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. |
| Molecular Weight | Losartan (potassium salt) 461.0 Da; Hydrochlorothiazide 297.74 Da; combination product: weighted composite not applicable. |
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 | Contraindicated due to risk of fetal renal dysfunction and oligohydramnios from angiotensin II receptor blocker component; thiazide may cause fetal electrolyte disturbances. Use alternatives. |
| 2nd trimester | Contraindicated. Losartan carries risk of fetal renal toxicity, oligohydramnios, and skull ossification defects. Hydrochlorothiazide may cause adverse fetal effects including jaundice and thrombocytopenia. |
| 3rd trimester | Contraindicated due to increased risk of fetal/neonatal morbidity, including oligohydramnios, renal failure, and hypotension from losartan; hydrochlorothiazide may cause neonatal electrolyte imbalance and thrombocytopenia. |
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 |
| Placental transfer | Hydrochlorothiazide crosses placenta readily; losartan is expected to cross due to molecular size. Evidence: detectable in cord blood and amniotic fluid. |
■ 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 |
Pregnancy (2nd and 3rd trimesters)AnuriaHistory of hypersensitivity to sulfonamide-derived drugs (hydrochlorothiazide)Concomitant aliskiren in patients with diabetes mellitusSevere renal impairment (CrCl <30 mL/min)
| 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 |
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| Breastfeeding | Both components are excreted in human milk. Hydrochlorothiazide may suppress lactation and cause neonatal electrolyte disturbances. Losartan exposure is low but theoretical risk of renal effects. Avoid breastfeeding during therapy; if unavoidable, monitor infant for hypotension, dehydration, and electrolyte imbalances. |
| Lactation Rating | L4 (Possibly Hazardous) |
| Teratogenic Risk | 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. |
| Food/Dietary | Avoid high-potassium foods (bananas, oranges, spinach, avocados, tomatoes) in large quantities unless directed; limit alcohol intake as it may exacerbate hypotension and electrolyte disturbances. |
| Clinical Pearls | Monitor serum potassium within 1-2 weeks after initiation or dose adjustment; avoid use in patients with anuria or hypersensitivity to sulfonamide-derived drugs; combine cautiously with NSAIDs as they may reduce antihypertensive effect and worsen renal function; losartan's half-life supports once-daily dosing, but hydrochlorothiazide's duration of action may necessitate split dosing in some patients for optimal 24-hour BP control. |
| Patient Advice | Take this medication exactly as prescribed, usually once daily with or without food. · Avoid salt substitutes or potassium supplements without consulting your doctor, as this drug contains a potassium-sparing component. · Report symptoms of electrolyte imbalance: muscle cramps, weakness, irregular heartbeat, excessive thirst, or confusion. · May cause dizziness or lightheadedness; rise slowly from sitting or lying position. · Use sunscreen and protective clothing as hydrochlorothiazide can increase sun sensitivity. |