Diabetic nephropathy, Heart failure, Hypertension
Combined antihypertensive preparations
Valsartan is an oral medication that belongs to a class of drugs called angiotensin receptor blockers (ARBs). It is orally active and specific angiotensin II antagonist acting on the AT1 subtype. Angiotensin's attachment to the receptors cause the blood vessels to narrow (vasoconstrict) which leads to an increase in blood pressure (hypertension). Valsartan blocks the angiotensin II receptor. By blocking the action of angiotensin, Valsartan dilates blood vessels and reduces blood pressure without affecting pulse rate. Valsartan has much greater affinity (about 20,000-fold) for the AT1 receptor than for the AT2 receptor. It does not bind or block other hormone receptors or ion channels known to be important in cardiovascular regulation.
Hydrochlorothiazide is a thiazide diuretic. Thiazides affect the renal tubular mechanisms of electrolyte reabsorption, directly increasing excretion of sodium and chloride in approximately equivalent amounts. Indirectly, the diuretic action of Hydrochlorothiazide reduces plasma volume, with consequent increases in plasma renin activity, increases in aldosterone secretion, increases in urinary potassium loss, and decreases in serum potassium. The renin-aldosterone link is mediated by angiotensin II, so co-administration of anangiotensin converting enzyme (ACE) inhibitor tends to reverse the potassium loss associated with these diuretics.
Per combination tablet contains valsartan/ hydrochlorothiazide: 80/12.5 mg; 160/12.5 mg; 160/25 mg; 320/12.5 mg; 320/25 mg: Initially, 80/12.5 mg once daily, titrate dose gradually according to response, up to 320/25 mg.
Valsartan:
Diuretics: Patient on diuretics may occasionally experience excessive reduction in blood pressure after initiation of therapy with Valsartan. No drug interaction of clinical significance has been identified with thiazide diuretics.
Agents increasing Serum Potassium: Since Valsartan decreases the production of aldosterone, potassium supplements or salt containing potassium substitutes may lead to hyperkalemia.
Lithium Salts: As with other drugs which eliminate sodium, lithium clearance may be reduced. Therefore, serum lithium levels should be monitored carefully if lithium salts are to be administered.
Other drugs showing interaction are Warfarin, Digoxin.
Hydrochlorothiazide:
When administered concurrently, the following drugs may interact with thiazide diuretics: alcohol, barbiturates, or narcotics may potentiate antihypertensive effect or orthostatic hypotension may occur.
Antidiabetic drugs (oral agents and insulin): dosage adjustment of the antidiabetic drug may be required.
Other antihypertensive drugs give additive effect.
Cholestyramine and colestipol resins: absorption of Hydrochlorothiazide is impaired in the presence of anionic exchange resins.
Hypersensitivity to valsartan, hydrochlorothiazide or sulphonamides. Severe hepatic impairment, creatinine clearance <30ml/min, anuria, cirrhosis, biliary obstruction, conditions where there is increased potassium loss (e.g. salt losing nephropathies and pre-renal impairment of kidney function), refractory hypokalaemia, hyponatraemia, hypercalcaemia, hyperuricaemia, history of gout and uric acid stones, untreated Addison's disease. Pregnancy and lactation. DM, postsympathectomy patients. May exacerbate SLE. Monitor serum potassium regularly. Observe for signs of fluid or electrolyte imbalance. Discontinue before testing for parathyroid function. May affect ability to drive or operate machinery. Elderly.
Headache, asthenia, fatigue, dizziness, somnolence, insomnia, orthostatic hypotension, paraesthesia, nasopharyngitis, tachycardia, palpitations, tinnitus, vertigo, dyspepsia, diarrhoea, flatulence, dry mouth, nausea, vomiting, abdominal pain, peripheral oedema, pyrexia, increased BUN, elevated LFT, anxiety, erectile dysfunction, glucose intolerance, increased serum cholesterol, triglycerides, uric acid. Electrolyte imbalances e.g. hypomagnesaemia, hypercalcaemia, hyponatraemia, hypochloraemic alkalosis.
Category D: There is positive evidence of human fetal risk, but the benefits from use in pregnant women may be acceptable despite the risk (e.g., if the drug is needed in a life-threatening situation or for a serious disease for which safer drugs cannot be used or are ineffective).
Valsartan: Limited data are available related to overdosage in humans. The most likely manifestations of overdosage would be hypotension and tachycardia; bradycardia could occur from parasympathetic (vagal) stimulation. If excessive hypotension occurs, the patient should be placed in the supine position and if necessary, has to be given an intravenous infusion of normal saline.
Hydrochlorothiazide: The most common signs and symptoms observed are those caused by electrolyte depletion (hypokalemia, hypochloremia, and dehydration) resulting from excessive diuresis. if digitalis has also been administered with it, hypokalemia, may accentuate cardiac arrhythmias. The degree to which Hydrochlorothiazide is removed by hemodialysis has not been established.
.png&w=384&q=75)