Quinapril + Hydrochlorothiazide

Oral
Hypertension

CrCl (mL/min)	Dosage
<30	Contraindicated.

May be taken with or without food.

Hypersensitivity. History of angioedema related to previous ACE inhibitor treatment, hereditary or idiopathic angioneurotic oedema, dynamic left ventricular outflow obstruction, anuria. Severe renal impairment. Pregnancy (2nd-3rd trimester). Concomitant use with aliskiren in patients with diabetes mellitus or renal impairment (GFR <60 mL/min/1.73 m²). Concomitant use with sacubitril/valsartan.

Patients with adrenal insufficiency (e.g. Addison’s disease), aortic stenosis, CV disease (e.g. ischaemic heart disease), cerebrovascular disease, collagen vascular disease, SLE, prediabetes or diabetes mellitus, salt or volume depletion, hypercholesterolaemia, hypercalcaemia, liver cirrhosis, hypertrophic cardiomyopathy with outflow obstruction, unstented unilateral/bilateral renal artery stenosis, parathyroid disease, history of allergy or bronchial asthma. Patients undergoing major surgery or during anaesthesia. Black race. Patients undergoing LDL apheresis with dextran sulfate cellulose or desensitisation treatment with hymenoptera venom. Renal and hepatic impairment. Pregnancy (1st trimester) and lactation.

Significant: Symptomatic hypotension with or without syncope, intestinal angioedema, electrolyte disturbances (e.g. hyperkalaemia, hypokalaemia, hypochloraemic alkalosis, hypomagnesaemia, hyponatraemia), cough, gout, haematologic effects (e.g. neutropenia, agranulocytosis, anaemia, thrombocytopenia), ocular effects (e.g. acute transient myopia, acute angle-closure glaucoma), sensitivity reactions (e.g. purpura, photosensitivity, necrotising angiitis, pneumonitis), non-melanoma skin cancer, Stevens-Johnson syndrome, SLE exacerbation or activation, elevated BUN, increased serum creatinine, oliguria, progressive azotaemia.
Cardiac disorders: Angina pectoris, tachycardia, palpitation.
Ear and labyrinth disorders: Tinnitus.
Eye disorders: Amblyopia, blurred vision.
Gastrointestinal disorders: Nausea, vomiting, diarrhoea, abdominal pain, dry mouth.
General disorders and admin site conditions: Fatigue, asthenia, pyrexia, oedema.
Hepatobiliary disorders: Hepatitis.
Immune system disorders: Urticaria.
Investigations: Elevated hepatic enzymes.
Metabolism and nutrition disorders: Hyperuricemia, impaired glucose tolerance.
Musculoskeletal and connective tissue disorders: Back pain, myalgia.
Nervous system disorders: Headache, dizziness, somnolence, vertigo.
Psychiatric disorders: Insomnia, confusion, depression.
Respiratory, thoracic and mediastinal disorders: Dyspnoea, bronchitis, sinusitis.
Skin and subcutaneous tissue disorders: Rash, pruritus, alopecia, hyperhidrosis.
Vascular disorders: Vasodilation, orthostatic hypotension.
Potentially Fatal: Laryngeal angioedema, arrhythmia. Rarely, cholestatic jaundice progressing to fulminant hepatic necrosis, acute renal failure, anaphylactoid reactions.

PO: D

This drug may cause dizziness and fatigue, if affected, do not drive or operate machinery.

Monitor blood pressure, BUN, serum creatinine, serum electrolytes (e.g. Na, K), and CBC with differential periodically. Assess for signs of skin lesions, photosensitivity and angioedema.

Symptoms: Severe hypotension, electrolyte depletion (e.g. hypokalaemia, hypochloraemia, hyponatremia), and dehydration. Management: Symptomatic and supportive treatment. If hypotension occurs, place patient in supine position and administer IV 0.9% NaCl if necessary.

May potentiate antihypertensive effects with nitrates, vasodilators and diuretics. Barbiturates and narcotics may potentiate orthostatic hypotensive effects. Reduced bioavailability with antacids.
Quinapril: Increased risk of hyperkalaemia with heparin, sulfamethoxazole/trimethoprim, K-sparing diuretics, K supplements or K-containing salts. May reduce the absorption of tetracyclines. Increased risk of angioedema with mammalian target of rapamycin (mTOR) inhibitors (e.g. temsirolimus, sirolimus), neutral endopeptidase (NEP) inhibitors (e.g. racecadotril), and dipeptidyl peptidase-IV (DPP-IV) inhibitors (e.g. vildagliptin). Increased risk of renal function deterioration and diminished antihypertensive effect with NSAIDs including selective COX-2 inhibitors. Increased risk of leucopenia with allopurinol, procainamide, cytostatic and immunosuppressive agents. May enhance hypoglycaemic effect of insulin and oral hypoglycaemics agents.
Hydrochlorothiazide: May increase the risk of lithium toxicity. May decrease arterial response to norepinephrine. May increase response to tubocurarine. NSAIDs may decrease the diuretic, antihypertensive and natriuretic effect of hydrochlorothiazide. Risk of hypokalaemia may be increased when given with drugs that induce torsades de pointes (e.g. digitalis glycosides), corticosteroids and ACTH. Reduced absorption with colestipol and colestyramine.
Potentially Fatal: Quinapril: Increased risk of hypotension, hyperkalaemia, and decreased renal function with aliskiren. Increased risk of angioedema with sacubitril/valsartan.

Orthostatic hypotensive effect may be potentiated by alcohol. Quinapril absorption may be reduced when taken with high fat meal.

Quinapril may cause false-negative aldosterone/renin ratio (ARR). Hydrochlorothiazide may interfere with parathyroid function test and may reduce serum iodine (protein bound) without signs of thyroid disturbance.

Description:
Mechanism of Action: Quinapril and hydrochlorothiazide both decrease blood pressure via different but complementary mechanisms. Diuretics lower blood pressure and volume although it results in increased angiotensin II levels which will be blocked by quinapril, causing additive antihypertensive effect.
Quinapril, a prodrug of quinaprilat, is an ACE inhibitor which prevents conversion of angiotensin I to angiotensin II thereby increasing plasma renin activity and reducing aldosterone secretion.
Hydrochlorothiazide, a thiazide diuretic, inhibits Na reabsorption in the distal tubules resulting to increased excretion of Na, K, Cl, Mg, water and hydrogen ions.
Onset: Quinapril: Antihypertensive: 1 hour.
Hydrochlorothiazide: Diuresis: Approx 2 hours.
Duration: Quinapril: 24 hours. (chronic dosing).
Hydrochlorothiazide: 6-12 hours.
Pharmacokinetics:
Absorption: Quinapril: Absorption may be reduced when taken with high fat meal. Bioavailability: 30-40% (quinaprilat). Time to peak plasma concentration: Approx 1 hour; approx 2 hours (quinaprilat).
Hydrochlorothiazide: Well absorbed from gastrointestinal tract. Bioavailability: 65-75%. Time to peak plasma concentration: Approx 1-5 hours.
Distribution: Quinapril: Enters breast milk (small amounts). Volume of distribution: 1.5 L/kg. Plasma protein binding: 97%; 97% (quinaprilat).
Hydrochlorothiazide: Crosses placenta and enters breast milk (small amounts). Volume of distribution: 3.6-7.8 L/kg. Plasma protein binding: Approx 40-68%.
Metabolism: Quinapril: Rapidly metabolised in the liver via hydrolysis by hepatic esterases to quinaprilat (active form) and to minor inactive metabolites.
Hydrochlorothiazide: Not metabolised.
Excretion: Quinapril: Mainly via urine (50-60% as quinaprilat). Elimination half-life: 0.8 hour; 3 hours (quinaprilat).
Hydrochlorothiazide: Mainly via urine (≥61% as unchanged drug). Elimination half-life: Approx 6-15 hours.

Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 54892, Quinapril. https://pubchem.ncbi.nlm.nih.gov/compound/Quinapril. Accessed Nov. 23, 2023.

Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 3639, Hydrochlorothiazide. https://pubchem.ncbi.nlm.nih.gov/compound/Hydrochlorothiazide. Accessed Oct. 24, 2023.

Store between 20-25°C. Protect from moisture.

ACE Inhibitors/Direct Renin Inhibitors

C09BA06 - quinapril and diuretics ; Belongs to the class of ACE inhibitors in combination with diuretics. Used in the treatment of cardiovascular disease.

Accuretic Tablet, Film-Coated (Parke-Davis Div of Pfizer Inc). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 03/06/2019.

Anon. Hydrochlorothiazide. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 03/06/2019.

Anon. Quinapril and Hydrochlorothiazide. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 03/06/2019.

Anon. Quinapril. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 03/06/2019.

Joint Formulary Committee. Quinapril with Hydrochlorothiazide. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 03/06/2019.

Quinapril/Hydrochlorothiazide 20/12.5 mg Film-Coated Tablets (Milpharm Limited). MHRA. https://products.mhra.gov.uk/. Accessed 03/06/2019.

Quinapril/Hydrochlorothiazide 20/25 mg Film-Coated Tablets (Milpharm Limited). MHRA. https://products.mhra.gov.uk/. Accessed 03/06/2019.