Ramipril + Hydrochlorothiazide

• Essential Hypertension:
• Treatment of high blood pressure when monotherapy with either ramipril or hydrochlorothiazide is insufficient to achieve adequate control.
• Off-label Uses:
• Occasionally used in managing edema associated with congestive heart failure or chronic kidney disease under specialist guidance.

• Adults:
• Initial dose: Typically 5 mg ramipril / 12.5 mg hydrochlorothiazide once daily.
• Maintenance dose: 5 mg/12.5 mg up to 10 mg/25 mg once daily based on clinical response.
• Maximum dose usually 10 mg ramipril / 25 mg hydrochlorothiazide daily.
• Elderly:
• Start at lower doses due to increased sensitivity; monitor blood pressure and renal function carefully.
• Renal Impairment:
• Use with caution if creatinine clearance is below 30 mL/min; dose adjustments or alternative therapies may be necessary.
• Hepatic Impairment:
• No specific dose adjustment, but monitor closely for adverse effects.
• Route:
• Oral administration, preferably at the same time each day.
• Duration:
• Chronic therapy as prescribed for long-term blood pressure control.

Ramipril is an angiotensin-converting enzyme (ACE) inhibitor that reduces the conversion of angiotensin I to angiotensin II, leading to vasodilation, decreased aldosterone secretion, and reduced sodium and water retention, resulting in lowered blood pressure. Hydrochlorothiazide is a thiazide diuretic that inhibits sodium and chloride reabsorption in the distal convoluted tubules of the kidneys, promoting diuresis and further decreasing plasma volume and blood pressure. The combination provides complementary effects to effectively reduce hypertension.

• Absorption:
• Ramipril is rapidly absorbed, with peak plasma concentrations within 1 hour; converted in the liver to active metabolite ramiprilat.
• Hydrochlorothiazide is well absorbed, reaching peak plasma levels within 1.5 to 5 hours.
• Bioavailability:
• Ramipril: Approximately 28%.
• Hydrochlorothiazide: Approximately 60-70%.
• Distribution:
• Ramiprilat is about 73% bound to plasma proteins.
• Metabolism:
• Ramipril undergoes hepatic metabolism; hydrochlorothiazide is not metabolized.
• Elimination:
• Ramiprilat eliminated mainly via kidneys; half-life 13-17 hours.
• Hydrochlorothiazide excreted unchanged in urine; half-life 6-15 hours.
• Onset of Action:
• Ramipril’s antihypertensive effect starts within one week.
• Hydrochlorothiazide’s diuretic effect begins within 2 hours, lasting up to 12 hours.

• Pregnancy:
• FDA Category D — contraindicated in the second and third trimesters due to fetal toxicity risk including renal failure and death. Discontinue immediately if pregnancy is detected.
• Lactation:
• Both drugs may pass into breast milk; caution advised. Use only if benefits outweigh risks.

• Antihypertensive combination agent
• ACE inhibitor (ramipril)
• Thiazide diuretic (hydrochlorothiazide)

• Known hypersensitivity to ramipril, hydrochlorothiazide, or any formulation components.
• History of angioedema related to ACE inhibitors.
• Anuria or severe renal impairment.
• Pregnancy and breastfeeding (unless benefits outweigh risks).
• Concomitant use with aliskiren in diabetic or renal impairment patients.

• Risk of angioedema: discontinue immediately if swelling of face, lips, tongue, or throat occurs.
• Monitor blood pressure to avoid symptomatic hypotension.
• Monitor serum potassium and renal function periodically.
• Use caution in patients with impaired renal or hepatic function.
• Avoid NSAIDs which may decrease effectiveness and increase renal risk.
• Patients should be advised to report signs of electrolyte imbalance (muscle weakness, cramps).

Common:

• Dizziness, hypotension
• Persistent dry cough (ramipril)
• Electrolyte disturbances: hypokalemia, hyponatremia
• Fatigue, headache
• Increased urination

Serious:

• Angioedema
• Hyperkalemia
• Acute renal failure
• Severe hypotension
• Blood dyscrasias (rare)

• Potassium supplements or potassium-sparing diuretics: increased risk of hyperkalemia.
• NSAIDs: may reduce antihypertensive effect and increase renal toxicity risk.
• Other antihypertensive agents: additive hypotensive effect.
• Lithium: increased lithium toxicity risk.
• Diuretics: may potentiate hypotensive effect.
• Aliskiren: contraindicated with ramipril in certain populations.

• Combination therapy is recommended in patients with inadequate control on monotherapy.
• Emphasis on monitoring for hyperkalemia and renal function during treatment.
• Reinforcement of pregnancy contraindication due to fetal risk.
• Updated guidelines confirm cardiovascular protective benefits with combination therapy.

• Store between 20°C and 25°C (68°F to 77°F).
• Protect from moisture and light.
• Keep in original packaging until use.
• Do not freeze.