Telma 80

Telma 80 which contains Telmisartan 80 mg belonging to the angiotensin II receptor blocker, acts as an antihypertensive agent, and is approved for use in the following clinical indications:

• Hypertension

Telma 80 is indicated for the treatment of hypertension, to lower blood pressure. Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions. These benefits have been seen in controlled trials of antihypertensive drugs from a wide variety of pharmacologic classes including the classes to which this drug principally belongs. There are no controlled trials demonstrating risk reduction with Telma 80.

• Cardiovascular Risk Reduction

Control of high blood pressure should be part of comprehensive cardiovascular risk management, including, as appropriate, lipid control, diabetes management, antithrombotic therapy, smoking cessation, exercise, and limited sodium intake. Many patients will require more than one drug to achieve blood pressure goals.

Telma 80 is indicated for reducing the risk of myocardial infarction, stroke, or death from cardiovascular causes in patients 55 years of age or older at high risk of developing major cardiovascular events who cannot take ACE inhibitors. A high risk for cardiovascular events can be evidenced by a history of coronary artery disease, peripheral arterial disease, stroke, transient ischemic attack, or high-risk diabetes (insulin-dependent or non-insulin-dependent) with evidence of end-organ damage. Telma 80 can be used in addition to other needed treatments (such as antihypertensive, antiplatelet, or lipid-lowering therapy)

• Delay Progression of Chronic Kidney Disease

Telma 80 effectively and safely reduced blood pressure and brought about regression of proteinuria in diabetic and nondiabetic, hypertensive, and proteinuric patients with chronic kidney disease, even in those with mild-to-moderate chronic renal failure.

Although not approved, there have been certain off-label indications. These include:

• ACE inhibitor replacement therapy

For patients who cannot tolerate ACE inhibitors because of the ACE inhibitor-induced chronic, non-productive cough.

Telma 80 which contains Telmisartan 80 mg belonging to the angiotensin II receptor blocker, acts as an antihypertensive agent and is available in the form of tablets.

• Hypertension

The initial dose of Telmisartan tablets is 40 mg once a day. The blood pressure response is dose-related over the range of 20 to 80 mg. Most of the antihypertensive effect is apparent within 2 weeks and maximal reduction is generally attained after 4 weeks. When additional blood pressure reduction beyond that achieved with 80 mg of Telma 80 is required, a diuretic may be added.

Telma 80 tablets may be administered with other antihypertensive agents. It may be administered with or without food.

• Cardiovascular Risk Reduction

The recommended dose of Telma 80 tablets is 80 mg once a day and can be administered with or without food. It is unknown whether doses lower than 80 mg of Telma 80 effectively reduce the risk of cardiovascular morbidity and mortality. When initiating Telma 80 therapy for cardiovascular risk reduction, monitoring of blood pressure is recommended, and if appropriate, adjustment of medications that lower blood pressure may be necessary.

• Hypertension

Avoid foods rich in potassium like bananas, nuts, and sweet potatoes when taking Telma 80, as it may cause hyperkalemia or high blood potassium levels.

The dietary restriction should be individualized as per patient requirements.

• Fetal Toxicity

The 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. The resulting oligohydramnios can be associated with fetal lung hypoplasia and skeletal deformities. Potential neonatal adverse effects include skull hypoplasia, anuria, hypotension, renal failure, and death. When pregnancy is detected, discontinue Telma 80 as soon as possible.

• Hypotension

In patients with an activated renin-angiotensin system, such as volume- or salt-depleted patients (e.g., those being treated with high doses of diuretics), symptomatic hypotension may occur after initiation of therapy with Telma 80. Either correct this condition prior to administration of Telma 80 or start treatment under close medical supervision with a reduced dose. If hypotension does occur, the patient should be placed in the supine position and, if necessary, given an intravenous infusion of normal saline. The transient hypotensive response is not a contraindication to further treatment, which usually can be continued without difficulty once the blood pressure has stabilized.

• Hyperkalemia

Hyperkalemia may occur in patients on ARBs, particularly in patients with advanced renal impairment, heart failure, renal replacement therapy, potassium supplements, potassium-sparing diuretics, potassium-containing salt substitutes, or other drugs that increase potassium levels. Consider periodic determinations of serum electrolytes to detect possible electrolyte imbalances, particularly in patients at risk.

• Impaired Hepatic Function

As the majority of Telma 80 is eliminated by biliary excretion, patients with biliary obstructive disorders or hepatic insufficiency can be expected to have reduced clearance. Initiate Telma 80 at low doses and titrate slowly in these patients.

• Impaired Renal Function

As a consequence of inhibiting the renin-angiotensin-aldosterone system, anticipate changes in renal function in susceptible individuals. In patients whose renal function may depend on the activity of the renin-angiotensin-aldosterone system (e.g., patients with severe congestive heart failure or renal dysfunction), treatment with angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor antagonists has been associated with oliguria and/or progressive azotemia and (rarely) with acute renal failure and/or death.

• Dual Blockade of the Renin-Angiotensin-Aldosterone System

As a consequence of inhibiting the renin-angiotensin-aldosterone system, changes in renal function (including acute renal failure) have been reported. Dual blockade of the renin-angiotensin-aldosterone system (e.g., by adding an ACE inhibitor to an angiotensin II receptor antagonist) should include close monitoring of renal function.

Pregnancy Categories C (first trimester) and D (second and third trimesters)

Telma 80 is an angiotensin II receptor antagonist that should not be initiated during pregnancy as it can lead to fetal harm when administered to pregnant women. When pregnancy is detected, discontinue Telma 80 as soon as possible because Telma 80 can reduce fetal renal function and result in oligohydramnios related to skeletal deformities. Patients planning pregnancy should be considered alternative antihypertensive treatments with an established safety profile for use in pregnancy.

The adverse reactions related to Telma 80 which contains Telmisartan 80 mg belonging to the angiotensin II receptor blocker, acts as an antihypertensive agent and can be categorized as

• Common: Serious adverse reactions include anaphylactic reaction, which causes swelling of the face, throat, tongue, lips, eyes, hands, feet, ankles, or lower legs and angioedema, which may occur rarely, and acute renal failure. Other adverse effects include hoarseness, difficulty breathing or swallowing, pain and cramping in the lower leg that comes and goes during walking or exercise, blistering of the skin, or rash.

• Infrequent adverse effects: Abdominal or stomach pain, back pain, bloating or gas, changes in appetite, increased sweating, diarrhea.

• Rare adverse effects: Changes in vision, dizziness, lightheadedness, or fainting, fast heartbeat, giant hives, painful urination, or changes in urinary frequency

The clinically relevant drug interactions of Telma 80 which contains Telmisartan 80 mg belonging to the angiotensin II receptor blocker, which acts as an antihypertensive agent, are briefly summarized here.

• Digoxin: When Telma 80 was co-administered with digoxin, median increases in digoxin peak plasma concentration (49%) and in trough concentration (20%) were observed. Therefore, monitor digoxin levels when initiating, adjusting, and discontinuing Telma 80 for the purpose of keeping the digoxin level within the therapeutic range.
• Lithium: Reversible increases in serum lithium concentrations and toxicity have been reported during concomitant administration of lithium with angiotensin II receptor antagonists including Telma 80. Therefore, monitor serum lithium levels during concomitant use.
• Non-Steroidal Anti-Inflammatory Agents including Selective Cyclooxygenase-2 Inhibitors (COX-2 Inhibitors): In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, co-administration of NSAIDs, including selective COX-2 inhibitors, with angiotensin II receptor antagonists, including Telma 80, may result in deterioration of renal function, including possible acute renal failure. These effects are usually reversible. Monitor renal function periodically in patients receiving Telma 80 and NSAID therapy. The antihypertensive effect of angiotensin II receptor antagonists, including Telma 80, may be attenuated by NSAIDs including selective COX-2 inhibitors.
• Diuretics: Hyperkalemia may occur with concomitant use of potassium-sparing diuretics and Telma 80, which requires periodic electrolyte monitoring, particularly in patients with increased risk of hyperkalemia—potassium-sparing diuretics such as Amiloride, Eplerenone, Spironolactone, Triamterene.
• Ramipril and Ramiprilat: Co-administration of Telma 80 80 mg once daily and ramipril 10 mg once daily to healthy subjects increases steady-state Cmax and AUC of ramipril 2.3- and 2.1-fold, respectively, and Cmax and AUC of ramiprilat 2.4- and 1.5-fold, respectively. In contrast, Cmax and AUC of Telma 80 decreased by 31% and 16%, respectively. When co-administering Telma 80 and ramipril, the response may be greater because of the possibly additive pharmacodynamic effects of the combined drugs, and also because of the increased exposure to ramipril and ramiprilat in the presence of Telma 80. Concomitant use of TELMA 80 and ramipril is not recommended.
• Other Drugs: Co-administration of Telma 80 did not result in a clinically significant interaction with acetaminophen, amlodipine, glyburide, simvastatin, hydrochlorothiazide, warfarin, or ibuprofen. Telma 80 is not metabolized by the cytochrome P450 system and had no effects in vitro on cytochrome P450 enzymes, except for some inhibition of CYP2C19. Telma 80 is not expected to interact with drugs that inhibit cytochrome P450 enzymes; it is also not expected to interact with drugs metabolized by cytochrome P450 enzymes, except for possible inhibition of the metabolism of drugs metabolized by CYP2C19.

The common side effects of Telma 80 include the following:

Major side effects

• Sinus pain and congestion
• Dizziness
• Stomach pain
• Low blood pressure
• Diarrhea
• Back pain
• Weakness
• Muscle pain
• Fever

Minor side effects

• Change in vision
• Difficulty or painful urination
• Increased heartbeat

The use of the Telma 80 should be prudent in the following group of special populations:

• Paediatric:

Appropriate studies to evaluate the safety and efficacy of Telma 80 have not been performed on the significance of age to the effects of Telma 80 in the pediatric population.

• Geriatric:

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of Telma 80 in the elderly.

• Pregnancy Categories C (first trimester) and D (second and third trimesters):

Telma 80 is an angiotensin II receptor antagonist that should not be initiated during pregnancy as it can lead to fetal harm when administered to pregnant women. When pregnancy is detected, discontinue Telma 80 as soon as possible because Telma 80 can reduce fetal renal function and result in oligohydramnios related to skeletal deformities. Patients planning pregnancy should be considered alternative antihypertensive treatments with an established safety profile for use in pregnancy.

• Nursing Mothers:

It is not known whether Telma 80 is excreted in human milk, but Telma 80 was shown to be present in the milk of lactating rats. 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.

• Hepatic Insufficiency:

Monitor carefully and up-titrate slowly in patients with biliary obstructive disorders or hepatic insufficiency.

Pharmacodynamics:

Telma 80 is an orally active nonpeptide angiotensin II antagonist that acts on the AT₁ receptor subtype. It has the highest affinity for the AT₁ receptor among commercially available ARBS and has minimal affinity for the AT₂ receptor. Telma 80 may also have PPARγ agonistic properties that could potentially confer beneficial metabolic effects, as PPARγ is a nuclear receptor that regulates specific gene transcription, and whose target genes are involved in the regulation of glucose and lipid metabolism, as well as anti-inflammatory responses. This observation is currently being explored in clinical trials. Angiotensin II is formed from angiotensin I in a reaction catalyzed by an 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. Telma 80 works by blocking the vasoconstrictor and aldosterone secretory effects of angiotensin II.

Pharmacokinetics:

• Absorption: After oral administration, peak concentrations of Telma 80 are reached in 0.5-1 hour after dosing. The bioavailability of Telma 80 is decreased with food, with a reduction in plasma concentration-time curve of about 6% with the 40 mgtablet. The absolute bioavailability of Telma 80 is dose dependent. At doses of 40 and 160 mg, the bioavailability was 42% and 58%, respectively. The pharmacokinetics of orally administered Telma 80 is nonlinear over the dose range of 20-160 mg, with more than proportional increases of plasma concentrations (Cmax and AUC) with increasing doses. Telma 80 shows a half-life of approximately 24 hours. The plasma concentrations of Telma 80 with once-daily dosing show about 10-25% of peak plasma concentrations. Telma 80 has an accumulation index in plasma which is repeated once-daily dosing.
• Distribution: There is high binding to plasma proteins, mainly including albumin and α1 - acid glycoprotein. Telma 80's distribution volume is approximately 500 liters, indicating additional tissue binding.
• Metabolism: Telma 80 is metabolized by the process of conjugation to form a pharmacologically inactive acyl glucuronide, the glucuronide of the parent compound and the only metabolite with been identified in human plasma and urine. The isoenzymes cytochrome P450 is not involved in the metabolism of Telma 80. The total plasma clearance of Telma 80 is >800 mL/min, irrespective of the dose.

• Elimination: After either intravenous or oral administration of 14C-labeled Telma 80, the majority of the administered dose is eliminated unchanged in feces through biliary excretion, and only minute amounts were found in the urine.