MICARDIS®

Side effects and safety

MICARDIS®¹

Clinical trials experience¹

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.¹

Hypertension¹

MICARDIS® has been evaluated for safety in more than 3,700 patients, including 1,900 treated for over 6 months and more than 1,300 for over one year. Adverse experiences have generally been mild and transient in nature and have infrequently required discontinuation of therapy.¹

In placebo-controlled trials involving 1,041 patients treated with various doses of MICARDIS® (20-160 mg) monotherapy for up to 12 weeks, the overall incidence of adverse events was similar to that in patients treated with placebo.¹

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

Table 1. Adverse events occurring at an incidence of ≥ 1% in patients treated with MICARDIS® and at a greater rate than patients treated with placebo

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 1,455 patients treated with MICARDIS® tablets and 6.1% of 380 placebo patients in placebo-controlled clinical trials.¹

The incidence of adverse events was not dose-related and did not correlate with gender, age, or race of patients.¹

The incidence of cough occurring with telmisartan in 6 placebo-controlled trials was identical to that noted for placebo-treated patients (1.6%).¹

In addition to those listed above, adverse events that occurred in more than 0.3% of 3,500 patients treated with MICARDIS® monotherapy in controlled or open trials are listed below. It cannot be determined whether these events were causally related to MICARDIS® tablets:¹

• 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 3,781 patients treated).¹

Cardiovascular Risk Reduction

Because common adverse reactions were well characterized in studies of telmisartan in hypertension, only adverse events leading to discontinuation and serious adverse events were recorded in subsequent studies of telmisartan for cardiovascular risk reduction. In TRANSCEND (N=5,926, 4 years and 8 months of follow-up), discontinuations for adverse events were 8.4% on telmisartan and 7.6% on placebo. The only serious adverse events at least 1% more common on telmisartan than placebo were intermittent claudication (7% vs. 6%) and skin ulcer (3% vs. 2%).

Postmarketing experience¹

The following adverse reactions have been identified during post-approval use of MICARDIS®. 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 factors¹:

• seriousness of the reaction,
• frequency of reporting, or
• strength of causal connection to MICARDIS®.

The most frequent 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 (more commonly seen in Japanese patients), 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).¹

Rare cases of rhabdomyolysis have been reported in patients receiving angiotensin II receptor blockers, including MICARDIS®.¹

Overdose¹

Limited data are available with regard to overdosage in humans. The most likely manifestation of overdosage with MICARDIS® tablets would be hypotension, dizziness and tachycardia; bradycardia could occur from parasympathetic (vagal) stimulation. If symptomatic hypotension should occur, supportive treatment should be instituted. Telmisartan is not removed by hemodialysis.¹

MICARDIS PLUS®²

Summary of the safety profile²

The overall incidence of adverse events reported with MICARDIS PLUS® was comparable to those reported with telmisartan alone in randomized controlled trials involving 1,471 patients receiving telmisartan plus hydrochlorothiazide (835) or telmisartan alone (636). There was no dose-relationship to undesirable effects and there was no correlation with gender, age or race of the patients.²

Tabulated summary of adverse reactions²

Adverse reactions reported in clinical trials with telmisartan plus hydrochlorothiazide are shown below according to system organ class. Adverse reactions not observed in clinical trials with telmisartan plus hydrochlorothiazide but expected during treatment with MICARDIS PLUS® based on the experience with telmisartan or hydrochlorothiazide alone are shown in the table below classified by MedDRA System organ class and MedDRA Preferred Terms.²

Overdose²

Symptoms²

Limited information is available for MICARDIS PLUS® with regard to overdose in humans. The most prominent manifestations of telmisartan overdose were hypotension and tachycardia; bradycardia also occurred. Overdose with hydrochlorothiazide is associated with electrolyte depletion (hypokalemia, hypochloremia) and dehydration resulting from excessive diuresis. The most common signs and symptoms of overdose are nausea and somnolence. Hypokalemia may result in muscle spasm and/or accentuate cardiac arrhythmias associated with the concomitant use of digitalis glycosides or certain anti-arrhythmic drugs.²

Therapy²

No specific information is available on the treatment of overdose with MICARDIS PLUS®. The patient should be closely monitored, and the treatment should be symptomatic and supportive depending on the time since ingestion and the severity of the symptoms. Serum electrolytes and creatinine should be monitored frequently. If hypotension occurs, the patient should be placed in a supine position, with salt and volume replacements given quickly. Telmisartan is not removed by hemodialysis. The degree to which hydrochlorothiazide is removed by hemodialysis has not been established.²