Telmisartan: uses, appearance and warnings

Telmisartanis an angiotensin II receptor blocker (ARB) indicated for: Treatment of hypertension to lower blood pressure. Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions(1.1) 1.1 Hypertension Telmisartan 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 class to which this drug principally belongs. 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. For specific advice on goals and management, see published guidelines, such as those of the National High Blood Pressure Education Program’s Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC). Numerous antihypertensive drugs, from a variety of pharmacologic classes and with different mechanisms of action, have been shown in randomized controlled trials to reduce cardiovascular morbidity and mortality, and it can be concluded that it is blood pressure reduction, and not some other pharmacologic property of the drugs, that is largely responsible for those benefits. The largest and most consistent cardiovascular outcome benefit has been a reduction in the risk of stroke, but reductions in myocardial infarction and cardiovascular mortality also have been seen regularly. Elevated systolic or diastolic pressure causes increased cardiovascular risk, and the absolute risk increase per mmHg is greater at higher blood pressures, so that even modest reductions of severe hypertension can provide substantial benefit. Relative risk reduction from blood pressure reduction is similar across populations with varying absolute risk, so the absolute benefit is greater in patients who are at higher risk independent of their hypertension (for example, patients with diabetes or hyperlipidemia), and such patients would be expected to benefit from more aggressive treatment to a lower blood pressure goal. Some antihypertensive drugs have smaller blood pressure effects (as monotherapy) in black patients, and many antihypertensive drugs have additional approved indications and effects (e.g., on angina, heart failure, or diabetic kidney disease). These considerations may guide selection of therapy. Telmisartan may be used alone or in combination with other antihypertensive agents [see Clinical Studies (14.1)] .

• 20 mg, white to off-white color, round, flat, beveled edge, uncoated tablets debossed with ‘L202’ on one side and plain on other side. • 40 mg, white to off-white color, oval shape, biconvex, uncoated tablets debossed with ‘L203’ on one side and plain on other side. • 80 mg, white to off-white color, oval shape, biconvex, uncoated tablets debossed with ‘L204’ on one side and plain on other side. Tablets: 20 mg, 40 mg, 80 mg (3)

Telmisartan Tablets, USP are supplied as below: 20 mg, white to off-white color, round, flat, beveled edge, uncoated tablets debossed with ‘L202’ on one side and plain on other side. NDC 46708-608-30 bottle of 30 units with child-resistant closure NDC 46708-608-91 bottle of 1000 units 40 mg, white to off-white color, oval shape, biconvex, uncoated tablets debossed with ‘L203’ on one side and plain on other side. NDC 46708-609-30 bottle of 30 units with child-resistant closure NDC 46708-609-91 bottle of 1000 units 80 mg, white to off-white color, oval shape, biconvex, uncoated tablets debossed with ‘L204’ on one side and plain on other side. NDC 46708-610-30 bottle of 30 units with child-resistant closure NDC 46708-610-91 bottle of 1000 units Storage Store at 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature]. Tablets should not be removed from bottles until immediately before administration.

Telmisartan is contraindicated in patients with known hypersensitivity (e.g., anaphylaxis or angioedema) to telmisartan or any other component of this product [see Adverse Reactions (6.2)] . Do not co-administer aliskiren with telmisartan in patients with diabetes [see Drug Interactions (7)]. Known hypersensitivity (e.g., anaphylaxis or angioedema)to telmisartan or any other component of this product (4) Do not co-administer aliskiren with telmisartan in patients with diabetes (4)

Avoid fetal or neonatal exposure (5.1) Hypotension: Correct any volume or salt depletion before initiating therapy. Observe for signs and symptoms of hypotension (5.2) Monitor carefully in patients with impaired hepatic (5.4) or renal function (5.5) Avoid concomitant use of an ACE inhibitor and angiotensin receptor blocker (5.6) 5.1 Fetal Toxicity 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 as soon as possible [see Use in Specific Populations (8.1)]. 5.2 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 telmisartan. Either correct this condition prior to administration of telmisartan, 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. A transient hypotensive response is not a contraindication to further treatment, which usually can be continued without difficulty once the blood pressure has stabilized. 5.3 Hyperkalemia Hyperkalemia may occur in patients on ARBs, particularly in patients with advanced renal impairment, heart failure, on renal replacement therapy, or on 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. 5.4 Impaired Hepatic Function As the majority of telmisartan is eliminated by biliary excretion, patients with biliary obstructive disorders or hepatic insufficiency can be expected to have reduced clearance. Initiate telmisartan at low doses and titrate slowly in these patients [see Use in Specific Populations (8.6) and Clinical Pharmacology (12.3)] . 5.5 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. Similar results have been reported with telmisartan [see Clinical Pharmacology (12.3)] . In studies of ACE inhibitors in patients with unilateral or bilateral renal artery stenosis, increases in serum creatinine or blood urea nitrogen were observed. There has been no long-term use of telmisartan in patients with unilateral or bilateral renal artery stenosis, but anticipate an effect similar to that seen with ACE inhibitors. 5.6 Dual Blockade of the Renin-Angiotensin-Aldosterone System (RAS) Dual blockade of the RAS with angiotensin-receptor blockers, ACE inhibitors, or aliskiren is associated with increased risks of hypotension, hyperkalemia, and changes in renal function (including acute renal failure) compared to monotherapy. The ONTARGET trial enrolled 25,620 patients ≥55 years old with atherosclerotic disease or diabetes with end-organ damage, randomizing them to telmisartan only, ramipril only, or the combination, and followed them for a median of 56 months. Patients receiving the combination of telmisartan and ramipril did not obtain any additional benefit compared to monotherapy, but experienced an increased incidence of renal dysfunction (e.g., acute renal failure) compared with groups receiving telmisartan alone or ramipril alone. In most patients no benefit has been associated with using two RAS inhibitors concomitantly. In general, avoid combined use of RAS inhibitors. Closely monitor blood pressure, renal function, and electrolytes in patients on telmisartan and other agents that affect the RAS. Do not co-administer aliskiren with telmisartan in patients with diabetes. Avoid concomitant use of aliskiren with telmisartan in patients with renal impairment (GFR <60 mL/min/1.73 m 2 ).

The following adverse reaction is described elsewhere in labeling: • Renal dysfunction upon use with ramipril [see Warnings and Precautions (5.6)] Hypertension: The most common adverse events (≥1%) reported in hypertension trials are back pain, sinusitis, and diarrhea (6.1) To report SUSPECTED ADVERSE REACTIONS, contact FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical studies are conducted under widely varying conditions, adverse reactions rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in practice. Hypertension Telmisartanhas been evaluated for safety in more than 3700 patients, including 1900 treated for over 6 months and more than 1300 for over one year. …

Aliskiren: Do not co-administer aliskiren with telmisartan in patients with diabetes. Avoid use of aliskiren with telmisartan in patients with renal impairment (GFR <60 ml/min). Digoxin : When telmisartan 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 telmisartan 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 telmisartan. Therefore, monitor serum lithium levels during concomitant use. …