telmisartan-hydrochlorothiazide 40-12.5 mg tb generic micardis hct

Uses

Hypertension

Telmisartan is used alone or in combination with other classes of antihypertensive agents in the management of hypertension. Angiotensin II receptor antagonists, such as telmisartan, are considered one of several preferred antihypertensive drugs for the initial management of hypertension; other options include angiotensin-converting enzyme (ACE) inhibitors, calcium-channel blockers, and thiazide diuretics. While there may be individual differences with respect to specific outcomes, these antihypertensive drug classes all produce comparable effects on overall mortality and cardiovascular, cerebrovascular, and renal outcomes. Angiotensin II receptor antagonists or ACE inhibitors may be particularly useful in the management of hypertension in patients with certain coexisting conditions such as diabetes mellitus or chronic kidney disease; angiotensin II receptor antagonists also may be preferred, generally as an alternative to ACE inhibitors, in hypertensive patients with heart failure or ischemic heart disease and/or postmyocardial infarction.

Efficacy of telmisartan in the treatment of hypertension has been established in several controlled studies in patients with hypertension of mild to moderate severity. In these patients, telmisartan dosages of 20-80 mg administered once daily decreased placebo-corrected systolic blood pressure by about 6-13 mm Hg and diastolic blood pressure by about 6-8 mm Hg 24 hours after dosing. After withdrawal of telmisartan, blood pressure gradually returns (within several days to 1 week) to pretreatment levels; rebound hypertension following abrupt withdrawal of the drug has not been reported. Clinical studies have shown that the hypotensive effect of telmisartan in patients with mild to moderate hypertension is greater than that of placebo and at least as effective as amlodipine, atenolol, enalapril, lisinopril, losartan, or valsartan.

Like ACE inhibitors, angiotensin II receptor antagonists such as telmisartan may produce a smaller blood pressure response in hypertensive black patients compared with nonblack patients.

For additional information on the management of hypertension, For information on overall principles and expert recommendations for treatment of hypertension,

Diabetic Nephropathy

Both angiotensin II receptor antagonists and ACE inhibitors have been shown to slow the rate of progression of renal disease in patients with diabetes mellitus and persistent albuminuria, and use of a drug from either class is recommended in such patients with modestly elevated (30-300 mg/24 hours) or higher (exceeding 300 mg/24 hours) levels of urinary albumin excretion. The usual precautions of angiotensin II receptor antagonist or ACE inhibitor therapy in patients with substantial renal impairment should be observed.(See Renal Effects under Warnings/Precautions: Other Warnings and Precautions, in Cautions). For additional information on the use of angiotensin II receptor antagonists in the treatment of diabetic nephropathy, and in .

Heart Failure

Angiotensin II receptor antagonists have been used in the management of heart failure.

Current guidelines for the management of heart failure in adults generally recommend a combination of drug therapies to reduce morbidity and mortality, including neurohormonal antagonists (e.g., ACE inhibitors, angiotensin II receptor antagonists, angiotensin receptor-neprilysin inhibitors [ARNIs], β-adrenergic blocking agents [β-blockers], aldosterone receptor antagonists) that inhibit the detrimental compensatory mechanisms in heart failure. Additional agents (e.g., cardiac glycosides, diuretics, sinoatrial modulators [i.e., ivabradine]) added to a heart failure treatment regimen in selected patients have been associated with symptomatic improvement and/or reduction in heart failure-related hospitalizations. Experts recommend that all asymptomatic patients with reduced left ventricular ejection fraction (LVEF) (American College of Cardiology Foundation [ACCF]/American Heart Association [AHA] stage B heart failure) receive therapy with an ACE inhibitor and β-blocker to prevent symptomatic heart failure and reduce morbidity and mortality. In patients with prior or current symptoms of chronic heart failure with reduced LVEF (ACCF/AHA stage C heart failure), ACCF, AHA, and the Heart Failure Society of America (HFSA) recommend inhibition of the renin-angiotensin-aldosterone (RAA) system with an ACE inhibitor, angiotensin II receptor antagonist, or ARNI in conjunction with a β-blocker, and an aldosterone antagonist in selected patients, to reduce morbidity and mortality. While ACE inhibitors have been the preferred drugs for inhibition of the RAA system because of their established benefits in patients with heart failure and reduced ejection fraction, some evidence indicates that therapy with sacubitril/valsartan, an ARNI, may be more effective than ACE inhibitor therapy (enalapril) in reducing cardiovascular death and heart failure-related hospitalization. ACCF, AHA, and HFSA recommend that patients with chronic symptomatic heart failure and reduced LVEF (New York Heart Association [NYHA] class II or III) who are able to tolerate an ACE inhibitor or angiotensin II receptor antagonist be switched to therapy containing an ARNI to further reduce morbidity and mortality. However, in patients in whom an ARNI is not appropriate, continued use of an ACE inhibitor for all classes of heart failure with reduced ejection fraction remains strongly advised. In patients in whom an ARNI or ACE inhibitor is not appropriate, an angiotensin II receptor antagonist may be used. For additional information on the use of angiotensin II receptor antagonists in the management of heart failure, and in .

While angiotensin II receptor antagonists are considered reasonable alternatives in patients who are unable to tolerate ACE inhibitors (e.g., because of cough or angioedema), angioedema has been reported rarely with the use of telmisartan during postmarketing experience.

Dosage and Administration

Administration

Telmisartan is administered orally. Although food may reduce the bioavailability of telmisartan, the manufacturers state that the drug can be taken without regard to meals.

Dosage

Hypertension

Dosage of telmisartan must be individualized and adjusted according to blood pressure response.

Telmisartan Therapy

The usual initial dosage of telmisartan is 40 mg once daily in adults without depletion of intravascular volume. The usual maintenance dosage of telmisartan in adults is 20-80 mg given once daily. Telmisartan dosages exceeding 80 mg daily (up to a dosage of 160 mg daily) do not appear to provide additional therapeutic benefit. The panel members appointed to the Eighth Joint National Committee on the Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 8 expert panel) state that evidence-based dosing information (i.e., dosages shown in randomized controlled trials to reduce complications of hypertension) should be used when available to determine target dosages of antihypertensive agents. Target dosages generally can be achieved within 2-4 weeks, but it may take up to several months. The manufacturers state that most of the antihypertensive effect of telmisartan is evident within 2 weeks, with a maximum reduction in blood pressure after 4 weeks.

Antihypertensive therapy should be titrated until goal blood pressure is achieved. If an adequate blood pressure response is not achieved with telmisartan monotherapy, another antihypertensive agent with demonstrated benefit may be added; if goal blood pressure is still not achieved with the use of 2 antihypertensive agents at optimal dosages, a third drug may be added. In patients who experience intolerable adverse effects with telmisartan, dosage reduction should be considered; if adverse effects worsen or fail to resolve, it may be necessary to discontinue the angiotensin II receptor antagonist and initiate another class of antihypertensive agent.

Telmisartan/Amlodipine Fixed-combination Therapy

The fixed-combination preparation containing telmisartan and amlodipine can be used as a substitute for the individually administered drugs; patients may be switched to the fixed-combination preparation containing the corresponding individual doses of telmisartan and amlodipine or, alternatively, the dosage of one or both components can be increased for additional antihypertensive effects. In addition, the manufacturers state that patients who do not respond adequately to monotherapy with telmisartan (or another angiotensin II receptor antagonist) or, alternatively, with amlodipine (or another dihydropyridine-derivative calcium-channel blocker) may be switched to therapy with the fixed-combination preparation containing telmisartan and amlodipine. Patients who experience dose-limiting adverse effects (e.g., edema) during monotherapy with amlodipine 10 mg may be switched to the fixed combination containing amlodipine 5 mg and telmisartan 40 mg to achieve similar blood pressure control. If needed, dosage of the fixed-combination preparation may be increased to a maximum dosage of 80 mg of telmisartan and 10 mg of amlodipine given once daily; because most of the antihypertensive effect of a given dosage is achieved within 2 weeks, dosage may be adjusted after at least 2 weeks, if needed, to attain blood pressure control.

Commercially available preparations containing telmisartan in fixed combination with amlodipine may be used for initial treatment of hypertension in patients likely to require combined therapy with multiple antihypertensive drugs to achieve blood pressure control. In such patients, therapy with the fixed-combination preparation usually should be initiated at a dosage of 40 mg of telmisartan and 5 mg of amlodipine once daily. An initial dosage of 80 mg of telmisartan and 5 mg of amlodipine once daily may be used in patients requiring larger blood pressure reductions. The decision to use the fixed combination of amlodipine and telmisartan for initial management of hypertension should be based on assessment of potential benefits and risks of such therapy, including consideration of whether the patient is likely to tolerate the lowest available dosage of the combined drugs. In patients whose baseline blood pressure is 160/110 mm Hg, the estimated probability of achieving control of systolic blood pressure (defined as systolic blood pressure of less than 140 mm Hg) is 46, 69, or 79% and of achieving control of diastolic blood pressure (defined as diastolic blood pressure of less than 90 mm Hg) is 26, 22, or 55% with telmisartan (80 mg daily) alone, amlodipine (10 mg daily) alone, or telmisartan combined with amlodipine (at the same dosages), respectively.

Telmisartan/Hydrochlorothiazide Fixed-combination Therapy

In patients who do not respond adequately to monotherapy with telmisartan or, alternatively, with hydrochlorothiazide, combined therapy with the drugs can be used. When combination therapy is necessary, the manufacturers state that commercially available preparations containing telmisartan in fixed combination with hydrochlorothiazide generally should not be used initially. Dosage preferably should first be adjusted by titrating the dosage of each drug separately; if it is determined that the optimum maintenance dosage corresponds to the ratio in the commercial combination preparation, this product may be used. The manufacturers state that combined therapy with the commercially available fixed-combination preparation containing 80 mg of telmisartan and 12.5 mg of hydrochlorothiazide can be initiated in adults whose blood pressure is not adequately controlled by monotherapy with 80 mg of telmisartan or 25 mg of hydrochlorothiazide or in those in whom control of blood pressure is maintained but hypokalemia is problematic at this hydrochlorothiazide dosage. If needed, the dosage with the fixed combination may be titrated up to 160 mg of telmisartan and 25 mg of hydrochlorothiazide.

Blood Pressure Monitoring and Treatment Goals

Careful monitoring of blood pressure during initial titration or subsequent upward adjustment in dosage of telmisartan is recommended.

The goal of hypertension management and prevention is to achieve and maintain optimal control of blood pressure; specific target levels of blood pressure should be individualized based on consideration of multiple factors, including patient age and comorbidities, and the currently available evidence from clinical studies.

For additional information on initiating and adjusting telmisartan dosage in the management of hypertension, .

Special Populations

The manufacturers recommend that patients with intravascular volume or salt depletion have this condition corrected prior to initiation of telmisartan therapy or that they be monitored closely and consideration given to administering a lower initial dose of the drug.

Telmisartan should be initiated under close medical supervision in patients with obstructive biliary disease or hepatic impairment. The commercially available preparation containing telmisartan in fixed combination with hydrochlorothiazide is not recommended for patients with severe hepatic impairment. The manufacturers state that an initial telmisartan dose of 40 mg is recommended in patients with biliary obstructive disease or mild to moderate hepatic impairment when receiving hydrochlorothiazide in fixed combination with the drug. Preparations containing telmisartan in fixed combination with amlodipine exceed the recommended initial dosage of amlodipine (2.5 mg daily) for patients with hepatic impairment.

The manufacturers state that no adjustment in initial telmisartan dosage is necessary in patients with renal impairment, including patients on hemodialysis. Blood pressure should be monitored closely in patients undergoing dialysis. The commercially available preparation containing telmisartan in fixed combination with hydrochlorothiazide is not recommended for patients with renal impairment whose creatinine clearance is less than 30 mL/minute. Dosage of the fixed combination of telmisartan and amlodipine should be titrated slowly in patients with severe renal impairment.

The manufacturers state that no adjustment in initial telmisartan dosage is necessary in geriatric patients. Preparations containing telmisartan in fixed combination with amlodipine exceed the recommended initial dosage of amlodipine (2.5 mg daily) for geriatric patients 75 years of age or older.

Cautions

Contraindications

Known hypersensitivity (e.g., anaphylaxis or angioedema) to telmisartan or any ingredient in the formulation.

Concomitant use of telmisartan and aliskiren in patients with diabetes mellitus.(See Drug Interactions: Drugs that Block the Renin-Angiotensin System.)

Warnings/Precautions

Warnings

Fetal/Neonatal Morbidity and Mortality

Drugs that act directly on the renin-angiotensin system (e.g., angiotensin-converting enzyme [ACE] inhibitors, angiotensin II receptor antagonists) can cause fetal and neonatal morbidity and mortality when used in pregnancy during the second and third trimesters. Telmisartan should be discontinued as soon as possible when pregnancy is detected, unless continued use is considered life-saving. Nearly all women can be transferred successfully to alternative therapy for the remainder of their pregnancy. For additional information on the risk of the use of such drugs during pregnancy, see Cautions: Pregnancy, Fertility, and Lactation, in and in .

Sensitivity Reactions

Sensitivity reactions, including various anaphylactoid reactions and/or angioedema, have been reported with use of angiotensin II receptor antagonists, including telmisartan. Extreme caution in patients with history of angioedema associated with or unrelated to ACE or angiotensin II receptor antagonist therapy.

Other Warnings and Precautions

Hypotension

Symptomatic hypotension may occur in patients with an activated renin-angiotensin system (e.g., patients with volume or salt depletion secondary to salt restriction or prolonged diuretic therapy).

If hypotension occurs in patients receiving telmisartan, the patient should be placed in the supine position; if hypotension is severe, IV infusion of 0.9% sodium chloride injection to expand fluid volume should be considered. Transient hypotension is not a contraindication to additional doses of telmisartan, and therapy with the drug can be reinstated cautiously after blood pressure has been stabilized (e.g., with volume expansion).

Malignancies

In July 2010, the US Food and Drug Administration (FDA) initiated a safety review of angiotensin II receptor antagonists after a published meta-analysis suggested a possible association between the use of these agents and an increased risk of cancer. The meta-analysis, which combined cancer-related findings from 5 randomized, controlled trials in over 60,000 patients, found a modest but significant increase in the risk of new cancer occurrence in patients receiving an angiotensin II receptor antagonist (mostly telmisartan) compared with those in control groups (7.2 versus 6%, respectively; risk ratio 1.08). However, because of several limitations of the study (e.g., trials included in the meta-analysis were not specifically designed to evaluate cancer outcomes, lack of individual patient data), the validity of these findings has been questioned.

Subsequent studies, including a larger, more comprehensive meta-analysis conducted by FDA, have not shown an increased risk of cancer in patients receiving angiotensin II receptor antagonists. FDA's meta-analysis, which included trial-level data from 31 randomized studies (total of approximately 156,000 patients), found no evidence of an increased risk of cancer in patients who received an angiotensin II receptor antagonist compared with those who received other treatments (placebo or active control). The overall rate of new cancer occurrence was essentially the same in both groups of patients (1.82 and 1.84 cases per 100 patient-years, respectively). In addition, there was no difference in the risk of cancer-related death, breast cancer, lung cancer, or prostate cancer between the groups. Based on these results and a review of all currently available data related to this potential safety concern, FDA has concluded that use of angiotensin II receptor antagonists is not associated with an increased risk of cancer.

Renal Effects

Because the renin-angiotensin-aldosterone (RAA) system appears to contribute substantially to maintenance of glomerular filtration in patients with heart failure in whom renal perfusion is severely compromised, renal function may deteriorate markedly (e.g., renal failure) in these patients during therapy with an ACE inhibitor or an angiotensin II receptor antagonist (e.g., telmisartan). Renal artery stenosis also is a risk factor for renal impairment during therapy with drugs that inhibit the RAA system. Although reports received to date have involved patients treated with ACE inhibitors, this adverse effect also would be expected to occur when drugs with similar pharmacologic activity (e.g., angiotensin II receptor antagonists) are used in a similar manner.

Fixed-combination Preparations

When telmisartan is used as a fixed combination that includes amlodipine or hydrochlorothiazide, the cautions, precautions, contraindications, and interactions associated with the concomitant agent must be considered in addition to those associated with telmisartan. Cautionary information applicable to specific populations (e.g., pregnant or nursing women, individuals with hepatic or renal impairment, geriatric patients) also should be considered for each drug in the fixed combination.

Specific Populations

Pregnancy

Category D.

Telmisartan can cause fetal and neonatal morbidity and mortality when administered to a pregnant woman. Telmisartan should be discontinued as soon as possible when pregnancy is detected.(See Fetal/Neonatal Morbidity and Mortality under Warnings/Precautions: Warnings, in Cautions.)

Lactation

It is not known whether telmisartan is distributed into breast milk. Because of the potential for serious adverse reactions to telmisartan in nursing infants, a decision should be made whether to discontinue nursing or the drug.

Pediatric Use

Safety and efficacy have not been established in children younger than 18 years of age. For information on overall principles and expert recommendations for treatment of hypertension in pediatric patients, .

Geriatric Use

No substantial differences in safety and efficacy of telmisartan in geriatric patients have been observed relative to younger adults, but increased sensitivity cannot be ruled out.

Renal Impairment

Telmisartan should be used with caution in patients with renal impairment.

Hepatic Impairment

While the manufacturer makes no specific recommendations for telmisartan dosage adjustment in patients with hepatic impairment, caution should be exercised in patients with obstructive biliary disease or hepatic insufficiency since the drug is eliminated by biliary excretion and such patients can be expected to have reduced hepatic clearance.

Black Patients

Blood pressure reduction may be smaller in black patients than in patients of other races.

Common Adverse Effects

Adverse effects occurring in 1% or more of patients receiving telmisartan include upper respiratory tract infection, sinusitis, pharyngitis, back pain, and diarrhea.

Drug Interactions

Drugs that Block the Renin-Angiotensin System

Increased risk of hypotension, hyperkalemia, and changes in renal function (e.g., renal impairment) with concomitant use of other angiotensin II receptor blockers or other drugs that block the renin-angiotensin system (e.g., angiotensin-converting enzyme [ACE] inhibitors, aliskiren); blood pressure, renal function, and serum concentrations of electrolytes should be monitored closely if telmisartan is used concomitantly with such drugs.(See Drug Interactions: Aliskiren.)

Drugs Affecting Hepatic Microsomal Enzymes

Inhibitors or inducers of the cytochrome P-450 (CYP) isoenzyme system; pharmacokinetic interactions unlikely.

Aliskiren

Concomitant use of telmisartan with aliskiren is contraindicated in patients with diabetes mellitus; in addition, such concomitant use should be avoided in patients with renal impairment (glomerular filtration rate [GFR] less than 60 mL/minute).

Digoxin

Pharmacokinetic interactions (increased plasma digoxin concentrations). It is recommended that serum digoxin concentrations be monitored when telmisartan therapy is initiated, adjusted, or discontinued in patients stabilized on digoxin.

Warfarin

Pharmacokinetic interactions (decreased plasma warfarin concentrations; international normalized ratio [INR] not affected).

Acetaminophen, Amlodipine, Glyburide, Ibuprofen, Simvastatin

Pharmacologic interactions unlikely.