Angiotensin II is formed from angiotensin I in a reaction catalyzed by angiotensin-converting enzyme (ACE, kininase II). Angiotensin II is the principal pressor agent of the renin-angiotensin system, with effects that include vasoconstriction, stimulation of synthesis and release of aldosterone, cardiac stimulation, and renal reabsorption of sodium.

Telmisartan blocks the vasoconstrictor and aldosterone-secreting effects of angiotensin II by selectively blocking the binding of angiotensin II to the AT1 receptor in many tissues, such as vascular smooth muscle and the adrenal gland. Its action is therefore independent of the pathways for angiotensin II synthesis.

There is also an AT2 receptor found in many tissues, but AT2 is not known to be associated with cardiovascular homeostasis. Telmisartan has much greater affinity (>3,000 fold) for the AT1 receptor than for the AT2 receptor.

Blockade of the renin-angiotensin system with ACE inhibitors, which inhibit the biosynthesis of angiotensin II from angiotensin I, is widely used in the treatment of hypertension. ACE inhibitors also inhibit the degradation of bradykinin, a reaction also catalyzed by ACE. Because telmisartan does not inhibit ACE (kininase II), it does not affect the response to bradykinin. Whether this difference has clinical relevance is not yet known.

Telmisartan does not bind to or block other hormone receptors or ion channels known to be important in cardiovascular regulation.

Blockade of the angiotensin II receptor inhibits the negative regulatory feedback of angiotensin II on renin secretion, but the resulting increased plasma renin activity and angiotensin II circulating levels do not overcome the effect of telmisartan on blood pressure.

Amlodipine

Amlodipine is a dihydropyridine calcium channel antagonist that inhibits the transmembrane influx of calcium ions into vascular smooth muscle and cardiac muscle.

Amlodipine inhibits calcium ion influx across cell membranes selectively, with a greater effect on vascular smooth muscle cells than on cardiac muscle cells.

Amlodipine is a peripheral arterial vasodilator that acts directly on vascular smooth muscle to cause a reduction in peripheral vascular resistance and reduction in blood pressure. Amlodipine reduces the total peripheral resistance (after-load) against which the heart works and reduces the rate pressure product, and thus myocardial oxygen demand, at any given level of exercise.

For the treatment of essential hypertension in adults only.

Dosage and administration

• Telmisartan and amlodipine tablets is contraindicated in patients who are hypersensitive to any component of this product.

• Second and third trimesters of pregnancy and lactation
• Biliary obstructive disorders
• Severe hepatic impairment
• Severe renal impairment.
• Paediatric use

Telmisartan: The most likely manifestation of overdosage with telmisartan would be hypotension, dizziness and tachycardia; bradycardia could occur from parasympathetic stimulation. If symptomatic hypotension should occur, supportive treatment should be instituted. Telmisartan is not removed by haemodialysis

Amlodipine: Gross overdosage could result in excessive peripheral vasodilatation and possibly reflex tachycardia.

The side effects have been mild and transient in nature and have only infrequently required discontinuation of therapy. The commonly observed side effects are back pain, diarrhoea, pharyngitis, headache, dizziness, pain, fatigue and nausea.

Angiotensin II is formed from angiotensin I in a reaction catalyzed by angiotensin-converting enzyme (ACE, kininase II). Angiotensin II is the principal pressor agent of the renin-angiotensin system, with effects that include vasoconstriction, stimulation of synthesis and release of aldosterone, cardiac stimulation, and renal reabsorption of sodium.

Telmisartan blocks the vasoconstrictor and aldosterone-secreting effects of angiotensin II by selectively blocking the binding of angiotensin II to the AT1 receptor in many tissues, such as vascular smooth muscle and the adrenal gland. Its action is therefore independent of the pathways for angiotensin II synthesis.

There is also an AT2 receptor found in many tissues, but AT2 is not known to be associated with cardiovascular homeostasis. Telmisartan has much greater affinity (>3,000 fold) for the AT1 receptor than for the AT2 receptor.

Blockade of the renin-angiotensin system with ACE inhibitors, which inhibit the biosynthesis of angiotensin II from angiotensin I, is widely used in the treatment of hypertension. ACE inhibitors also inhibit the degradation of bradykinin, a reaction also catalyzed by ACE. Because telmisartan does not inhibit ACE (kininase II), it does not affect the response to bradykinin. Whether this difference has clinical relevance is not yet known.

Telmisartan does not bind to or block other hormone receptors or ion channels known to be important in cardiovascular regulation.

Blockade of the angiotensin II receptor inhibits the negative regulatory feedback of angiotensin II on renin secretion, but the resulting increased plasma renin activity and angiotensin II circulating levels do not overcome the effect of telmisartan on blood pressure.

Hydrochlorothiazide

Hydrochlorothiazide affects the distal renal tubular mechanism of electrolyte reabsorption. At maximal therapeutic dosage all the thiazides are approximately equal in their diuretic efficacy. Hydrochlorothiazide increases the excretion of sodium and chloride in approximately equivalent amounts. Natriuresis may be accompanied by some loss of potassium and bicarbonates.

For the treatment of essential hypertension as second line therapy.

The recommended dose of Telmisartan and Hydrochlorothiazide fixed dose combination is one tablet daily. To minimize dose dependent side effects, it is usually appropriate to begin combination therapy only after the patient has failed to achieve the desired effect with monotherapy.

• Telmisartan and Hydrochlorothiazide tablet is contra indicated in patients who are hypersensitive to any component of this product.
• Pregnancy & lactation.
• Biliary obstructive disorders.
• Severe hepatic impairment.
• Paediatric use.

Telmisartan

The most likely manifestations of overdosage with Telmisartan would be hypotension, dizziness and tachycardia; bradycardia could occur from parasympathetic (vagal) stimulation. If symptomatic hypotension should occur, supportive treatment should be instituted. Telmisartan is not removed by hemodialysis. Suggested measures include induction of emesis and / or gastric lavage. Activated charcoal may be useful in the treatment of over dosage. Serum electrolytes and creatinine should be monitored frequently.

Hydrochlorothiazide

In the event of overdosage, symptomatic and supportive measures should be employed. Emesis should be induced or gastric lavage performed. Correct dehydration, electrolyte imbalance, hepatic coma and hypotension by established procedures. If required, give oxygen or artificial respiration for respiratory impairment.

The most frequently found side effects are back pain, sinusitis, diarrhoea, pharyngitis, upper respiratory tract infection.