Micardis

Pregnancy category: 1st trimester, C; 2nd and 3rd trimesters, D

Lactation: Not known whether drug is excreted in breast milk; avoid using

Pregnancy Categories

A:Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B:May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C:Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D:Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X:Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA:Information not available.

Telmisartan may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away:

• back pain
• sinus pain and congestion
• diarrhea

Some side effects can be serious. If you experience any of these symptoms, or those listed in the SPECIAL PRECAUTIONS section, call your doctor immediately:

• swelling of the face, throat, tongue, lips, eyes, hands, feet, ankles, or lower legs
• hoarseness
• difficulty breathing or swallowing
• pain and cramping in the lower leg that comes and goes during walking or exercise
• blistering of the skin or rash

Telmisartan may cause other side effects. Call your doctor if you have any unusual problems while taking this medication.

If you experience a serious side effect, you or your doctor may send a report to the Food and Drug Administration's (FDA) MedWatch Adverse Event Reporting program online (http://www.fda.gov/Safety/MedWatch) or by phone (1-800-332-1088).

Before taking Micardis, tell your doctor about all prescription, non-prescription, illegal, recreational, herbal, nutritional, or dietary drugs you're taking, especially those listed in the Warning section and the following:

• Angiotensin-converting enzyme (ACE) inhibitors such as Accupril, in Accuretic, in Quinaretic (quinapril), Aceon (perindopril), Altace (ramipril), Capoten, in Capozide (captopril), in Monopril (fosinopril), in Prinzide (lisinopril), Lotensin, in Lotrel (benazepril), Mavik, in Tarka (trandolapril), Univasc, in Uniretic (moexipril), Vasotec (enalapril)
• Diuretics (water pills) including Aldactone, in Aldactazide (spironolactone)
• Lithobid (lithium)
• Non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin, Advil or Motrin (ibuprofen), Aleve or Naprosyn (naproxen), and Celebrex (celecoxib)
• Lanoxin (digoxin)
• Potassium supplements

Micardis and Other Interactions

Micardis may cause drowsiness or dizziness. Don't drive a car or operate machinery until you know how this medicine affects you.

Micardis and Alcohol

Avoid consuming alcohol while taking Micardis. It can lower your blood pressure and may increase some of the side effects of the drug.

MICARDIS is a non-peptide angiotensin II receptor (type AT1) antagonist.

Telmisartan is chemically described as 4'-[(1,4'-dimethyl-2'-propyl [2,6'-bi-1H-benzimidazol]-1'-yl)methyl]-[1,1'-biphenyl]-2-carboxylic acid. Its empirical formula is C33H30N4O2, its molecular weight is 514.63, and its structural formula is:

Telmisartan is a white to slightly yellowish solid. It is practically insoluble in water and in the pH range of 3 to 9, sparingly soluble in strong acid (except insoluble in hydrochloric acid), and soluble in strong base.

MICARDIS is available as tablets for oral administration, containing 20 mg, 40 mg or 80 mg of telmisartan. The tablets contain the following inactive ingredients: sodium hydroxide, meglumine, povidone, sorbitol, and magnesium stearate. MICARDIS tablets are hygroscopic and require protection from moisture.

Dosage Forms And Strengths

• 20 mg, white or off-white, round, uncoated tablets imprinted with BI logo on one side and 50 H on the other side
• 40 mg, white or off-white, oblong, uncoated tablets imprinted with BI logo on one side and 51 H on the other side
• 80 mg, white or off-white, oblong, uncoated tablets imprinted with BI logo on one side and 52 H on the other side

Storage And Handling

MICARDIS is available as white or off-white, uncoated tablets containing telmisartan 20 mg, 40 mg, or 80 mg. Tablets are marked with the BOEHRINGER INGELHEIM logo on one side, and on the other side, with either 50H, 51H, or 52H for the 20 mg, 40 mg, and 80 mg strengths, respectively. Tablets are provided as follows:

MICARDIS tablets 20 mg are round and individually blister-sealed in cartons of 30 tablets as 3 x 10 cards (NDC 0597-0039-37).

MICARDIS tablets 40 mg are oblong shaped and individually blister-sealed in cartons of 30 tablets as 3 x 10 cards (NDC 0597-0040-37).

MICARDIS tablets 80 mg are oblong shaped and individually blister-sealed in cartons of 30 tablets as 3 x 10 cards (NDC 0597-0041-37).

Store at 25°C (77°F); excursions permitted to 15°-30°C (59°-86°F) [see USP Controlled Room Temperature]. Tablets should not be removed from blisters until immediately before administration.

Distributed by: Boehringer Ingelheim Pharmaceuticals, Inc. Ridgefield, CT 06877 USA. Licensed from: Boehringer Ingelheim International GmbH, Ingelheim, Germany. Revised: December 2014

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.

Your pharmacist can provide more information about telmisartan.

Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.

Every effort has been made to ensure that the information provided by Cerner Multum, Inc. ('Multum') is accurate, up-to-date, and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. Multum information has been compiled for use by healthcare practitioners and consumers in the United States and therefore Multum does not warrant that uses outside of the United States are appropriate, unless specifically indicated otherwise. Multum's drug information does not endorse drugs, diagnose patients or recommend therapy. Multum's drug information is an informational resource designed to assist licensed healthcare practitioners in caring for their patients and/or to serve consumers viewing this service as a supplement to, and not a substitute for, the expertise, skill, knowledge and judgment of healthcare practitioners. The absence of a warning for a given drug or drug combination in no way should be construed to indicate that the drug or drug combination is safe, effective or appropriate for any given patient. Multum does not assume any responsibility for any aspect of healthcare administered with the aid of information Multum provides. The information contained herein is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. If you have questions about the drugs you are taking, check with your doctor, nurse or pharmacist.

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• Boehringer Ingelheim Pharmaceuticals, Inc.

Tell your doctor if you are pregnant or plan to become pregnant.

The FDA categorizes medications based on safety for use during pregnancy. Five categories - A, B, C, D, and X, are used to classify the possible risks to an unborn baby when a medication is taken during pregnancy.

Micardis falls into category D. See the “FDA Warning” section for more information.

Take Micardis exactly as prescribed.

Micardis comes in tablet form and is given once a day. Take Micardis at the same time each day.

Micardis can be taken with or without food.

If you miss a dose, take the missed dose as soon as you remember. If it is almost time for the next dose, skip the missed dose and take your next dose at the regular time. Do not take two doses of Micardis at the same time.

Take Micardis exactly as prescribed by your doctor. Follow the directions on your prescription label carefully.

The Micardis dose your doctor recommends will be based on the following:

• the condition being treated
• other medical conditions you have
• other medications you are taking
• how you respond to this medication
• your age

The recommended dose range of Micardis for the treatment of high blood pressure in adults is 20 to 80 mg once a day.

The recommended dose of Micardis for reducing the risk of heart problems in adults over 55 years old is 80 mg once a day.

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

In the U.S.

• Micardis

Available Dosage Forms:

• Tablet

Therapeutic Class: Cardiovascular Agent

Pharmacologic Class: Angiotensin II Receptor Antagonist

It is very important that your doctor check your progress at regular visits to make sure this medicine is working properly. Blood tests may be needed to check for unwanted effects.

Using this medicine while you are pregnant can harm your unborn baby. Use an effective form of birth control to keep from getting pregnant. If you think you have become pregnant while using this medicine, tell your doctor right away.

Dizziness, lightheadedness, or fainting may occur with this medicine, especially when you get up suddenly from a lying or sitting position. Make sure you know how you react to this medicine before you drive, use machines, or do anything else that could be dangerous if you are dizzy or not alert. If you feel dizzy, lie down so you do not faint. Then sit for a few moments before standing to prevent the dizziness from returning.

Check with your doctor right away if you become sick while taking this medicine, especially with severe or continuing nausea, vomiting, or diarrhea. These conditions may cause you to lose too much water and may lead to low blood pressure. You can also lose water by sweating, so drink plenty of water during exercise or in hot weather.

Ask your doctor before you use medicines, supplements, or salt substitutes that contain potassium.

Do not take other medicines unless they have been discussed with your doctor. This especially includes nonprescription medicines for appetite control, asthma, colds, cough, hay fever, or sinus problems, since they may increase your blood pressure.

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

• Changes in vision
• dizziness, lightheadedness, or fainting
• fast heartbeat
• large hives
• painful urination or changes in urinary frequency
• swelling in the hands, lower legs, and feet

• Blurred vision
• chest pain or discomfort
• confusion
• dark-colored urine
• decreased urine output
• dilated neck veins
• extreme fatigue
• flushing
• hives or welts
• hoarseness
• irregular breathing
• irritation
• itching
• joint pain, stiffness, or swelling
• large, hive-like swelling on the face, eyelids, lips, tongue, throat, hands, legs, feet, or sex organs
• muscle cramps or stiffness
• numbness or tingling in the hands, feet, or lips
• pain or discomfort in the arms, jaw, back, or neck
• pounding in the ears
• rash
• redness of the skin
• slow, fast, or irregular heartbeat
• sweating
• swelling of the eyelids, face, or lips
• tightness in the chest
• trouble breathing or swallowing
• trouble with speaking or walking
• trouble with thinking
• unusual tiredness or weakness
• unusually warm skin
• weakness or heaviness of the legs
• weakness, numbness, or tingling in the arms or legs
• weight gain

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Abdominal or stomach pain
• back pain
• bloating or gas
• changes in appetite
• coughing
• diarrhea
• dry mouth
• ear pain or hearing problems
• fever
• general tiredness or weakness
• headache
• heartburn
• increased sweating
• muscle pain or spasm
• nausea
• nervousness
• runny or stuffy nose
• sneezing
• sore throat

• Acid or sour stomach
• belching
• decreased interest in sexual intercourse
• difficulty with moving
• inability to have or keep an erection
• indigestion
• joint pain
• lack or loss of strength
• leg cramps
• loss in sexual ability, desire, drive, or performance
• muscle aching
• stomach discomfort or upset
• swelling
• weakness

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

• Tell all of your health care providers that you take this medicine (Micardis). This includes your doctors, nurses, pharmacists, and dentists.
• Avoid driving and doing other tasks or actions that call for you to be alert until you see how this medicine affects you.
• To lower the chance of feeling dizzy or passing out, rise slowly if you have been sitting or lying down. Be careful going up and down stairs.
• Have your blood pressure checked often. Talk with your doctor.
• Have blood work checked as you have been told by the doctor. Talk with the doctor.
• If you are on a low-salt or salt-free diet, talk with your doctor.
• If you are taking a salt substitute that has potassium, potassium-sparing diuretics, or potassium, talk with your doctor.
• If you are taking this medicine (Micardis) and have high blood pressure, talk with your doctor before using OTC products that may raise blood pressure. These include cough or cold drugs, diet pills, stimulants, ibuprofen or like products, and some natural products or aids.
• Talk with your doctor before you drink alcohol.
• Be careful in hot weather or while being active. Drink lots of fluids to stop fluid loss.
• Tell your doctor if you have too much sweat, fluid loss, throwing up, or loose stools. This may lead to low blood pressure.
• This medicine may affect how much of some other drugs are in your body. If you are taking other drugs, talk with your doctor. You may need to have your blood work checked more closely while taking this medicine with your other drugs.
• This medicine may not work as well in black patients. Talk with the doctor.

Use this medicine (Micardis) as ordered by your doctor. Read all information given to you. Follow all instructions closely.

• Take with or without food.
• To gain the most benefit, do not miss doses.
• Keep taking this medicine as you have been told by your doctor or other health care provider, even if you feel well.
• Take this medicine (Micardis) at the same time of day.
• Drink lots of noncaffeine liquids unless told to drink less liquid by your doctor.

What do I do if I miss a dose?

• Take a missed dose as soon as you think about it.
• If it is close to the time for your next dose, skip the missed dose and go back to your normal time.
• Do not take 2 doses at the same time or extra doses.

• Store in the original container at room temperature.
• Protect from light.
• Store in a dry place. Do not store in a bathroom.
• Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
• Check with your pharmacist about how to throw out unused drugs.

Micardis is contraindicated in patients with known hypersensitivity (e.g., anaphylaxis or angioedema) to telmisartan or any other component of this product [see Adverse Reactions (6.2)].

Do not co-administer aliskiren with Micardis in patients with diabetes [see Drug Interactions (7)].

The following adverse reaction is described elsewhere in labeling:

        Renal dysfunction upon use with ramipril [see Warnings and Precautions (5.6)]

  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.

Hypertension
Micardis has been evaluated for safety in more than 3700 patients, including 1900 treated for over 6 months and more than 1300 for over one year.  Adverse experiences have generally been mild and transient in nature and have infrequently required discontinuation of therapy.

In placebo-controlled trials involving 1041 patients treated with various doses of Micardis (20 to 160 mg) monotherapy for up to 12 weeks, the overall incidence of adverse events was similar to that in patients treated with placebo.

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 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 1455 patients treated with Micardis 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.

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 above, adverse events that occurred in more than 0.3% of 3500 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:

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, non-specific 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 Micardis 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 because of 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 because of 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 because of abnormal hepatic function.

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=5926, 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 Experience

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 factors:  (1) seriousness of the reaction, (2) frequency of reporting, or (3) 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, 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).

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

  Mechanism of Action

Angiotensin II is formed from angiotensin I in a reaction catalyzed by angiotensin-converting enzyme (ACE, kininase II). Angiotensin II is the principal pressor agent of the renin-angiotensin system, with effects that include vasoconstriction, stimulation of synthesis and release of aldosterone, cardiac stimulation, and renal reabsorption of sodium.  Telmisartan blocks the vasoconstrictor and aldosterone-secreting effects of angiotensin II by selectively blocking the binding of angiotensin II to the AT1 receptor in many tissues, such as vascular smooth muscle and the adrenal gland.  Its action is therefore independent of the pathways for angiotensin II synthesis.

There is also an AT2 receptor found in many tissues, but AT2 is not known to be associated with cardiovascular homeostasis. Telmisartan has much greater affinity (>3,000 fold) for the AT1 receptor than for the AT2 receptor.

Blockade of the renin-angiotensin system with ACE inhibitors, which inhibit the biosynthesis of angiotensin II from angiotensin I, is widely used in the treatment of hypertension. ACE inhibitors also inhibit the degradation of bradykinin, a reaction also catalyzed by ACE. Because telmisartan does not inhibit ACE (kininase II), it does not affect the response to bradykinin. Whether this difference has clinical relevance is not yet known. Telmisartan does not bind to or block other hormone receptors or ion channels known to be important in cardiovascular regulation.

Blockade of the angiotensin II receptor inhibits the negative regulatory feedback of angiotensin II on renin secretion, but the resulting increased plasma renin activity and angiotensin II circulating levels do not overcome the effect of telmisartan on blood pressure.

  Pharmacodynamics

In normal volunteers, a dose of telmisartan 80 mg inhibited the pressor response to an intravenous infusion of angiotensin II by about 90% at peak plasma concentrations with approximately 40% inhibition persisting for 24 hours.

Plasma concentration of angiotensin II and plasma renin activity (PRA) increased in a dose-dependent manner after single administration of telmisartan to healthy subjects and repeated administration to hypertensive patients. The once-daily administration of up to 80 mg telmisartan to healthy subjects did not influence plasma aldosterone concentrations. In multiple dose studies with hypertensive patients, there were no clinically significant changes in electrolytes (serum potassium or sodium), or in metabolic function (including serum levels of cholesterol, triglycerides, HDL, LDL, glucose, or uric acid).

In 30 hypertensive patients with normal renal function treated for 8 weeks with telmisartan 80 mg or telmisartan 80 mg in combination with hydrochlorothiazide 12.5 mg, there were no clinically significant changes from baseline in renal blood flow, glomerular filtration rate, filtration fraction, renovascular resistance, or creatinine clearance.

  Pharmacokinetics

Following oral administration, peak concentrations (Cmax) of telmisartan are reached in 0.5 to 1 hour after dosing. Food slightly reduces the bioavailability of telmisartan, with a reduction in the area under the plasma concentration-time curve (AUC) of about 6% with the 40 mg tablet and about 20% after a 160 mg dose. The absolute bioavailability of telmisartan is dose dependent. At 40 and 160 mg the bioavailability was 42% and 58%, respectively. The pharmacokinetics of orally administered telmisartan are nonlinear over the dose range 20 to 160 mg, with greater than proportional increases of plasma concentrations (Cmax and AUC) with increasing doses. Telmisartan shows bi-exponential decay kinetics with a terminal elimination half life of approximately 24 hours. Trough plasma concentrations of telmisartan with once daily dosing are about 10% to 25% of peak plasma concentrations. Telmisartan has an accumulation index in plasma of 1.5 to 2.0 upon repeated once daily dosing.

Distribution
Telmisartan is highly bound to plasma proteins (>99.5%), mainly albumin and α1 - acid glycoprotein. Plasma protein binding is constant over the concentration range achieved with recommended doses. The volume of distribution for telmisartan is approximately 500 liters indicating additional tissue binding.

Metabolism and Elimination
Following either intravenous or oral administration of 14C-labeled telmisartan, most of the administered dose (>97%) was eliminated unchanged in feces via biliary excretion; only minute amounts were found in the urine (0.91% and 0.49% of total radioactivity, respectively).

Telmisartan is metabolized by conjugation to form a pharmacologically inactive acyl glucuronide; the glucuronide of the parent compound is the only metabolite that has been identified in human plasma and urine. After a single dose, the glucuronide represents approximately 11% of the measured radioactivity in plasma. The cytochrome P450 isoenzymes are not involved in the metabolism of telmisartan.

Total plasma clearance of telmisartan is >800 mL/min. Terminal half-life and total clearance appear to be independent of dose.

Specific Populations
Renal Insufficiency
No dosage adjustment is necessary in patients with decreased renal function. Telmisartan is not removed from blood by hemofiltration [see Warnings and Precautions (5.5) and Dosage and Administration (2.1)].

Hepatic Insufficiency
In patients with hepatic insufficiency, plasma concentrations of telmisartan are increased, and absolute bioavailability approaches 100% [see Warnings and Precautions (5.4) and Use in Specific Populations (8.6)].

Gender
Plasma concentrations of telmisartan are generally 2 to 3 times higher in females than in males. In clinical trials, however, no significant increases in blood pressure response or in the incidence of orthostatic hypotension were found in women. No dosage adjustment is necessary.

Geriatric Patients
The pharmacokinetics of telmisartan do not differ between the elderly and those younger than 65 years [see Dosage and Administration (2.1)].

Pediatric Patients
Telmisartan pharmacokinetics have not been investigated in patients <18 years of age.

Applies to telmisartan: oral tablet

General

The most common adverse events reported in hypertension trials were back pain, sinusitis, and diarrhea. The most common adverse events reported in cardiovascular risk reduction trials were intermittent claudication and skin ulcer.[Ref]

Gastrointestinal

Common (1% to 10%): Diarrhea, dyspepsia, nausea, abdominal pain
Uncommon (0.1% to 1%): Flatulence, vomiting, dry mouth, stomach discomfort, constipation, gastritis, hemorrhoids, gastroenteritis, enteritis, gastroesophageal reflux, toothache[Ref]

Cardiovascular

Common (1% to 10%): Hypotension, palpitation, intermittent claudication, hypertension
Uncommon (0.1% to 1%): Bradycardia, orthostatic hypotension, tachycardia, angina pectoris, flushing, dependent edema, abnormal ECG
Postmarketing reports: Atrial fibrillation, congestive heart failure, myocardial infarction, blood pressure increased, hypertension aggravated[Ref]

Respiratory

Common (1% to 10%): Coughing, upper respiratory tract infection, sinusitis, pharyngitis, bronchitis
Uncommon (0.1% to 1%): Dyspnea, asthma, epistaxis, rhinitis
Very rare (less than 0.01%): Interstitial lung disease[Ref]

Musculoskeletal

Common (1% to 10%): Back pain, myalgia, arthralgia, muscle spasms
Uncommon (0.1% to 1%): Gout, pain in extremity, arthritis
Rare (less than 0.1%): Tendon pain, blood creatine phosphokinase increased
Postmarketing reports: Rhabdomyolysis[Ref]

Psychiatric

Common (1% to 10%): Insomnia, anxiety, depression
Uncommon (0.1% to 1%): Nervousness[Ref]

Nervous system

Common (1% to 10%): Headache, dizziness
Uncommon (0.1% to 1%): Syncope, somnolence, migraine, paresthesia, hypoesthesia, cerebrovascular disorder
Rare (less than 0.1%): Dysgeusia[Ref]

Dermatologic

Common (1% to 10%): Rash, skin ulcer
Uncommon (0.1% to 1%): Pruritus, hyperhidrosis, eczema, dermatitis, sweating increased
Rare (less than 0.1%): Erythema, urticaria, drug eruption, toxic skin eruption[Ref]

Genitourinary

Common (1% to 10%): Urinary tract infection
Uncommon (0.1% to 1%): Micturition frequency, impotence, cystitis
Postmarketing reports: Erectile dysfunction[Ref]

Other

Common (1% to 10%): Pain, fatigue, influenza-like illness, chest pain, peripheral edema
Uncommon (0.1% to 1%): Vertigo, asthenia, tinnitus, earache, malaise, fever, leg edema
Postmarketing reports: Face edema[Ref]

Immunologic

Uncommon (0.1% to 1%): Infection, fungal infection, abscess, otitis media, allergy, sepsis
Rare (less than 0.1%): Anaphylactic reaction, angioedema, hypersensitivity
Postmarketing reports: Angioneurotic edema[Ref]

Metabolic

Uncommon (0.1% to 1%): Hyperkalemia, hypercholesterolemia, diabetes mellitus
Rare (less than 0.1%): Hypoglycemia in diabetic patients[Ref]

Hematologic

Uncommon (0.1% to 1%): Anemia, hemoglobin decreased
Rare (less than 0.1%): Eosinophilia, thrombocytopenia[Ref]

Renal

Uncommon (0.1% to 1%): Renal impairment including acute renal failure, blood creatinine increased
Rare (less than 0.1%): Blood uric acid increased
Frequency not reported: Acute renal failure[Ref]

Ocular

Uncommon (0.1% to 1%): Conjunctivitis, visual disturbance[Ref]

Hepatic

Rare (less than 0.1%): Hepatic function abnormal/liver disorder, hepatic enzyme increased[Ref]

Some side effects of Micardis may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

Animal studies have revealed evidence of fetal and postnatal toxicity. In humans, use of drugs that act on the renin angiotensin system (RAS) during the second and third trimesters increases fetal and neonatal morbidity and death. There are no controlled data in human pregnancy. AU TGA pregnancy category D: Drugs which have caused, are suspected to have caused or may be expected to cause, an increased incidence of human fetal malformations or irreversible damage. These drugs may also have adverse pharmacological effects. Accompanying texts should be consulted for further details. US FDA pregnancy category D: There is positive evidence of human fetal risk based on adverse reaction data from investigational or marketing experience or studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks.

AU and UK: Use is not recommended during the first trimester of pregnancy and is contraindicated during the second and third trimesters. US: This drug should not be used during pregnancy unless there are no alternatives and the benefit outweighs the risk to the fetus. AU TGA pregnancy category: D US FDA pregnancy category: D Comments: Adequate methods of contraception should be encouraged.