LOSARTAN POTASSIUM AND HYDROCHLOROTHIAZIDE
Clinical safety rating: avoid
NSAIDs may diminish the antihypertensive effect Lithium levels may be increased Use in pregnancy can cause injury and death to the developing fetus.
Losartan is an angiotensin II receptor blocker (ARB) that selectively antagonizes AT1 receptors, blocking vasoconstriction and aldosterone secretion. Hydrochlorothiazide is a thiazide diuretic inhibiting sodium and chloride reabsorption in the distal convoluted tubule, reducing plasma volume and peripheral resistance.
| Metabolism | Losartan is metabolized via CYP2C9 and CYP3A4 to its active metabolite E-3174. Hydrochlorothiazide is not extensively metabolized; eliminated unchanged in urine. |
| Excretion | Losartan: 35% renal, 60% biliary/fecal; Hydrochlorothiazide: >95% renal (tubular secretion). |
| Half-life | Losartan: 2 hours; Active metabolite E-3174: 6-9 hours. Hydrochlorothiazide: 6-15 hours (mean 10 hours) with prolonged elimination in renal impairment. |
| Protein binding | Losartan: 99% (albumin); E-3174: 99% (albumin); Hydrochlorothiazide: 40-68% (albumin). |
| Volume of Distribution | Losartan: 34 L (approx 0.5 L/kg); E-3174: 12 L (approx 0.17 L/kg); Hydrochlorothiazide: 3-6 L/kg (distributes in erythrocytes). |
| Bioavailability | Losartan: 33% (oral); E-3174: formed via CYP2C9 and CYP3A4; Hydrochlorothiazide: 70% (oral) but reduced with food. |
| Onset of Action | Losartan: 1 hour (peak effect 6 hours); Hydrochlorothiazide: 2 hours (diuresis), maximal antihypertensive effect at 4-6 weeks. |
| Duration of Action | Losartan: 24 hours (once-daily dosing); Hydrochlorothiazide: 12-16 hours (diuresis), antihypertensive effect persists 24 hours with chronic therapy. |
Initial: losartan 50 mg/hydrochlorothiazide 12.5 mg orally once daily. Titrate to maximum losartan 100 mg/hydrochlorothiazide 25 mg once daily. Usual maintenance: losartan 50-100 mg/hydrochlorothiazide 12.5-25 mg once daily.
| Dosage form | TABLET |
| Renal impairment | GFR 30-89 mL/min: No adjustment needed. GFR <30 mL/min: Not recommended (thiazide ineffective). Contraindicated in anuria. |
| Liver impairment | Child-Pugh A (mild): initial losartan 25 mg/hydrochlorothiazide 12.5 mg once daily. Child-Pugh B or C: contraindicated (losartan not recommended). |
| Pediatric use | Not recommended for use in pediatric patients (safety and efficacy not established). |
| Geriatric use | Start at lower end of dosing range (losartan 25-50 mg/hydrochlorothiazide 12.5 mg). Monitor renal function and electrolytes; avoid dehydration. |
| 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 Use in pregnancy can cause injury and death to the developing fetus.
| FDA category | Contraindicated |
| Breastfeeding | Hydrochlorothiazide is excreted in breast milk in small amounts; losartan is likely excreted but data are insufficient. M/P ratio not established. Generally not recommended, especially in nursing of preterm or jaundiced infants. Alternative antihypertensives preferred. |
| Teratogenic Risk |
■ FDA Black Box Warning
Fetal toxicity: Drugs acting directly on the renin-angiotensin system can cause injury and death to the developing fetus. Discontinue as soon as possible when pregnancy is detected.
| Common Effects | Nausea Taste change Diarrhea Upset stomach Headache Dizziness Cold extremities Weakness Numbness of extremity Increased uric acid level in blood Increased blood lipid level Decreased magnesium level in blood Slow heart rate Decreased sodium level in blood Decreased blood pressure |
| Serious Effects |
["Anuria","Hypersensitivity to sulfonamide-derived drugs (hydrochlorothiazide)","History of angioedema with ARBs or ACE inhibitors","Concomitant aliskiren in patients with diabetes or renal impairment (eGFR <60 mL/min/1.73m²)","Pregnancy"]
| Precautions | ["Hypotension in volume-depleted patients","Renal function deterioration, especially in renal artery stenosis","Electrolyte imbalances (hypokalemia, hyponatremia, hypomagnesemia) from thiazide","Acute angle-closure glaucoma (sulfonamide reaction)","Exacerbation of systemic lupus erythematosus","Metabolic effects: hyperglycemia, hyperuricemia, dyslipidemia"] |
Loading safety data…
| First trimester: Limited human data; animal studies show adverse effects (fetal renal toxicity, oligohydramnios). Second and third trimesters: Known risk of fetal renal dysfunction, oligohydramnios, skull ossification defects, and neonatal hypotension/anuria; significant risk of fetal and neonatal morbidity and mortality. Avoid use in pregnancy. |
| Fetal Monitoring | Monitor maternal blood pressure, serum potassium, creatinine, and BUN periodically. If inadvertent exposure in later pregnancy, monitor fetal ultrasound for oligohydramnios and fetal wellbeing; serial amniotic fluid index assessment. Neonatal monitoring for hypotension, hyperkalemia, and renal function. |
| Fertility Effects | Losartan: No specific human data; rat studies show no adverse effects on fertility. Hydrochlorothiazide: No known effects on fertility. Combination unlikely to impair fertility. |