AVAPRO
Clinical safety rating: caution
Comprehensive clinical and safety monograph for AVAPRO (AVAPRO).
Angiotensin II receptor antagonist (ARB) that selectively blocks the binding of angiotensin II to the AT1 receptor, leading to vasodilation, reduced aldosterone secretion, and decreased blood pressure.
| Metabolism | Primarily hepatic via glucuronidation and oxidation by CYP2C9. |
| Excretion | Primarily biliary (fecal) and renal tubular secretion; ~60% fecal (including parent and metabolites), ~20% renal (mostly metabolites, <1% unchanged), ~20% recovered in feces as unchanged drug. |
| Half-life | Terminal elimination half-life is 9–13 hours; in patients with renal impairment (CrCl <30 mL/min), half-life is prolonged to ~20 hours; in hepatic impairment, mild increases observed. |
| Protein binding | 90% bound to serum proteins (primarily albumin). |
| Volume of Distribution | ~53 L (0.53 L/kg for a 70 kg adult); indicates extensive distribution into extravascular tissues. |
| Bioavailability | Oral: ~60–70% (with linear kinetics up to 600 mg); high-fat meal reduces Cmax by ~25% but does not significantly affect AUC. |
| Onset of Action | Oral: 1–2 hours (therapeutic effect on blood pressure); once-daily dosing. |
| Duration of Action | 24 hours (once-daily dosing); consistently reduces blood pressure over the entire dosing interval; may be slightly shorter in some patients. |
| Molecular Weight | 428.5 |
150 mg to 300 mg orally once daily.
| Dosage form | TABLET |
| Renal impairment | No adjustment required for GFR ≥30 mL/min. Not recommended for GFR <30 mL/min due to limited data. |
| Liver impairment | No adjustment required for mild to moderate hepatic impairment (Child-Pugh A or B). Not studied in severe impairment (Child-Pugh C); use with caution. |
| Pediatric use | For hypertension in children ≥6 years: 0.7 mg/kg once daily (max 75 mg). Can be titrated up to 1.3 mg/kg (max 150 mg) once daily. |
| Geriatric use | Initiate at 75 mg once daily if elderly with renal impairment or volume depletion; otherwise, start at 150 mg once daily. |
| 1st trimester | Teratogenic risk not definitively established; avoid use if possible due to potential for oligohydramnios and fetal renal dysfunction. |
| 2nd trimester | Associated with oligohydramnios, fetal renal dysfunction, skull ossification defects, and hypotension; contraindicated. |
| 3rd trimester | Same risks as second trimester; use contraindicated. |
Clinical note
Comprehensive clinical and safety monograph for AVAPRO (AVAPRO).
| Placental transfer | Yes; crosses placenta. Fetal exposure demonstrated in animal studies and human case reports. |
| Breastfeeding | Limited data; present in breast milk at low levels. Monitor infant for hypotension, renal impairment, or hyperkalemia. Use with caution, especially in neonates. |
| Lactation Rating |
■ FDA Black Box Warning
When pregnancy is detected, discontinue AVAPRO as soon as possible. Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus.
| Serious Effects |
Pregnancy (especially second and third trimesters)History of angioedema related to previous ACE inhibitor or ARB therapyConcomitant use with aliskiren in patients with diabetes mellitus or renal impairment (eGFR < 60 mL/min/1.73 m²)Bilateral renal artery stenosisHypersensitivity to irbesartan or any component of the formulation
| Precautions | Fetal/neonatal morbidity and mortality, Hypotension in volume-depleted patients, Renal function impairment, especially in patients with bilateral renal artery stenosis, Hyperkalemia, Angioedema (rare) |
| Food/Dietary | No specific food restrictions, but avoid high-potassium foods (e.g., bananas, oranges, spinach) and salt substitutes with potassium, especially in renal impairment. |
Loading safety data…
| L3 (Moderately Safe) |
| Teratogenic Risk | First trimester: Limited human data; risk of fetal renal damage and oligohydramnios based on animal studies and mechanism of action (RAAS blockade). Second and third trimesters: Known fetal toxicity including oligohydramnios, fetal renal dysfunction, skull ossification defects, and neonatal renal failure; contraindicated. |
| Fetal Monitoring | Monitor fetal ultrasound for amniotic fluid volume and renal function; assess maternal blood pressure and renal function (serum creatinine, BUN) regularly. If oligohydramnios detected, consider discontinuation or alternative therapy. |
| Fertility Effects | No human fertility studies; animal studies showed no impairment of fertility at clinically relevant doses. Possible reversible reduction in spermatogenesis based on class effects of ARBs. |
| Clinical Pearls | AVAPRO (irbesartan) is an angiotensin II receptor blocker (ARB) used for hypertension and diabetic nephropathy. Onset of action is 2-4 weeks; dose titration should be gradual. Monitor renal function and serum potassium, especially in patients with renal impairment or on potassium-sparing diuretics/NSAIDs. Avoid in pregnancy (category D). |
| Patient Advice | Take exactly as prescribed, usually once daily. · May take with or without food. · Avoid potassium supplements and salt substitutes containing potassium without consulting your doctor. · May cause dizziness or lightheadedness; avoid driving until you know how it affects you. · Do not stop taking without consulting your doctor. · Inform your doctor if you become pregnant. · Common side effects include dizziness, diarrhea, and fatigue. · Seek medical attention for signs of angioedema (swelling of face, lips, tongue, throat). |