Imidapril HCl, hydrochlorothiazide.
Each tablet contains imidapril HCl 10 mg and hydrochlorothiazide 12.5 mg.
Pharmacology: Imidapril and hydrochlorothiazide (HCTZ) are used together in a once-daily oral preparation to manage hypertension. Imidapril is an angiotensin-converting enzyme (ACE) inhibitor while hydrochlorothiazide is a thiazide diuretic. The effects of both drugs on blood pressure are additive. Greater antihypertensive efficacy is generally achieved by adding a small dose of a thiazide diuretic eg, hydrochlorothiazide to the ACE inhibitor. Imidapril lowers blood pressure by ACE inhibition and consequent reduction in angiotensin II, resulting in dilatation of peripheral vessels and reduction in vascular resistance. Hydrochlorothiazide, on the other hand, lowers blood pressure by increasing the renal excretion of sodium.
Imidapril is an ester prodrug that is hydrolyzed after absorption to imidaprilat, the active metabolite. Imidaprilat has potent ACE inhibitory effects, 1.2 and 2.6 times that of enalaprilat and captopril, respectively.
The hypotensive effect of imidapril is mainly due to ACE inhibition and consequent reduction in angiotensin II, resulting in dilatation of peripheral vessels and reduction in vascular resistance. The hypotensive effect of imidapril is comparable to enalapril and 5-10 times more potent than that of captopril.
Imidapril decreases total peripheral vascular resistance without increase in heart rate or cardiac contractility. Imidapril increases renal blood flow and reduces renal vascular resistance mainly due to dilatation of the efferent arteriole. Imidapril showed no specific effect on the CNS, digestive, respiratory, smooth muscle, reproductive, urologic, hematologic and metabolic systems.
Hydrochlorothiazide: Thiazide diuretics increase the excretion of water by inhibiting the reabsorption of sodium and chloride ions at the distal renal tubule. The natriuretic effects are accompanied by a secondary loss of potassium and bicarbonate which can cause a mild hypokalemic and hypochloremic alkalosis. Thiazides also decrease the elimination of calcium and uric acid. Thiazide diuretics usually do not affect normal blood pressure. When chronically administered, thiazide diuretics decrease peripheral vascular resistance. The exact mechanism responsible for lowered peripheral resistance is not known. However, excretion of urinary sodium by the kidneys is required to achieve blood pressure reduction. Initially, diuretics lower blood pressure by decreasing cardiac output, plasma volume and extracellular fluid volume. Cardiac output eventually returns to normal, plasma and extracellular fluid values return slightly less than normal, but peripheral vascular resistance is reduced, resulting in lower blood pressure.
Pharmacokinetics: Imidapril: About 25-40% of imidapril is absorbed following single oral administration of imidapril HCl 10 mg in healthy subjects.
Imidapril HCl is metabolized to 4 metabolites in addition to unchanged imidapril HCl. Only the dicarboxylic acid form (imidaprilat) is pharmacologically active among the 4 metabolites.
Imidapril reached peak plasma concentration in about 2 hrs and was eliminated from the plasma with a t½ of about 2 hrs. Imidaprilat, the active metabolite of imidapril, reached peak plasma concentration (about 15 ng/mL) 6-8 hrs after administration, and was gradually eliminated from the plasma with a t½ of about 8 hrs.
Imidapril and imidaprilat were shown to be about 85% and 51% protein-bound, respectively.
Hydrochlorothiazide: Hydrochlorothiazide is variably absorbed from the gastrointestinal tract depending on the formulation and dose. The systemic bioavailability is approximately 50-60%. After oral administration of hydrochlorothiazide, diuresis begins within 2 hrs, peaks in about 4 hrs and lasts about 6-12 hrs. The duration of action ranges from 6-12 hrs. The drug crosses the placenta, and is distributed in breast milk. However, it does not cross the blood-brain barrier.
Hydrochlorothiazide is not metabolized but is eliminated rapidly as unchanged drug in the urine. At least 61% of the oral dose is eliminated unchanged within 24 hrs. The elimination t½ of hydrochlorothiazide was originally reported to range from 5.6-14.8 hrs when plasma levels were followed for at least 24 hrs. A more recent study reports a mean elimination t½ of 2.5 hrs in patients with normal renal function. The elimination t½ is estimated to increase 12-20 hrs in patients with severe renal disease (eg, CrCl <10 mL/min).
Treatment of hypertension.
Initial Dose: 1 tab once daily. Vascoride is not intended as first-line therapy. It should be initiated in hypertensive patients whose blood pressure is not controlled (>140/90 mmHg) with single-dose antihypertensive treatment.
Adjust dosage based on clinical response.
Known hypersensitivity to any of the components of Vascoride. Sulfonamide hypersensitivity or thiazide diuretic hypersensitivity because of the risk of cross-sensitivity.
History of angioneurotic edema.
Renal failure and anuria since thiazide diuretics are considered ineffective when the CrCl <30 mL/min.
Use in pregnancy: When used in pregnancy during the 2nd and 3rd trimesters, drugs that act directly on the renin-angiotensin system can cause injury and even death to the developing fetus. Discontinue imidapril-hydrochlorothiazide as soon as possible when pregnancy is detected.
Use with caution in patients with the following conditions:
Sodium depletion or hypovolemia, and those undergoing dialysis, major surgery or during anesthesia since severe hypotension may occur.
Renal disease, especially among elderly patients. Old age and impaired renal function may decrease the urinary excretion of imidapril and its metabolites. Hydrochlorothiazide may also decrease glomerular filtration rate and may precipitate azotemia in these patients.
Unilateral or bilateral artery stenosis since increase in BUN and serum creatinine may occur.
Renal dysfunction that is critically dependent on the activity of the renin-angiotensin-aldosterone system (RAS) (eg, patients with heart failure) since angiotensin-II receptor antagonists affect the RAS system and have caused increases in serum creatinine and renal failure in susceptible individuals.
Hepatic disease since minor alterations of fluid and electrolyte balance may precipitate hepatic coma.
Gout or hyperuricemia since thiazide diuretics eg, hydrochlorothiazide have been reported to reduce the clearance of uric acid.
History of pancreatitis since thiazide diuretics have been reported to cause pancreatitis.
Imidapril HCl is well tolerated. The most common adverse reactions were cough, dizziness, hypotension, headache, strange sensation of pharynx, and rash.
Adverse reactions reported with hydrochlorothiazide use include weakness, hypotension, pancreatitis, jaundice, diarrhea, vomiting, nausea, thrombocytopenia, urticaria, rash, electrolyte imbalance, hyperglycemia, hyperuricemia, vertigo, headache, renal dysfunction, alopecia, impotence.
Imidapril and hydrochlorothiazide may reduce renal clearance of lithium and increase risk of lithium toxicity.
Concomitant administration of imidapril with potassium-sparing diuretics (eg, amiloride, spironolactone, or triamterene), potassium supplements, or potassium-sparing salt substitutes may lead to hyperkalemia.
Indomethacin and other NSAIDs can reduce the antihypertensive effect of imidapril as well as the diuretic, natriuretic and antihypertensive effects of hydrochlorothiazide in some patients.
C09BA - ACE inhibitors and diuretics ; Used in the treatment of cardiovascular diseases.