Ctd-T

A benzenesulfonamide-phthalimidine that tautomerizes to a benzophenones form. It is considered a thiazide-like diuretic. [PubChem]

Telmisartan (Ctd-T) is an angiotensin II receptor antagonist (ARB) used in the management of hypertension. Generally, angiotensin II receptor blockers (ARBs) such as Telmisartan (Ctd-T) 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 Telmisartan (Ctd-T) may also have PPAR-gamma agonistic properties that could potentially confer beneficial metabolic effects.

Treatment of arterial hypertension, essential or nephrogenic or isolated systolic. Treatment of stable, chronic heart failure of mild to moderate degree (New York Heart Association, NYHA: functional class II or III).

Oedema of specific origin

• Ascites due to cirrhosis of the liver in stable patients under close control.

• Oedema due to nephrotic syndrome.

Diabetes Insipidus.

Hypertension

Telmisartan (Ctd-T) 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

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

Studies of Telmisartan (Ctd-T) in this setting do not exclude the possibility that Telmisartan (Ctd-T) 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 Telmisartan (Ctd-T) with an ACE inhibitor is not recommended.

Chlorthalidone (Ctd-T) 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. High blood pressure may also increase the risk of heart attacks. These problems may be less likely to occur if blood pressure is controlled.

Chlorthalidone (Ctd-T) is also used to treat fluid retention (edema) that is caused by congestive heart failure, severe liver disease (cirrhosis), kidney disease, or treatment with a hormone or steroid medicine.

Chlorthalidone (Ctd-T) is a diuretic (water pill). It reduces the amount of water in the body by increasing the flow of urine, which helps to lower blood pressure.

Chlorthalidone (Ctd-T) is available only with your doctor's prescription.

Telmisartan (Ctd-T) 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.

Telmisartan (Ctd-T) 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.

Telmisartan (Ctd-T) 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, Telmisartan (Ctd-T) relaxes the blood vessels. This lowers blood pressure and increases the supply of blood and oxygen to the heart.

Telmisartan (Ctd-T) is available only with your doctor's prescription.

Usual Adult Dose for Edema

Initial dose: 50-100 mg orally once a day.

Maintenance dose: 25-100 mg once a day or

50-200 mg every other day.

Usual Adult Dose for Hypertension

Initial dose: 25 mg orally once a day (15 mg for Thalitone).

Maintenance dose: 25-100 mg once a day (15-50 mg for Thalitone).

Renal Dose Adjustments

Chlorthalidone (Ctd-T) is not expected to be filtered into the renal tubule (its site of action) when the glomerular filtration rate is less than 10 mL/min.

Liver Dose Adjustments

Data not available

Dose Adjustments

Dosage adjustments are recommended to be made no more frequently than weekly. Patients with liver disease or renal dysfunction should have dosage adjustments made cautiously.

Precautions

Chlorthalidone (Ctd-T) is contraindicated in patients with anuria.

Chlorthalidone (Ctd-T) therapy should be used with caution in severe renal disease. In patients with renal disease, Chlorthalidone (Ctd-T) or related drugs may precipitate azotemia. Cumulative effects may develop in patients with impaired renal function. If progressive renal impairment becomes evident, as indicated by a rising nonprotein nitrogen or blood urea nitrogen, a careful reappraisal of the treatment is necessary with consideration given to withholding or discontinuing diuretic therapy.

Chlorthalidone (Ctd-T) therapy should be used with caution in patients with impaired hepatic function or progressive liver disease, since minor alterations of fluid and electrolyte balance may precipitate hepatic coma.

Sensitivity reactions may be observed in patients with a history of allergy or bronchial asthma.

The possibility of exacerbation or activation of systemic lupus erythematosus has been observed with thiazide diuretics, which are structurally related to Chlorthalidone (Ctd-T). However, systemic lupus erythematosus has not been observed following Chlorthalidone (Ctd-T) administration.

Hypokalemia may develop with Chlorthalidone (Ctd-T) as with any other diuretic, especially with brisk diuresis when severe cirrhosis is present. Interference with adequate oral electrolyte intake will also contribute to hypokalemia.

Any chloride deficit is generally mild and usually does not require specific therapy except under extraordinary circumstances (as in liver disease or renal disease). Dilutional hyponatremia may be observed in edematous patients in hot weather, appropriate therapy is water restriction, rather than administration of salt except in rare instances when the hyponatremia is life threatening. In actual salt depletion, appropriate replacement is the treatment of choice.

Hyperuricemia may occur or frank gout may be precipitated in certain patients receiving Chlorthalidone (Ctd-T) therapy. Thiazide-like diuretics have been shown to increase the urinary excretion of magnesium, which may result in hypomagnesemia.

The antihypertensive effects Chlorthalidone (Ctd-T) may be enhanced in the post-sympathectomy patient.

Calcium excretion is decreased by thiazide-like agents. Pathological changes in the parathyroid gland with hypercalcemia and hypophosphatemia have been reported in few patients on thiazide therapy. The common complications of hyperparathyroidism such as renal lithiasis, bone resorption and peptic ulceration have not been observed.

Periodic determination of serum electrolytes to detect possible electrolyte imbalance should be conducted at appropriate intervals.

Electrolyte abnormalities (i.e., hypokalemia, hyponatremia) and glucose intolerance may occur during Chlorthalidone (Ctd-T) therapy.

Safety and effectiveness have not been established in pediatric patients (less than 18 years of age).

Dialysis

Data not available

Other Comments

The maximum daily dose for hypertension is 100 mg (50 mg for Thalitone).

The maximum daily dose for edema is 200 mg (120 mg for Thalitone).

Periodic monitoring of electrolytes is recommended, particularly in elderly patients and in patients receiving a high dose.

Hypertension

Dosage must be individualized. The usual starting dose of Telmisartan (Ctd-T) 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 Telmisartan (Ctd-T) 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.

Telmisartan (Ctd-T) tablets may be administered with other antihypertensive agents.

Telmisartan (Ctd-T) tablets may be administered with or without food.

Cardiovascular Risk Reduction

The recommended dose of Telmisartan (Ctd-T) 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 Telmisartan (Ctd-T) are effective in reducing the risk of cardiovascular morbidity and mortality.

When initiating Telmisartan (Ctd-T) 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

Telmisartan (Ctd-T) is available as white or off-white, uncoated tablets containing Telmisartan (Ctd-T) 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:

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

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

Telmisartan (Ctd-T) 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 Chlorthalidone (Ctd-T)?

Hypersensitivity to Chlorthalidone (Ctd-T), other sulfonamide-derived drugs, or any component of the formulation; anuria

Note: Although the FDA approved product labeling states this medication is contraindicated with other sulfonamide-containing drug classes, the scientific basis of this statement has been challenged. See "Warnings/Precautions" for more detail.

Documentation of allergenic cross-reactivity for drugs thiazide-type diuretics is limited. However, because of similarities in chemical structure and/or pharmacologic actions, the possibility of cross-sensitivity cannot be ruled out with certainty.

See also:
What is the most important information I should know about Telmisartan (Ctd-T)?

Hypersensitivity to Telmisartan (Ctd-T) or to any of the excipients of Telmisartan (Ctd-T).

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 Telmisartan (Ctd-T), the use of Telmisartan (Ctd-T) 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 Telmisartan (Ctd-T) 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: Telmisartan (Ctd-T) is contraindicated during lactation since it is not known whether it is excreted in human milk.

Animal studies have shown excretion of Telmisartan (Ctd-T) in breast milk.

Use Chlorthalidone (Ctd-T) as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• Take Chlorthalidone (Ctd-T) by mouth with food, preferably in the morning.
• Chlorthalidone (Ctd-T) will increase urination. If you are taking 1 dose of Chlorthalidone (Ctd-T) daily, take it in the morning to prevent this from affecting your sleep.
• If you miss a dose of Chlorthalidone (Ctd-T), 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 Chlorthalidone (Ctd-T).

Use Telmisartan (Ctd-T) as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• An extra patient leaflet is available with Telmisartan (Ctd-T). Talk to your pharmacist if you have questions about this information.
• Take Telmisartan (Ctd-T) by mouth with or without food.
• Do not remove the tablet from the blister seal until you are ready to take your dose.
• Take Telmisartan (Ctd-T) on a regular schedule to get the most benefit from it. Taking Telmisartan (Ctd-T) at the same time each day will help you remember to take it.
• Continue to take Telmisartan (Ctd-T) even if you feel well. Do not miss any doses.
• If you miss a dose of Telmisartan (Ctd-T), 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 Telmisartan (Ctd-T).

Use: Labeled Indications

Edema: Adjunctive treatment of edema associated with heart failure, renal impairment, hepatic cirrhosis, or corticosteroid and estrogen therapy.

Hypertension: Management of hypertension.

Guideline recommendations: The 2017 Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults recommends if monotherapy is warranted, in the absence of comorbidities (eg, cerebrovascular disease, chronic kidney disease, diabetes, heart failure, ischemic heart disease, etc), that thiazide-like diuretics or dihydropyridine calcium channel blockers may be preferred options due to improved cardiovascular endpoints (eg, prevention of heart failure and stroke). ACE inhibitors and ARBs are also acceptable for monotherapy. Combination therapy may be required to achieve blood pressure goals and is initially preferred in patients at high risk (stage 2 hypertension or atherosclerotic cardiovascular disease [ASCVD] risk ≥10%) (ACC/AHA [Whelton 2017]).

Off Label Uses

Calcium nephrolithiasis

Data from a prospective, double-blind, randomized, placebo-controlled study support the use of Chlorthalidone (Ctd-T) for the prevention of recurrent calcium nephrolithiasis.

Based on the European Society of Endocrinology consensus statement on the standards of care for hypoparathyroidism in adults, the Endocrine Society guidelines on the management of hypoparathyroidism, and the European Society of Endocrinology guidelines on the treatment of chronic hypoparathyroidism, Chlorthalidone (Ctd-T), usually in combination with a low-salt diet, may be considered in the management of chronic hypoparathyroidism to reduce urinary calcium losses.

Telmisartan (Ctd-T) 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 Chlorthalidone (Ctd-T)?

Allopurinol

Concurrent use may increase incidence of hypersensitivity reactions to allopurinol.

Amphotericin B, corticosteroids

May intensify potassium depletion.

Anticholinergics

May increase Chlorthalidone (Ctd-T) absorption.

Anticoagulants

May diminish anticoagulant effects.

Bile acid sequestrants

May reduce Chlorthalidone (Ctd-T) absorption. Give Chlorthalidone (Ctd-T) at least 2 h before bile acid sequestrant.

Calcium salts

Hypercalcemia may develop.

Diazoxide

May cause hyperglycemia.

Digitalis glycosides

Diuretic-induced hypokalemia and hypomagnesemia may precipitate digitalis-induced arrhythmias.

Lithium

May decrease renal excretion of lithium.

Loop diuretics

Synergistic effects may result in profound diuresis and serious electrolyte abnormalities.

Methenamines, NSAIDs

May decrease effectiveness of Chlorthalidone (Ctd-T).

Sulfonylureas, insulin

May decrease hypoglycemic effect of sulfonylureas.

Laboratory Test Interactions

Increased serum bilirubin levels. Serum magnesium levels in uremic patients may be increased.

See also:
What other drugs will affect Telmisartan (Ctd-T)?

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

Digoxin: When Telmisartan (Ctd-T) 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 (Ctd-T) 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 (Ctd-T). 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 Telmisartan (Ctd-T), may result in deterioration of renal function, including possible acute renal failure. These effects are usually reversible. Monitor renal function periodically in patients receiving Telmisartan (Ctd-T) and NSAID therapy.

The antihypertensive effect of angiotensin II receptor antagonists, including Telmisartan (Ctd-T) may be attenuated by NSAIDs including selective COX-2 inhibitors.

Ramipril and Ramiprilat: Co-administration of Telmisartan (Ctd-T) 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 Telmisartan (Ctd-T) decrease by 31% and 16%, respectively. When co-administering Telmisartan (Ctd-T) 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 Telmisartan (Ctd-T). Concomitant use of Telmisartan (Ctd-T) and ramipril is not recommended.

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

Applies to Chlorthalidone (Ctd-T): oral tablet

In addition to its needed effects, some unwanted effects may be caused by Chlorthalidone (Ctd-T) (the active ingredient contained in Chlorthalidone (Ctd-T)). In the event that any of these side effects do occur, they may require medical attention.

Major Side Effects

You should check with your doctor immediately if any of these side effects occur when taking Chlorthalidone (Ctd-T):

Incidence not known:

• Abdominal or stomach pain
• black, tarry stools
• bleeding gums
• blistering, peeling, or loosening of skin
• bloating
• blood in urine or stools
• blurred vision
• burning, crawling, itching, numbness, prickling, "pins and needles", or tingling feelings
• chest pain
• chills
• clay-colored stools
• cold sweats
• confusion
• constipation
• cough or hoarseness
• coughing up blood
• darkened urine
• diarrhea
• dizziness, faintness, or lightheadedness when getting up from a lying or sitting position suddenly
• dry mouth
• fast heartbeat
• fatigue
• fever
• flushed, dry skin
• fruit-like breath odor
• general feeling of tiredness or weakness
• headache
• increased hunger
• increased thirst
• increased urination
• indigestion
• itching
• joint pain, stiffness, or swelling
• loss of appetite
• lower back or side pain
• nausea
• pain in joints or muscles
• painful or difficult urination
• pains in stomach, side, or abdomen, possibly radiating to the back
• pinpoint red spots on skin
• red irritated eyes
• red skin lesions, often with a purple center
• redness, soreness or itching skin
• shortness of breath
• skin rash
• sore throat
• sores, ulcers, or white spots on lips or in mouth
• sores, welting, or blisters
• sugar in the urine
• sweating
• swelling of feet or lower legs
• swollen glands
• tightness in chest
• troubled breathing
• unpleasant breath odor
• unusual bleeding or bruising
• unusual tiredness or weakness
• unusual weight loss
• vomiting
• vomiting of blood
• weight loss
• wheezing
• yellow eyes or skin

Minor Side Effects

Some of the side effects that can occur with Chlorthalidone (Ctd-T) may not need medical attention. As your body adjusts to the medicine during treatment these side effects may go away. Your health care professional may also be able to tell you about ways to reduce or prevent some of these side effects. If any of the following side effects continue, are bothersome or if you have any questions about them, check with your health care professional:

Incidence not known:

• Cramping
• decreased interest in sexual intercourse
• difficulty having a bowel movement (stool)
• feeling of constant movement of self or surroundings
• hives
• inability to have or keep an erection
• increased sensitivity of skin to sunlight
• loss in sexual ability, desire, drive, or performance
• muscle spasm
• redness or other discoloration of skin
• restlessness
• sensation of spinning
• severe sunburn
• weakness

See also:
What are the possible side effects of Telmisartan (Ctd-T)?

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

Telmisartan (Ctd-T) 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 Telmisartan (Ctd-T) (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 Telmisartan (Ctd-T) 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 Telmisartan (Ctd-T) 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 Telmisartan (Ctd-T) 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 Telmisartan (Ctd-T) 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 Telmisartan (Ctd-T) monotherapy in controlled or open trials are listed below. It cannot be determined whether these events were causally related to Telmisartan (Ctd-T) 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 Telmisartan (Ctd-T) tablets.

Hemoglobin: A greater than 2 g/dL decrease in hemoglobin was observed in 0.8% Telmisartan (Ctd-T) 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% Telmisartan (Ctd-T) patients compared with 0.3% placebo patients. One Telmisartan (Ctd-T)-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 Telmisartan (Ctd-T); all marked elevations occurred at a higher frequency with placebo. No Telmisartan (Ctd-T)-treated patients discontinued therapy because of abnormal hepatic function.

Cardiovascular Risk Reduction

Because common adverse reactions were well characterized in studies of Telmisartan (Ctd-T) in hypertension, only adverse events leading to discontinuation and serious adverse events were recorded in subsequent studies of Telmisartan (Ctd-T) for cardiovascular risk reduction. In TRANSCEND (N=5926, 4 years and 8 months of follow-up), discontinuations for adverse events were 8.4% on Telmisartan (Ctd-T) and 7.6% on placebo. The only serious adverse events at least 1% more common on Telmisartan (Ctd-T) 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 Telmisartan (Ctd-T). 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 Telmisartan (Ctd-T).

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 Telmisartan (Ctd-T).