Side Effects of Micardis (telmisartan)

Micardis (telmisartan) is an angiotensin receptor blocker (ARB) used to treat high blood pressure (hypertension) and to reduce the risk of heart attack, stroke, or death from cardiovascular causes in patients 55 years of age or older who are at high risk for developing major cardiovascular events and unable to take ACE inhibitors. 

Angiotensin, formed in the blood by the action of angiotensin converting enzyme (ACE), is a powerful chemical that attaches to angiotensin receptors found in many tissues but primarily on muscle cells of blood vessels. Angiotensin’s attachment to the receptors causes muscle cells to shorten and narrow the blood vessels (vasoconstrict), which leads to an increase in blood pressure (hypertension). 

Micardis blocks the angiotensin receptor. By blocking the action of angiotensin, Micardis widens blood vessels (vasodilate) and reduces blood pressure. 

Common side effects of Micardis include:

• headache,
• dizziness,
• back pain,
• fatigue,
• stomach upset,
• upper respiratory tract infections,
• high blood potassium (hyperkalemia),
• impotence, and
• diarrhea.

Serious side effects of Micardis include:

• reduced kidney function allergic reactions,
• rhabdomyolysis (inflammation and destruction of muscle), and
• angioedema (swelling of soft tissues including those of the throat and larynx).

Drug interactions of Micardis include digoxin and lithium because it can increase blood concentration of these drugs. 

Combining Micardis with potassium-sparing diuretics may lead to elevated potassium in the blood (hyperkalemia), including:

• potassium supplements, or
• salt substitutes containing potassium. 

Combining Micardis or other ARBs with nonsteroidal anti-inflammatory drugs (NSAIDs) in patients who are elderly, fluid-depleted (including those on diuretic therapy), or with poor kidney function may result in reduced kidney function, including kidney failure. 

Aspirin and other NSAIDs may reduce the effects of ARBs. 

Medications that interfere with the angiotensin converting enzyme system, such as Micardis, have been found to cause fetal and neonatal toxicity and death when taken by pregnant women. Pregnant mothers should discontinue use of Micardis as soon as they know they are pregnant. 

It is unknown if Micardis is secreted into breast milk. Since most medicines are secreted into breast milk, potential risks and benefits need to be assessed in women who are nursing to determine if breastfeeding or Micardis should be discontinued.

Like other angiotensin receptor blockers, telmisartan generally is well-tolerated. The most common side effects are:

• headache,
• dizziness,
• back pain,
• fatigue,
• stomach upset,
• upper respiratory tract infections,
• hyperkalemia, and
• diarrhea.

Patients also may experience impotence, reduced renal function, and allergic reactions. Rhabdomyolysis (inflammation and destruction of muscle) and angioedema (swelling of soft tissues including those of the throat and larynx) are rare but serious side effects of telmisartan.

The following adverse reactions are discussed elsewhere in labeling:

• Hypotension
• Renal Impairment
• Electrolytes and Metabolic Disorders

Clinical Trials Experience

Because clinical studies are conducted under widely varying conditions, adverse reaction 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.

Micardis HCT has been evaluated for safety in more than 1700 patients, including 716 treated for hypertension for longer than 6 months and 420 for more than 1 year. Adverse reactions have been limited to those that have been previously reported with telmisartan and/or hydrochlorothiazide.

Adverse reactions occurring at an incidence of =2% in patients treated with telmisartan/hydrochlorothiazide and at a greater rate than in patients treated with placebo, are presented in Table 1.

Table 1 Adverse Reactions Occurring at an Incidence of ≥2% in Patients Treated with Telmisartan/Hydrochlorothiazide and at a Greater Rate Than in Patients Treated with Placebo*

Other adverse reactions observed for telmisartan/hydrochlorothiazide were:

• pain (including back and abdominal),
• dyspepsia,
• erythema,
• vomiting,
• bronchitis, and
• pharyngitis.

Adverse reactions occurred at approximately the same rates in men and women, older and younger patients, and black and non-black patients.

Telmisartan

Other adverse events that have been reported with telmisartan are listed below:

Autonomic Nervous System: impotence, increased sweating, flushing

Body as a Whole: allergy, fever, leg pain, chest pain

Cardiovascular: palpitation, angina pectoris, abnormal ECG, hypertension, peripheral edema

Central Nervous System: insomnia, somnolence, migraine, paresthesia, involuntary muscle contractions, hypoesthesia

Gastrointestinal: flatulence, constipation, gastritis, dry mouth, hemorrhoids, gastroesophageal reflux, toothache

Hepato-biliary: elevations of liver enzymes or serum bilirubin

Metabolic: gout, hypercholesterolemia, diabetes mellitus

Musculoskeletal: arthritis, arthralgia, leg cramps, myalgia

Psychiatric: anxiety, depression, nervousness

Resistance Mechanism: 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

Hydrochlorothiazide

Other adverse events that have been reported with hydrochlorothiazide 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

Musculoskeletal: muscle spasm

Nervous System/Psychiatric: restlessness

Renal: interstitial nephritis

Skin: erythema multiforme including Stevens-Johnson syndrome, exfoliative dermatitis including toxic epidermal necrolysis

Special Senses: transient blurred vision, xanthopsia

Clinical Laboratory Findings

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 because of an increase in BUN or creatinine.

Postmarketing Experience

The following adverse reactions have been identified during post-approval use of Micardis HCT. 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.

Blood and Lymphatic System Disorders: eosinophilia

Cardiac Disorders: atrial fibrillation, congestive heart failure, myocardial infarction, tachycardia, bradycardia

Ear and Labyrinth Disorders: vertigo

General Disorders and Administration Site Conditions: asthenia, edema

Hepato-biliary: Abnormal hepatic function/liver disorder

Immune System Disorders: anaphylactic reaction

Infections and Infestations: urinary tract infection

Investigations: increased CPK

Metabolism and Nutrition Disorders: hypoglycemia (in diabetic patients)

Musculoskeletal and Connective Tissue Disorders: tendon pain (including tendonitis, tenosynovitis), rhabdomyolysis

Nervous System Disorders: syncope, headache

Renal and Urinary Disorders: renal failure, renal impairment including acute renal failure

Reproductive System and Breast Disorders: erectile dysfunction

Respiratory, Thoracic and Mediastinal Disorders: coughing

Skin and Subcutaneous Tissue Disorders: drug eruption (toxic skin eruption mostly reported as toxicoderma, rash, and urticaria), angioedema (with fatal outcome)

Vascular Disorder: orthostatic hypotension

Agents Increasing Serum Potassium

Co-administration of telmisartan with other drugs that raise serum potassium levels may result in hyperkalemia. Monitor serum potassium in such patients.

Lithium

Increases in serum lithium concentrations and lithium toxicity have been reported with concomitant use of thiazide diuretics or angiotensin II receptor antagonists, including telmisartan. Monitor lithium levels in patients receiving Micardis HCT and lithium.

Non-Steroidal Anti-Inflammatory Agents Including Selective Cyclooxygenas E-2 Inhibitors

Telmisartan

Non-Steroidal Anti-Inflammatory Agents including Selective Cyclooxygenase-2 Inhibitors (COX-2 Inhibitors): In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, co-administration of NSAIDs, including selective COX-2 inhibitors, with ARBs, including telmisartan, may result in deterioration of renal function, including possible acute renal failure. These effects are usually reversible. The antihypertensive effect of ARBs may be attenuated by NSAIDs. Therefore, monitor renal function and blood pressure periodically in patients receiving Micardis HCT and NSAIDs.

Hydrochlorothiazide

Administration of a non-steroidal anti-inflammatory agent, including a selective COX2 inhibitor, can reduce the diuretic, natriuretic, and antihypertensive effects of diuretics. Therefore, when Micardis HCT and non-steroidal anti-inflammatory agents including selective COX2 inhibitors are used concomitantly, observe closely to determine if the desired effect of the diuretic is obtained.

Dual Blockade Of The Renin-Angiotens In-Aldosterone System And Changes In Renal Function

Dual blockade of the renin-angiotensin-aldosterone system (RAS) with angiotensin blockers, ACE inhibitors, or aliskiren is associated with increased risks of hypotension, hyperkalemia, and renal impairment. The ONTARGET trial enrolled 25,620 patients ≥55 years old with atherosclerotic disease or diabetes with end-organ damage, randomizing them to telmisartan (ARB) only, ramipril (ACE inhibitor) only, or the combination, and followed them for a median of 56 months.

Patients who received the combination of ARB and ACE inhibitor did not obtain any additional benefit (no additional reduction of risk of cardiovascular death, myocardial infarction, stroke, or hospitalization from heart failure) compared to ARB monotherapy or ACE inhibitor monotherapy, but experienced an increased incidence of renal dysfunction (e.g., acute renal failure) compared with monotherapy groups.

In general, avoid combined use of RAS inhibitors. Closely monitor blood pressure, renal function and electrolytes in patients on Micardis HCT and other agents that affect the RAS.

Do not co-administer aliskiren with Micardis HCT in patients with diabetes. Avoid concomitant use of aliskiren with Micardis HCT in patients with renal impairment (GFR <60 mL/min/1.73 m²).

Digoxin

When telmisartan was co-administered with digoxin, median increases in digoxin peak plasma concentration (49%) and in trough concentration (20%) were observed. Monitor digoxin levels in patients taking concomitant Micardis HCT and digoxin.

Antidiabetic Drugs (Oral Agents And Insulin)

Dosage adjustment of antidiabetic drugs may be required when coadministered with hydrochlorothiazide.

Cholestyramine And Colestipol Resins

Absorption of hydrochlorothiazide is impaired in the presence of anionic exchange resins. Stagger the dosage of hydrochlorothiazide and the resin such that hydrochlorothiazide is administered at least 4 hours before or 4 to 6 hours after the administration of the resin.