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:

• Oral: Initial: 5 mg twice day; gradually increase the dosage at weekly intervals to an effective level, often 10–20 mg twice daily.
• 20 mg twice daily is the target dose.

Quinapril (Accupril) Dose for Hypertension:

• Oral: Initial: 10–20 mg once daily; adjust dosage as necessary every two weeks in accordance with patient response.
• 80 mg/day in one or two divided doses is the maximum dose.

Quinapril (Accupril) Dose in Childrens

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

• Children and Adolescents:

  • Oral: Initial: 5 mg once a day; may titrate every 2 weeks, Maximum daily dose: 80 mg/day
  • For younger patients or those who are small for age, start with the lower end of the range.
    • 0.2 mg/kg single dose produces similar serum concentration to 10mg single dose.

Pregnancy Risk Factor D

• [US Boxed Warn] Medications that interfere with the renin-angiotensin systems can harm or kill a developing foetus.
• Once you are aware that you are pregnant, discontinue your use of the drug.
• Quinapril crosses over to the placenta
• Drugs that have renin/angiotensin system effects can result in oligohydramnios. Reduced foetal renal function is the cause of this.
• Additionally, it may result in foetal lung hypoplasia and skeletal abnormalities.
• Oligohydramnios is not possible after foetal injury that cannot be repaired.
• These drugs can also cause anuria and hypotension in pregnancy. Neonatal patients may require dialysis or exchange transfusion.
• Teratogenic effects are most common with ACE inhibitors in the first trimester.
• Adverse occurrences, however, have been documented in the second and third trimesters.
• Chronic maternal hypertension can lead to adverse events for both the mother and baby.
• It is not advised to be used while pregnant.
• Long-term foetal exposure to ACE inhibitors requires thorough monitoring for hyperkalemia, hypotension, and oliguria in children.
• ACE inhibitors shouldn't be taken when pregnant for the treatment of hypertension or chronic heart failure.
• Women of reproductive age should avoid ACE inhibitors.

Use during breastfeeding:

• Breast milk contains Quinapril.
• It is recommended to be used with caution during lactation.

Quinapril (Accupril) Dose in Kidney Disease:

• Heart failure: Oral:

• If the patient tolerates the initial dose, increase to twice a day the following day and then adjust dose at weekly intervals to optimal response:
  • CrCl >30 mL/minute: Initial: 5 mg once a day
  • CrCl 10 - 30 mL/minute: Initial: 2.5 mg once a day
  • CrCl <10 mL/minute: Manufacturer has not provided any dose adjustment

• Hypertension: Oral:

  • CrCl >60 mL/minute: Initial: 10 mg once a day
  • CrCl 30 - 60 mL/minute: Initial: 5 mg once a day
  • CrCl 10 - 30 mL/minute: Initial: 2.5 mg once a day
  • CrCl <10 mL/minute: Manufacturer has not provided any dose adjustment

Dose in Liver disease:

The manufacturer has not provided dose adjustment in labeling.

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):

• Hypersensitivity to any ingredient of the formulation
• Angioedema after prior exposure to ACE inhibitor.
• Patients with diabetes mellitus should take aliskiren together.
• use within 36 hours of transitioning to or from a neprilysin inhibitor or concurrent use with a neprilysin inhibitor (such as sacubitril).

There is not much proof that ACE inhibitors and allergens interact. It cannot, however, be completely ruled out.

Canadian labeling:

• pregnancy, planning for conception
• Women with childbearing potential who are not using appropriate contraception
• Hyperkalemia
• Breastfeeding
• Patients with moderate-to-severe renal impairment (GFR 60 mL/minute/1.73 m2) should not take aliskiren, angiotensin-receptor blockers (ARBs), or other ACE inhibitors.
• Hypotension and heart failure
• the administration of ACE inhibitors or other angiotensin receptor blockers to diabetics who have end-organ damage
  Hereditary conditions include glucose galactose malabsorption, lactase deficiency in Lapps, and galactose intolerance.

Warnings and precautions

• Angioedema

  • Angioedema can occur at any point during treatment, however it is more prevalent after the first dose.
  • Abdominal pain may result from the airway or intestinale compressing as a result of the head and neck.
  • Patients with hereditary angioedema, African Americans, and those using mTOR inhibitors (such as everolimus) or neprilysin inhibitors (such as sacubitril) concurrently are at greater risk.
  • A prior history of airway surgery could raise the risk.
  • In cases where the tongue, glottis, or larynx are implicated, prolonged observation may be required because these structures have the potential to clog the airways.
  • Contraindicated if there is angioedema caused by an ACE inhibitor

• Cholestatic jaundice

  • ACE inhibitors may cause hepatic fulminant neoplasm, which can lead to cholestatic jaundice. If there are elevated levels of hepatic transaminases and jaundice, therapy should be stopped.

• Cough:

  • A dry cough is usually the result of initial treatment with ACE inhibitors. This condition resolves within a month with no further treatment.
  • Before quitting the medication, it's crucial to rule out other diseases, such as pulmonary congestion in heart failure patients.

• Hematologic effects

  • Agranulocytosis, anaemia, thrombocytopenia, neutropenia, and myeloid hypoplasia have all been linked to captopril, another ACE inhibitor.
  • Neutropenia is substantially more likely to occur in patients with renal impairment or collagen vascular disease, such as systemic lupus erythematosus.
  • These patients require regular CBC monitoring.

• Hyperkalemia:

  • ACE inhibitors may result in hyperkalemia.
  • Dehydration, DM and metabolic acidosis are all risk factors.
  • These agents require continuous potassium monitoring

• Hypersensitivity reactions

  • ACE inhibitors may result in an anaphylactic/anaphylactoid reaction
  • In rare cases, anaphylactic reactions can also happen during low density lipoprotein apheresis using dextran sulfatecellulose and hemodialysis utilising high-flux dialysis membranes (such as polyacrylonitrile).
  • Patients who get ACE inhibitors and have had Hymenoptera (bee or wasp) venom sensitization have a low incidence of anaphylactoid responses.

• Hypotension/syncope

  • Hypotension and syncope may result from ACE inhibitors.
  • Hypovolemia can increase the risk, so volume correction before beginning treatment is recommended.
  • BP monitoring is important throughout therapy, particularly when dose escalation is involved.
  • Particularly for patients with heart disease, hypotension shouldn't be used as a justification to stop receiving ACE inhibitor treatment in the future. A dose reduction, however, might be required if a decrease in systolic pressure is desired.
  • Patients with hemodynamic instability following an acute MI shouldn't use it.

• Renal function deterioration:

  • This could lead to an increase in serum creatinine
  • Patients with low renal blood flow, such as those suffering from oliguria or acute renal failure, can experience complications like progressive azotemia and renal dysfunction.
  • A significant impairment in renal function should not be considered a reason to stop taking the drug.

• Aortic stenosis

  • Be cautious if you have severe aorticstenosis. It may cause reduced coronary perfusion and ischemia.

• Ascites:

  • It should be avoided in patients suffering from ascites caused by cirrhosis, refractory or other causes.
  • Patients with ascites from cirrhosis should be monitored regularly for BP and RFTs to prevent the rapid progression of renal failure.

• Cardiovascular disease

  • Patients with ischemic heart disease, cerebrovascular disease or heart failure can experience hypotension. Therefore, it is important to be closely monitored.
  • Once the fluid replacement has been completed, therapy can be resumed.
  • Patients with hypotension recurrence should stop therapy.

• Collagen vascular disease:

  • Collagen vascular disease, especially when combined with concomitant kidney impairment, increases the risk of hematological toxicities. Therefore it is important to be cautious.

• Hypertrophic cardiomyopathy and outflow tract obstruction

  • Hypertrophic cardiomyopathy or outflow obstruction may be worsened by a reduction in afterload. It should be used with caution.

• Renal artery stenosis

  • Patients with un-stented unilateral/bilateral kidney artery stenosis should use quinapril with caution
  • If you have un-stented bilateral renal arterial stenosis, it should be avoided. There is a higher risk of renal dysfunction.

• Renal impairment

  • If you have renal impairment, be cautious. To stop dose escalation, the dosage may need to be changed.

Quinapril: Drug Interaction

Monitoring parameters:

• Renal function
• Blood pressure
• Serum electrolytes especially potassium
• Patients with collagen vascular disease and/or renal impairment should have their CBCs checked on a regular basis with a differential.

Heart Failure:

• Reevaluate renal function and serum potassium within 1-2 weeks of initiating ACE inhibitors, especially in patients with pre-existing hypotension, hyponatremia, diabetes, azotemia, or concurrent use of potassium supplements.

Hypertension: 2017 Guideline for Adults:

Confirmed hypertension and CVD or 10-year ASCVD risk ≥10%:

• Target blood pressure <130/80 mm Hg is recommended

Confirmed hypertension without markers of increased ASCVD risk:

• Target blood pressure <130/80 mm Hg may be reasonable

Diabetes and hypertension: The American Diabetes Association (ADA) guidelines (ADA 2019):

• Patients 18 - 65 years of age, without ASCVD, and 10-year ASCVD risk <15%:
  • Target BP <140/90 mm Hg is recommended.
• Patients 18 - 65 years of age and known ASCVD or 10-year ASCVD risk >15%:
  • Target BP <130/80 mm Hg may be appropriate if it can be safely attained.
• Patients >65 years of age (healthy or complex/intermediate health):
  • Target BP <140/90 mm Hg is recommended.
• Patients >65 years of age (very complex/poor health):
  • Target BP <150/90 mm Hg is recommended.

How to administer Quinapril (Accupril)?

Oral: Can be taken with or without food

Mechanism of action of Quinapril (Accupril):

• The angiotensin-converting enzyme is inhibited by quinapril in a competitive manner (ACE).
• As a result, the synthesis of angiotensin 2 declines, plasma renin activity rises, and aldosterone levels drop.
• It also prevents angiotensin I from angiotensin III (a powerful vasoconstrictor).
• Angiotensin II may increase adrenergic output from the CNS.
• This could explain why there is a hypotensive effect.
• Vasoactive kallikreins decrease in active hormone conversion by ACE inhibitors. This leads to lower blood pressure

The onset of action:

• 1 hour;
• Peak effect: 2 - 4 hours after the dose

Duration:

• 24 hours (chronic dosing)

Absorption:

• Quinapril: ≥60%

Protein binding:

• Quinapril: 97%; Quinaprilat: 97%

Metabolism:

• Rapidly hydrolyzed to quinaprilat, the active metabolite (~38% of an oral dose)

Half-life elimination:

• Infants and Children <7 years: Quinaprilat: 2.3 hours
• Adults: Quinapril: 0.8 hours; Quinaprilat: 3 hours; increases as CrCl decreases

Time to peak, serum:

• Infants and Children <7 years: 1.7 hours (range: 1 - 4 hours)
• Adults: Quinapril: 1 hour; Quinaprilat: ~2 hours

Excretion:

• Urine (50% - 60% primarily as quinaprilat)

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: