Tablet contains a combination of three medicines, Telmisartan, Amlodipine and Chlorthalidone which help to control high blood pressure. Lowering blood pressure helps to reduce your risk of having a heart attack or a stroke in the future. Telmisartan is an angiotensin receptor blocker (ARB). It works by blocking the hormone angiotensin, thereby relaxing the blood vessels. This allows the blood to flow more smoothly and the heart to pump more efficiently. Amlodipine is a calcium channel blocker which inhibit the entry of calcium ion and leads to dilation (widens) of blood vessels and improves blood flow. Amlodipine is indicated for hypertension. Lowering blood pressure prevents cardiovascular diseases such as stroke or heart attack. Chlorthalidone is a thiazide-like diuretic used for the treatment of hypertension and for management of edema caused by conditions such as heart failure or renal impairment. Chlorthalidone improves blood pressure and swelling by preventing water absorption from the kidneys through inhibition of the Na+/Cl− symporter in the distal convoluted tubule cells in the kidney.

Indications and Usage:
● Diabetic Nephropathies
● High Blood Pressure (Hypertension)
● Severe Hypertension
● Moderate Hypertension
● Coronary Artery Disease


Mechanism of Action:
Telmisartan is used to treat hypertension. Lowering high blood pressure helps prevent cardiovascular diseases and renal problems. Telmisartan is categorized as angiotensin receptor blockers (ARBs). It works by dilating blood vessels so that blood can perfuse more easily. Telmisartan blocks angiotensin II receptor that shows high affinity about 3000 times greater for AT1 than AT2. In addition it inhibits RAS, telmisartan acts as a selective modulator of peroxisome proliferator-activated receptor gamma (PPAR-γ), a central regulator of insulin and glucose metabolism. It is also believed that in diabetes and cardiovascular disease (CVD), telmisartan provide protective benefits against the vascular and renal damage caused.  Telmisartan's activity at the peroxisome proliferator-activated receptor delta (PPAR-δ) receptor has prompted speculation around its potential as a sport doping agent as an alternative. Telmisartan activates PPAR-δ receptors in several tissues. Telmisartan also has a PPARγ agonist activity.
Telmisartan is quickly but to varying degrees absorbed from the GIT.
Absolute bioavailability depends on dosage.
Food slightly decreases the bioavailability.
Volume of distribution: 500 L
Protein binding:
Highly bound to plasma protein which is over 99.5%, mainly to albumin and alpha-1-acid glycoprotein.
Binding is not dose-dependent.
Metabolism: Less than 3% of telmisartan is metabolised by glucuronidation in the liver.
Eliminated unchanged in feces via biliary excretion
Minute amounts were found in the urine
Half-life of approximately 24 hours.

Amlodipine is a popular calcium channel blockers categorized as dihydropyridine and is intensively used as antihypertensive. It shows selectivity for the peripheral blood vessels, dihydropyridine calcium channel blockers are associated with a lower incidence of myocardial depression and cardiac conduction abnormalities than other calcium channel blockers. Amlodipine is commonly indicated for high blood pressure and angina. Amlodipine exhibits antioxidant properties and an ability to enhance the production of nitric oxide (NO), an important endogenous vasodilator that decreases blood pressure. It has maximum half-life among DHP and usually requires once daily administration. The contraction of cardiac muscle and vascular smooth muscle are dependent on the movement of extracellular calcium ions into these cells by specific ion channels. Amlodipine blocks influx of calcium ion across cell membranes with selectivity. A stronger effect of amlodipine is exerted on vascular smooth muscle cells than on cardiac muscle cells.
Absorbed slowly and almost completely from the gastrointestinal tract
Peak plasma concentrations are achieved 6-12 hours after oral administration
The estimated bioavailability of amlodipine is 64-90%
Steady-state plasma amlodipine levels are achieved after 7-8 days of consecutive daily dosing
Absorption is not affected by food
Volume of distribution: 21 L/kg
Protein binding: About 98%
Metabolism: Metabolised in liver and converted into inactive metabolites with 10% of the parent compound and 60% of the metabolites found excreted in the urine.
The terminal elimination half-life of about 30–50 hours

Chlorthalidone prevents reabsorption of sodium and chloride through inhibition of the Na+/Cl- symporter in the cortical diluting segment of the ascending limb of the loop of Henle. Reduction of sodium reabsorption subsequently reduces extracellular fluid and plasma volume via an osmotic, sodium-driven diuresis. By increasing the delivery of sodium to the distal renal tubule, Chlorthalidone indirectly increases potassium excretion via the sodium-potassium exchange mechanism. It is thought that increased diuresis results in decreased plasma and extracellular fluid volume which therefore requires decreased cardiac output and overall lowers blood pressure. Chlorthalidone has also been shown to decrease platelet aggregation and vascular permeability, as well as promote angiogenesis in vitro, which is thought to be partly the result of reductions in carbonic anhydrase–dependent pathways. These pathways may play a role in chlorthalidone's cardiovascular risk reduction effects.
Volume of distribution: Chlorthalidone has been shown to rapidly concentrate within erythrocytes and subsequently equilibrate via a slow diffusion back into the serum compartment, resulting in a large volume of distribution
Protein binding: Approximately 75 percent of the drug is bound to plasma proteins, 58 percent of the drug being bound to albumin
Metabolism: Liver
Route of elimination: Approximately 50% of the administered dose is excreted unmetabolized through the kidney, and excretion is characterized by biphasic elimination with a rapid phase followed by a slow secretory phase
Half-life of chlorthalidone is approximately 40-50 hours.

Side Effects
The common side effects of combination are as follows:
● Tiredness or extreme sleepiness
● Stomach pain
● Nausea
● Dizziness.
● Hot or warm feeling in your face (flushing)
● Irregular heart rate (arrhythmia)
● Very fast heart rate (palpitations)
● Diarrhea
● Back pain
● Flu-like symptoms

Do not consume this medication in the following conditions:
● Severe narrowing of the aortic heart valve
● Significantly low blood pressure
● Severe liver disease
● Type 2 diabetes mellitus
● Low amount of sodium in the blood
● High levels of potassium in the blood
● Renal artery stenosis
● Low blood pressure
● Acute kidney failure
● Pregnancy
● Decreased blood volume
● Diarrhea due to intestinal malabsorption

Drug Interaction
Following drugs may interact with this medication:
● Aliskiren 
● Digoxin 
● Lithium
  ● Angiotensin-converting enzyme (ACE) blockers such as benazepril, captopril, enalapril, and fosinopril.
● Angiotensin receptor II blockers such as azilsartan, losartan , olmesartan and valsartan.
● Diuretics such as acetazolamide, amiloride , chlorothiazide and furosemide.
● Aspirin and other NSAIDs (nonsteroidal anti-inflammatory drugs).