1  INDICATIONS AND USAGE

1.1  Hypertension

MICARDIS is indicated for the treatment of hypertension. Itmay be used alone or in combination with other antihypertensive agents [seeClinical Studies (14.1)].

1.2  Cardiovascular Risk Reduction

MICARDIS is indicated forreduction of the risk of myocardial infarction, stroke, or death fromcardiovascular causes in patients 55 years of age or older at high risk ofdeveloping major cardiovascular events who are unable to take ACE inhibitors.

High risk for cardiovascular events can beevidenced by a history of coronary artery disease, peripheral arterial disease,stroke, transient ischemic attack, or high-riskdiabetes (insulin-dependent or non-insulin dependent) with evidence ofend-organ damage [see Clinical Studies (14.2)]. MICARDIS can be used inaddition to other needed treatment (such as antihypertensive, antiplatelet orlipid-lowering therapy) [see Clinical Studies (14.2)].

Studies of telmisartan in thissetting do not exclude that it may not preserve a meaningful fraction of theeffect of the ACE inhibitor to which it was compared. Consider using the ACEinhibitor first, and, if it is stopped for cough only, consider re-trying theACE inhibitor after the cough resolves.

Use of telmisartan with an ACEinhibitor is not recommended [see Warnings and Precautions (5.6)].

2  DOSAGE AND ADMINISTRATION

2.1  Hypertension

Dosage must be individualized. The usual starting dose of MICARDIStablets is 40 mg once a day. Blood pressure response is dose-related over therange of 20-80 mg [see Clinical Studies (14.1)].

Most of the antihypertensive effect is apparent within 2 weeksand maximal reduction is generally attained after 4 weeks. When additionalblood pressure reduction beyond that achieved with 80 mg MICARDIS is required,a diuretic may be added.

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

MICARDIS tablets may be administered with otherantihypertensive agents.

MICARDIS tablets may be administered with or without food.

2.2  Cardiovascular Risk Reduction

Therecommended dose of MICARDIS tablets is 80 mg once a day and can beadministered with or without food. It is not known whether doses lower than 80mg of telmisartan are effective in reducing the risk of cardiovascularmorbidity and mortality.

Wheninitiating MICARDIS therapy for cardiovascular risk reduction, monitoring ofblood pressure is recommended, and if appropriate adjustment of medicationsthat lower blood pressure may be necessary.

3  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

4  CONTRAINDICATIONS

None.

5  WARNINGS AND PRECAUTIONS

5.1  Fetal/Neonatal Morbidity and Mortality

Drugs that act directly on the renin-angiotensin system cancause fetal and neonatal morbidity and death when administered to pregnantwomen. Several dozen cases have been reported in the world literature inpatients who were taking angiotensin converting enzyme inhibitors. When pregnancyis detected, discontinue MICARDIS tablets as soon as possible [see BoxedWarning].

The use of drugs that act directly on the renin-angiotensinsystem during the second and third trimesters of pregnancy has been associatedwith fetal and neonatal injury, including hypotension, neonatal skullhypoplasia, anuria, reversible or irreversible renal failure, and death.Oligohydramnios has also been reported, presumably resulting from decreasedfetal renal function; oligohydramnios in this setting has been associated withfetal limb contractures, craniofacial deformation, and hypoplastic lungdevelopment. Prematurity, intrauterine growth retardation, and patent ductusarteriosus have also been reported, although it is not clear whether theseoccurrences were related to exposure to the drug.

These adverse effects do not appear to have resulted fromintrauterine drug exposure that has been limited to the first trimester. Informmothers whose embryos and fetuses are exposed to an angiotensin II receptor antagonistonly during the first trimester that most reports of fetal toxicity have beenassociated with second and third trimester exposure. Nonetheless, whenpatients become pregnant or are considering pregnancy, have the patientdiscontinue the use of MICARDIS tablets as soon as possible.

Rarely (probably less often than once in every thousandpregnancies), no alternative to an angiotensin II receptor antagonist will befound. In these rare cases, the mothers should be apprised of the potentialhazards to their fetuses, and serial ultrasound examinations should beperformed to assess the intra-amniotic environment.

If oligohydramnios is observed, MICARDIS should bediscontinued unless they are considered life-saving for the mother.Contraction stress testing (CST), a non-stress test (NST), or biophysicalprofiling (BPP) may be appropriate, depending upon the week of pregnancy.Patients and physicians should be aware, however, that oligohydramnios may notappear until after the fetus has sustained irreversible injury.

Infants with histories of in utero exposure to anangiotensin II receptor antagonist should be closely observed for hypotension,oliguria, and hyperkalemia. If oliguria occurs, attention should be directedtoward support of blood pressure and renal perfusion. Exchange transfusion ordialysis may be required as a means of reversing hypotension and/orsubstituting for disordered renal function.

5.2  Hypotension

In patients with an activated renin-angiotensin system, suchas volume- or salt-depleted patients (e.g., those being treated with high dosesof diuretics), symptomatic hypotension may occur after initiation of therapywith MICARDIS. Either correct this condition prior to administration of MICARDIS,or start treatment under close medical supervision with a reduced dose.

If hypotension does occur, the patient should be placed in thesupine position and, if necessary, given an intravenous infusion of normalsaline. A transient hypotensive response is not a contraindication to further treatment,which usually can be continued withoutdifficulty 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, onrenal replacement therapy, or on potassium supplements, potassium-sparingdiuretics, potassium-containing salt substitutes or other drugs that increasepotassium levels. Consider periodic determinations of serum electrolytes todetect possible electrolyte imbalances, particularly in patients at risk.

5.4  Impaired Hepatic Function

As the majority of telmisartan is eliminated by biliaryexcretion, patients with biliary obstructive disorders or hepatic insufficiencycan be expected to have reduced clearance. Initiatetelmisartan at low doses and titrate slowly in these patients [see Usein Specific Populations (8.6) and Clinical Pharmacology (12.3)].

5.5  Impaired Renal Function

As a consequence of inhibiting therenin-angiotensin-aldosterone system, anticipate changes in renal function insusceptible individuals. In patients whose renal function may depend on theactivity of the renin-angiotensin-aldosterone system (e.g., patients withsevere congestive heart failure or renal dysfunction), treatment withangiotensin-converting enzyme (ACE) inhibitors and angiotensin receptorantagonists has been associated with oliguria and/or progressive azotemia and(rarely) with acute renal failure and/or death. Similar results have beenreported with MICARDIS [see Clinical Pharmacology (12.3)].

In studies of ACE inhibitors in patients with unilateral orbilateral renal artery stenosis, increases in serum creatinine or blood ureanitrogen were observed. There has been no long term use of MICARDIS inpatients with unilateral or bilateral renal artery stenosis, but anticipate aneffect similar to that seen with ACE inhibitors.

5.6  Dual Blockade of the Renin-Angiotensin-Aldosterone System

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

TheONTARGET trial enrolled 25,620 patients ≥55 years old withatherosclerotic disease or diabetes with end-organ damage, randomizing them totelmisartan only, ramipril only, or the combination, and followed them for amedian of 56 months. Patients receiving the combination of MICARDIS andramipril did not obtain any additional benefit compared to monotherapy, butexperienced an increased incidence of renal dysfunction (e.g., acuterenal failure) compared with groups receiving telmisartan alone or ramiprilalone. Concomitant use of MICARDIS and ramipril is not recommended.

6  ADVERSE REACTIONS

The following adverse reaction is described elsewhere inlabeling:

Renal dysfunction upon use with ramipril [seeWarnings and Precautions (5.6)]

6.1  Clinical Trials Experience

Becauseclinical studies are conducted under widely varying conditions, adversereactions rates observed in the clinical studies of a drug cannot be directlycompared to rates in the clinical studies of another drug andmay not reflect the rates observed in practice.

Hypertension
MICARDIS has been eva luated for safety in more than 3700patients, including 1900 treated for over 6 months and more than 1300 for overone year. Adverse experiences have generally been mild and transient in natureand have infrequently required discontinuation of therapy.

In placebo-controlled trials involving 1041 patients treatedwith various doses of MICARDIS (20-160 mg) monotherapy for up to 12 weeks, theoverall incidence of adverse events was similar to that in patients treatedwith placebo.

Adverse events occurring at an incidence of ≥1% inpatients treated with MICARDIS and at a greater rate than in patients treatedwith placebo, irrespective of their causal association, are presented in Table1.

Table 1 Adverse Events Occurring at an Incidence of ≥1% inPatients Treated with MICARDIS and at a Greater Rate Than Patients Treated withPlacebo

In addition to the adverse events in the table, the followingevents occurred at a rate of ≥1% but were at least as frequent in theplacebo group: influenza-like symptoms, dyspepsia, myalgia, urinary tractinfection, abdominal pain, headache, dizziness, pain, fatigue, coughing,hypertension, chest pain, nausea, and peripheral edema. Discontinuation oftherapy because of adverse events was required in 2.8% of 1455 patients treatedwith MICARDIS tablets and 6.1% of 380 placebo patients in placebo-controlledclinical trials.

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

The incidence of cough occurring with telmisartan in 6placebo-controlled trials was identical to that noted for placebo-treatedpatients (1.6%).

In addition to those listed above, adverse events thatoccurred in more than 0.3% of 3500 patients treated with MICARDIS monotherapyin controlled or open trials are listed below. It cannot be determined whetherthese events were causally related to MICARDIS 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, abnormalECG; CNS: insomnia, somnolence, migraine, vertigo, paresthesia,involuntary muscle contractions, hypoesthesia; Gastrointestinal:flatulence, constipation, gastritis, vomiting, dry mouth, hemorrhoids,gastroenteritis, enteritis, gastroesophageal reflux, toothache, non-specificgastrointestinal disorders; Metabolic: gout, hypercholesterolemia, diabetesmellitus; Musculoskeletal: arthritis, arthralgia, leg cra