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. |
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 | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
NSAIDs may diminish the antihypertensive effect Lithium levels may be increased Risk of angioedema can occur at any time discontinue immediately.
| Breastfeeding | Quinapril: Minimal excretion into breast milk (M/P ratio not available in literature); consider alternative ACE inhibitors with more data. HCTZ: Excreted in breast milk in low concentrations; may suppress lactation with high doses. M/P ratio for HCTZ is approx 0.5-1.0. Use lowest effective dose if indicated; monitor infant for electrolyte imbalances and hypotension. |
| 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. |
■ FDA Black Box Warning
No FDA black box warning.
| Common Effects | heart failure |
| Serious Effects |
["Pregnancy (especially second and third trimesters)","History of angioedema related to ACE inhibitor therapy","Anuria or hypersensitivity to sulfonamide-derived drugs","Concurrent use with aliskiren in patients with diabetes mellitus or renal impairment (GFR < 60 mL/min)"]
| 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"] |
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| 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. |