OLMESARTAN MEDOXOMIL, AMLODIPINE AND HYDROCHLOROTHIAZIDE

Clinical safety rating: avoid

Contraindicated (not allowed)

How it works

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.

What the body does with it

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.

Classification & Brands

Dosing & administration

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.

Use during pregnancy

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.

Breastfeeding

Olmesartan: Limited data; not recommended due to potential renal effects in neonates. Amlodipine: Excreted in breast milk in low concentrations; estimated relative infant dose ~3-4%; M/P ratio ~1.0; considered compatible with caution. Hydrochlorothiazide: Excreted in breast milk; may suppress lactation and cause electrolyte abnormalities in infant; caution advised. Combination: Use only if benefit outweighs risk; monitor infant for hypotension, electrolyte disturbances.

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.

Warnings & precautions

■ FDA Black Box Warning

None.

Side Effect Profile

Common Effects	Hyperkalemia
Serious Effects

Absolute Contraindications

["Anuria","Hypersensitivity to any component (including sulfonamide-derived drugs for hydrochlorothiazide)","Concomitant use with aliskiren in patients with diabetes"]

Clinical Precautions

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."]

Clinical Tips & Counseling

Drug interactions

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