OLMESARTAN MEDOXOMIL, AMLODIPINE AND HYDROCHLOROTHIAZIDE
Clinical safety rating: avoid
Contraindicated (not allowed)
Olmesartan medoxomil is an angiotensin II receptor blocker (ARB) that selectively blocks AT1 receptors, inhibiting vasoconstriction and aldosterone secretion. Amlodipine is a dihydropyridine calcium channel blocker that inhibits calcium influx across vascular smooth muscle and cardiac muscle, causing vasodilation. Hydrochlorothiazide is a thiazide diuretic that inhibits sodium reabsorption in the distal convoluted tubule, increasing excretion of sodium and water.
| Metabolism | Olmesartan is metabolized by intestinal wall esterases to the active metabolite olmesartan; negligible CYP450 metabolism. Amlodipine is extensively metabolized in the liver via CYP3A4 to inactive metabolites. Hydrochlorothiazide is not metabolized; eliminated unchanged by the kidney. |
| Excretion | Olmesartan: ~40% excreted in urine (10-20% unchanged, rest as metabolites), ~60% in feces via bile. Amlodipine: ~60% excreted in urine (10% unchanged), 20-25% in feces. Hydrochlorothiazide: >95% excreted unchanged in urine. |
| Half-life | Olmesartan: terminal half-life 10-15 hours; supports once-daily dosing. Amlodipine: terminal half-life 30-50 hours; allows once-daily dosing with steady state reached after 7-8 days. Hydrochlorothiazide: terminal half-life 6-15 hours; prolonged in renal impairment. |
| Protein binding | Olmesartan: >99% bound to albumin. Amlodipine: ~93% bound to albumin. Hydrochlorothiazide: ~68% bound to albumin. |
| Volume of Distribution | Olmesartan: 17-24 L (approx 0.3 L/kg). Amlodipine: 21 L/kg; extensive extravascular distribution. Hydrochlorothiazide: 3-5 L/kg; accumulates in erythrocytes. |
| Bioavailability | Olmesartan: oral bioavailability 26-29%; prodrug olmesartan medoxomil is hydrolyzed to active olmesartan. Amlodipine: oral bioavailability 64-90%. Hydrochlorothiazide: oral bioavailability ~70%. |
| Onset of Action | Olmesartan: 1-2 weeks for maximal antihypertensive effect; single dose onset within 2 hours. Amlodipine: gradual onset, 2-4 hours to peak effect after oral dose. Hydrochlorothiazide: diuretic effect begins within 2 hours, peaks at 4-6 hours after oral administration. |
| Duration of Action | Olmesartan: 24 hours; sustained BP reduction over dosing interval. Amlodipine: 24 hours; consistent antihypertensive effect over 24 hours. Hydrochlorothiazide: diuretic effect lasts 6-12 hours; antihypertensive effect persists >24 hours with chronic dosing. |
| Molecular Weight | Olmesartan medoxomil: 558.59 Da; Amlodipine besylate: 567.1 Da; Hydrochlorothiazide: 297.74 Da |
Oral, one tablet once daily. Initial dose: olmesartan 20 mg/amlodipine 5 mg/hydrochlorothiazide 12.5 mg. Titrate based on response, max dose: olmesartan 40 mg/amlodipine 10 mg/hydrochlorothiazide 25 mg daily.
| Dosage form | TABLET |
| Renal impairment | Contraindicated if GFR <30 mL/min/1.73 m2. For GFR 30-60: use with caution, monitor potassium and creatinine. No dose adjustment for GFR ≥60. |
| Liver impairment | Child-Pugh A: no adjustment. Child-Pugh B: olmesartan and amlodipine not recommended due to limited data; avoid hydrochlorothiazide if ascites. Child-Pugh C: contraindicated. |
| Pediatric use | Safety and efficacy not established in pediatric patients (<18 years). |
| Geriatric use | Start at lowest available dose (olmesartan 20 mg/amlodipine 5 mg/hydrochlorothiazide 12.5 mg). Titrate slowly due to risk of hypotension and electrolyte disturbances. Monitor renal function. |
| 1st trimester | Avoid in first trimester; potential for fetal renal impairment and oligohydramnios associated with angiotensin II receptor antagonists (ARBs). |
| 2nd trimester | Contraindicated in second trimester due to risk of fetal renin-angiotensin system suppression, oligohydramnios, and neonatal hypotension/anuria. |
| 3rd trimester | Contraindicated in third trimester; severe fetal oligohydramnios, neonatal renal failure, and skull ossification defects reported. |
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.
| Placental transfer | Olmesartan crosses placenta (animal studies); amlodipine crosses placenta (human data limited); hydrochlorothiazide crosses placenta and may cause fetal/neonatal electrolyte disturbances. |
| Breastfeeding | Amlodipine and hydrochlorothiazide are excreted into breast milk; olmesartan is poorly excreted. Potential adverse effects on nephron development in neonates due to ARB exposure. Avoid breastfeeding until further data; consider alternative antihypertensives. |
■ FDA Black Box Warning
None.
| Common Effects | Hyperkalemia |
| Serious Effects |
Pregnancy (second and third trimesters)AnuriaHypersensitivity to sulfonamide-derived drugs (hydrochlorothiazide)Concomitant use with aliskiren in patients with diabetes mellitus or renal impairment (GFR <60 mL/min)
| Precautions | Avoid use in pregnancy; can cause fetal harm., Monitor for hypotension, syncope, and electrolyte imbalances., Risk of acute angle-closure glaucoma with hydrochlorothiazide (sulfonamide derivative)., May exacerbate renal impairment; monitor renal function., Exacerbation of angina or myocardial infarction, especially in coronary artery disease patients upon initiation or dose increase of amlodipine., May cause hyperkalemia with olmesartan, especially in renal impairment or with potassium-sparing diuretics. |
| Food/Dietary |
Loading safety data…
| Lactation Rating | L5 (Contraindicated) |
| Teratogenic Risk | First trimester: No clear evidence of major malformations with angiotensin II receptor blockers (ARBs) or calcium channel blockers (CCBs). However, ARBs carry a theoretical risk based on fetal renin-angiotensin system blockade. Hydrochlorothiazide (HCTZ) has been associated with rare adverse effects. Second/third trimesters: ARBs are contraindicated due to fetal renal hypoperfusion, oligohydramnios, anuria, renal failure, skull ossification defects, and neonatal death. CCBs like amlodipine are generally considered lower risk, but limited data. HCTZ may cause electrolyte imbalances, thrombocytopenia, and fetal or neonatal jaundice. Overall, combination is not recommended in pregnancy. |
| Fetal Monitoring | Maternal: Blood pressure, renal function (serum creatinine, BUN), electrolytes (especially potassium, sodium), and uric acid levels. Fetal/neonatal: Ultrasound monitoring for fetal growth, amniotic fluid volume, and renal function after exposure in second/third trimester. Neonates exposed in utero should be monitored for hypotension, oliguria, hyperkalemia, and electrolyte imbalances. |
| Fertility Effects | Olmesartan: No direct evidence of fertility impairment. Amlodipine: No adverse effects on fertility in animal studies. Hydrochlorothiazide: No known effect on fertility. Clinical data insufficient; combination unlikely to cause significant fertility issues. |
| Avoid high-potassium foods (bananas, oranges, spinach, potatoes) if at risk for hyperkalemia. Avoid excessive salt intake. Can be taken with or without food; food may reduce GI upset. |
| Clinical Pearls | Olmesartan/amlodipine/HCTZ is a fixed-dose combination for hypertension not controlled on dual therapy. Amlodipine may cause peripheral edema, especially in combination with HCTZ; dose adjustments may be needed. HCTZ can cause hypokalemia and hyponatremia; monitor electrolytes. Olmesartan carries a rare risk of sprue-like enteropathy (diarrhea, weight loss). Avoid use in pregnancy (ARB/ACEI risk). |
| Patient Advice | Take this medication exactly as prescribed, usually once daily. · Do not use if pregnant or planning pregnancy; use effective contraception. · Avoid salt substitutes containing potassium unless approved by your doctor. · Report symptoms of severe diarrhea or weight loss to your healthcare provider. · Rise slowly from sitting or lying to avoid dizziness from low blood pressure. · Limit alcohol intake as it can increase blood pressure and worsen side effects. · Take in the morning to avoid nighttime urination from the diuretic. |