A1,
A2,
B,
C1,
C2,
D,
E,
F,
G-H,
I-K,
L,
M,
N,
O,
P1,
P2,
Q-R,
S,
T,
U-V,
W-Z
Micardis Side Effects, and Drug Interactions - Telmisartan/Hydrochlorothiazide
Micardis Side Effects, and Drug Interactions - Telmisartan/Hydrochlorothiazide
SIDE EFFECTS
MICARDIS HCT (telmisartan/hydrochlorothiazide) 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, 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 ³ 2% of Telmisartan/Hydrochlorothiazide
(HCTZ) Patients*
|
|
|
Telm/HCTZ (N=414) (%)
|
Placebo (N=74) (%)
|
Telm (N=209) (%)
|
HCTZ (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
|
|
* includes all doses of telmisartan (20-160 mg), hydrochlorothiazide
(6.25-25 mg), and combinations thereof
|
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 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). In post-marketing experience, additional
cases of angioedema and urticaria have been noted.
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.
Clinical Laboratory Findings
In controlled trials, clinically relevant changes in standard
laboratory test parameters were rarely associated with administration of MICARDIS
HCT tablets.
Hemoglobin and Hematocrit: Decreases in hemoglobin (³
2 g/dL) and hematocrit (³ 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 (³
11.2 mg/dL) and serum creatinine (³ 0.5 mg/dL) were
observed in 2.8% and 1.4%, respectively, of patients with essential hypertension
treated with MICARDIS HCT in controlled trials. No patient discontinued treatment
with MICARDIS HCT 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
Telmisartan
Digoxin: When telmisartan was coadministered with digoxin,
median increases in digoxin peak plasma concentration (49%) and in trough concentration
(20%) were observed. It is, therefore, recommended that digoxin levels be monitored
when initiating, adjusting, and discontinuing telmisartan to avoid possible
over- or under-digitalization.
Warfarin: Telmisartan administered for 10 days
slightly decreased the mean warfarin trough plasma concentration; this decrease
did not result in a change in International Normalized Ratio (INR).
Other Drugs: Coadministration of telmisartan
did not result in a clinically significant interaction with acetaminophen, amlodipine,
glibenclamide, simvastatin, hydrochlorothiazide or ibuprofen. Telmisartan 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
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.
Hydrochlorothiazide: When administered concurrently,
the following drugs may interact with thiazide diuretics: Alcohol, barbiturates,
or narcotics: Potentiation of orthostatic hypotension may occur.
Antidiabetic drugs (oral agents and insulin): Dosage adjustment
of the antidiabetic drug may be required.
Other antihypertensive drugs: Additive effect
or potentiation.
Cholestyramine and colestipol resins: Absorption of hydrochlorothiazide
is impaired in the presence of anionic exchange resins. Single doses of either
cholestyramine or colestipol resins bind the hydrochlorothiazide and reduce
its absorption from the gastrointestinal tract by up to 85% and 43%, respectively.
Corticosteroids, ACTH: Intensified electrolyte
depletion, particularly hypokalemia.
Pressor amines (e.g., norepinephrine): Possible
decreased response to pressure amines but not sufficient to preclude their use.
Skeletal muscle relaxants, nondepolarizing (e.g., tubocurarine):
Possible increased responsiveness to the muscle relaxant.
Lithium: Should not generally be given with diuretics.
Diuretic agents reduce the renal clearance of lithium and add a high risk of
lithium toxicity. Refer to the package insert for lithium preparations before
use of such preparations with MICARDIS HCT.
Non-steroidal anti-inflammatory drugs: In some
patients, the administration of a non-steroidal antiinflammatory agent can reduce
the diuretic, natriuretic, and antihypertensive effects of loop, potassium-sparing
and thiazide diuretics. Therefore, when MICARDIS HCT and non-steroidal anti-inflammatory
agents are used concomitantly, the patient should be observed closely to determine
if the desired effect of the diuretic is obtained.
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