AMLODIPINE AND OLMESARTAN MEDOXOMIL
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.
Amlodipine is a dihydropyridine calcium channel blocker that inhibits the transmembrane influx of calcium ions into vascular smooth muscle and cardiac muscle, leading to vasodilation and reduced peripheral vascular resistance. Olmesartan medoxomil is an angiotensin II receptor blocker (ARB) that selectively blocks the binding of angiotensin II to AT1 receptors, resulting in vasodilation and decreased aldosterone secretion.
| Metabolism | Amlodipine: extensively metabolized in the liver via CYP3A4 to inactive metabolites. Olmesartan medoxomil: rapidly de-esterified to active olmesartan in the gastrointestinal tract; olmesartan is metabolized by the liver via CYP2C9 and glucuronidation. |
| Excretion | Amlodipine: ~60% renal (10% unchanged, 50% as metabolites), ~20-25% biliary/fecal. Olmesartan: ~35-50% renal (unchanged), ~50-65% biliary/fecal (unchanged). |
| Half-life | Amlodipine: 30-50 hours (steady-state achieved after 7-8 days; permits once-daily dosing). Olmesartan: 10-15 hours. |
| Protein binding | Amlodipine: ~93-97% (plasma proteins, primarily albumin). Olmesartan: >99% (albumin). |
| Volume of Distribution | Amlodipine: 21 L/kg (large Vd indicates extensive tissue binding). Olmesartan: 17-31 L (approx 0.2-0.4 L/kg; indicates moderate distribution). |
| Bioavailability | Amlodipine: 64-90% oral (high, no significant first-pass). Olmesartan: 26-28% oral (limited by incomplete absorption and first-pass metabolism). |
| Onset of Action | Amlodipine: 30-60 minutes oral. Olmesartan: ~1-2 hours oral. Combined: antihypertensive effect within 2 weeks of therapy. |
| Duration of Action | Amlodipine: 24+ hours (once-daily dosing). Olmesartan: ~24 hours (once-daily dosing). |
| Molecular Weight | Amlodipine: 408.88 Da; Olmesartan medoxomil: 558.59 Da; Combination average molecular weight: 967.47 Da (sum of both) |
Initial: 5 mg/20 mg orally once daily. Titrate after 1-2 weeks. Maximum: 10 mg/40 mg daily.
| Dosage form | TABLET |
| Renal impairment | No adjustment for GFR ≥30 mL/min. Not recommended for GFR <30 mL/min or dialysis. |
| Liver impairment | Child-Pugh A: caution, no specific dose recommendation. Child-Pugh B: 2.5 mg/20 mg initially. Child-Pugh C: contraindicated. |
| Pediatric use | Safety and efficacy not established in patients <18 years. |
| Geriatric use | Elderly (≥65 years): initial 2.5 mg/20 mg daily due to decreased clearance, especially with hepatic impairment or other antihypertensives. |
| 1st trimester | Use is not recommended during the first trimester. Animal studies have shown adverse effects, and there are no adequate human studies. |
| 2nd trimester | Use is not recommended during the second trimester. Drugs acting on the renin-angiotensin system can cause fetal harm, including oligohydramnios and neonatal renal dysfunction. |
| 3rd trimester | Use is contraindicated during the third trimester due to the risk of fetal and neonatal morbidity and death from renin-angiotensin system blockade. |
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 | Both components cross the placenta. Olmesartan is known to cross the placenta in animals and is likely in humans; amlodipine crosses the placenta in humans. |
■ FDA Black Box Warning
Fetal toxicity: Drugs acting directly on the renin-angiotensin system (RAS) can cause injury and death to the developing fetus. Discontinue as soon as possible when pregnancy is detected.
| Common Effects | Hyperkalemia |
| Serious Effects |
Hypersensitivity to amlodipine, olmesartan, or any component of the formulationPregnancy (particularly second and third trimesters)Concomitant use with aliskiren in patients with diabetes mellitus
| Precautions | Avoid use in pregnancy, Avoid concomitant use with aliskiren in patients with diabetes or renal impairment, Symptomatic hypotension, especially in volume- or salt-depleted patients, Monitor renal function and serum potassium, Increased angina or myocardial infarction upon initiation or dose increase |
| Food/Dietary |
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| Breastfeeding | Amlodipine is excreted in human milk in small amounts; olmesartan is excreted in rat milk but unknown in humans. Due to potential for adverse effects in the nursing infant, caution is advised. Alternative agents are preferred, especially when nursing a premature or low-birth-weight infant. |
| Lactation Rating | L3 (Moderately Safe) |
| Teratogenic Risk | First trimester: Based on animal studies, olmesartan medoxomil exposure during organogenesis may increase risk of fetal renal abnormalities, but data in humans are limited. Amlodipine shows no clear teratogenic risk in animal studies. Second and third trimesters: Drugs acting on the renin-angiotensin system (olmesartan) are associated with oligohydramnios, fetal renal dysfunction, skull ossification defects, and neonatal hypotension. Amlodipine may cause fetal hypoxia due to vasodilation. Avoid in second and third trimesters. |
| Fetal Monitoring | Monitor maternal blood pressure, renal function (serum creatinine, BUN), and electrolytes. Fetal monitoring includes ultrasound for amniotic fluid volume, fetal growth, and renal anatomy (especially if olmesartan exposure in second/third trimester). Neonates should be monitored for hypotension, oliguria, and hyperkalemia. |
| Fertility Effects | Amlodipine: No significant effects on human fertility reported. Olmesartan: Animal studies show reduced fertility at high doses; human data lacking. Clinical impact unknown. |
| Avoid grapefruit and grapefruit juice as they may increase amlodipine levels. Avoid high-potassium foods (e.g., bananas, oranges, spinach) and salt substitutes containing potassium if renal impairment or with other potassium-sparing drugs. |
| Clinical Pearls | Avoid in pregnancy (D category); if switching from amlodipine or olmesartan monotherapy, titrate slowly to prevent hypotension; monitor serum potassium and renal function, especially in elderly or volume-depleted patients; combination increases risk of angioedema compared to ACE inhibitors; use with caution in severe aortic stenosis or hypertrophic cardiomyopathy. |
| Patient Advice | Take once daily at the same time each day, with or without food. · Avoid grapefruit or grapefruit juice while taking this medication. · Do not become pregnant; use effective contraception and notify your doctor immediately if pregnancy occurs. · Do not stop abruptly without consulting your doctor; may cause rapid increase in blood pressure. · Report symptoms of excessive hypotension (dizziness, fainting) or angioedema (swelling of face, lips, throat). · Maintain adequate hydration, especially during exercise or hot weather. |