MOEXIPRIL HYDROCHLORIDE AND HYDROCHLOROTHIAZIDE
Clinical safety rating: safe
Other antihypertensive drugs can have additive effects Lithium levels may be increased Can cause hypokalemia and hyponatremia.
Moexipril 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 and chloride reabsorption in the distal convoluted tubule, increasing diuresis and reducing plasma volume.
| Metabolism | Moexipril is metabolized primarily via hepatic esterases to its active metabolite, moexiprilat. Hydrochlorothiazide is not significantly metabolized and is excreted unchanged in urine. |
| Excretion | Moexipril is eliminated primarily by renal excretion (about 50% as unchanged drug and metabolites) and biliary/fecal excretion (about 50%). Hydrochlorothiazide is eliminated largely unchanged by renal excretion (≥95% via glomerular filtration and tubular secretion). |
| Half-life | Moexiprilat (active metabolite) terminal half-life is approximately 2–9 hours (mean ~9 hours in hypertension; prolonged in renal impairment). Hydrochlorothiazide terminal half-life is 6–15 hours (mean ~9 hours; prolonged in renal impairment). Clinical context: Twice-daily dosing may be needed for 24-hour BP control; renal impairment requires dose adjustment. |
| Protein binding | Moexipril and moexiprilat: ~73% (primarily to albumin). Hydrochlorothiazide: ~40% (albumin and possibly alpha-1-acid glycoprotein). |
| Volume of Distribution | Moexiprilat: Vd ~180 L (approx. 2.6 L/kg for a 70 kg adult); extensive tissue distribution. Hydrochlorothiazide: Vd ~4.6–9.6 L (approx. 0.1–0.14 L/kg); primarily extracellular fluid and not extensively distributed into tissues. |
| Bioavailability | Moexipril: Absolute oral bioavailability is ~13% (converted to active metabolite moexiprilat; food reduces absorption). Hydrochlorothiazide: Oral bioavailability is ~65–70%. |
| Onset of Action | Moexipril: Onset of antihypertensive effect occurs within 1–2 hours after oral administration. Hydrochlorothiazide: Onset of diuretic effect occurs within 2 hours (peak natriuresis at 4–6 hours). |
| Duration of Action | Moexipril: Antihypertensive effect lasts approximately 24 hours with once-daily dosing, though some patients may require twice-daily dosing for full 24-hour control. Hydrochlorothiazide: Diuretic effect lasts 6–12 hours; antihypertensive effect may persist for up to 24 hours with chronic dosing. |
| Molecular Weight | Moexipril HCl: 498.95 Da; HCTZ: 297.74 Da; combination product reported as 498.95/297.74 |
One tablet (7.5 mg moexipril / 12.5 mg hydrochlorothiazide or 15 mg moexipril / 25 mg hydrochlorothiazide) orally once daily.
| Dosage form | TABLET |
| Renal impairment | GFR 30-60 mL/min: initiate with 3.75 mg/12.5 mg once daily; maximum 15 mg/25 mg daily. GFR <30 mL/min: contraindicated. |
| Liver impairment | Child-Pugh A: no adjustment. Child-Pugh B or C: initiate with 3.75 mg/12.5 mg once daily; use with caution. |
| Pediatric use | Not established; safety and efficacy in pediatric patients not determined. |
| Geriatric use | Initiate at lowest dose (3.75 mg/12.5 mg once daily); monitor renal function and electrolytes. |
| 1st trimester | Contraindicated due to risk of teratogenicity (renal agenesis, oligohydramnios) based on ACE inhibitor class effects; requires careful risk-benefit assessment. |
| 2nd trimester | Contraindicated; associated with fetal toxicity including oligohydramnios, renal dysfunction, skull ossification defects, and hypotension. Avoid use in second trimester. |
| 3rd trimester | Contraindicated; high risk of neonatal hypotension, renal failure, hyperkalemia, and oligohydramnios-related complications. |
Clinical note
Other antihypertensive drugs can have additive effects Lithium levels may be increased Can cause hypokalemia and hyponatremia.
| FDA category | Animal |
| Placental transfer | Moexipril crosses the placenta (animal studies); HCTZ crosses the placenta and is distributed in fetal tissues. Evidence suggests significant transfer, especially in second and third trimesters. |
■ FDA Black Box Warning
Fetal toxicity: Drugs acting directly on the renin-angiotensin system (RAS) can cause injury and death to the developing fetus. Discontinue as soon as pregnancy is detected.
| Common Effects | edema |
| Serious Effects |
AnuriaHypersensitivity to moexipril, HCTZ, or any sulfonamide-derived drugHistory of ACE inhibitor-induced angioedemaHereditary/idiopathic angioedemaConcomitant use with aliskiren in patients with diabetesSevere renal impairment (CrCl <30 mL/min)Pregnancy
| Precautions | Fetal/neonatal morbidity and mortality, Hypotension in salt/volume-depleted patients, Neutropenia/agranulocytosis with ACE inhibitors, Angioedema (including intestinal angioedema), Hepatic failure and cholestatic jaundice, Renal impairment monitoring, Electrolyte disturbances (e.g., hypokalemia, hyponatremia), Sulfonamide hypersensitivity due to hydrochlorothiazide, Acute angle-closure glaucoma (hydrochlorothiazide), Non-melanoma skin cancer risk with hydrochlorothiazide, Systemic lupus erythematosus exacerbation, Cough and taste disturbances |
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| Breastfeeding | Not recommended. Moexipril is excreted in human milk in unknown amounts; HCTZ is present in milk and may suppress lactation. Monitor infant for hypotension, electrolyte imbalance. Use alternative antihypertensive during breastfeeding. |
| Lactation Rating | L4 - Possibly Hazardous |
| Teratogenic Risk | First trimester: ACE inhibitors are associated with increased risk of major congenital malformations, particularly cardiovascular and central nervous system defects. Second and third trimesters: Exposure is associated with oligohydramnios, fetal renal dysfunction, skull ossification defects, hypotension, and anuria. Hydrochlorothiazide: Crosses placenta; risk of electrolyte disturbances, jaundice, and thrombocytopenia in neonate. |
| Fetal Monitoring | Monitor maternal blood pressure, serum electrolytes, renal function, and urinalysis. Fetal ultrasound to assess amniotic fluid volume, fetal growth, and renal anatomy. Neonatal monitoring for hypotension, hyperkalemia, and oliguria. |
| Fertility Effects | No specific human fertility studies. ACE inhibitors may theoretically affect spermatogenesis (based on animal data). Hydrochlorothiazide may cause reversible sexual dysfunction in males. |
| Food/Dietary | Avoid potassium-rich foods (bananas, oranges, spinach, tomatoes) and salt substitutes containing potassium chloride unless monitored due to risk of hyperkalemia from ACE inhibitor component. Limit alcohol intake as it may exacerbate hypotension. Avoid high-sodium foods as they may reduce antihypertensive efficacy. Grapefruit juice may alter moexipril absorption; avoid large quantities. |
| Clinical Pearls | First-dose orthostatic hypotension may occur, especially in volume-depleted patients; consider starting at lower moexipril dose and monitor BP. Combination therapy enhances antihypertensive efficacy but increases risk of electrolyte disturbances; monitor potassium and creatinine. Moexipril is a prodrug activated by hepatic esterases; caution in severe hepatic impairment. Hydrochlorothiazide may cause photosensitivity; advise sun protection. Avoid use in pregnancy (ACE inhibitors fetotoxic) and in anuria or sulfonamide allergy. |
| Patient Advice | Take exactly as prescribed; do not double up if a dose is missed. · Rise slowly from sitting or lying to prevent dizziness. · Monitor blood pressure regularly and keep a log. · Avoid potassium supplements and salt substitutes containing potassium unless approved by your doctor. · Report any signs of infection, angioedema (swelling of face, lips, throat), or unexplained rash. · Stay hydrated but avoid excessive water intake. · Use sunscreen and protective clothing as hydrochlorothiazide increases sun sensitivity. · Do not discontinue abruptly; tapering may be needed under medical supervision. · Inform all healthcare providers that you are taking this combination. · Avoid alcohol which may enhance hypotensive effects. |