QUINAPRIL HYDROCHLORIDE AND HYDROCHLOROTHIAZIDE
Clinical safety rating: avoid
Contraindicated (not allowed)
Quinapril is an ACE inhibitor that inhibits the conversion of angiotensin I to angiotensin II, reducing vasoconstriction and aldosterone secretion; hydrochlorothiazide is a thiazide diuretic that inhibits sodium reabsorption in the distal convoluted tubule, increasing excretion of sodium and water.
| Metabolism | Quinapril is hydrolyzed to its active metabolite quinaprilat, which is further metabolized by esterases; hydrochlorothiazide is not extensively metabolized and is excreted unchanged in urine. |
| Excretion | Renal excretion of quinaprilat (active metabolite) ~50-60% unchanged; hydrochlorothiazide ~70% unchanged. Biliary/fecal elimination accounts for <10% for both components. |
| Half-life | Quinaprilat terminal half-life ~25 hours (effective half-life ~12 hours); hydrochlorothiazide ~6-15 hours (increased in renal impairment). |
| Protein binding | Quinaprilat: 97% bound (mostly to albumin). Hydrochlorothiazide: ~68% bound (to albumin). |
| Volume of Distribution | Quinaprilat ~0.3 L/kg; hydrochlorothiazide ~3-5 L/kg (distributes into extracellular fluid). |
| Bioavailability | Quinapril: ~60% (hydrolized to active quinaprilat). Bioavailability of HCTZ: ~70%. |
| Onset of Action | Oral: Antihypertensive effect within 1-2 hours. |
| Duration of Action | Once-daily dosing maintains 24-hour blood pressure reduction. Diuretic effect of HCTZ peaks at 4-6 hours and lasts up to 12 hours. |
| Molecular Weight | Quinapril hydrochloride: 474.98 Da; Hydrochlorothiazide: 297.74 Da |
Initial: 10/12.5 mg (quinapril/hydrochlorothiazide) orally once daily. Titrate based on response to a maximum of 40/25 mg once daily.
| Dosage form | TABLET |
| Renal impairment | CrCl >60 mL/min: no adjustment; CrCl 30-60 mL/min: maximum 20/12.5 mg daily; CrCl <30 mL/min: not recommended (use loop diuretics instead). |
| Liver impairment | No adjustment required, but caution in severe hepatic impairment (Child-Pugh C) due to potential risk of hypotension and renal impairment. |
| Pediatric use | Safety and efficacy not established in pediatric patients (<18 years). |
| Geriatric use | Initial dose: 5/12.5 mg orally once daily, titrate slowly due to increased risk of hypotension and renal impairment. |
| 1st trimester | Use is not recommended during the first trimester due to potential risk of fetal renal impairment and oligohydramnios associated with ACE inhibitors, though the absolute risk is low. Hydrochlorothiazide use in first trimester has been associated with conflicting data on congenital malformations. |
| 2nd trimester | Contraindicated in second and third trimesters because of fetal toxicity including oligohydramnios, fetal renal dysfunction, skull hypoplasia, and neonatal hypotension/anuria with ACE inhibitors; hydrochlorothiazide may cause fetal or neonatal jaundice, thrombocytopenia, and electrolyte disturbances. |
| 3rd trimester | Same as second trimester: contraindicated due to risk of fetal and neonatal morbidity and mortality. |
Clinical note
NSAIDs may diminish the antihypertensive effect Lithium levels may be increased Risk of angioedema can occur at any time discontinue immediately.
| Placental transfer | Both quinapril (and its active metabolite quinaprilat) and hydrochlorothiazide cross the placenta. Quinaprilat has been detected in cord blood. Hydrochlorothiazide freely crosses the placenta and distributes into amniotic fluid. |
■ FDA Black Box Warning
No FDA black box warning.
| Common Effects | heart failure |
| Serious Effects |
History of angioedema related to previous ACE inhibitor therapyHereditary or idiopathic angioedemaConcomitant aliskiren in patients with diabetes mellitusAnuria (due to hydrochlorothiazide component)Sulfonamide allergy (hydrochlorothiazide is a sulfonamide derivative)Severe renal impairment (creatinine clearance <30 mL/min) as combination not recommended
| Precautions | Fetal toxicity (oligohydramnios, fetal injury) if used during pregnancy, Angioedema risk (especially in patients with history of angioedema), Hypotension, especially in volume-depleted patients, Renal impairment monitoring, Electrolyte imbalances (hypokalemia, hyponatremia) due to hydrochlorothiazide, Acute angle-closure glaucoma risk with sulfonamide derivatives |
| Food/Dietary |
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| Breastfeeding | Quinapril is excreted into breast milk in low amounts; however, hydrochlorothiazide may suppress lactation and is present in breast milk. Use during breastfeeding is not recommended, especially in premature infants or those with impaired renal function, due to potential adverse effects on electrolyte balance and cardiovascular function. Consider alternative antihypertensives with more safety data. |
| Lactation Rating | L4 - Possibly Hazardous |
| Teratogenic Risk | First trimester: Potential for fetal renal impairment and oligohydramnios, though risk lower than second/third trimester. Second and third trimesters: ACE inhibitor (quinapril) can cause fetal hypotension, renal dysplasia, oligohydramnios, skull ossification defects, and neonatal anuria, hypotension, and hyperkalemia. Hydrochlorothiazide (HCTZ) may cause fetal or neonatal jaundice, thrombocytopenia, and electrolyte disturbances. Both are associated with reduced placental perfusion. Fetal risk is highest from second trimester onward. |
| Fetal Monitoring | Maternal: Blood pressure, serum creatinine, BUN, electrolytes (especially potassium, sodium), complete blood count, uric acid, and urine protein. Fetal: Serial ultrasound for fetal growth, amniotic fluid volume (oligohydramnios detection), and fetal anatomy. Doppler studies if hypertension is severe. Neonatal: Monitor for hypotension, oliguria, hyperkalemia, and electrolyte disturbances. |
| Fertility Effects | No direct adverse effects on fertility reported for either component. However, untreated maternal hypertension may impair placental perfusion and fertility outcomes. ACE inhibitors may rarely cause reversible erectile dysfunction in males. |
| Avoid high-potassium foods (bananas, oranges, tomatoes, salt substitutes) due to risk of hyperkalemia from quinapril. Hydrochlorothiazide may cause electrolyte depletion; encourage adequate intake of potassium-rich foods, but monitor closely. Grapefruit juice may slightly increase quinapril absorption; consistent intake advised. Limit alcohol to avoid orthostatic hypotension. |
| Clinical Pearls | Monitor serum potassium and creatinine within 2 weeks of initiation or dose adjustment. Quinapril may cause cough; switch to ARB if intolerable. Hydrochlorothiazide may exacerbate gout; check uric acid. Avoid use in pregnancy (angioedema risk). Use with caution in renal artery stenosis. Maximum antihypertensive effect may take 4-6 weeks. Do not use with aliskiren in diabetic patients. |
| Patient Advice | Take this medication exactly as prescribed, usually once daily. · Report any persistent cough, swelling of face or throat (angioedema), or difficulty breathing immediately. · Avoid salt substitutes containing potassium unless directed by your doctor. · Drink adequate fluids to prevent dehydration, but avoid excessive intake if you have heart failure. · This drug may cause dizziness; avoid driving until you know how it affects you. · Stay out of direct sunlight or use sunscreen; this medication may increase sun sensitivity. · Do not use during pregnancy; use effective contraception if of childbearing potential. |