UNIRETIC
Clinical safety rating: caution
Comprehensive clinical and safety monograph for UNIRETIC (UNIRETIC).
Uniretic is a combination of an angiotensin-converting enzyme (ACE) inhibitor (moexipril) and a thiazide diuretic (hydrochlorothiazide). Moexipril inhibits ACE, preventing conversion of angiotensin I to angiotensin II, reducing vasoconstriction and aldosterone secretion. Hydrochlorothiazide inhibits sodium reabsorption in distal convoluted tubule, increasing excretion of sodium and water.
| Metabolism | Moexipril: Hepatic (ester hydrolysis to active moexiprilat), further glucuronidation; Hydrochlorothiazide: Not metabolized. |
| Excretion | Renal: 50-70% unchanged; biliary/fecal: 10-15% as metabolites |
| Half-life | Terminal elimination half-life 13-17 hours; clinical context: supports once-daily dosing |
| Protein binding | 95% to albumin |
| Volume of Distribution | 4.5 L/kg; indicates extensive extravascular distribution |
| Bioavailability | Oral: 73% |
| Onset of Action | Oral: 1-2 hours for maximal antihypertensive effect; steady-state in 1-2 weeks |
| Duration of Action | 24 hours; clinical note: consistent blood pressure control over 24 hours with single daily dose |
| Molecular Weight | 363.4 |
1-2 tablets (each containing hydrochlorothiazide 25 mg and spironolactone 25 mg) orally once daily. Maximum dose: 4 tablets/day.
| Dosage form | TABLET |
| Renal impairment | GFR 30-60 mL/min: initiate at lowest dose (1 tablet daily) and monitor electrolytes. GFR <30 mL/min: contraindicated due to risk of hyperkalemia and azotemia. |
| Liver impairment | Child-Pugh A: no adjustment needed. Child-Pugh B: use with caution, consider dose reduction to 1 tablet daily. Child-Pugh C: contraindicated. |
| Pediatric use | Safety and efficacy not established; use not recommended in pediatric patients. |
| Geriatric use | Initiate at lowest dose (1 tablet daily); monitor renal function, electrolytes, and orthostatic blood pressure closely. |
| 1st trimester | Contraindicated due to risk of fetal renal impairment and oligohydramnios. |
| 2nd trimester | Contraindicated due to risk of fetal renal impairment and oligohydramnios. |
| 3rd trimester | Contraindicated due to risk of fetal renal impairment, oligohydramnios, and neonatal hypotension. |
Clinical note
Comprehensive clinical and safety monograph for UNIRETIC (UNIRETIC).
| Placental transfer | Crosses the placenta; detectable in fetal blood and amniotic fluid. |
| Breastfeeding | Excreted in human milk; potential for serious adverse reactions in nursing infants; avoid breastfeeding or discontinue drug. |
| Lactation Rating |
■ FDA Black Box Warning
Fetal toxicity: Drugs acting directly on renin-angiotensin system can cause injury and death to developing fetus. Discontinue as soon as pregnancy is detected.
| Serious Effects |
PregnancyHistory of angioedema with ACE inhibitorsBilateral renal artery stenosisHypersensitivity to hydrochlorothiazide or sulfonamides
| Precautions | Fetal toxicity, Hypotension in volume-depleted patients, Renal impairment, Electrolyte imbalances (hyperkalemia, hyponatremia, hypomagnesemia), Acute angle-closure glaucoma (with HCTZ), Sulfonamide allergy (cross-reactivity with HCTZ), Cough, angioedema (ACE inhibitor) |
| Food/Dietary | Avoid high-potassium foods (bananas, oranges, spinach, potatoes) in large amounts due to risk of hyperkalemia from moexipril. Limit sodium intake to enhance antihypertensive effect. Avoid salt substitutes containing potassium chloride. Grapefruit juice may reduce moexipril absorption; separate intake by several hours. |
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| L5 - Contraindicated |
| Teratogenic Risk | UNIRETIC (hydrochlorothiazide and spironolactone) is contraindicated in pregnancy. First trimester: Limited human data; animal studies suggest potential risk based on spironolactone's antiandrogenic effects. Second and third trimesters: Hydrochlorothiazide may cause fetal/neonatal jaundice, thrombocytopenia, and electrolyte disturbances. Spironolactone's antiandrogenic effects may impact male fetal genital development. Use only if potential benefit justifies risk to fetus. |
| Fetal Monitoring | Monitor maternal blood pressure, serum electrolytes (especially potassium, sodium, chloride), renal function (BUN, creatinine), and uric acid levels. Assess for signs of hyperkalemia or hyponatremia. Fetal monitoring includes serial ultrasound for growth and amniotic fluid volume due to diuretic effect. Neonatal monitoring for electrolyte disturbances and jaundice after delivery. |
| Fertility Effects | Spironolactone may cause antiandrogenic effects including menstrual irregularities, gynecomastia in males, and potential reversible impairment of fertility due to hormonal disruption. Hydrochlorothiazide has no known direct effects on fertility. In preclinical studies, spironolactone showed adverse effects on reproductive function. |
| Clinical Pearls | Uniretic is a combination of hydrochlorothiazide (HCTZ) 25 mg and moexipril 7.5 mg or 15 mg. Monitor renal function (BUN, creatinine) and electrolytes especially potassium before and during therapy. Assess for hypotension after the first dose, particularly in patients on diuretics or with heart failure. Use with caution in renal artery stenosis due to risk of acute renal failure. Avoid in pregnancy (ACE inhibitor component; category D in second/third trimester). |
| Patient Advice | Take exactly as prescribed, usually once daily in the morning to avoid nocturnal urination. · Avoid potassium supplements or salt substitutes containing potassium unless advised by your doctor. · Report symptoms of hypotension like dizziness, fainting, or excessive tiredness. · Do not use if you are pregnant or planning to become pregnant; seek immediate medical advice if pregnancy occurs. · May cause dry, persistent cough; notify your physician if this becomes bothersome. · Avoid alcohol and NSAIDs (like ibuprofen) which can increase the risk of hypotension and kidney impairment. |