Fosinopril is a medication used to treat high blood pressure (hypertension) and certain heart conditions. It belongs to a class of drugs known as angiotensin-converting enzyme (ACE) inhibitors. ACE inhibitors work by relaxing blood vessels, which helps lower blood pressure and improve the heart's pumping ability.

Angiotensin-converting enzyme inhibitors like fosinopril (Monopril) are used to treat heart failure and hypertension in individuals.

Fosinopril Uses:

• Heart failure:
  • Adjunctive treatment of heart failure (HF)
  • Guideline recommendations:
    • The American College of Cardiology/American Heart Association (ACC/AHA) 2013 Heart Failure Guidelines recommend using ACE inhibitors along with other guideline-directed medical therapies to treat patients with symptomatic heart failure and reduced ejection fraction in order to lower mortality and morbidity or to prevent progression of HF and reduced ejection fraction in asymptomatic patients with or without a history of myocardial infarction (Stage B HF) (Stage C HFrEF).
• Hypertension:
  • Management of hypertension
  • Guideline recommendations:
    • In the absence of comorbidities (such as cerebrovascular disease, ischemic heart disease, chronic kidney disease, diabetes, heart failure, etc.), the 2017 Guideline for the Prevention and Management of High Blood Pressure in Adults suggests that thiazide-like diuretics or dihydropyridine calcium channel blockers may be preferable options due to improved cardiovascular endpoints (eg, prevention of heart failure and stroke).
    • ARBs and ACE inhibitors are also suggested for monotherapy.
    • Combination therapy is initially chosen in individuals who are at high risk (stage 2 hypertension or an atherosclerotic cardiovascular disease [ASCVD] risk of 10%) in order to reach blood pressure targets.
• Off Label Use of Fosinopril in Adults:
  • HIV-associated nephropathy
  • Stable coronary artery disease
  • Non–ST-elevation acute coronary syndrome
  • ST-elevation acute coronary syndrome

Fosinopril Dose in Adults

Fosinopril Dose in the treatment of Heart failure:

• Start with 10 mg once a day by mouth.
• Gradually, over a few weeks, increase the dose if you can tolerate it.
• The usual range is between 20 to 40 mg once a day, with a maximum of 40 mg per day.
• The goal is to reach 40 mg once a day, according to guidelines from the American College of Cardiology and the American Heart Association in 2013.

If you feel dizzy, get lightheaded when standing up, or if your kidney function worsens during this process, your doctor might reduce the dose of any other diuretics you're taking alongside fosinopril. This adjustment helps manage these side effects.

Fosinopril Dose in the treatment of Hypertension:

• Start with 10 mg once a day by mouth.
• Adjust the dose as necessary depending on how the patient responds.
• The maximum dose should not exceed 80 mg per day.
• The usual dose range is between 10 to 40 mg once a day, following the 2017 guidelines from the American College of Cardiology and the American Heart Association.

Fosinopril Dose in the treatment of HIV-associated nephropathy (HIVAN) (off-label):

• Take 10 mg of fosinopril once a day by mouth, as recommended by a study conducted in 2003 (Wei 2003).

Fosinopril Dose in Childrens

Fosinopril Dose in the treatment of Hypertension:

For children weighing up to 50 kg:

• Start with an initial dose of 0.1 mg per kilogram of body weight, taken once a day.
• Adjust the dose as needed, but the maximum daily dose should not exceed 0.6 mg per kilogram of body weight, up to a maximum of 40 mg per day.

Some children may require a lower initial dose.

For children weighing over 50 kg:

• Begin with an initial dose of 5 mg once a day as monotherapy (using fosinopril alone).
• The maximum daily dose should not exceed 40 mg per day.

Pregnancy Risk Factor D

• Fosinopril, like other drugs that affect the renin-angiotensin system, can be very harmful to a developing baby during pregnancy.
• It's essential to stop taking fosinopril as soon as you know you're pregnant because it can lead to serious problems like decreased fetal kidney function, underdeveloped lungs, and birth defects.
• In some cases, it can even be fatal for the baby.
• If a pregnant woman has been taking fosinopril, her baby should be closely monitored for issues like high potassium levels, low blood pressure, and reduced urine output.
• Oligohydramnios, a condition where there's too little amniotic fluid around the baby, can be a sign of these problems but might show up too late to prevent harm.
• It's generally recommended not to use ACE inhibitors like fosinopril for uncomplicated high blood pressure during pregnancy, and some guidelines specifically say not to use them for hypertension or heart failure in pregnancy at all.
• If a pregnant woman needs treatment for high blood pressure or heart failure, other medications should be considered instead.
• Additionally, women of childbearing age should generally avoid ACE inhibitors unless there are no other suitable options for their condition.

Fosinopril use during breastfeeding:

• Fosinopril is known to pass into breast milk, and as a result, the manufacturer does not recommend breastfeeding while taking this medication.

Fosinopril Dose in Kidney Disease:

Moderate to Severe Kidney Impairment (Heart Failure Patients):

• In these cases, it is recommended to start with a lower initial dose of 5 mg of fosinopril once daily for heart failure patients. No further dose adjustments are typically needed because fosinopril is eliminated from the body partly through the liver, which can help compensate for reduced kidney elimination.

Hemodialysis:

• Fosinopril is not effectively removed during hemodialysis, so there is generally no need for supplemental doses. This means that the regular prescribed dose can be taken without adjustment.

Peritoneal Dialysis:

• Similar to hemodialysis, fosinopril is not effectively removed during peritoneal dialysis. Therefore, supplemental doses are not required, and the regular prescribed dose can be taken.

Dose in Liver disease:

• The manufacturer's labeling for fosinopril may not include specific dosage adjustments for individuals with hepatic (liver) impairment.
• This might be because fosinopril is primarily eliminated from the body through the kidneys, rather than the liver.

Frequency of side effects not defined.

• Data from trials on hypertension and heart failure are included in the frequency ranges.
• Patients with CHF have often been found to experience higher rates of adverse effects.
• However, this cohort also has a higher frequency of placebo-related side effects.

Common Side Effects of Fosinopril:

• Central nervous system:
  • Dizziness

Less Common Side Effects of Fosinopril:

• Cardiovascular:
  • Palpitations
  • Orthostatic Hypotension
• Central Nervous System:
  • Fatigue
  • Noncardiac Chest Pain
  • Headache
• Endocrine & Metabolic:
  • Hyperkalemia
• Gastrointestinal:
  • Nausea And Vomiting
  • Diarrhea
• Hepatic:
  • Increased Serum Transaminases
• Neuromuscular & Skeletal:
  • Weakness
  • Musculoskeletal Pain
• Renal:
  • Renal Function Decompensation
  • Increased Serum Creatinine
• Respiratory:
  • Upper Respiratory Infection
  • Cough

Contraindications to Fosinopril:

• Do not take fosinopril if you are allergic to fosinopril itself, any other ACE inhibitor, or any part of the medicine.
• If you had swelling of your face, lips, tongue, or throat because of a previous ACE inhibitor, don't use fosinopril either.
• Additionally, if you have diabetes, don't take fosinopril along with aliskiren, as it can cause problems.

Warnings and precautions

Angioedema

• When taking ACE inhibitors like fosinopril, it's essential to be aware that angioedema, which is a rare but severe swelling, can happen at any time, especially after the first dose.
• This swelling might affect your head, neck (which can be dangerous for breathing), or your intestines (causing stomach pain).
• Some people, like African-Americans or those with a history of angioedema, might be at a higher risk.
• Be cautious if you're also using an mTOR inhibitor like everolimus.
• If your tongue, throat, or voice box is involved, it could block your airway, so close monitoring is crucial.
• If you've had angioedema from an ACE inhibitor before, you shouldn't use fosinopril.
• If you ever experience angioedema while taking fosinopril, seek immediate medical attention for proper care.

Cholestatic jaundice

• In rare cases, ACE inhibitors like fosinopril can lead to a condition called cholestatic jaundice, which affects the liver and can cause yellowing of the skin and eyes (jaundice).
• This condition may become severe and lead to liver damage.
• If you notice a significant increase in liver enzymes in your blood or if you develop jaundice while taking fosinopril, it's crucial to stop the medication and seek immediate medical attention for proper evaluation and management.
• This side effect should not be ignored, and discontinuing the medication is necessary if it occurs.

Cough:

• Some people taking ACE inhibitors like fosinopril may develop a persistent dry cough, typically within the first few months of starting the medication.
• This cough can be bothersome but is usually nonproductive (no mucus) and doesn't involve other symptoms like a runny nose or fever.
• It's essential to consider other potential causes of the cough, especially if you have heart failure and pulmonary congestion, before deciding to stop taking the ACE inhibitor.

Hyperkalemia:

• When taking ACE inhibitors like fosinopril, there's a risk of developing high levels of potassium in your blood, a condition called hyperkalemia.
• Several factors can increase this risk, including kidney problems, diabetes, taking potassium-sparing diuretics, or using potassium supplements or salt substitutes.
• If you have any of these risk factors, your healthcare provider should use ACE inhibitors cautiously, if at all, and closely monitor your potassium levels.

Hypersensitivity reactions

• While taking ACE inhibitors like fosinopril, it's important to be aware of the possibility of hypersensitivity reactions, including anaphylactic or anaphylactoid reactions, which are severe allergic responses.
• In rare cases, these reactions can occur, especially during certain medical procedures like hemodialysis with specific types of dialysis membranes or low-density lipoprotein apheresis with dextran sulfate cellulose.
• There have also been isolated reports of these reactions in individuals receiving hymenoptera (bee or wasp) venom sensitization treatment while on ACE inhibitors.
• If you experience severe allergic symptoms such as difficulty breathing, swelling of the face, lips, tongue, or throat, or a severe rash, seek immediate medical attention.

Syncope and hypotension:

• When starting ACE inhibitors like fosinopril, it's possible to experience low blood pressure (hypotension), which can lead to symptoms like feeling faint or even passing out (syncope).
• This is more likely to happen with the first few doses, particularly in individuals who are dehydrated or have low blood volume.
• It's important to address any signs of low blood volume before starting ACE inhibitors, and your healthcare provider should closely monitor your blood pressure, especially when you first begin taking the medication or when your dose is increased.
• If hypotension occurs, it doesn't necessarily mean you have to stop using ACE inhibitors, especially if you have heart failure.
• Lowering blood pressure is often a goal in heart failure management.

Neutropenia/agranulocytosis:

• While taking ACE inhibitors like fosinopril, it's important to be aware of the potential risk of a condition called neutropenia or agranulocytosis.
• These are rare but severe conditions where your white blood cell count, specifically the neutrophil count, becomes dangerously low.
• Another ACE inhibitor, captopril, has been associated with these rare cases.
• People with kidney problems are at a higher risk of developing neutropenia.
• If you have both kidney problems and a collagen vascular disease like systemic lupus erythematosus, your risk is even higher.
• To monitor for these potential issues, your healthcare provider may periodically check your complete blood count (CBC) with a differential to assess your white blood cell levels.

Renal function deterioration:

• When using ACE inhibitors like fosinopril, it's important to be aware that they can sometimes lead to a decline in kidney function or an increase in serum creatinine levels, especially in individuals with conditions that affect renal blood flow like renal artery stenosis or heart failure.
• This can be because ACE inhibitors affect the way angiotensin II works in the kidneys.
• In some cases, this deterioration can lead to problems like decreased urine output (oliguria), acute renal failure, and increased levels of waste products in the blood (azotemia).
• Small increases in serum creatinine may occur when you first start taking an ACE inhibitor, but this doesn't necessarily mean you need to stop the medication.

Aortic stenosis

• If you have severe aortic stenosis, you should use ACE inhibitors like fosinopril with caution.
• These medications may reduce the blood supply to the coronary arteries, potentially leading to a condition called ischemia, where the heart muscle doesn't receive enough oxygen.
• It's important to work closely with your healthcare provider if you have this condition, as they will monitor your response to the medication and ensure that it doesn't exacerbate your aortic stenosis or lead to any adverse cardiac effects.

Ascites:

• If you have ascites, which is a condition where excess fluid accumulates in the abdominal cavity, especially due to cirrhosis or refractory ascites, it's generally best to avoid using ACE inhibitors like fosinopril.
• However, in some cases where the medication is necessary, it should be used with extreme caution, and your blood pressure and kidney function should be closely monitored.
• Using ACE inhibitors in individuals with ascites due to cirrhosis can potentially lead to rapid kidney function deterioration, so careful medical supervision is essential.

Cardiovascular disease

• If you have cardiovascular disease, particularly ischemic heart disease or cerebrovascular disease, starting ACE inhibitor therapy like fosinopril requires close monitoring.
• These medications can sometimes lower blood pressure, and in individuals with cardiovascular disease, this could potentially lead to serious consequences like a heart attack (MI) or stroke.
• If your blood pressure drops significantly after starting ACE inhibitors, your healthcare provider may recommend fluid replacement to restore your blood pressure, and then they may cautiously resume the therapy.
• However, if hypotension recurs or becomes problematic, discontinuing the medication may be necessary.

Collagen vascular disease:

• If you have a collagen vascular disease, you should use ACE inhibitors like fosinopril with caution, especially if you also have kidney problems.
• Individuals with collagen vascular diseases may be at an increased risk for hematologic toxicity when taking these medications.
• Hematologic toxicity refers to problems related to the blood, such as low blood cell counts.
• Your healthcare provider will carefully assess the potential risks and benefits of using ACE inhibitors in your specific situation and may monitor your blood counts and renal function more closely during treatment to ensure your safety.

Hypertrophic cardiomyopathy with outflow tract obstruction (HCM)

• In individuals with hypertrophic cardiomyopathy (HCM) who have outflow tract obstruction, ACE inhibitors like fosinopril should be used cautiously.
• This is because ACE inhibitors can reduce the afterload (the force the heart needs to pump against), which may worsen the symptoms associated with this condition.
• Before starting or adjusting ACE inhibitor therapy, especially in patients with HCM and outflow tract obstruction, it's crucial to consult with a healthcare provider who is experienced in managing this condition.
• They will carefully evaluate the potential risks and benefits and make treatment decisions that best suit your specific medical situation, considering your cardiac health and overall well-being.

Hepatic impairment

• In individuals with hepatic impairment (liver problems), caution is necessary when using fosinopril.
• Fosinopril undergoes both liver and gut wall metabolism to become its active form, fosinoprilat.
• In people with conditions like alcoholic or biliary cirrhosis (types of liver disease), the process of fosinoprilat formation can slow down, leading to a decrease in its clearance from the body.
• This can result in higher levels of the medication accumulating in the bloodstream, as indicated by a doubling of the area under the curve (AUC).
• Therefore, if you have liver impairment, your healthcare provider will need to carefully assess the dosing and use of fosinopril to ensure it is safe and effective for your specific condition.
• Regular monitoring may also be necessary to make any needed adjustments in your treatment plan.

Renal artery stenosis

• If you have unstented unilateral (one-sided) or bilateral (both sides) renal artery stenosis (narrowing of the renal arteries), you should use ACE inhibitors like fosinopril with caution.
• When unstented bilateral renal artery stenosis is present, ACE inhibitors are generally avoided due to the elevated risk of worsening renal function, unless the potential benefits of using the medication outweigh the risks.

Renal impairment

• If you have preexisting renal (kidney) insufficiency, you should use ACE inhibitors like fosinopril with caution.
• Your healthcare provider may need to adjust the dosage to ensure it is appropriate for your level of kidney function.
• It's important to avoid rapid increases in dosage, as this can potentially worsen renal function.

Fosinopril: Drug Interaction

Monitoring parameters:

• Blood Pressure: Keep an eye on your blood pressure regularly.
• BUN, Serum Creatinine, and Potassium: Monitoring these blood tests is important, especially if you have kidney issues or collagen vascular disease.
• CBC with Differential: If you have collagen vascular disease and/or kidney problems, your doctor may periodically check your complete blood count (CBC) with a differential to assess your overall blood health.

Heart Failure Management

• Renal Function and Serum Potassium: Within 1 to 2 weeks after starting treatment for heart failure, and at regular intervals afterward, your healthcare provider will assess your kidney function and potassium levels. This is particularly crucial if you have preexisting low blood pressure, low sodium levels, diabetes, kidney problems, or if you're taking potassium supplements.

High Blood Pressure (Hypertension) Treatment Guidelines

• Blood Pressure Targets:
  • If you have confirmed hypertension and known cardiovascular disease (CVD) or a high risk of heart disease, the target blood pressure is recommended to be less than 130/80 mm Hg.
  • If you have confirmed hypertension without markers of increased heart disease risk, it may be reasonable to aim for a target blood pressure of less than 130/80 mm Hg.
• Diabetes and Hypertension:
  • For patients aged 18 to 65 without CVD and with a low risk of heart disease, the target blood pressure is less than 140/90 mm Hg.
  • If you're aged 18 to 65, have known heart disease or a high risk of heart disease, and your blood pressure can be safely lowered, a target of less than 130/80 mm Hg may be appropriate.
  • If you're over 65 and generally healthy, aim for a target blood pressure of less than 140/90 mm Hg.
  • For individuals over 65 with more complex or poor health, the target blood pressure is less than 150/90 mm Hg.

How to administer Fosinopril?

• It may taken after meals to reduce the gastrointestinal side effects.
• To avoid the first-dose effect, administer it after dinner and ask the patient to remain seated for about half an hour after the first dose.

Mechanism of action of Fosinopril:

• Fosinopril is a medication that works as a competitive inhibitor of angiotensin-converting enzyme (ACE).
• Its main function is to block the conversion of angiotensin I to angiotensin II, which is a powerful substance that constricts blood vessels.
• By inhibiting this conversion, fosinopril leads to lower levels of angiotensin II in the body.
• This, in turn, causes an increase in plasma renin activity (a hormone related to blood pressure regulation) and a decrease in aldosterone secretion (a hormone that regulates salt and water balance).
• Fosinopril may also have an effect on the central nervous system (CNS) by reducing adrenergic outflow, which can help lower blood pressure.
• Additionally, it might decrease the activity of vasoactive kallikreins, leading to a reduction in active hormones that affect blood pressure.
• Overall, fosinopril works to lower blood pressure through several mechanisms.

Onset of Action:

• It typically starts working within 1 hour after administration.

Duration:

• Its effects can last for about 24 hours.

Absorption:

• Fosinopril is absorbed moderately well by the body, with an absorption rate of about 36%.

Protein Binding:

• More than 99% of the drug in the bloodstream is bound to proteins.

Metabolism:

• Fosinopril is considered a prodrug, meaning it's an inactive form of the medication that gets converted into its active form, fosinoprilat, by enzymes in the intestinal wall and the liver. Fosinopril can also be metabolized into a glucuronide conjugate and another metabolite called p-hydroxy metabolite of fosinoprilat.

Bioavailability:

• About 36% of the administered dose reaches the bloodstream in its active form.

Half-life:

• The half-life of elimination for fosinoprilat (the active form) varies depending on the patient's age and health condition. For adults with congestive heart failure (CHF), it's approximately 14 hours. In adults without CHF, it's around 12 hours, and in children and adolescents aged 6-16 years, it ranges from 11 to 13 hours.

Time to Peak:

• It takes about 3 hours for fosinopril levels in the bloodstream to reach their highest point after administration.

Excretion:

• Fosinopril and its metabolites are eliminated from the body primarily through urine and feces, with roughly equal proportions being excreted through both routes.

International Brands of Fosinopril:

• APO-Fosinopril
• CO Fosinopril
• Fosinopril-10
• Fosinopril-20
• JAMP-Fosinopril
• MYLAN-Fosinopril
• PMS-Fosinopril
• RAN-Fosinopril
• RIVA-Fosinopril
• TEVA-Fosinopril
• Acenor-M
• BPNorm
• Dynacil
• Fonosil
• Forsine
• Fosavis
• Fosicard
• Fosinil
• Fosinorm
• Fosipres
• Fosipril
• Fositen
• Fositens
• Fovas
• Fozitec
• Monace
• Monopril
• Newace
• Notionpril
• Sapril
• Sinotic
• Staril

Fosinopril Brand Names in Pakistan: