IRBESARTAN 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.
Irbesartan is an angiotensin II receptor antagonist that selectively blocks AT1 receptors, inhibiting vasoconstriction and aldosterone secretion. Hydrochlorothiazide is a thiazide diuretic that inhibits sodium and chloride reabsorption in the distal convoluted tubule, reducing plasma volume.
| Metabolism | Irbesartan undergoes hepatic glucuronidation and oxidation via CYP2C9; Hydrochlorothiazide is not metabolized and excreted unchanged in urine. |
| Excretion | Irbesartan: primarily fecal (80%) via biliary excretion, with ~20% renal. Hydrochlorothiazide: primarily renal (≥95% as unchanged drug) via tubular secretion. |
| Half-life | Irbesartan: 11–15 hours terminal half-life; supports once-daily dosing with steady state by 3 days. Hydrochlorothiazide: 6–15 hours terminal half-life; prolonged in renal impairment (up to 20+ hours) requiring dose adjustment. |
| Protein binding | Irbesartan: 90% bound to serum proteins (mainly albumin and α1-acid glycoprotein). Hydrochlorothiazide: 40–68% bound to plasma proteins (primarily albumin). |
| Volume of Distribution | Irbesartan: 53–93 L (0.7–1.1 L/kg) indicating extensive extravascular distribution. Hydrochlorothiazide: 3–5 L/kg (210–350 L) reflecting wide tissue distribution, including placenta and breast milk. |
| Bioavailability | Irbesartan: oral bioavailability 60–80%; food does not affect absorption. Hydrochlorothiazide: oral bioavailability 65–75%; food may reduce absorption slightly. |
| Onset of Action | Irbesartan: 2 hours after oral administration (antihypertensive effect). Hydrochlorothiazide: 2 hours for diuresis; antihypertensive effect may take 3–4 days. |
| Duration of Action | Irbesartan: 24 hours (blood pressure reduction) with once-daily dosing; sustained trough effect. Hydrochlorothiazide: 6–12 hours for diuresis; antihypertensive effect persists 24 hours with chronic use. |
Oral, 150 mg irbesartan/12.5 mg hydrochlorothiazide once daily, titrated to 300 mg irbesartan/25 mg hydrochlorothiazide once daily based on BP response.
| Dosage form | TABLET |
| Renal impairment | Contraindicated if GFR < 30 mL/min. No adjustment for GFR 30-60 mL/min; monitor renal function. Not for use in dialysis. |
| Liver impairment | No adjustment required for mild-moderate hepatic impairment (Child-Pugh A or B). Avoid in severe hepatic impairment (Child-Pugh C) due to hydrochlorothiazide component. |
| Pediatric use | Not recommended for pediatric patients; safety and efficacy not established. |
| Geriatric use | Start at lowest dose (150/12.5 mg once daily); titrate cautiously. Monitor renal function and electrolytes due to age-related decline. |
| 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 | Irbesartan: Excreted into rat milk; no human data. Hydrochlorothiazide: Excreted into human breast milk in small amounts; M/P ratio not determined. Risk of neonatal electrolyte disturbances, jaundice, thrombocytopenia. Generally not recommended during breastfeeding; alternative antihypertensives preferred. |
| Teratogenic Risk |
■ FDA Black Box Warning
None.
| Common Effects | diabetic nephropathy |
| Serious Effects |
["Anuria","Hypersensitivity to sulfonamide-derived drugs (HCTZ)","Concomitant aliskiren in diabetes","Severe renal impairment (CrCl <30 mL/min)"]
| Precautions | ["Fetal toxicity: discontinue if pregnancy detected","Hypotension in volume-depleted patients","Renal impairment: monitor renal function","Electrolyte disturbances: hyponatremia, hypokalemia, hyperkalemia","Acute angle-closure glaucoma (sulfonamide component)","Non-melanoma skin cancer risk (HCTZ)","Systemic lupus erythematosus exacerbation"] |
Loading safety data…
| First trimester: Possible increased risk of congenital malformations, particularly cardiovascular and central nervous system defects, based on limited human data for angiotensin receptor blockers. Second and third trimesters: Fetal toxicity including oligohydramnios, fetal renal dysfunction, skull ossification defects, and neonatal renal failure, hypotension, hyperkalemia. Risks are similar to ACE inhibitors. |
| Fetal Monitoring | Serial fetal ultrasound to assess amniotic fluid volume and fetal renal function; monitor maternal blood pressure and renal function (serum creatinine, potassium); assess for fetal growth restriction. In neonates, monitor for hypotension, oliguria, hyperkalemia. |
| Fertility Effects | No adverse effects on fertility reported in preclinical studies. No human data; theoretical impact via renin-angiotensin system blockade unlikely to impair fertility. |