This combination tablet is indicated for the treatment of mild to moderate hypertension in patients who require combination therapy and have been stabilized on the individual components in the same proportion.

Ramipril: Ramipril is an angiotensin-converting enzyme (ACE) inhibitor. After conversion to its active form ramiprilat, it inhibits the conversion of angiotensin I to angiotensin II, a potent vasoconstrictor. This results in reduced angiotensin II levels, leading to decreased vasoconstriction and reduced aldosterone secretion. Consequently, blood pressure is lowered. Ramipril is also used in heart failure and in reducing the risk of stroke, myocardial infarction, and other cardiovascular events. It is long-acting, well tolerated, and suitable for long-term therapy.

Hydrochlorothiazide: Hydrochlorothiazide is a thiazide diuretic that acts on the renal tubules to inhibit sodium and chloride reabsorption, increasing their excretion in approximately equal amounts. Its diuretic effect reduces plasma volume, which leads to increased plasma renin activity, increased aldosterone secretion, increased potassium loss in urine, and decreased serum potassium levels. Since the renin–aldosterone system is mediated by angiotensin II, co-administration of an ACE inhibitor such as ramipril helps counteract the potassium loss caused by thiazide diuretics.

A patient whose blood pressure is not adequately controlled with Ramipril (or another ACE inhibitor) alone or with Hydrochlorothiazide (or another thiazide diuretic) alone may be switched to this combination therapy. The usual starting dose is one tablet once daily. If necessary, the dose may be increased to two tablets once daily.

Dosage in renal impairment: In patients with a creatinine clearance between 60 and 30 ml/min, treatment should be initiated with Ramipril 1.25 mg monotherapy. If blood pressure is not adequately controlled, the dose of Ramipril may be increased to 2.5 mg. If blood pressure is still not controlled, patient may be switched to one tablet of Ramipril BP 2.5 mg and Hydrochlorothiazide BP 12.5 mg once daily. Dosage may be titrated upward to Ramipril BP 5 mg and Hydrochlorothiazide BP 25 mg until blood pressure is controlled.

Ramipril: Concomitant use with diuretics may cause severe hypotension, and with potassium-sparing diuretics may lead to dangerous hyperkalemia. Co-administration with lithium may increase serum lithium levels. NSAIDs may reduce the antihypertensive effect of ramipril and may worsen renal function.

Hydrochlorothiazide: When used with alcohol, barbiturates, or narcotics, enhanced hypotensive effects may occur. Antidiabetic drugs (oral agents and insulin) may require dose adjustment. Concurrent use with other antihypertensive agents may produce additive or potentiated effects.

This combination is contraindicated in patients with hypersensitivity to ramipril, hydrochlorothiazide, or other thiazide diuretics. It is also contraindicated in patients with hereditary angioedema, severe renal impairment, hemodynamically significant renal artery stenosis (unilateral or bilateral), mitral or aortic stenosis, hypotensive patients, or those with unstable circulatory conditions where a severe fall in blood pressure or renal failure may occur. It is also contraindicated in patients with clinically significant electrolyte disturbances such as hypokalemia, hyponatremia, or hypercalcemia, which may worsen during treatment.

Ramipril: May cause severe hypotension, renal impairment, and persistent dry cough. Other effects include angioedema (sometimes delayed), rash with itching or urticaria, pancreatitis, sinusitis, and rhinitis. Gastrointestinal effects such as nausea, vomiting, dyspepsia, diarrhea, and constipation may occur. Liver dysfunction, cholestatic jaundice, and hepatitis have been reported. Hematological disorders such as thrombocytopenia, leukopenia, neutropenia, and hemolytic anemia may also occur. Other effects include headache, dizziness, fatigue, taste disturbances, bronchospasm, fever, and photosensitivity.

Hydrochlorothiazide: May cause tachycardia, serum sickness-like reactions, weight loss, maculopapular rash, photosensitivity, flushing, and metabolic acidosis.

Pregnancy must be excluded before starting ramipril, and its use should be avoided during pregnancy. Exposure to ACE inhibitors during the second or third trimester is associated with oligohydramnios and neonatal hypotension, anuria, or renal failure. Animal studies suggest reduced uteroplacental perfusion and possible fetal effects. Although teratogenicity has not been consistently shown, ACE inhibitors have demonstrated fetotoxicity in some species. Ramipril is contraindicated during breastfeeding.

Use with caution in patients with renal impairment, hyperkalemia, hypotension, hepatic dysfunction, and those undergoing surgery or anesthesia.

Ramipril: Overdose may cause severe hypotension due to vasodilation and hypovolemia. Treatment includes intravenous infusion of normal saline.

Hydrochlorothiazide: Overdose may result in electrolyte depletion (hypokalemia, hypochloremia) and dehydration due to excessive diuresis. If digitalis is used, hypokalemia may worsen arrhythmias. The effectiveness of hemodialysis in removing hydrochlorothiazide is not well established.

Combined antihypertensive preparations

Store in a cool, dry place, protected from light.