AZILSARTAN MEDOXOMIL
Clinical safety rating
cautionComprehensive clinical and safety monograph for AZILSARTAN MEDOXOMIL (AZILSARTAN MEDOXOMIL).
Angiotensin II receptor blocker (ARB) that selectively inhibits angiotensin II binding to AT1 receptors, reducing vasoconstriction, aldosterone secretion, and sympathetic activity.
| Metabolism | Primarily metabolized by CYP2C9 to inactive metabolites; also undergoes esterase-mediated hydrolysis to azilsartan. |
| Excretion | Biliary/fecal (55% unchanged), renal (42% as inactive metabolites, <1% unchanged) |
| Half-life | Terminal half-life approximately 11 hours; supports once-daily dosing with sustained antihypertensive effect over 24 hours. |
| Protein binding | High (>99%) to serum albumin. |
| Volume of Distribution | Vd of about 16 L (0.23 L/kg for a 70 kg individual); indicates limited extravascular distribution. |
| Bioavailability | Oral bioavailability approximately 60% under fed conditions (food reduces absorption); absolute bioavailability not determined in humans. |
| Onset of Action | Oral: 1-2 hours for peak plasma concentration; antihypertensive effect begins within 2-3 hours. |
| Duration of Action | Duration of antihypertensive effect exceeds 24 hours; steady state achieved by day 7. |
| Molecular Weight | 456.49 |
40 mg orally once daily. May increase to 80 mg once daily if needed.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for GFR ≥15 mL/min/1.73 m². Not recommended for GFR <15 mL/min/1.73 m² due to lack of data. |
| Liver impairment | No dose adjustment required for mild to moderate hepatic impairment (Child-Pugh A and B). Not recommended for severe hepatic impairment (Child-Pugh C) due to lack of data. |
| Pediatric use | Not approved for use in pediatric patients (safety and efficacy not established). |
| Geriatric use | No specific dose adjustment recommended; initiate at 40 mg once daily. Monitor renal function and blood pressure carefully due to increased sensitivity. |
| 1st trimester | Avoid. Teratogenic risk from fetal exposure to angiotensin II receptor antagonists during the first trimester is low but cannot be excluded; alternatives preferred. |
| 2nd trimester | Contraindicated. Associated with fetal renal dysfunction, oligohydramnios, skull ossification defects, and neonatal anuria/hypotension; risk is highest in second and third trimesters. |
| 3rd trimester | Contraindicated. Same risks as second trimester; may cause fetal injury or death. |
Clinical note
Comprehensive clinical and safety monograph for AZILSARTAN MEDOXOMIL (AZILSARTAN MEDOXOMIL).
| Placental transfer | Crosses placenta in animals; human data limited but presumed to cross due to low molecular weight and known fetal toxicity. |
| Breastfeeding | Excretion into human milk is unknown; due to potential for adverse effects on infant kidney function, use during breastfeeding is not recommended. If used, monitor infant for hypotension and renal impairment. |
| Lactation Rating | L4 - Possibly Hazardous |
| Teratogenic Risk | First trimester: Limited human data; animal studies show no teratogenicity. Second and third trimesters: Drugs acting directly on the renin-angiotensin system can cause fetal oligohydramnios, fetal renal dysfunction, skull ossification defects, and neonatal anuria, hypotension, and death. |
| Fetal Monitoring | Monitor fetal growth via ultrasound, assess amniotic fluid volume (oligohydramnios), and fetal renal function. Postnatal monitoring of infant for hypotension and hyperkalemia. |
| Fertility Effects | No human data; animal studies at high doses showed reduced fertility. Effects likely mediated by altered renin-angiotensin system. |
■ FDA Black Box Warning
none
| Serious Effects |
Hypersensitivity to azilsartan medoxomil or any componentHistory of angioedema related to previous ARB therapyConcomitant use with aliskiren in patients with diabetes mellitusPregnancy (second and third trimesters)
| Precautions | Fetal toxicity: avoid use in pregnancy, Hypotension in volume-depleted patients, Renal impairment: monitor renal function, Hyperkalemia: monitor potassium levels |
| Food/Dietary | No significant food interactions; can be taken with or without food. Avoid excessive potassium intake from high-potassium foods (e.g., bananas, oranges, spinach, potatoes) or potassium-containing salt substitutes. Limit alcohol intake as it may increase blood pressure or cause dizziness. |
| Clinical Pearls | Azilsartan medoxomil has the highest affinity for AT1 receptors among ARBs; may cause a rapid decrease in blood pressure in volume-depleted patients; avoid use in pregnancy (Category D); monitor renal function and serum potassium; less CYP450 interaction potential than losartan or irbesartan; can be taken without regard to meals; dose adjustment not required in mild-to-moderate hepatic impairment. |
| Patient Advice | Take once daily at the same time each day with or without food. · Avoid becoming dehydrated; drink adequate fluids unless directed otherwise. · Do not use if pregnant or planning to become pregnant; notify your doctor immediately if pregnancy occurs. · Do not take with aliskiren if you have diabetes or renal impairment. · Report any signs of angioedema (swelling of face, lips, tongue, difficulty breathing) or severe dizziness. · May cause dizziness, especially during first few days; avoid driving until you know how the medication affects you. · Avoid potassium supplements and salt substitutes containing potassium unless approved by your doctor. · Do not stop taking the medication without talking to your doctor. |
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