Generic Name

Hydrochlorothiazide

Mechanism

• Hydrochlorothiazide: Thiazide diuretic that blocks the sodium‑chloride co‑transporter in the distal convoluted tubule. This inhibition → increased sodium excretion → osmotic diuresis → volume depletion and vasodilation.
• Olmesartan: Angiotensin II receptor blocker that competitively inhibits the AT1 receptor on vascular smooth muscle and juxtaglomerular cells. This blocks vasoconstriction, aldosterone secretion, and renin release, resulting in vasodilation and reduced sodium retention.

The dual action lowers intravascular volume and sympathetic tone, enhancing mean arterial pressure reduction beyond either agent alone.

Pharmacokinetics

Combination tablets allow dose‑specific bioequivalence to the single components.

Indications

• Primary hypertension: first‑line or adjunctive therapy when BP is inadequately controlled
• Hypertensive emergency when rapid, oral BP reduction is feasible (with caution)
• Heart failure with preserved ejection fraction – volume control and neurohumoral inhibition
• Chronic edema secondary to renal, hepatic, or cardiac disease (HCTZ component)
• Combination therapy for stage 1–2 hypertension when monotherapy insufficient

Combination therapy is FDA‑approved for hypertension and is widely used in clinical practice guidelines for initial treatment of uncomplicated hypertension.

Contraindications

• Contraindications
• Allergy to sulfonamides (HCTZ) or ARB
• Severe renal impairment or bilateral renal artery stenosis (HCTZ)
• Hyperkalemia or impaired renal potassium excretion (olmesartan)
• Pregnancy (category D for HCTZ; ARBs are teratogenic)
• Lactation (avoid while on HCTZ)
• Warnings
• Gout: HCTZ may precipitate attacks by raising uric acid.
• Hyponatremia and hypokalemia: monitor electrolytes, especially with diuretic therapy.
• Renal dysfunction: dose adjustment or monitoring required.
• Liver disease: caution; no need for dose reduction but follow renal function.
• Glucose intolerance: both agents may modestly worsen glycemic control.

Dosing

• Take in the morning with or without food.
• Hold dose if serum potassium >5.5 mmol/L or serum creatinine rises >30 % from baseline.

Combination tablet: 12.5 mg HCTZ + 20 mg olmesartan (12.5/20) or 25 mg HCTZ + 40 mg olmesartan (25/40).

Monitoring

• Blood pressure: home or clinic readings, aim ≤ 140/90 mmHg.
• Serum electrolytes: K⁺, Na⁺, Cl⁻, bicarbonate at baseline, 1–2 weeks, then monthly.
• Renal function: creatinine, eGFR baseline, 1–2 weeks, then every 3–6 months.
• Serum glucose: fasting glucose or HbA₁c baseline, every 3–6 months if diabetic.
• Serum uric acid: monitor if prone to gout.
• Clinical signs: swelling, dizziness, skin lesions, changes in urine output.

Clinical Pearls

• Start low, go slow: In elderly or renal‑impaired patients, begin with 12.5 mg HCTZ + 20 mg olmesartan and titrate cautiously.
• Potassium support: Consider potassium‑sparing agents (amiloride) or potassium supplements if hypokalemia persists despite dose adjustment.
• Gout prevention: Low‑dose HCTZ (12.5 mg) with a urate‑lowering agent can be used in patients with prior gout flares.
• Combination advantage: The fixed‑dose combination improves medication adherence by ~25 % compared to separate capsules.
• Avoid second‑generation thiazides: Hydrochlorothiazide retains better safety profile and clearer evidence for cardiovascular outcomes.
• Pregnancy check‑in: A thorough pregnancy test before initiating therapy; discontinue immediately if pregnancy confirmed.
• Dosing schedule: Morning dosing reduces nocturia associated with HCTZ and improves adherence.
• Lipids and weight: Monitor, as diuretics may increase triglycerides; advise a low‑salt, low‑fat diet to mitigate weight gain.

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• References: UpToDate®, KDIGO Hypertension Guideline (2023), NICE Guideline NG23, FDA prescribing information (2024).