Angiotensin-converting enzyme inhibitors (ACE-I), such as quinapril (Accupril), are used to treat individuals with hypertension, heart failure, and proteinuria.

Quinapril Uses:

• Heart failure:
  • It is prescribed as a supplement to heart failure treatment (HF)
  • Guidelines:
    • The 2013 Heart Failure Guidelines from the American College of Cardiology/American Heart Association (ACC/AHA): ACE inhibitors should be taken along with other medical treatments that follow recommended guidelines (GMDT)
      • To stop the progression of HF and a decreased ejection fraction in asymptomatic individuals (with or without a history of MI)
      • Reduced ejection fraction in symptomatic HF to lower morbidity and mortality
• Hypertension:
  • It is used for the managing high blood pressure
  • Guidelines:
    • Thiazide-like diuretics or dihydropyridine calcium channel blockers can be chosen if monotherapy is necessary and the patient has no comorbidities (CVD, CKD, IHD, DM, heart failure), as these antihypertensives have enhanced cardiovascular outcomes (eg, prevention of heart failure and stroke).
    • ARBs and ACE inhibitors are also suitable for monotherapy.
    • Combination therapy is initially favoured in individuals at high risk (stage 2 hypertension or an atherosclerotic cardiovascular disease [ASCVD] risk of 10%). Combination therapy may be necessary to reach blood pressure targets.
• Off Label Use of Quinapril in Adults:
  • ST-elevation acute coronary syndrome
  • Stable coronary artery disease
  • Non–ST-elevation acute coronary syndrome

Quinapril (Accupril) Dose in Adults

Quinapril (Accupril) Dose in the treatment of Heart failure:

• Start with 5 mg (milligrams) of quinapril twice a day, taken by mouth.
• Every week, your doctor may increase the dose if needed.
• The usual effective dose is 10 to 20 mg twice a day.
• The goal is to reach a dose of 20 mg twice a day.

This is a standard guideline for using quinapril to treat heart failure, as recommended by the American College of Cardiology and the American Heart Association in 2013.

Quinapril (Accupril) Dose for Hypertension:

• Start with 10 to 20 mg (milligrams) of quinapril once a day, taken by mouth.
• Every two weeks, your doctor may adjust the dose depending on how your body responds.
• You can take up to 80 mg per day, either in one dose or split into two doses.

This is a standard guideline for using quinapril to treat high blood pressure, as recommended by the American College of Cardiology and the American Heart Association in 2017.

Quinapril (Accupril) Dose in Childrens

Quinapril (Accupril) Dose in the treatment of Hypertension: Limited data available:

In children and adolescents:

• Start with 5 mg (milligrams) of quinapril once a day, taken by mouth.
• Every two weeks, the doctor may adjust the dose if needed.
• The maximum daily dose is 80 mg per day.
• If the child or adolescent is younger or smaller for their age, the doctor may start with a lower dose.
• Some studies suggest that a 0.2 mg/kg dose in very young children (less than 7 years old) gave similar results to a 10 mg dose in adults.
• However, there isn't enough data on the long-term use of weight-based dosing in children, so doctors may be cautious.

Pregnancy Risk Factor D

• there's a serious warning about drugs like quinapril that affect the renin-angiotensin system: they can harm and even cause the death of a developing baby if taken during pregnancy.
• If someone becomes pregnant while taking these drugs, they should stop using them immediately.
• Quinapril can cross into the baby's environment in the womb and can lead to problems like low levels of amniotic fluid (oligohydramnios), which can affect the baby's lung and bone development.
• These drugs have also been linked to other serious issues like kidney problems and even death in the baby.
• Using these drugs during pregnancy is generally not recommended.
• If a baby was exposed to these drugs in the womb, doctors should watch for certain complications like high potassium levels, low blood pressure, and low urine output in the baby.
• Sometimes, special treatments like blood transfusions or dialysis might be needed.
• If a pregnant woman has high blood pressure or heart problems, there are other medications that should be used instead of these drugs.

Use during breastfeeding:

• Quinapril can be found in breast milk, so it's important for breastfeeding women to be cautious when taking this medication.
• The manufacturer advises being careful when using quinapril while breastfeeding.
• This caution is because the drug could potentially be passed on to the baby through breast milk, and the effects on the baby are not well understood.

Quinapril (Accupril) Dose in Kidney Disease:

For Heart Failure:

• If the CrCl is greater than 30 mL/minute, start with 5 mg of quinapril once a day. If it's tolerated well, you can increase to twice daily the next day and adjust the dose every week until you find the right dose for you.
• If the CrCl is between 10 and 30 mL/minute, start with 2.5 mg of quinapril once a day.
• For people with a CrCl less than 10 mL/minute, there are no specific dosage adjustments provided in the manufacturer's guidelines.

For Hypertension:

• If the CrCl is greater than 60 mL/minute, start with 10 mg of quinapril once a day.
• If the CrCl is between 30 and 60 mL/minute, start with 5 mg once a day.
• If the CrCl is between 10 and 30 mL/minute, start with 2.5 mg once a day.
• For people with a CrCl less than 10 mL/minute, there are no specific dosage adjustments provided in the manufacturer's guidelines.

These dosages take into account how well your kidneys are functioning because quinapril is eliminated from the body primarily through the kidneys.

Quinapril Dose in Liver disease:

The manufacturer's labeling for quinapril does not provide specific dosage adjustments for individuals with hepatic impairment (liver impairment) because the drug's use in this population has not been extensively studied.

Data from trials on hypertension and heart failure are included in the frequency ranges. Patients with congestive heart failure typically experience higher rates of adverse effects.

Side Effects of Quinapril (Accupril):

• Cardiovascular:
  • Hypotension
  • Chest Pain
• Central Nervous System:
  • Dizziness
  • Headache
  • Fatigue
• Endocrine & Metabolic:
  • Hyperkalemia
• Gastrointestinal:
  • Nausea
  • Vomiting
  • Diarrhea
  • Abdominal Pain
• Neuromuscular & Skeletal:
  • Back Pain
• Renal:
  • Increased Serum Creatinine
  • Increased Blood Urea Nitrogen
• Respiratory:
  • Cough

Contraindications to Quinapril (Accupril):

Do NOT Use Quinapril If:

• You are allergic to quinapril or any part of the medication.
• You had a serious swelling condition called angioedema because of a previous ACE inhibitor.
• You are taking aliskiren and have diabetes.
• You are taking a neprilysin inhibitor like sacubitril or have switched to/from it within the last 36 hours.

Use Quinapril with Caution If:

• You are pregnant, planning to become pregnant, or could become pregnant without using proper birth control (Canadian labeling).
• You are breastfeeding (Canadian labeling).
• You have moderate-to-severe kidney problems, high blood potassium levels, or heart failure and your blood pressure is low. Avoid using it with other medications like angiotensin receptor blockers (ARBs) or other ACE inhibitors (Canadian labeling).
• You have diabetes and damage to your organs. Be careful when using it with ARBs or other ACE inhibitors (Canadian labeling).
• You have certain rare conditions like galactose intolerance, glucose-galactose malabsorption, or Lapp lactase deficiency (Canadian labeling).

Warnings and precautions

Angioedema

• Angioedema, which is a rare but serious side effect, can happen at any time while using ACE inhibitors like quinapril.
• It can affect the head and neck, potentially making it hard to breathe, or it can affect the intestines, causing abdominal pain.
• People of African-American descent and those with a history of unexplained or hereditary angioedema might be at a higher risk.
• The risk may also increase if you're taking certain other medications like mTOR inhibitors (e.g., everolimus) or neprilysin inhibitors (e.g., sacubitril).
• Keep a close watch, especially if the swelling affects your tongue, throat, or voice box, as this can block your airway.
• If you've had surgery on your airway in the past, you might have a higher risk of airway blockage.
• It's crucial to act quickly and get proper treatment if angioedema occurs.
• If you've had angioedema in the past because of an ACE inhibitor, using quinapril is not recommended and should be avoided.

Cholestatic jaundice

• A rare but serious side effect of ACE inhibitors like quinapril is cholestatic jaundice.
• This condition can lead to severe liver problems, including fulminant hepatic necrosis.
• If you experience a significant increase in liver enzymes or develop jaundice (yellowing of the skin and eyes), stop taking quinapril immediately.
• It's essential to seek medical attention promptly if these symptoms occur, as liver issues can be severe in this case.

Cough:

• Some people taking ACE inhibitors like quinapril may develop a specific type of cough.
• This cough is typically dry, persistent, and doesn't produce any phlegm.
• It often starts within the first few months of taking the medication.
• The good news is that this cough usually goes away within 1 to 4 weeks after you stop taking the ACE inhibitor.
• Before discontinuing the medication, it's important for your healthcare provider to explore and rule out other potential causes of the cough, especially if you have heart failure, as pulmonary congestion could be a reason for coughing.

Hematologic effects

• Some ACE inhibitors, like captopril, have been linked to certain blood-related issues.
• These issues can include neutropenia (a low level of a type of white blood cell), myeloid hypoplasia (insufficient development of bone marrow cells), and agranulocytosis (a severe decrease in white blood cells).
• Other blood-related problems reported with ACE inhibitors include anemia (low red blood cell count) and thrombocytopenia (a decrease in platelets, which help with blood clotting).
• Patients with kidney problems are at a higher risk of developing neutropenia.
• If a person has both kidney issues and a collagen vascular disease like systemic lupus erythematosus, their risk of developing neutropenia is even higher.
• To monitor for these blood-related problems, it's important to periodically check a complete blood count (CBC) with a differential (which looks at different types of white blood cells) in patients with these risk factors. This helps catch any potential issues early on.

Hyperkalemia:

• Hyperkalemia, which means having too much potassium in your blood, can happen when taking ACE inhibitors like quinapril.
• Several factors can increase the risk of hyperkalemia, including kidney problems, diabetes, and using medications like potassium-sparing diuretics, potassium supplements, or products containing potassium salts.
• If you have these risk factors, it's crucial to use ACE inhibitors with caution or consider alternative medications.

Hypersensitivity reactions

• ACE inhibitors, including quinapril, can sometimes trigger severe allergic reactions known as anaphylactic or anaphylactoid reactions.
• These reactions can be very serious and may include symptoms like difficulty breathing, swelling, and a drop in blood pressure.
• In rare cases, especially during certain medical procedures like high-flux hemodialysis with specific dialysis membranes or low-density lipoprotein apheresis with dextran sulfate cellulose, severe anaphylactoid reactions may occur.
• There have also been rare reports of anaphylactoid reactions in individuals undergoing allergy desensitization treatment for bee or wasp venom while taking ACE inhibitors.
• If you experience any signs of a severe allergic reaction while taking quinapril, seek immediate medical attention. These reactions require prompt treatment and should not be ignored.

Hypotension/syncope

• ACE inhibitors like quinapril can lead to low blood pressure (hypotension) and, in some cases, fainting (syncope).
• This effect is more likely to happen, especially with the first few doses, in patients who have low blood volume or are dehydrated. It's essential to correct any volume depletion before starting the medication.
• Patients should be closely monitored, especially when starting the medication or when the dose is increased.
• The rate at which blood pressure is lowered should be appropriate for the patient's specific health condition.
• Even though a reduction in dose may be necessary to manage hypotension, it's generally not a reason to stop using ACE inhibitors in the future. This is especially true for patients with heart failure, where lowering systolic blood pressure is often a desired outcome.

Renal function deterioration:

• Taking ACE inhibitors like quinapril can sometimes lead to a decline in kidney function or an increase in serum creatinine levels.
• This is more likely to occur in patients who already have reduced blood flow to their kidneys, such as those with conditions like renal artery stenosis or heart failure.
• In some cases, this deterioration can be severe and result in conditions like oliguria (low urine output), acute renal failure, or progressive azotemia (an increase in waste products in the blood).
• It's important to note that small increases in serum creatinine may occur when starting ACE inhibitors. However, discontinuation of the medication is generally considered only in patients who experience a significant and progressive decline in kidney function.

Aortic stenosis

• If you have severe aortic stenosis (a heart valve condition where the aortic valve doesn't open properly), you should be cautious when using ACE inhibitors like quinapril.
• These medications can potentially reduce the blood flow to the coronary arteries, which can lead to a lack of oxygen (ischemia) in the heart muscle.

Ascites:

• If you have ascites (abdominal fluid buildup) caused by cirrhosis or refractory ascites (ascites that doesn't respond to treatment), you should generally avoid using quinapril.
• However, if there's a specific medical reason to use quinapril in such cases, it's crucial to monitor your blood pressure and kidney function very carefully.
• The use of quinapril in patients with ascites due to cirrhosis can potentially lead to rapid kidney failure, so close monitoring is essential.

Cardiovascular disease

• If you have cardiovascular diseases like ischemic heart disease (reduced blood flow to the heart) or cerebrovascular disease (related to blood vessels in the brain), it's essential to be closely monitored when starting quinapril therapy.
• Taking quinapril can potentially lead to a drop in blood pressure, which could have serious consequences such as a heart attack (MI) or stroke.
• If your blood pressure falls too low, fluid replacement may be necessary to restore your blood pressure to a safe level.

Collagen vascular disease:

• If you have a collagen vascular disease (a group of autoimmune diseases affecting connective tissues) and especially if you also have kidney problems, you should be cautious when using quinapril.
• Patients with collagen vascular diseases, when combined with renal impairment, may be at an increased risk for hematologic toxicity (blood-related issues).

Hypertrophic cardiomyopathy and outflow tract obstruction

• If you have hypertrophic cardiomyopathy with outflow tract obstruction (a condition where the heart muscle is abnormally thick and obstructs blood flow), be cautious when considering the use of quinapril.
• Quinapril can reduce the afterload (the pressure the heart has to overcome to pump blood), which might worsen the symptoms associated with this heart condition.

Renal artery stenosis

• If you have renal artery stenosis (a narrowing of the arteries supplying the kidneys) that is not treated with stents, you should use quinapril with caution.
• When there is unstented bilateral renal artery stenosis (narrowing in both kidneys), quinapril use is typically avoided because it can increase the risk of worsening kidney function.
• The decision to use quinapril in these cases should only be made if the potential benefits clearly outweigh the risks, and it should be done under close medical supervision.

Renal impairment

• If you have kidney problems or renal impairment, be cautious when using quinapril.
• Depending on the severity of your kidney condition, a dosage adjustment may be necessary.
• It's important not to increase the dosage of quinapril rapidly, as this can potentially worsen your kidney function.

Quinapril: Drug Interaction

Monitoring parameters:

Blood Pressure Monitoring:

• Regularly monitor your blood pressure when taking quinapril.
• If you have collagen vascular disease and/or kidney problems, periodic monitoring of a complete blood count (CBC) with differential may be necessary.

For Heart Failure:

• For individuals with heart failure, assess renal function and serum potassium within 1 to 2 weeks after starting quinapril.
• Periodically reevaluate renal function and potassium levels, especially if you have preexisting conditions like hypotension, hyponatremia, diabetes, azotemia (increased levels of nitrogen waste products in the blood), or if you're taking potassium supplements.

For Hypertension:

• If you have confirmed hypertension and known atherosclerotic cardiovascular disease (ASCVD) or a 10-year ASCVD risk of ≥10%, the target blood pressure should be less than 130/80 mm Hg.
• If you have confirmed hypertension without markers of increased ASCVD risk, a target blood pressure of less than 130/80 mm Hg may be reasonable.
• For individuals with both diabetes and hypertension:
  • If you're 18 to 65 years old without ASCVD and have a 10-year ASCVD risk of <15%, the target blood pressure is less than 140/90 mm Hg.
  • If you're 18 to 65 years old with known ASCVD or a 10-year ASCVD risk of >15%, a target blood pressure of less than 130/80 mm Hg may be appropriate if it can be safely attained.
  • If you're over 65 years old and in healthy or complex/intermediate health, the target blood pressure is less than 140/90 mm Hg.
  • If you're over 65 years old and in very complex/poor health, the target blood pressure is less than 150/90 mm Hg.

How to administer Quinapril (Accupril)?

You can take quinapril by mouth with or without food. It doesn't matter if you have it with a meal or on an empty stomach.

Mechanism of action of Quinapril (Accupril):

• Quinapril works by blocking an enzyme called angiotensin-converting enzyme (ACE).
• This enzyme usually changes a substance called angiotensin I into another one called angiotensin II, which narrows blood vessels.
• When you take quinapril, it lowers the levels of angiotensin II, which makes your body produce more of a substance called renin and reduces the release of aldosterone.
• This helps to relax blood vessels and lower blood pressure.
• There's also a possibility that quinapril affects the brain and decreases the activity of angiotensin II in the nervous system.
• Additionally, it might reduce the production of certain hormones that can raise blood pressure.

Onset of Action:

• It starts working about 1 hour after you take it.

Peak Effect (Antihypertensive):

• The strongest effect on lowering blood pressure happens between 2 to 4 hours after taking it.

Duration:

• It keeps working for about 24 hours when taken regularly.

Absorption:

• When you take quinapril, your body absorbs more than 60% of it.

Distribution:

• In babies and children under 6 years old, it's found in the body at a rate of 0.7 liters per kilogram (can vary from 0.27 to 1.48 liters per kilogram).
• In adults, it's distributed in the body at a rate of 1.5 liters per kilogram.

Protein Binding:

• About 97% of quinapril and its active form, quinaprilat, attach to proteins in your blood.

Metabolism:

• Quinapril quickly changes into quinaprilat, which is the active form (around 38% of what you take by mouth).

Half-Life Elimination:

• In infants and children under 7 years old, quinaprilat stays in the body for about 2.3 hours.
• In adults, quinapril stays for about 0.8 hours, and quinaprilat for about 3 hours. This time increases if your kidney function is not normal.

Time to Peak in Blood:

• In infants and children under 7 years old, it takes about 1.7 hours to reach the highest level in the blood (can vary from 1 to 4 hours).
• In adults, quinapril peaks in about 1 hour, and quinaprilat peaks in about 2 hours.

Excretion:

• Your body gets rid of quinapril and quinaprilat mostly through urine (about 50% to 60% of it is eliminated this way).

International Brand Names of Quinapril:

• Accupril
• Accuprin
• Accupro
• Accupron
• Acequin
• Acquin
• Acuitel
• Acupil
• Acuprel
• Acupril
• Acuprofire
• Ectren
• Korec
• Lidaltrin
• Q-Pril
• Qpril
• Quinaspen
• Quinazil
• Quinsil
• Quiprex
• Yiheng

Quinapril Brand Names in Pakistan: