Telmi 40

Telmi 40 is an angiotensin II receptor antagonist (ARB) used in the management of hypertension. Generally, angiotensin II receptor blockers (ARBs) such as Telmi 40 bind to the angiotensin II type 1 (AT1) receptors with high affinity, causing inhibition of the action of angiotensin II on vascular smooth muscle, ultimately leading to a reduction in arterial blood pressure. Recent studies suggest that Telmi 40 may also have PPAR-gamma agonistic properties that could potentially confer beneficial metabolic effects.

Hypertension

Telmi 40 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.

It may be used alone or in combination with other antihypertensive agents.

Cardiovascular Risk Reduction

Telmi 40 is indicated for reduction of 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 are unable to take ACE inhibitors.

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. Telmi 40 can be used in addition to other needed treatment (such as antihypertensive, antiplatelet or lipid-lowering therapy).

Studies of Telmi 40 in this setting do not exclude the possibility that Telmi 40 may not preserve a meaningful fraction of the effect of the ACE inhibitor to which it was compared. Consider using the ACE inhibitor first, and, if it is stopped for cough only, consider re-trying the ACE inhibitor after the cough resolves.

Use of Telmi 40 with an ACE inhibitor is not recommended.

Telmi 40 is used alone or together with other medicines to treat high blood pressure (hypertension). High blood pressure adds to the workload of the heart and arteries. If it continues for a long time, the heart and arteries may not function properly. This can damage the blood vessels of the brain, heart, and kidneys, resulting in a stroke, heart failure, or kidney failure. Lowering blood pressure can reduce the risk of strokes and heart attacks.

Telmi 40 is also used to lower the risk of heart attacks or stroke in patients 55 years of age and older who have diabetes or heart problems.

Telmi 40 is an angiotensin II receptor blocker (ARB). It works by blocking a substance in the body that causes blood vessels to tighten. As a result, Telmi 40 relaxes the blood vessels. This lowers blood pressure and increases the supply of blood and oxygen to the heart.

Telmi 40 is available only with your doctor's prescription.

Hypertension

Dosage must be individualized. The usual starting dose of Telmi 40 tablets is 40 mg once a day. 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 Telmi 40 is required, a diuretic may be added.

No initial dosage adjustment is necessary for elderly patients or patients with renal impairment, including those on hemodialysis. Patients on dialysis may develop orthostatic hypotension; their blood pressure should be closely monitored.

Telmi 40 tablets may be administered with other antihypertensive agents.

Telmi 40 tablets may be administered with or without food.

Cardiovascular Risk Reduction

The recommended dose of Telmi 40 tablets is 80 mg once a day and can be administered with or without food. It is not known whether doses lower than 80 mg of Telmi 40 are effective in reducing the risk of cardiovascular morbidity and mortality.

When initiating Telmi 40 therapy for cardiovascular risk reduction, monitoring of blood pressure is recommended, and if appropriate, adjustment of medications that lower blood pressure may be necessary.

How supplied

Dosage Forms And Strengths

• 20 mg, white or off-white, round, uncoated tablets imprinted with BI logo on one side and 50 H on the other side
• 40 mg, white or off-white, oblong, uncoated tablets imprinted with BI logo on one side and 51 H on the other side
• 80 mg, white or off-white, oblong, uncoated tablets imprinted with BI logo on one side and 52 H on the other side

Storage And Handling

Telmi 40 is available as white or off-white, uncoated tablets containing Telmi 40 20 mg, 40 mg, or 80 mg. Tablets are marked with the BOEHRINGER INGELHEIM logo on one side, and on the other side, with either 50H, 51H, or 52H for the 20 mg, 40 mg, and 80 mg strengths, respectively. Tablets are provided as follows:

Telmi 40 tablets 20 mg are round and individually blister-sealed in cartons of 30 tablets as 3 x 10 cards (NDC 0597-0039-37).

Telmi 40 tablets 40 mg are oblong shaped and individually blister-sealed in cartons of 30 tablets as 3 x 10 cards (NDC 0597-0040-37).

Telmi 40 tablets 80 mg are oblong shaped and individually blister-sealed in cartons of 30 tablets as 3 x 10 cards (NDC 0597-0041-37).

Storage

Store at 25°C (77°F); excursions permitted to 15°-30°C (59°-86°F). Tablets should not be removed from blisters until immediately before administration.

Distributed by: Boehringer Ingelheim Pharmaceuticals, Inc. Ridgefield, CT 06877 USA. Licensed from: Boehringer Ingelheim International GmbH, Ingelheim, Germany. Revised: December 2014

See also:
What is the most important information I should know about Telmi 40?

Hypersensitivity to Telmi 40 or to any of the excipients of Telmi 40.

Biliary obstructive disorders and severe hepatic impairment.

The concomitant use with aliskiren is contraindicated in patients with diabetes mellitus or renal impairment (GFR <60 mL/min/1.73 m²).

In case of rare hereditary conditions that may be incompatible with an excipient of Telmi 40, the use of Telmi 40 is contraindicated.

Use in pregnancy: The use of angiotensin II receptor antagonists is not recommended during the 1st trimester of pregnancy and should not be initiated during pregnancy.

Nonclinical studies with Telmi 40 do not indicate teratogenic effect, but have shown fetotoxicity.

Angiotensin II receptor antagonist exposure during the 2nd and 3rd trimester is known to induce human fetotoxicity (decreased renal function, oligohydramnios, skull ossification retardation) and neonatal toxicity (renal failure, hypotension, hyperkalemia).

Unless continued and angiotensin II receptor antagonist therapy is considered essential, patients planning pregnancy should be changed to alternative antihypertensive treatments which have an established safety profile for use in pregnancy. When pregnancy is diagnosed, treatment with angiotensin II receptor antagonist should be stopped immediately and if appropriate, alternative therapy should be started.

Should exposure to angiotensin II receptor antagonists have occurred from the 2nd trimester of pregnancy, ultrasound check of renal function and skull is recommended.

Infants whose mothers have taken angiotensin II receptor antagonist should be closely observed for hypotension.

Use in lactation: Telmi 40 is contraindicated during lactation since it is not known whether it is excreted in human milk.

Animal studies have shown excretion of Telmi 40 in breast milk.

Use Telmi 40 as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• An extra patient leaflet is available with Telmi 40. Talk to your pharmacist if you have questions about this information.
• Take Telmi 40 by mouth with or without food.
• Do not remove the tablet from the blister seal until you are ready to take your dose.
• Take Telmi 40 on a regular schedule to get the most benefit from it. Taking Telmi 40 at the same time each day will help you remember to take it.
• Continue to take Telmi 40 even if you feel well. Do not miss any doses.
• If you miss a dose of Telmi 40, take it as soon as possible. If it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not take 2 doses at once.

Ask your health care provider any questions you may have about how to use Telmi 40.

Telmi 40 belongs to a class of medicines known as angiotensin II receptor blockers. It is used to treat high blood pressure, prevention and treatment of heart attack (myocardial Infarction) and heart failure; when heart is unable to pump sufficient blood. It is also used for kidney failure in patients with diabetes.

See also:
What other drugs will affect Telmi 40?

Aliskiren: Do not co-administer aliskiren with Telmi 40 in patients with diabetes. Avoid use of aliskiren with Telmi 40 in patients with renal impairment (GFR < 60 mL/min).

Digoxin: When Telmi 40 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 Telmi 40 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 Telmi 40. 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 Telmi 40, may result in deterioration of renal function, including possible acute renal failure. These effects are usually reversible. Monitor renal function periodically in patients receiving Telmi 40 and NSAID therapy.

The antihypertensive effect of angiotensin II receptor antagonists, including Telmi 40 may be attenuated by NSAIDs including selective COX-2 inhibitors.

Ramipril and Ramiprilat: Co-administration of Telmi 40 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 Telmi 40 decrease by 31% and 16%, respectively. When co-administering Telmi 40 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 Telmi 40. Concomitant use of Telmi 40 and ramipril is not recommended.

Other Drugs: Co-administration of Telmi 40 did not result in a clinically significant interaction with acetaminophen, amlodipine, glyburide, simvastatin, hydrochlorothiazide, warfarin, or ibuprofen. Telmi 40 is not metabolized by the cytochrome P450 system and had no effects in vitro on cytochrome P450 enzymes, except for some inhibition of CYP2C19. Telmi 40 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.

See also:
What are the possible side effects of Telmi 40?

The following adverse reaction is described elsewhere in labeling:

Renal dysfunction upon use with ramipril

  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

Telmi 40 has been evaluated for safety in more than 3700 patients, including 1900 treated for over 6 months and more than 1300 for over one year. Adverse experiences have generally been mild and transient in nature and have infrequently required discontinuation of therapy.

In placebo-controlled trials involving 1041 patients treated with various doses of Telmi 40 (20 to 160 mg) monotherapy for up to 12 weeks, the overall incidence of adverse events was similar to that in patients treated with placebo.

Adverse events occurring at an incidence of ≥1% in patients treated with Telmi 40 and at a greater rate than in patients treated with placebo, irrespective of their causal association, are presented in Table 1.

Table 1 Adverse Events Occurring at an Incidence of ≥1% in Patients Treated with Telmi 40 and at a Greater Rate Than Patients Treated with Placebo

In addition to the adverse events in the table, the following events occurred at a rate of ≥1% but were at least as frequent in the placebo group: influenza-like symptoms, dyspepsia, myalgia, urinary tract infection, abdominal pain, headache, dizziness, pain, fatigue, coughing, hypertension, chest pain, nausea, and peripheral edema. Discontinuation of therapy because of adverse events was required in 2.8% of 1455 patients treated with Telmi 40 tablets and 6.1% of 380 placebo patients in placebo-controlled clinical trials.

The incidence of adverse events was not dose-related and did not correlate with gender, age, or race of patients.

The incidence of cough occurring with Telmi 40 in 6 placebo-controlled trials was identical to that noted for placebo-treated patients (1.6%).

In addition to those listed above, adverse events that occurred in more than 0.3% of 3500 patients treated with Telmi 40 monotherapy in controlled or open trials are listed below. It cannot be determined whether these events were causally related to Telmi 40 tablets:

Autonomic Nervous System: impotence, increased sweating, flushing; Body as a Whole: allergy, fever, leg pain, malaise; Cardiovascular: palpitation, dependent edema, angina pectoris, tachycardia, leg edema, abnormal ECG; CNS: insomnia, somnolence, migraine, vertigo, paresthesia, involuntary muscle contractions, hypoesthesia; Gastrointestinal: flatulence, constipation, gastritis, vomiting, dry mouth, hemorrhoids, gastroenteritis, enteritis, gastroesophageal reflux, toothache, non-specific gastrointestinal disorders; Metabolic: gout, hypercholesterolemia, diabetes mellitus; Musculoskeletal: arthritis, arthralgia, leg cramps; Psychiatric: anxiety, depression, nervousness; Resistance Mechanism: infection, fungal infection, abscess, otitis media; Respiratory: asthma, bronchitis, rhinitis, dyspnea, epistaxis; Skin: dermatitis, rash, eczema, pruritus; Urinary: micturition frequency, cystitis; Vascular: cerebrovascular disorder; and Special Senses: abnormal vision, conjunctivitis, tinnitus, earache.

During initial clinical studies, a single case of angioedema was reported (among a total of 3781 patients treated).

Clinical Laboratory Findings

In placebo-controlled clinical trials, clinically relevant changes in standard laboratory test parameters were rarely associated with administration of Telmi 40 tablets.

Hemoglobin: A greater than 2 g/dL decrease in hemoglobin was observed in 0.8% Telmi 40 patients compared with 0.3% placebo patients. No patients discontinued therapy because of anemia.

Creatinine: A 0.5 mg/dL rise or greater in creatinine was observed in 0.4% Telmi 40 patients compared with 0.3% placebo patients. One Telmi 40-treated patient discontinued therapy because of increases in creatinine and blood urea nitrogen.

Liver Enzymes: Occasional elevations of liver chemistries occurred in patients treated with Telmi 40; all marked elevations occurred at a higher frequency with placebo. No Telmi 40-treated patients discontinued therapy because of abnormal hepatic function.

Cardiovascular Risk Reduction

Because common adverse reactions were well characterized in studies of Telmi 40 in hypertension, only adverse events leading to discontinuation and serious adverse events were recorded in subsequent studies of Telmi 40 for cardiovascular risk reduction. In TRANSCEND (N=5926, 4 years and 8 months of follow-up), discontinuations for adverse events were 8.4% on Telmi 40 and 7.6% on placebo. The only serious adverse events at least 1% more common on Telmi 40 than placebo were intermittent claudication (7% vs 6%) and skin ulcer (3% vs 2%).

  Postmarketing Experience

The following adverse reactions have been identified during post-approval use of Telmi 40. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to estimate reliably their frequency or establish a causal relationship to drug exposure. Decisions to include these reactions in labeling are typically based on one or more of the following factors: (1) seriousness of the reaction, (2) frequency of reporting, or (3) strength of causal connection to Telmi 40.

The most frequent spontaneously reported events include: headache, dizziness, asthenia, coughing, nausea, fatigue, weakness, edema, face edema, lower limb edema, angioneurotic edema, urticaria, hypersensitivity, sweating increased, erythema, chest pain, atrial fibrillation, congestive heart failure, myocardial infarction, blood pressure increased, hypertension aggravated, hypotension (including postural hypotension), hyperkalemia, syncope, dyspepsia, diarrhea, pain, urinary tract infection, erectile dysfunction, back pain, abdominal pain, muscle cramps (including leg cramps), myalgia, bradycardia, eosinophilia, thrombocytopenia, uric acid increased, abnormal hepatic function/liver disorder, renal impairment including acute renal failure, anemia, increased CPK, anaphylactic reaction, tendon pain (including tendonitis, tenosynovitis), drug eruption (toxic skin eruption mostly reported as toxicoderma, rash, and urticaria), hypoglycemia (in diabetic patients), and angioedema (with fatal outcome).

Rare cases of rhabdomyolysis have been reported in patients receiving angiotensin II receptor blockers, including Telmi 40.