LISINOPRIL AND HYDROCHLOROTHIAZIDE
Clinical safety rating: avoid
NSAIDs may diminish the antihypertensive effect Lithium levels may be increased Risk of angioedema can occur at any time discontinue immediately.
Lisinopril is an ACE inhibitor that prevents 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 diuresis and lowering blood pressure.
| Metabolism | Lisinopril is not metabolized. Hydrochlorothiazide is minimally metabolized. |
| Excretion | Lisinopril: primarily renal (100% unchanged in urine). Hydrochlorothiazide: renal (≥95% unchanged via tubular secretion). |
| Half-life | Lisinopril: terminal half-life 12 hours, effective half-life ~30 hours due to prolonged ACE inhibition. Hydrochlorothiazide: terminal half-life 5.6-14.8 hours (mean 9.6 hours) in patients with normal renal function. |
| Protein binding | Lisinopril: negligible (<10%, no specific binding proteins identified). Hydrochlorothiazide: 40-68%, primarily to albumin. |
| Volume of Distribution | Lisinopril: Vd ~1.3 L/kg (0.9-1.7 L/kg), indicating extensive tissue binding. Hydrochlorothiazide: Vd ~0.8 L/kg (0.5-1.2 L/kg), distributed primarily in extracellular fluid. |
| Bioavailability | Lisinopril: oral bioavailability 25% (range 6-60%), unaffected by food. Hydrochlorothiazide: oral bioavailability 65-75% (mean 70% absolute). |
| Onset of Action | Lisinopril: 1 hour for peak effect, with antihypertensive effect seen within 1-2 hours. Hydrochlorothiazide: diuresis begins within 2 hours, maximal effect at 4-6 hours, antihypertensive effect takes days to weeks. |
| Duration of Action | Lisinopril: antihypertensive effect persists for 24 hours with once-daily dosing. Hydrochlorothiazide: diuretic effect lasts 6-12 hours; antihypertensive effect persists for 24 hours with chronic dosing. |
Initial dose: 10 mg/12.5 mg orally once daily. Titrate based on blood pressure response; maximum 40 mg/25 mg per day.
| Dosage form | TABLET |
| Renal impairment | eGFR ≥30 mL/min: No adjustment. eGFR <30 mL/min: Not recommended. Avoid in severe renal impairment. |
| Liver impairment | Mild to moderate impairment (Child-Pugh A or B): No adjustment. Severe impairment (Child-Pugh C): Not recommended. |
| Pediatric use | Safety and efficacy not established; use not recommended under 18 years. |
| Geriatric use | Start at lower end of dosing (e.g., 10 mg/12.5 mg) due to increased risk of hypotension and electrolyte disturbances. Monitor renal function and electrolytes closely. |
| 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.
| FDA category | Contraindicated |
| Breastfeeding | Lisinopril levels in breast milk are low (M/P ratio unknown); hydrochlorothiazide is excreted in milk (low concentrations). Potential for adverse effects on neonatal renal function and electrolyte balance. Avoid in breastfeeding unless essential; use lowest effective dose if prescribed. |
| Teratogenic Risk |
■ FDA Black Box Warning
WARNING: ACE inhibitors cause fetal harm when used in pregnancy. Discontinue as soon as pregnancy is detected.
| Common Effects | heart failure |
| Serious Effects |
["Hypersensitivity to lisinopril, hydrochlorothiazide, or sulfonamides","History of ACE inhibitor-induced angioedema","Pregnancy","Anuria","Severe renal impairment (CrCl <30 mL/min)"]
| Precautions | ["Angioedema","Hypotension","Renal impairment","Hyperkalemia","Hepatic impairment (thiazides)","Electrolyte imbalance","Acute angle closure glaucoma (thiazides)"] |
Loading safety data…
| First trimester: Exposure associated with increased risk of congenital malformations (cardiac, CNS) per ACE inhibitor class; limited data specific to combination. Second/third trimester: Oligohydramnios, fetal renal dysfunction, skull ossification defects, hypotension, hyperkalemia, and anuria due to fetal renin-angiotensin system depression. Hydrochlorothiazide crosses placenta; may cause fetal/neonatal electrolyte abnormalities and thrombocytopenia. |
| Fetal Monitoring | Baseline and serial renal function, serum electrolytes (potassium, sodium, chloride), blood pressure, urine output. Fetal ultrasound assessment for oligohydramnios, renal anomalies, and growth restriction after second trimester exposure. Neonatal monitoring for hypotension, electrolyte disturbances, and renal function. |
| Fertility Effects | No specific data; ACE inhibitors and thiazides are not known to impair fertility in humans. Animal studies show no significant reproductive toxicity. |