IRBESARTAN 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.
Irbesartan is an angiotensin II receptor antagonist that selectively blocks the binding of angiotensin II to AT1 receptors, inhibiting vasoconstriction and aldosterone secretion. Hydrochlorothiazide is a thiazide diuretic that inhibits the sodium-chloride symporter in the distal convoluted tubule, increasing excretion of sodium and water.
| Metabolism | Irbesartan: primarily metabolized by CYP2C9 (glucuronidation and oxidation). Hydrochlorothiazide: not significantly metabolized; excreted unchanged in urine. |
| Excretion | Irbesartan: primarily biliary (80%) and renal (20%); Hydrochlorothiazide: renal (≥95% as unchanged drug). |
| Half-life | Irbesartan: 11-15 hours; Hydrochlorothiazide: 6-15 hours. Steady state achieved in 3-5 days. |
| Protein binding | Irbesartan: 90-95% (primarily albumin and alpha-1-acid glycoprotein); Hydrochlorothiazide: 40-68% (primarily albumin). |
| Volume of Distribution | Irbesartan: 53-93 L; Hydrochlorothiazide: 3-5 L/kg. Indicates extensive extravascular distribution for irbesartan and predominant extracellular distribution for HCTZ. |
| Bioavailability | Irbesartan: 60-80% (oral); Hydrochlorothiazide: 65-75% (oral). |
| Onset of Action | Irbesartan: 1-2 hours; Hydrochlorothiazide: 2 hours. Antihypertensive effect evident within 1-2 weeks, maximal at 4-6 weeks. |
| Duration of Action | Irbesartan: 24 hours; Hydrochlorothiazide: 6-12 hours. Once-daily dosing provides 24-hour blood pressure control. |
Oral: 1 tablet (irbesartan 150 mg / hydrochlorothiazide 12.5 mg or irbesartan 300 mg / hydrochlorothiazide 12.5 mg or irbesartan 300 mg / hydrochlorothiazide 25 mg) once daily, with or without food. Maximum: irbesartan 300 mg/hydrochlorothiazide 25 mg daily.
| Dosage form | TABLET |
| Renal impairment | GFR ≥30 mL/min: No adjustment. GFR <30 mL/min: Contraindicated due to thiazide ineffectiveness and risk of accumulation. |
| Liver impairment | Child-Pugh A: No dose adjustment. Child-Pugh B or C: Use with caution; hydrochlorothiazide may precipitate hepatic encephalopathy. No specific dose guidelines available; start with lowest dose if necessary. |
| Pediatric use | Not recommended for use in pediatric patients; safety and efficacy not established. |
| Geriatric use | Start at lower end of dosing range (e.g., irbesartan 150 mg/hydrochlorothiazide 12.5 mg daily) due to increased risk of hypotension, electrolyte imbalance, and renal impairment. Monitor blood pressure, electrolytes, and renal function closely. |
| 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 is excreted in rat milk, unknown in humans. Hydrochlorothiazide is excreted in breast milk in low amounts (M/P ratio: 1.0). Limited human data; avoid if possible, especially in neonates, due to potential for electrolyte disturbances and hypotension. Use lowest effective dose if essential. |
| Teratogenic Risk |
■ FDA Black Box Warning
No FDA black box warning.
| Common Effects | diabetic nephropathy |
| Serious Effects |
["Anuria","Hypersensitivity to any component","Concomitant use with aliskiren in patients with diabetes mellitus","Pregnancy (especially second and third trimesters)"]
| Precautions | ["Fetal toxicity (use in pregnancy, especially second and third trimesters, can cause injury and death to developing fetus; discontinue as soon as possible)","Hypotension in volume- or salt-depleted patients","Impaired renal function (monitor serum creatinine and potassium)","Electrolyte and fluid imbalances (hypokalemia, hyponatremia, hypomagnesemia, hypercalcemia, hyperuricemia)","Acute angle-closure glaucoma (with hydrochlorothiazide)","Sulfonamide allergy cross-reactivity (hydrochlorothiazide is a sulfonamide derivative)","Exacerbation or activation of systemic lupus erythematosus (hydrochlorothiazide)"] |
Loading safety data…
| First trimester: Limited data, but increased risk of cardiovascular and CNS defects suggested by ACE inhibitor data. Second and third trimesters: Irbesartan exposure associated with oligohydramnios, fetal renal dysfunction, skull ossification defects, hypotension, hyperkalemia, and death. Hydrochlorothiazide may cause neonatal thrombocytopenia, electrolyte disturbances, and hypoglycemia. |
| Fetal Monitoring | Monitor maternal blood pressure, serum electrolytes (potassium, sodium, chloride, bicarbonate), renal function (creatinine, BUN), and fetal ultrasound for amniotic fluid volume (oligohydramnios) and fetal growth in second and third trimesters. Consider serial fetal monitoring for renal function. |
| Fertility Effects | No specific human data. Animal studies with irbesartan showed no fertility impairment. Thiazides may cause transient impotence in males. Overall, likely minimal effect on fertility. |