Mitosan Plus tablet is indicated for the treatment of hypertension, to lower blood pressure. Mitosan Plus can be used alone or with other antihypertensive agents. Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions.

Telmisartan: 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 aldosteronesecreting 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.

Telmisartan does not inhibit ACE (kininase II) nor does it 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 is a thiazide diuretic. Thiazides affect the renal tubular mechanisms of electrolyte reabsorption, directly increasing excretion of sodium salt 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 coadministration of an ARB tends to reverse the potassium loss associated with these diuretics. The mechanism of the antihypertensive effect of thiazides is not fully understood.

Initiate a patient whose blood pressure is not adequately controlled with-

• Telmisartan monotherapy 80 mg: Telmisartan and Hydrochlorothiazide 80 mg/12.5 mg once daily. Dose can be titrated up to 160 mg/25 mg after 2 to 4 weeks, if necessary.
• Hydrochlorothiazide 25 mg once daily, or is controlled but who experiences hypokalemia with this regimen: Telmisartan and Hydrochlorothiazide 80 mg/12.5 mg once daily. Dose can be titrated up to 160 mg/25 mg after 2 to 4 weeks, if necessary.

Telmisartan and Hydrochlorothiazide may be administered with other antihypertensive drugs.

Caution should be exercised before taking Mitosan Plus if you are taking aliskiren, digoxin, lithium, other medicines for high blood pressure, NSAIDs (such as aspirin, ibuprofen, naproxen, others), corticosteroids (such as prednisone, hydrocortisone, others), angiotensin-converting enzyme (ACE) blockers (such as benazepril, enalapril, lisinopril) angiotensin II receptor blockers (such as losartan, olmesartan, valsartan). Mitosan Plus may interfere with certain laboratory tests (including parathyroid test, protein-bound iodide test), possibly causing false test results.

This is contraindicated in patients with known hypersensitivity (e.g., anaphylaxis or angioedema) to Telmisartan, Hydrochlorothiazide or any other component of this product. Do not co-administer Aliskiren with this tablet in patients with Diabetes.

Common side effects include dizziness, drowsiness, tired feeling, flushing (warmth, redness, or tingly feeling), back pain, nausea, diarrhea, stomach pain. Other adverse events include allergy, fever, leg pain, chest pain, insomnia, somnolence, and dry mouth, elevations of liver enzymes or serum bilirubin, leg cramps, myalgia, dermatitis. Other adverse events that have been reported includes weakness, gastric irritation, photosensitivity, urticaria, muscle spasm, restlessness.

Pregnancy Category D. Use of drugs that act on the renin-angiotensin system during the second and third trimesters of pregnancy reduces fetal renal function and increases fetal and neonatal morbidity and death. Resulting oligohydramnios can be associated with fetal lung hypoplasia and skeletal deformations. Potential neonatal adverse effects include skull hypoplasia, anuria, hypotension, renal failure, and death. When pregnancy is detected, discontinue Telmisartan and hydrochlorothiazide as soon as possible.

Nursing Mothers: It is not known whether telmisartan is excreted in human milk, but telmisartan was shown to be present in the milk of lactating rats. Thiazides appear in human milk. Because of the potential for adverse effects on the nursing infant, decide whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.

Before using this medication, tell your doctor about your medical history, especially of kidney disease, liver disease, bile duct blockage, loss of too much body water and/or minerals (dehydration), untreated mineral imbalance (such as low or high potassium), gout, lupus. If you have diabetes, this medication may affect your blood sugar. Check your blood sugar regularly as directed by your doctor. Mitosan Plus may affect your body potassium levels. Before using potassium supplements or salt substitutes that contain potassium, consult your doctor. Mitosan Plus may make you dizzy. Do not drive, use machinery, or do anything that needs alertness until you can do it safely. Report prolonged diarrhea or vomiting to your doctor. Be sure to drink enough fluids to prevent dehydration unless your doctor directs you otherwise.

Pediatric Use: Safety and effectiveness of Telmisartan and Hydrochlorothiazide in pediatric patients have not been established.

Geriatric Use: In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal or cardiac function and of concomitant diseases or other drug therapy.

Use in Patients with Hepatic Impairment: Patients with biliary obstructive disorders or hepatic insufficiency should initiate treatment under close medical supervision.

Use in Patients with Renal Impairment: Safety and effectiveness of Telmisartan and Hydrochlorothiazide in patients with severe renal impairment (Cr.Cl. <30 ml/min) have not been established. In patients with severe renal impairment, Telmisartan and Hydrochlorothiazide tablets are not recommended. No dose adjustment is required in patients with mild (Cr.Cl. 60 to 90 ml/min) or moderate (Cr.Cl. 30 to 60 ml/min) renal impairment.

The most likely manifestations of overdosage are hypertension, dizziness, tachycardia, bradycardia, hypokalemia, hypochloremia, hyponatremia and dehydration etc. Telmisartan is not removed by hemodialysis and the degree to which hydrochlorothiazide is removed by hemodialysis has not been established.

Combined antihypertensive preparations

Keep out of the reach of children. Keep in a cool and dry place. Protect from light.