WARNING: FETAL TOXICITY When pregnancy is detected, discontinue MICARDIS HCT as soon as possible. Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus (see WARNINGS, Fetal Toxicity ).
INDICATIONS AND USAGE Micardis® HCT (telmisartan and hydrochlorothiazide) tablets are indicated for the treatment of hypertension. This fixed dose combination is not indicated for initial therapy (see DOSAGE AND ADMINISTRATION ).
CONTRAINDICATIONS MICARDIS HCT tablets are contraindicated in patients with known hypersensitivity (e.g., anaphylaxis or angioedema) to telmisartan, hydrochlorothiazide, or any other component of this product (see ADVERSE REACTIONS ). Because of the hydrochlorothiazide component, this product is contraindicated in patients with anuria or hypersensitivity to other sulfonamide-derived drugs. Do not co-administer aliskiren with MICARDIS HCT in patients with diabetes (see PRECAUTIONS, Drug Interactions ).
ADVERSE REACTIONS Micardis® HCT (telmisartan and hydrochlorothiazide) tablets has been evaluated for safety in over 1700 patients, including 716 treated for over six months and 420 for over one year. In clinical trials with MICARDIS HCT tablets, no unexpected adverse events have been observed. Adverse experiences have been limited to those that have been previously reported with telmisartan and/or hydrochlorothiazide. The overall incidence of adverse experiences reported with the combination was comparable to placebo. Most adverse experiences were mild in intensity and transient in nature and did not require discontinuation of therapy. Adverse events occurring at an incidence of 2% or more in patients treated with telmisartan/hydrochlorothiazide 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 in ≥ 2% of Telmisartan/Hydrochlorothiazide (HCTZ) Patients* * includes all doses of telmisartan (20-160 mg), hydrochlorothiazide (6.25-25 mg), and combinations thereof Telm/HCTZ Placebo Telm HCTZ (N=414) (N=74) (N=209) (N=121) (%) (%) (%) (%) Body as a whole Fatigue 3 1 3 3 Influenza-like symptoms 2 1 2 3 Central/peripheral nervous system Dizziness 5 1 4 6 Gastrointestinal system Diarrhea 3 0 5 2 Nausea 2 0 1 2 Respiratory system disorder Sinusitis 4 3 3 6 Upper respiratory tract infection 8 7 7 10 The following adverse events were reported at a rate less than 2% in patients treated with telmisartan/hydrochlorothiazide and at a greater rate than in patients treated with placebo: back pain, dyspepsia, vomiting, tachycardia, hypokalemia, bronchitis, pharyngitis, rash, hypotension postural, abdominal pain. Finally, the following adverse events were reported at a rate of 2% or greater in patients treated with telmisartan/hydrochlorothiazide, but were as, or more common in the placebo group: pain, headache, cough, urinary tract infection. Adverse events occurred at approximately the same rates in men and women, older and younger patients, and black and non-black patients. In controlled trials (n=1017), 0.3% of patients treated with Micardis® HCT (telmisartan and hydrochlorothiazide) tablets 40/12.5 mg, 80/12.5 mg or 80/25 mg discontinued due to orthostatic hypotension, and the incidence of dizziness was 4%, 7%, and 1%, respectively. Telmisartan Other adverse experiences that have been reported with telmisartan, without regard to causality, are listed below: Autonomic Nervous System : impotence, increased sweating, flushing Body as a Whole : allergy, fever, leg pain, malaise, chest pain Cardiovascular : palpitation, dependent edema, angina pectoris, leg edema, abnormal ECG, hypertension, peripheral edema CNS : insomnia, somnolence, migraine, vertigo, paresthesia, involuntary muscle contractions, hypoaesthesia Gastrointestinal : flatulence, constipation, gastritis, dry mouth, hemorrhoids, gastroenteritis, enteritis, gastroesophageal reflux, toothache, non-specific gastrointestinal disorders Metabolic : gout, hypercholesterolemia, diabetes mellitus Musculoskeletal : arthritis, arthralgia, leg cramps, myalgia Psychiatric : anxiety, depression, nervousness Resistance Mechanism : infection, fungal infection, abscess, otitis media Respiratory : asthma, rhinitis, dyspnea, epistaxis Skin : dermatitis, eczema, pruritus Urinary : micturition frequency, cystitis Vascular : cerebrovascular disorder Special Senses : abnormal vision, conjunctivitis, tinnitus, earache A single case of angioedema was reported (among a total of 3781 patients treated with telmisartan). Hydrochlorothiazide Other adverse experiences that have been reported with hydrochlorothiazide, without regard to causality, are listed below: Body as a whole : weakness Digestive : pancreatitis, jaundice (intrahepatic cholestatic jaundice), sialadenitis, cramping, gastric irritation Hematologic : aplastic anemia, agranulocytosis, leukopenia, hemolytic anemia, thrombocytopenia Hypersensitivity : purpura, photosensitivity, urticaria, necrotizing angiitis (vasculitis and cutaneous vasculitis), fever, respiratory distress including pneumonitis and pulmonary edema, anaphylactic reactions Metabolic : hyperglycemia, glycosuria, hyperuricemia Musculoskeletal : muscle spasm Nervous System/Psychiatric : restlessness Renal : renal failure, renal dysfunction, interstitial nephritis Skin : erythema multiforme including Stevens-Johnson syndrome, exfoliative dermatitis including toxic epidermal necrolysis Special Senses : transient blurred vision, xanthopsia Post-Marketing Experience The following adverse reactions have been identified during post-approval use of Micardis® (telmisartan) tablets. 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 MICARDIS tablets. The most frequently 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 MICARDIS tablets. Clinical Laboratory Findings In controlled trials, clinically relevant changes in standard laboratory test parameters were rarely associated with administration of Micardis® HCT (telmisartan and hydrochlorothiazide) tablets. Hemoglobin and Hematocrit : Decreases in hemoglobin (≥ 2 g/dL) and hematocrit (≥ 9%) were observed in 1.2% and 0.6% of telmisartan/hydrochlorothiazide patients, respectively, in controlled trials. Changes in hemoglobin and hematocrit were not considered clinically significant and there were no discontinuations due to anemia. Creatinine, Blood Urea Nitrogen (BUN) : Increases in BUN (≥ 11.2 mg/dL) and serum creatinine (≥ 0.5 mg/dL) were observed in 2.8% and 1.4%, respectively, of patients with essential hypertension treated with MICARDIS HCT tablets in controlled trials. No patient discontinued treatment with MICARDIS HCT tablets due to an increase in BUN or creatinine. Liver Function Tests : Occasional elevations of liver enzymes and/or serum bilirubin have occurred. No telmisartan/hydrochlorothiazide treated patients discontinued therapy due to abnormal hepatic function. Serum Electrolytes : See PRECAUTIONS .
Drug Interactions : See PRECAUTIONS, Drug Interactions .