Cardialta Adverse Reactions

Clinical Trials Experience: Because clinical studies are conducted under widely varying conditions, adverse reactions rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in practice.
Telmisartan + Amlodipine: Adverse reactions have generally been mild and transient in nature and have only infrequently required discontinuation of therapy.
The frequency of adverse reactions was not related to gender, age, or race.
In the placebo-controlled factorial design study, the population treated with a telmisartan and amlodipine combination had a mean age of 53 years and included approximately 50% males, 79% were Caucasian, 17% Blacks, and 4% Asians. Patients received doses ranging from 20/2.5 mg to 80/10 mg orally, once daily.
The frequency of adverse reactions was not related to gender, age, or race.
The adverse reactions that occurred in the placebo-controlled factorial design trial in patients treated with Telmisartan + Amlodipine and at a higher incidence in Telmisartan + Amlodipine treated patients than placebo-treated patients were peripheral edema, dizziness, and back pain. Edema (other than peripheral edema), hypotension, and syncope were reported in the placebo-controlled factorial design trial, discontinuation due to adverse events occurred in 2.2% of all treatment cells of patients in the telmisartan/amlodipine treated patients and in 4.3% in the placebo-treated group. The most common reasons for discontinuation of therapy with Telmisartan + Amlodipine were peripheral edema, dizziness, and hypotension.
Peripheral edema is a known, dose-dependent adverse reaction of amlodipine, but not of telmisartan. In the factorial design study, the incidence of peripheral edema during the 8 week, randomized, double-blind treatment period was highest with amlodipine 10 mg monotherapy. The incidence was notably lower when telmisartan was used in combination with amlodipine 10 mg. (See Table 1.)

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Telmisartan: Adverse experiences have generally been mild and transient in nature and have only in frequently required discontinuation of therapy. Adverse events occurring at an incidence of ≥1% in patients treated with telmisartan and at a greater rate than in patients treated with placebo, irrespective of their causal association, are upper respiratory tract infection, back pain, sinusitis, diarrhea and pharyngitis. (See Table 2.)

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In addition to the adverse events in the table, the following events occurred at a rate of ≥1% but were at least as frequent in the placebo group: influenza-like symptoms, dyspepsia, myalgia, urinary tract infection, abdominal pain, headache, dizziness, pain, fatigue, coughing, hypertension, chest pain, nausea, and peripheral edema. Discontinuation of therapy because of adverse events was required in 2.8% of 1455 patients treated with telmisartan tablets and 6.1% of 380 placebo patients in placebo-controlled clinical trials.
The incidence of adverse events was not dose-related and did not correlate with gender, age, or race of patients.
In addition to those listed previously, adverse events that occurred in >0.3% of patients treated with telmisartan monotherapy in controlled or open trials are listed as follows. It cannot be determined whether these events were causally related to telmisartan tablets. The incidence of cough occurring with telmisartan in 6 placebo-controlled trials was identical to that noted for placebo-treated patients (1.6%). In addition to those listed previously, adverse events that occurred in >0.3% of 3500 patients treated with telmisartan monotherapy in controlled or open trials are listed as follows. It cannot be determined whether these events were causally related to telmisartan 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, abnormal ECG; CNS: insomnia, somnolence, migraine, vertigo, paresthesia, involuntary muscle contractions, hypoesthesia; Gastrointestinal: flatulence, constipation, gastritis, vomiting, dry mouth, hemorrhoids, gastroenteritis, enteritis, gastroesophageal reflux, toothache, nonspecific gastrointestinal disorders; Metabolic: gout, hypercholesterolemia, diabetes mellitus; Musculoskeletal: arthritis, arthralgia, leg cramps; Psychiatric: anxiety, depression, nervousness; Resistance Mechanism: infection, fungal infection, abscess, otitis media; Respiratory: asthma, bronchitis, rhinitis, dyspnea, epistaxis; Skin: dermatitis, rash, eczema, pruritus; Urinary: micturition frequency, cystitis; Vascular: cerebrovascular disorder, and Special Senses: abnormal vision, conjunctivitis, tinnitus, earache.
During initial clinical studies, a single case of angioedema was reported (among a total of 3781 patients treated).
Clinical Laboratory Findings: In placebo-controlled clinical trials, clinically relevant changes in standard laboratory test parameters were rarely associated with administration of telmisartan tablets.
Hemoglobin: A greater than 2 g/dL decrease in hemoglobin was observed in 0.8% telmisartan patients compared with 0.3% placebo patients. No patients discontinued therapy due to anemia.
Creatinine: A 0.5 mg/dL rise or greater in creatinine was observed in 0.4% telmisartan patients compared with 0.3% placebo patients. One telmisartan-treated patient discontinued therapy due to increases in creatinine and blood urea nitrogen.
Liver Enzymes: Occasional elevations of liver chemistries occurred in patients treated with telmisartan; all marked elevations occurred at a higher frequency with placebo. No telmisartan-treated patients discontinued therapy due to abnormal hepatic function.
Amlodipine: Most adverse reactions reported during therapy with amlodipine were of mild or moderate severity. In controlled clinical trials directly comparing amlodipine in doses up to 10 mg to placebo, discontinuation of amlodipine due to adverse reactions was required in only about 1.5% of amlodipine-treated patients and was not significantly different from that seen in placebo-treated patients. The most common side effects were headache and edema.
Other adverse experiences which were not clearly dose related but which were reported with an incidence greater than 1% in placebo-controlled clinical trials are headache, fatigue, nausea, abdominal pain and somnolence.
The following events occurred in 0.1% of patients in controlled clinical trials or under conditions of open trials or marketing experience where a causal relationship is uncertain; they are listed to alert the physician to a possible relationship: Cardiovascular: arrhythmia (including ventricular tachycardia and atrial fibrillation), bradycardia, chest pain, hypotension, peripheral ischemia, syncope, tachycardia, postural dizziness, postural hypotension, vasculitis, Central and Peripheral Nervous System: hypoesthesia, neuropathy peripheral, paresthesia, tremor, vertigo; Gastrointestinal: anorexia, constipation, dyspepsia, dysphagia, diarrhea, flatulence, pancreatitis, vomiting, gingival hyperplasia, change of bowel habit; General: allergic reaction, asthenia, back pain, hot flushes, malaise, pain, rigors, weight gain, weight decrease; Musculoskeletal System: arthralgia, arthrosis, muscle cramps, myalgia; Psychiatric: sexual dysfunction (male and female), insomnia, nervousness, depression, abnormal dreams, anxiety, depersonalization, mood change; Respiratory System: dyspnea, epistaxis; Skin and Appendages: angioedema, erythema multiforme, pruritus, rash, rash erythematous, rash maculopapular; Special Senses: abnormal vision, conjunctivitis, diplopia, eye pain, tinnitus; Urinary System: micturition frequency, micturition disorder, nocturia; Autonomic Nervous System: dry mouth, sweating increased; Metabolic and Nutritional: hyperglycemia, thirst; Hemopoietic: leukopenia, purpura, thrombocytopenia. The following events occurred in <0.1% of patients: cardiac failure, pulse irregularity, extra systoles, skin discoloration, urticaria, skin dryness, alopecia, dermatitis, muscle weakness, twitching, ataxia, hypertonia, migraine, cold and clammy skin, apathy, agitation, amnesia, gastritis, increased appetite, loose stools, coughing rhinitis, dysuria, polyuria, parosmia, taste perversion, abnormal visual accommodation, and xerophthalmia.
Other reactions occurred sporadically and cannot be distinguished from medications or concurrent disease states such as myocardial infarction and angina. Amlodipine has not been associated with clinically significant changes in routine laboratory tests. No clinically relevant changes were noted in serum potassium, serum glucose, total triglycerides, total cholesterol, HDL cholesterol, uric acid, blood urea nitrogen, or creatinine.
Amlodipine has been used safely in patients with chronic obstructive pulmonary disease, well-compensated congestive heart failure, coronary artery disease, peripheral vascular disease, diabetes mellitus, and abnormal lipid profiles.