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* | Telm/HCTZ | Placebo | Telm | HCTZ |
| (N=414) | (N=74) | (N=209) | (N=121) |
| (%) | (%) | (%) | (%) |
| * includes all doses of telmisartan (20-160 mg), hydrochlorothiazide (6.25-25 mg), and combinations thereof |
| 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).
Cardiovascular Risk Reduction Trials
In clinical studies with patients at high risk of developing major cardiovascular events, cases of sepsis, including some with fatal outcomes, have been reported.
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, and tendon pain (including tendonitis, tenosynovitis).
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.
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