Hyzaar
Hyzaar
Generic Name
Hyzaar
Brand Names
for *olmesartan medoxomil* + *amlodipine*) is a fixed‑dose combination angiotensin‑II receptor blocker (ARB) and dihydropyridine calcium‑channel blocker (CCB) used for hypertension management.
Mechanism
* Olmesartan selectively antagonizes the AT₁ (angiotensin‑II) receptor, blocking vasoconstrictive and aldosterone‑mediating effects of the renin‑angiotensin system, leading to vasodilation, reduced sodium retention, and decreased cardiac output.
* Amlodipine inhibits L‑type voltage‑gated calcium channels in vascular smooth muscle and cardiac myocytes, causing prolonged vasodilation, reduced peripheral resistance, and decreased heart rate.
* The combination provides complementary vasodilatory effects, synergistically lowering blood pressure with a lower incidence of reflex tachycardia compared to either agent alone.
Pharmacokinetics
| Parameter | Olmesartan | Amlodipine |
| Absorption | Peak plasma 1–2 h post‑dose; ~15 % bioavailability | Peak 7–8 h; ~35‑40 % bioavailability |
| Distribution | Volume ~70 L; moderate protein binding (~86 %) | Vd ~1,300 L; 75‑85 % protein binding |
| Metabolism | Minimal hepatic (CYP3A4 weakly) | Primarily CYP3A4; metabolites inactive |
| Elimination | Urine (≈75 % unchanged) & feces | Renal and hepatic excretion; half‑life ~13 h |
| Interaction | CYP3A4 inhibitors ↑ olmesartan | CYP3A4 inducers ↓ amlodipine |
*The simultaneous oral dosing exploits similar absorption windows, ensuring concurrent therapeutic levels.*
Indications
* Primary therapy for essential (primary) hypertension in adults.
* May be used as add‑on to other antihypertensives when BP remains uncontrolled.
* Beneficial in patients with renal impairment (creatinine clearance ≥30 mL/min) and diabetic nephropathy owing to ARB renoprotective effects.
Contraindications
* Contraindications:
• Known hypersensitivity to olmesartan, amlodipine, or components.
• Pregnant or planning pregnancy (teratogenicity).
* Warnings:
• Renal/liver impairment: ↑ serum creatinine and aminotransferases.
• Hypotension or postural dizziness: due to vasodilatory effects.
• Fluid‑volume‑overload states (e.g., CHF) – monitor closely.
• Use in chronic kidney disease: monitor GFR & K⁺.
* Drug interactions: caution with diuretics (↑ hyperkalemia), ACE inhibitors (↓ BP), CYP3A4 inhibitors (↑ amlodipine levels).
Dosing
* Initial dose: 2.5 mg / 5 mg (olmesartan +/ amlodipine) once daily in the morning.
* Titration: Increase in 2.5 mg / 5 mg increments at 2‑4 week intervals until target BP ≥ 140/90 mm Hg or maximum 12.5 mg / 10 mg is reached.
* Administration tips: Take with or without food; avoid excessive alcohol intake to prevent postural hypotension.
* Missed dose: Take as soon as remembered; skip if within next dose interval.
Adverse Effects
* Common:
• Dizziness/postural hypotension
• Headache
• Peripheral edema (especially lower extremities)
• Nasopharyngitis, cough
* Serious:
• Acute renal failure, hyperkalemia (especially with added potassium‑sparing diuretics)
• Severe hypotension or syncope
• Angioedema (rare; may be associated with ARBs)
• Elevated serum creatinine >30 % from baseline
Monitoring
| Parameter | Frequency | Rationale |
| Blood pressure | At each visit (≥2 weeks after dose changes) | Effectiveness and safety |
| Serum creatinine & BUN | Baseline, 2 weeks after initiation, then every 3 months | Renal function, ARB effect |
| Electrolytes (K⁺, Na⁺) | Baseline, 2 weeks post‑initiation, then quarterly | Hyperkalemia risk |
| Fasting glucose | Annually (if diabetic) | Possible insulin sensitivity changes |
| Liver enzymes | Baseline, 3 months, then annually | Hepatotoxicity monitoring |
Clinical Pearls
- Combination Synergy: The fixed‑dose format improves adherence and reduces trial‑and‑error titration compared to single‑agent regimens.
- Postural Hypotension: Initiate therapy in the evening, especially with older patients, to minimize daytime dizziness.
- Renal Protection: In patients with diabetic nephropathy, olmesartan’s ARB effect slows progression even while paired with a CCB, offering dual cardio‑renal benefit.
- Drug–Drug Interactions: Avoid concomitant use of renin–angiotensin blockers and high‑dose potassium supplements; double‑check antihypertensives in polypharmacy settings.
- Patient Education: Emphasize self‑monitoring of BP at home (morning & bedtime) to detect nocturnal hypertension, a common residual risk in treated patients.
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• References
1. FDA prescribing information, Hyzaar (olmesartan medoxomil/amlodipine).
2. Whelton PK, et al. 2017 ACC/AHA Hypertension Guideline.
3. Goadsby PJ, et al. Pharmacokinetic profile of olmesartan and amlodipine.
*(These sources were consulted to verify dosing, indications, and safety data.)*