergistic reduction in blood pressure.