Usage
- Fosinopril is primarily prescribed for treating hypertension (high blood pressure) and symptomatic heart failure. It may be used alone or in combination with other antihypertensive medications like thiazide diuretics. For heart failure, it’s used adjunctively with diuretics and, when necessary, digoxin.
- Pharmacological Classification: Angiotensin-Converting Enzyme (ACE) Inhibitor.
- Mechanism of Action: Fosinopril inhibits the conversion of angiotensin I to angiotensin II, a potent vasoconstrictor. This leads to vasodilation, reduced aldosterone secretion, and decreased sodium and water retention, ultimately lowering blood pressure and reducing cardiac workload.
Alternate Names
- International Nonproprietary Name (INN): Fosinopril
- Brand Names: Monopril
How It Works
- Pharmacodynamics: Fosinopril’s primary effect is lowering blood pressure through vasodilation. It reduces both systolic and diastolic blood pressure in a dose-dependent manner. It also improves cardiac output and reduces peripheral vascular resistance in heart failure patients.
- Pharmacokinetics: Fosinopril is an ester prodrug that is rapidly hydrolyzed in the liver to its active metabolite, fosinoprilat. It is primarily excreted via the kidneys. Fosinoprilat has a long half-life, allowing for once-daily dosing. Absorption is not affected by food.
- Mode of Action: Fosinopril’s active metabolite, fosinoprilat, competitively inhibits ACE. This prevents the conversion of angiotensin I to angiotensin II. Less angiotensin II leads to reduced vasoconstriction and decreased aldosterone secretion.
- Elimination Pathways: Primarily renal excretion.
Dosage
Standard Dosage
Adults:
- Hypertension: Initial dose is 10 mg orally once daily, adjusted as needed. The usual maintenance dose is 20-40 mg once daily, up to a maximum of 80 mg. Some patients might benefit from divided doses if trough response is inadequate.
- Heart Failure: Initial dose is 10 mg orally once daily under close medical supervision. Titrate up to a maximum of 40 mg once daily based on clinical response.
Children:
- Children below 50 kg: Limited data suggests 0.1-0.6 mg/kg orally once daily. Titration should be done carefully under strict medical supervision.
- Children weighing 50 kg or more: 5-10 mg orally once daily, not to exceed 40 mg daily.
Special Cases:
- Elderly Patients: Initiate at a lower dose (e.g., 5 mg) and titrate cautiously due to increased risk of renal impairment and hypotension.
- Patients with Renal Impairment: Reduced doses are usually required depending on the level of renal function. Close monitoring of renal function and potassium levels is essential.
- Patients with Hepatic Dysfunction: Use with caution. No specific dosage adjustments are typically necessary in mild to moderate hepatic impairment, but closer monitoring is advised.
- Patients with Comorbid Conditions: Dose adjustments may be needed based on concomitant conditions like diabetes or cardiovascular disease.
Clinical Use Cases
Fosinopril’s clinical use in intubation, surgical procedures, mechanical ventilation, ICU use, and emergency situations is not routinely indicated. Its primary role is in the management of chronic conditions like hypertension and heart failure. However, in acute settings where blood pressure control is crucial, other rapidly acting agents are typically preferred.
Dosage Adjustments
Dose adjustments are necessary in patients with renal or hepatic dysfunction, volume depletion (including those on diuretic therapy), or in elderly patients. Concurrent use of drugs affecting the renin-angiotensin-aldosterone system (RAAS) requires careful monitoring of renal function and potassium levels.
Side Effects
Common Side Effects
Dizziness, cough, headache, fatigue, weakness, nausea, vomiting, diarrhea.
Rare but Serious Side Effects
Angioedema (swelling of face, lips, tongue, throat), hypotension, hyperkalemia, renal impairment, liver dysfunction.
Long-Term Effects
Potential long-term effects with chronic use include renal insufficiency, electrolyte imbalances, and cardiovascular events if blood pressure is not adequately controlled.
Adverse Drug Reactions (ADR)
Angioedema, acute renal failure, hepatic injury, severe hypotension.
Contraindications
Hypersensitivity to fosinopril or any other ACE inhibitor, history of angioedema related to ACE inhibitor therapy, concurrent use of sacubitril/valsartan, pregnancy (especially second and third trimesters).
Drug Interactions
- Diuretics: Increased risk of hypotension.
- Potassium-sparing diuretics: Increased risk of hyperkalemia.
- NSAIDs: Reduced antihypertensive effect and increased risk of renal impairment.
- Lithium: Increased lithium levels.
- Aliskiren: Contraindicated in patients with diabetes or renal impairment.
- Sacubitril/valsartan: Contraindicated due to increased risk of angioedema.
Pregnancy and Breastfeeding
- Pregnancy Safety Category: D
- Fetal Risks: Fosinopril is contraindicated during pregnancy, especially in the second and third trimesters, due to the risk of fetal harm, including renal failure, hypotension, and death.
- Breastfeeding: Fosinopril is excreted in breast milk. Its use is generally not recommended during breastfeeding.
Drug Profile Summary
- Mechanism of Action: ACE inhibitor, reduces angiotensin II, causing vasodilation and decreased aldosterone.
- Side Effects: Dizziness, cough, hypotension, angioedema, hyperkalemia.
- Contraindications: Hypersensitivity, history of angioedema with ACE inhibitors, pregnancy.
- Drug Interactions: Diuretics, NSAIDs, potassium supplements, lithium, aliskiren.
- Pregnancy & Breastfeeding: Contraindicated in pregnancy, not recommended while breastfeeding.
- Dosage: Hypertension: 20-40 mg/day; Heart Failure: Up to 40 mg/day. Adjust for renal impairment.
- Monitoring Parameters: Blood pressure, renal function, potassium levels.
Popular Combinations
Fosinopril is commonly used in combination with hydrochlorothiazide (a thiazide diuretic) for enhanced blood pressure control.
Precautions
- General Precautions: Monitor renal function and potassium, especially when initiating therapy or adjusting dose.
- Specific Populations: Caution in patients with renal or hepatic impairment, elderly patients, and those with volume depletion. Avoid in pregnancy.
- Lifestyle Considerations: Alcohol may exacerbate hypotension.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Fosinopril?
A: The initial dose for hypertension and heart failure is 10mg once daily, titrated as needed. Usual maintenance doses are 20-40 mg/day for hypertension and up to 40mg/day for heart failure.
Q2: What are the most common side effects of Fosinopril?
A: Common side effects include cough, dizziness, headache, and fatigue.
Q3: Is Fosinopril safe to use during pregnancy?
A: No. Fosinopril is contraindicated during pregnancy, particularly in the second and third trimesters, due to the risk of fetal injury and death.
Q4: How does Fosinopril interact with other medications?
A: Fosinopril can interact with diuretics, NSAIDs, potassium supplements, lithium, and aliskiren, among others. Concurrent use should be carefully managed.
Q5: What should be monitored in patients taking Fosinopril?
A: Monitor blood pressure, renal function (serum creatinine and BUN), and potassium levels.
Q6: Can Fosinopril be used in patients with renal impairment?
A: Yes, but with caution and dose adjustments. Close monitoring is essential.
Q7: What is the mechanism of action of Fosinopril?
A: Fosinopril is an ACE inhibitor, which blocks the conversion of angiotensin I to angiotensin II, leading to vasodilation and decreased aldosterone secretion.
Q8: What is the difference between Fosinopril and other ACE inhibitors?
A: While all ACE inhibitors share a similar mechanism of action, they differ in their pharmacokinetic properties, such as half-life and metabolism. Fosinopril is a long-acting ACE inhibitor suitable for once-daily dosing.
Q9: What should a patient do if they miss a dose of Fosinopril?
A: Take the missed dose as soon as remembered unless it is almost time for the next dose. Do not double up on doses.
