Usage
- Enalapril + Losartan is prescribed for the management of hypertension (high blood pressure), heart failure, and diabetic nephropathy (kidney disease in patients with type 2 diabetes).
- Pharmacological Classification: This combination comprises an Angiotensin-Converting Enzyme (ACE) inhibitor (Enalapril) and an Angiotensin II Receptor Blocker (ARB) (Losartan).
- Mechanism of Action: Enalapril reduces blood pressure by inhibiting the conversion of angiotensin I to angiotensin II, a potent vasoconstrictor. Losartan blocks the binding of angiotensin II to its receptors, further preventing vasoconstriction and promoting vasodilation. The combined effect lowers blood pressure and reduces the workload on the heart.
Alternate Names
- No formally recognized alternate names for the combination exist. Individual components are known by their generic names (enalapril maleate and losartan potassium).
- Brand Names: Several brand names exist depending on the manufacturer and region; however, it’s crucial to confirm the composition as some brands might contain only one of the components.
How It Works
- Pharmacodynamics: The combination exerts its antihypertensive effects primarily through vasodilation. It reduces peripheral vascular resistance, decreases afterload on the heart, and may have modest effects on preload. In heart failure, it improves cardiac output and reduces symptoms. In diabetic nephropathy, it helps protect kidney function by reducing proteinuria and slowing the progression of kidney damage.
- Pharmacokinetics:
- Enalapril: Orally administered enalapril is absorbed and converted to its active metabolite, enalaprilat. It is primarily excreted by the kidneys.
- Losartan: Orally administered losartan is well-absorbed and metabolized in the liver to an active metabolite. It is excreted via both biliary and renal pathways.
- Mode of Action: Enalapril inhibits ACE, preventing the conversion of angiotensin I to angiotensin II. Losartan competitively blocks the binding of angiotensin II to the AT1 receptor. This dual blockade synergistically inhibits the renin-angiotensin-aldosterone system (RAAS), leading to vasodilation and reduced blood pressure.
- Receptor Binding/Enzyme Inhibition: Enalapril acts through enzyme inhibition (ACE), while losartan acts through receptor blockade (AT1 receptor).
- Elimination Pathways: Enalapril (enalaprilat) is primarily eliminated renally. Losartan and its active metabolite are eliminated through both biliary and renal routes.
Dosage
Standard Dosage
Adults:
- Initial dosage: Enalapril 2.5 mg + Losartan 25 mg once daily.
- Titration: The dosage can be gradually increased (e.g., 5/50 mg, 10/75 mg, up to a maximum of 20/100 mg) based on individual blood pressure response and tolerability. Each dose increase is typically made at weekly intervals.
Children:
- Dosage in children should be determined by a physician based on the child’s weight, age, and clinical condition.
Special Cases:
- Elderly Patients: Initiate therapy at the lowest dose (2.5 mg/25 mg) and titrate cautiously.
- Patients with Renal Impairment: Reduced dosages are necessary; consult specific guidelines based on creatinine clearance or estimated glomerular filtration rate (eGFR).
- Patients with Hepatic Dysfunction: Exercise caution, initiate at a lower dose, and monitor closely.
- Patients with Comorbid Conditions: Careful monitoring is essential, especially for those with diabetes or cardiovascular disease.
Clinical Use Cases
The combination of Enalapril and Losartan isn’t typically adjusted for specific procedures like intubation, surgery, or mechanical ventilation. Rather, the existing regimen is continued, and blood pressure is closely monitored and managed as needed with other interventions.
Dosage Adjustments
- Dosage adjustments should be individualized based on the patient’s response, renal function, and potential drug interactions. Close monitoring of blood pressure, renal function (serum creatinine, eGFR), and electrolytes (especially potassium) is crucial.
Side Effects
Common Side Effects:
- Dizziness
- Fatigue
- Cough
- Nausea
- Hypotension
- Hyperkalemia (high potassium levels)
Rare but Serious Side Effects:
- Angioedema (swelling of face, lips, tongue, throat)
- Acute renal failure
- Severe hypotension
Long-Term Effects:
- Potential for renal impairment with prolonged use, especially in patients with pre-existing kidney disease.
Adverse Drug Reactions (ADR):
- Angioedema requires immediate medical attention.
- Severe hypotension or hyperkalemia necessitates prompt intervention.
Contraindications
- Hypersensitivity to enalapril or losartan.
- History of angioedema related to ACE inhibitors or ARBs.
- Pregnancy (especially second and third trimesters).
- Bilateral renal artery stenosis.
- Concomitant use of aliskiren in patients with diabetes or kidney disease.
Drug Interactions
- Other antihypertensive medications (additive hypotensive effect).
- Potassium supplements or salt substitutes (increased risk of hyperkalemia).
- NSAIDs (may reduce antihypertensive effect and increase risk of renal impairment).
- Lithium (increased lithium levels).
- Diuretics (additive hypotensive effect).
- CYP3A4 inhibitors (may increase losartan levels).
Pregnancy and Breastfeeding
- Pregnancy Safety Category: Contraindicated in the second and third trimesters. Not recommended during the first trimester.
- Fetal Risks: Renal damage, oligohydramnios, growth retardation, fetal death.
- Breastfeeding: Limited information available. Alternative medications may be preferred.
Drug Profile Summary
- Mechanism of Action: Dual blockade of the RAAS via ACE inhibition (enalapril) and AT1 receptor blockade (losartan), resulting in vasodilation.
- Side Effects: Dizziness, fatigue, cough, nausea, hypotension, hyperkalemia. Angioedema (rare but serious).
- Contraindications: Hypersensitivity, pregnancy, bilateral renal artery stenosis, concomitant aliskiren use in patients with diabetes or kidney disease.
- Drug Interactions: Other antihypertensives, potassium supplements, NSAIDs, lithium, diuretics.
- Pregnancy & Breastfeeding: Contraindicated in pregnancy. Caution advised during breastfeeding.
- Dosage: Start with enalapril 2.5 mg/losartan 25 mg and titrate as needed.
- Monitoring Parameters: Blood pressure, renal function (serum creatinine, eGFR), electrolytes (potassium).
Popular Combinations
The combination of enalapril and losartan is itself a combined therapy. Adding a thiazide diuretic (e.g., hydrochlorothiazide) to this combination may be considered for patients whose blood pressure remains uncontrolled despite dual RAAS blockade.
Precautions
- Assess renal function, electrolytes, and blood pressure regularly.
- Monitor for signs of angioedema.
- Caution in patients with hepatic impairment or volume depletion.
- Avoid in pregnancy.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Enalapril + Losartan?
A: The starting dose is usually enalapril 2.5 mg + losartan 25 mg once daily. It can be titrated up to a maximum of enalapril 20 mg + losartan 100 mg daily based on blood pressure response and tolerability.
Q2: How does Enalapril + Losartan differ from monotherapy with either drug alone?
A: The combination provides synergistic blood pressure lowering and potentially greater renin-angiotensin system suppression compared to using either drug alone at the maximum dose.
Q3: What are the most serious side effects of Enalapril + Losartan?
A: Angioedema, severe hypotension, acute renal failure, and hyperkalemia are rare but potentially life-threatening adverse effects.
Q4: Can Enalapril + Losartan be used in pregnant or breastfeeding women?
A: The combination is contraindicated during pregnancy, especially the second and third trimesters. Use during breastfeeding is not recommended unless clearly necessary and no suitable alternatives exist.
Q5: How should the dosage be adjusted in patients with renal impairment?
A: Dose reduction is usually necessary. Specific adjustments depend on the degree of renal impairment (creatinine clearance or eGFR). Consult renal dosing guidelines.
Q6: What are the key drug interactions to watch for with Enalapril + Losartan?
A: Co-administration with other antihypertensives, potassium supplements, NSAIDs, lithium, and diuretics can potentially lead to clinically significant interactions.
Q7: How often should patients on Enalapril + Losartan be monitored?
A: Monitoring frequency depends on the patient’s condition and stability. Initially, more frequent monitoring is recommended, especially after dosage changes. Regular assessment of blood pressure, renal function, and electrolytes is essential.
Q8: Can Enalapril + Losartan be abruptly discontinued?
A: Generally, abrupt discontinuation is not recommended. Gradual tapering of the dose might be necessary, especially in patients with heart failure. Consult a physician before discontinuing therapy.
Q9: What should patients be advised regarding lifestyle modifications while on Enalapril + Losartan?
A: Patients should be encouraged to adopt a healthy lifestyle including a balanced diet, regular exercise, weight management, and sodium restriction to optimize blood pressure control.
