Usage
- This fixed-dose combination is prescribed for the treatment of hypertension (high blood pressure) in patients whose blood pressure is not adequately controlled by losartan or perindopril alone. It is also used to reduce the risk of cardiovascular events like heart attack in patients with stable coronary artery disease.
- Pharmacological Classification: This combination includes two types of antihypertensive medications:
- Angiotensin II Receptor Blocker (ARB) - Losartan.
- Angiotensin-Converting Enzyme (ACE) inhibitor - Perindopril.
- Mechanism of Action: Losartan blocks the action of angiotensin II, a hormone that causes blood vessels to constrict, while Perindopril inhibits the formation of angiotensin II. The combined effect leads to vasodilation (widening of blood vessels), reducing blood pressure.
Alternate Names
- No internationally recognized non-proprietary name exists for this combination.
- Brand Names: Several brand names are available depending upon the region and manufacturer. A few brand names observed include ADPACE.
How It Works
- Pharmacodynamics: Losartan + Perindopril erbumine lowers blood pressure by blocking the renin-angiotensin-aldosterone system (RAAS). Losartan blocks angiotensin II receptors, preventing vasoconstriction. Perindopril inhibits ACE, reducing angiotensin II production. This dual action leads to vasodilation, decreased peripheral resistance, and lowered blood pressure.
- Pharmacokinetics:
- Absorption: Both drugs are orally absorbed, but perindopril’s bioavailability is affected by food.
- Metabolism: Losartan is metabolized to an active metabolite, while perindopril is largely excreted unchanged.
- Elimination: Losartan and its metabolite are eliminated primarily in bile and urine, while perindopril is mainly excreted renally.
- Mode of Action: Losartan competitively binds to AT1 receptors, blocking angiotensin II binding and its vasoconstricting effects. Perindopril inhibits ACE, preventing the conversion of angiotensin I to angiotensin II, thereby decreasing vasoconstriction and aldosterone secretion.
- Receptor Binding, Enzyme Inhibition: Losartan acts via AT1 receptor blockade. Perindopril inhibits ACE.
- Elimination Pathways: Losartan is eliminated hepatically (bile) and renally (urine). Perindopril is primarily excreted renally.
Dosage
Standard Dosage
Adults:
- Initial dose: Losartan 50 mg + Perindopril 4 mg once daily.
- The dose may be increased, as directed by the physician to Losartan 100 mg + Perindopril 8 mg once daily, depending on the patient’s response.
- Maximum Dosage: Losartan 100 mg + Perindopril 8 mg once daily.
Children: This fixed dose combination is not recommended for children.
Special Cases:
- Elderly Patients: Start with a lower dose (Losartan 25 mg + Perindopril 2 mg) and titrate upwards as tolerated.
- Patients with Renal Impairment: Dose adjustment is required; start with lower doses and monitor renal function closely. In patients with severe renal impairment (CrCl < 30 mL/min), this combination is contraindicated.
- Patients with Hepatic Dysfunction: Caution is advised in patients with hepatic impairment; dose adjustment may be necessary.
- Patients with Comorbid Conditions: Close monitoring is essential in patients with conditions like diabetes or heart failure.
Clinical Use Cases The clinical use cases listed are not typical for this combination medication. It is primarily used to manage hypertension. The dosages for intubation, surgical procedures, mechanical ventilation, ICU use, and emergencies are not applicable to this combination.
Dosage Adjustments
- Adjust dosages based on renal function, hepatic function, and individual patient response. Monitor blood pressure, electrolytes (especially potassium), and renal function regularly. Genetic polymorphisms affecting drug metabolism may influence dosage requirements.
Side Effects
Common Side Effects:
- Dizziness
- Headache
- Cough (especially with perindopril)
- Fatigue
- Hypotension
Rare but Serious Side Effects:
- Angioedema (swelling of face, lips, tongue, throat)
- Renal failure
- Hyperkalemia (high potassium levels)
- Neutropenia (low white blood cell count)
- Hepatic dysfunction
Long-Term Effects:
- Potential for renal damage with long-term use, especially in patients with pre-existing renal disease.
- Electrolyte imbalances
Adverse Drug Reactions (ADR):
- Angioedema, acute renal failure, severe hypotension, hyperkalemia are serious ADRs requiring urgent attention.
Contraindications
- Hypersensitivity to losartan, perindopril, or any other ACE inhibitor.
- History of angioedema related to ACE inhibitor therapy.
- Pregnancy (especially second and third trimesters).
- Bilateral renal artery stenosis.
- Concomitant use of aliskiren in patients with diabetes.
Drug Interactions
- Potassium-sparing diuretics, potassium supplements: Increased risk of hyperkalemia.
- NSAIDs: Reduced antihypertensive effect and increased risk of renal impairment.
- Lithium: Increased lithium levels.
- Other antihypertensives: Additive hypotensive effect.
- CYP450 interactions: Limited interactions are known.
Pregnancy and Breastfeeding
- Pregnancy Safety Category: D (contraindicated). Fetal harm, including renal and lung damage, can occur.
- Breastfeeding: Not recommended, potential for neonatal hypotension.
Drug Profile Summary
- Mechanism of Action: Dual RAAS blockade: ARB and ACE inhibitor.
- Side Effects: Dizziness, headache, cough, hypotension, hyperkalemia, angioedema.
- Contraindications: Hypersensitivity, pregnancy, bilateral renal artery stenosis.
- Drug Interactions: Potassium-sparing diuretics, NSAIDs, lithium, other antihypertensives.
- Pregnancy & Breastfeeding: Contraindicated in pregnancy, not recommended during breastfeeding.
- Dosage: Initial: Losartan 50 mg + Perindopril 4 mg; Max: Losartan 100 mg + Perindopril 8 mg.
- Monitoring Parameters: Blood pressure, renal function, potassium levels.
Popular Combinations
- While this drug itself is a combination, the use of a thiazide diuretic like hydrochlorothiazide in conjunction with losartan/perindopril is sometimes seen clinically, especially in patients whose hypertension is not adequately controlled by the dual therapy.
Precautions
- General Precautions: Monitor renal function, electrolytes, and blood pressure regularly.
- Specific Populations: Avoid in pregnancy; caution in breastfeeding, elderly, and those with renal/hepatic impairment.
- Lifestyle Considerations: Advise patients to avoid excessive alcohol intake, which can exacerbate hypotension.
FAQs (Frequently Asked Questions)
Q1: What is the recommended starting dosage for Losartan + Perindopril erbumine?
A: The usual starting dosage is Losartan 50 mg + Perindopril 4 mg once daily.
Q2: What is the maximum daily dose for this drug?
A: The maximum daily dose is Losartan 100 mg + Perindopril 8 mg.
Q3: What are the most common side effects?
A: The most common side effects are dizziness, headache, cough, and fatigue.
Q4: What are the serious side effects of this combination?
A: Serious side effects can include angioedema, renal failure, and hyperkalemia.
Q5: Can Losartan + Perindopril erbumine be used in pregnancy?
A: No, this combination is contraindicated in pregnancy, especially during the second and third trimesters.
Q6: What should be monitored when a patient takes this drug?
A: Closely monitor blood pressure, renal function (serum creatinine, blood urea nitrogen), and potassium levels.
Q7: Can this fixed-dose combination be used in patients with renal impairment?
A: Caution is advised in patients with renal impairment, and dose adjustments are usually required. It is contraindicated in severe renal impairment (CrCl < 30ml/min)
Q8: What are the potential drug interactions with Losartan + Perindopril?
A: Potential interactions include NSAIDs (reduced efficacy and increased renal risks), potassium-sparing diuretics (hyperkalemia), and lithium (increased lithium levels).
Q9: What is the mechanism by which Losartan + Perindopril exerts its effects?
A: Both drugs target the renin-angiotensin-aldosterone system (RAAS) but through different pathways. Losartan blocks angiotensin II from its receptor, and perindopril blocks the enzyme which makes angiotensin II. This combined effect leads to vasodilation and reduced blood pressure.
