Quinapril

Registered South African indications:

• Hypertension - mild to moderate
• Congestive cardiac failure

Contraindications

South African recommendations

• In patients who are hypersensitive to any component of this product
• History of angioedema related to previous therapy with ACE inhibitors or angiotensin receptor blockers (ARBs). These patients must never again be given these medicines
• Hereditary or idiopathic angioedema
• Hypertrophic obstructive cardiomyopathy (HOCM)
• Moderate to severe renal function impairment (CrCl<30ml/min)
• Bilateral renal artery stenosis
• Renal artery stenosis in patients with a single kidney
• Aortic stenosis
• Concomitant therapy with potassium-sparing diuretics such as spironolactone, triamterene, amiloride
• Porphyria
• Thiazide diuretics in (fixed dose) combination with quinapril should not be given to patients with Addison's disease. This therapy is also contraindicated in patients with severe renal impairment or anuria and in patients who show hypersensitivity to other sulphonamide-derived medicines
• Lithium therapy: Concomitant administration with quinapril may lead to toxic blood concentrations of lithium
• Pregnancy
• Lactation

Recommendations in other jurisdictions 

• Hypersensitivity to the active substance or any of the excipients
• In the second and third trimesters of pregnancy
• History of angioedema related to previous treatment with angiotensin-converting enzyme (ACE) inhibitors
• Hereditary or idiopathic angioneurotic oedema
• Dynamic left ventricular outflow obstruction
• Coadministration with aliskiren-containing products in patients with diabetes mellitus or renal impairment (glomerular filtration rate [GFR]<60ml/min/1.73 m²)
• Combination with sacubitril/valsartan due to the increased risk of angioedema

Cautions

• First trimester of pregnancy (Recommendations in other jurisdictions)
• Breastfeeding (Recommendations in other jurisdictions)
• Mild renal impairment (South African recommendations)
• Renal impairment (CrCl<40ml/min) (Recommendations in other jurisdictions)
• Hepatic impairment
• Elderly
• Aortic stenosis
• Atopic patients
• Risk factors for hyperkalaemia
• Renal artery stenosis
• Black patients
• Salt depleted patients
• Volume depleted patients
• Ischaemic heart disease
• Cerebrovascular disease
• Collagen vascular disease
• Diabetes mellitus
• Haemodialysis with high-flux polyacrylonitrile
• Low-density lipoprotein aphoresis with dextran-sulphate
• Hymenoptera venom desensitising treatment
• Galactose intolerance
• Lapp lactase deficiency 
• Glucose-galactose malabsorption

Forms avail. in SA and covered in this monograph: tab

Dosages below include:

• South African registered indications and dosages

South African registered indications and dosages

Hypertension - mild to moderate
- Monotherapy in patients not on diuretics

• Oral (tab): Initial: 10mg, dly; Titrate by doubling the dose at 4 week intervals based on clinical response; Maintenance: 20-40mg/day, in 1-2 divided doses

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Dosage adjustments should generally be made at intervals of 4 weeks or as per the patient's response. Antihypertensive activity commences within 1 hour, with peak effects usually achieved by 2-4 hours after dosing. Maximum blood pressure lowering effects may require 2 weeks of therapy in some patients

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Long-term control is maintained in most patients with a single daily dosage regimen

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- With concomitant diuretics

• Oral (tab): Initial: 5mg, dly in order to determine if excess hypotension will occur; Titrate by doubling the dose at 4 week intervals to the optimal response; Maintenance: 20-40mg/day, in 1-2 divided doses

Congestive cardiac failure (Additional agent required)
- Unresponsive systolic left ventricular failure of various aetiologies where afterload reduction is advocated

• Oral (tab): Initial: 5mg, as a single dose and monitor closely for symptomatic hypotension; Titrate up to 40mg/day, in 2 divided doses with concomitant diuretic and/or cardiac glycoside therapy; Maintenance: Usually 10-20mg/day, in 1-2 divided doses with concomitant therapy

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Quinapril may be administered without regard to meals

Not established for use in children

Pregnancy

South African recommendations

• Contraindicated
• There are no adequate and well-controlled studies in pregnant women. Quinapril is contraindicated throughout pregnancy
• Should a woman become pregnant while receiving an angiotensin-converting-enzyme (ACE) inhibitor, the treatment must be stopped promptly and switched to a different class of medicine
• Should a woman receiving an ACE inhibitor, contemplate pregnancy, the doctor must consider alternative medication
• ACE-inhibitors pass through the placenta and can be presumed to cause disturbance in foetal blood pressure regulatory mechanisms. Oligohydramnios as well as hypotension, oliguria and anuria in newborns have been reported after administration of ACE-inhibitors in the second and third trimester. Cases of defective skull ossification have been observed. Prematurity and low birth mass can occur

Recommendations in other jurisdictions 

• Second and third trimester: Contraindicated
• First trimester: Caution; not recommended
• The use of ACE inhibitors is not recommended during the first trimester of pregnancy
• The use of ACE inhibitors is contraindicated during the 2nd and 3rd trimester of pregnancy
• Epidemiological evidence regarding the risk of teratogenicity following exposure to ACE inhibitors during the first trimester of pregnancy has not been conclusive, but a small increase in risk cannot be excluded
• ACE inhibitors should not be initiated during pregnancy. Unless continued ACE inhibitor therapy is considered essential, patients planning pregnancy should be changed to alternative antihypertensive treatments with an established safety profile for use in pregnancy
• When pregnancy is diagnosed, treatment with ACE inhibitors should be stopped immediately, and, if appropriate, alternative therapy should be started
• Exposure to ACE inhibitor therapy during the second and third trimesters is known to induce human foetotoxicity (decreased renal function, oligohydramnios, skull ossification retardation and/or newborn death) and neonatal toxicity (renal failure, hypotension, hyperkalaemia)
• If exposure to ACE inhibitors has occurred from the second trimester of pregnancy, an ultrasound check of renal function and skull is recommended
• Limb contractures, craniofacial deformities, hypoplastic lung development, and intrauterine growth retardation have been reported in association with oligohydramnios
• Infants whose mothers have taken ACE inhibitors should be closely observed for hypotension, oliguria, and hyperkalaemia
• If oliguria occurs, attention should be directed towards support of blood pressure and renal perfusion

Breastfeeding

South African recommendations

• Contraindicated
• Quinapril and its metabolites are secreted in human milk

Recommendations in other jurisdictions 

• Caution; not recommended
• Limited pharmacokinetic data demonstrate very low concentrations in breast milk
• Although these concentrations seem to be clinically irrelevant, the use of quinapril in breastfeeding is not recommended for preterm infants and for the first few weeks after delivery, because of the hypothetical risk of cardiovascular and renal effects and because there is not enough clinical experience
• In the case of an older infant, the use of quinapril in a breastfeeding mother may be considered if this treatment is necessary for the mother and the child is observed for any adverse effect

Renal Impairment

South African recommendations

• Mild: Caution; no dose adjustment recommended
  Patients should commence therapy at the lowest recommended daily dose and be titrated upwards based upon response
• Moderate to severe: Contraindicated

Recommendations in other jurisdictions 

• CrCl≥40ml/min: No dose adjustment recommended
• CrCl<40ml/min: Caution; dose adjustment recommended
  In patients with a creatinine clearance of less than 40ml/min, an initial dosage in essential hypertension of 2.5mg is recommended followed by titration to the optimal response
• CrCl<10ml/min: Caution; not recommended

Hepatic Impairment

• Caution; no dose adjustment recommended

Elderly

• Caution; no dose adjustment recommended 

Porphyria Information

South African recommendations

• Contraindicated

Recommendations in other jurisdictions

• Not porphyrinogenic (NP)

Drugs in Sport

• Permitted - No warnings

Central Nervous System Disorders

• Insomnia
• Confusion
• Depression
• Nervousness
• Dizziness
• Headache
• Paraesthesia
• Transient ischaemic attack
• Somnolence
• Balance disorder
• Syncope
• Cerebrovascular accident
• Cerebral haemorrhage
• Fatigue

Cardiovascular Disorders

• Myocardial infarction
• Angina pectoris
• Tachycardia
• Palpitations
• Hypotension
• Vasodilatation
• Orthostatic hypotension
• Chest pain

Respiratory Disorders

• Upper airway obstruction
• Dyspnoea
• Cough
• Dry throat
• Eosinophilic pneumonia
• Bronchospasm
• Pharyngitis
• Rhinitis
• Bronchitis
• Upper respiratory tract infection
• Sinusitis

Gastrointestinal Disorders

• Diarrhoea
• Dyspepsia
• Abdominal pain
• Nausea and vomiting
• Flatulence
• Dry mouth
• Glossitis
• Constipation
• Dysgeusia
• Ileus
• Small bowel angioedema
• Pancreatitis

Hepatobiliary Disorders

• Hepatitis
• Cholestatic jaundice 

Genitourinary Disorders

• Renal impairment
• Proteinuria
• Erectile dysfunction
• Urinary tract infection

Endocrine and Metabolic Disorders

• Hyperkalaemia

Musculoskeletal Disorders

• Back pain
• Myalgia

Skin and Subcutaneous Tissue Disorders

• Angioedema
• Rash
• Pruritus
• Hyperhidrosis
• Erythema multiforme
• Pemphigus
• Urticaria
• Dermatitis psoriasiform
• Stevens Johnson syndrome
• Toxic epidermal necrolysis exfoliative dermatitis
• Alopecia
• Photosensitivity reaction 
• Inflammation of serous tissues

Immune, Blood and Lymphatic System Disorders

• Agranulocytosis
• Haemolytic anaemia
• Neutropenia
• Thrombocytopenia
• Anaphylactoid reaction
• Hypersensitivity reaction

Sensory Disorders

• Amblyopia
• Blurred vision
• Vertigo
• Tinnitus

• Sacubitril/valsartan
• Aliskiren-containing products
• Potassium-sparing diuretics
• Spironolactone
• Triamterene
• Amiloride
• Tetracycline
• Diuretics
• Thiazide diuretics
• Agents that increase serum potassium
• Anaesthetic agents
• Lithium
• Non-steroidal anti-inflammatory drugs 
• mTOR inhibitors
• Dipeptidyl-peptidase 4 inhibitors
• Gold
• Antihypertensive agents
• Central nervous system depressants
• Allopurinol
• Cytostatic and immunosuppressive agents
• Corticosteroids
• Procainamide
• Antacids
• Antidiabetic agents
• Agents acting on the renin-angiotensin-aldosterone system

• Renal function
• Electrolytes

Specific cases may require

• Full blood count

Quinapril is a potent angiotensin-converting enzyme (ACE) inhibitor. This enzyme functions to convert angiotensin I to angiotensin II which is involved in vascular control and functions through many different mechanisms, including stimulation of aldosterone secretion. By inhibiting the ACE, quinapril prevents the downstream vasopressor activity and aldosterone secretion effected by angiotensin II.

Tablet 5mg

• Quinagen (Mylan)

Tablet 10mg

• Accumax (Pfizer)
• Accupril (Pfizer) originator
• Quinagen (Mylan)
• Quinaspen (Pharmacare)

Tablet 20mg

• Accumax (Pfizer)
• Accupril (Pfizer) originator
• Quinagen (Mylan)
• Quinaspen (Pharmacare)

Tablet 40mg

• Accupril (Pfizer) originator
• Quinagen (Mylan)