Side Effects of Micardis (telmisartan)

Micardis(telmisartan) is an angiotensin receptor blocker (ARB) used to treathigh blood pressure(hypertension) and to reduce the risk ofheart 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 takeACE 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官网地址bwin(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 functionallergicreactions,
• rhabdomyolysis(inflammation and destruction of muscle), and
• angioedema(swelling of soft tissues including those of the throat and larynx).

Drug interactionsof Micardis includedigoxinandlithiumbecause it can increase blood concentration of thesedrugs.

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

• potassiumsupplements, or
• salt substitutes containing potassium.

Combining Micardis or otherARBswith 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, includingkidney failure.

Aspirinand 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 andneonataltoxicity and death when taken bypregnantwomen. Pregnant mothers should discontinue use of Micardis as soon as they know they are pregnant.

It is unknown if Micardis is secreted intobreast milk. Since most medicines are secreted into breast milk, potential risks and benefits need to be assessed in women who arenursingto determine ifbreastfeedingor 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 experienceimpotence, reduced renal function, and allergic reactions. Rhabdomyolysis (inflammation and destruction of muscle) andangioedema(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
• Electrolytesand 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.

MicardisHCThas been evaluated for safety in more than 1700 patients, including 716 treated forhypertensionfor 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/orhydrochlorothiazide.

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*

	Telmisartan/ Hydrochlorothiazide (n = 414)	Placebo (n = 74)	Telmisartan (n = 209)	Hydrochlorothiazide (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 to 160 mg), hydrochlorothiazide (6.25 to 25 mg), and combinations thereof

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, increasedsweating, flushing

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

Cardiovascular:palpitation,angina pectoris, abnormalECG, hypertension, peripheraledema

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

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

Hepato-biliary:elevations ofliver enzymesor serumbilirubin

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 cholestaticjaundice), sialadenitis, cramping, gastric irritation

Hematologic:aplasticanemia, agranulocytosis, leukopenia, hemolyticanemia,thrombocytopenia

Hypersensitivity:purpura,photosensitivity,urticaria, necrotizingangiitis(vasculitisand cutaneousvasculitis),fever, respiratory distress including pneumonitis andpulmonary edema, anaphylactic reactions

Metabolic:hyperglycemia, glycosuria

Musculoskeletal:muscle spasm

Nervous System/Psychiatric:restlessness

Renal:interstitial nephritis

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

Special Senses:transientblurred vision, xanthopsia

Clinical Laboratory Findings

Creatinine, Blood Urea Nitrogen (BUN)

Increases in BUN (=11.2 mg/dL) and serumcreatinine(=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 andLabyrinth障碍:vertigo

General Disorders and Administration Site Conditions:asthenia, edema

Hepato-biliary:Abnormal hepatic function/liverdisorder

Immune System Disorders:anaphylactic reaction

Infections and Infestations:urinary tract infection

Investigations:increased CPK

Metabolism andNutrition障碍:hypoglycemia(in diabetic patients)

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

Nervous System Disorders:syncope,headache

Renal and Urinary Disorders:renal failure, renal impairment includingacute renal failure

生殖系统和乳房疾病:erectile dysfunction

Respiratory, Thoracic and Mediastinal Disorders:coughing

皮肤和Subcutaneous Tissue Disorders:drug eruption (toxic skin eruption mostly reported as toxicoderma,rash, andurticaria), 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 ofthiazide diureticsor 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 selectiveCOX-2抑制剂,ARBs药物,包括替米沙坦,阿美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 ofhypotension, hyperkalemia, and renal impairment. The ONTARGET trial enrolled 25,620 patients ≥55 years old withatheroscleroticdisease ordiabeteswith 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 fromheart 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.

一般来说,避免使用RAS抑制剂相结合。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 withdiabetes. 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.

消胆胺和降脂树脂ⅱ号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.