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Micardis

Pronunciation

Generic Name: Telmisartan
Class: Angiotensin II Receptor Antagonists
VA Class: CV805
Chemical Name: 4′ - [1(1,4′ - Dimethyl - 2′ - propyl[2,6′ - bi - 1H - benzimidazol] - 1′ - yl)methyl] - [1,1′ - biphenyl] - 2 - carboxylic acid
Molecular Formula: C33H30N4O2
CAS Number: 144701-48-4

Warning(s)

  • May cause fetal and neonatal morbidity and mortality if used during pregnancy.1 2 49 50 (See Fetal/Neonatal Morbidity and Mortality under Cautions.)

  • If pregnancy is detected, discontinue as soon as possible.1 2 50

Introduction

Angiotensin II receptor (AT1) antagonist.1 2 3 16

Uses for Micardis

Hypertension

Management of hypertension (alone or in combination with other classes of antihypertensive agents).1 2 3 17 19 500

Angiotensin II receptor antagonists are recommended as one of several preferred agents for the initial management of hypertension; other options include ACE inhibitors, calcium-channel blockers, and thiazide diuretics.501 502 503 504 While there may be individual differences with respect to specific outcomes, these antihypertensive drug classes all produce comparable effects on overall mortality and cardiovascular, cerebrovascular, and renal outcomes.501 502 503 504 Individualize choice of therapy; consider patient characteristics (e.g., age, ethnicity/race, comorbidities, cardiovascular risk) as well as drug-related factors (e.g., ease of administration, availability, adverse effects, cost).500 501 502 503 504 515

Angiotensin II receptor antagonists or ACE inhibitors may be preferred in hypertensive patients with diabetes mellitus or chronic kidney disease; angiotensin II receptor antagonists also may be preferred, as an alternative to ACE inhibitors, in hypertensive patients with heart failure or ischemic heart disease and/or post-MI.500 501 502 504 520 523 524 527 534 535 536 543

Slideshow: 2014 Update - First Time Brand-to-Generic Switches

Black hypertensive patients generally tend to respond better to monotherapy with calcium-channel blockers or thiazide diuretics than to angiotensin II receptor antagonists.500 501 504 However, diminished response to an angiotensin II receptor antagonist is largely eliminated when administered concomitantly with a calcium-channel blocker or thiazide diuretic.500 504

The optimum BP threshold for initiating antihypertensive drug therapy is controversial.501 504 505 506 507 508 515 523 530 Further study needed to determine optimum BP thresholds/goals; individualize treatment decisions.501 503 507 515 526 530

JNC 7 recommends initiation of drug therapy in all patients with uncomplicated hypertension and BP ≥140/90 mm Hg;500 JNC 8 panel recommends SBP threshold of 150 mm Hg for patients ≥60 years of age.501 Although many experts agree that SBP goal of <150 mm Hg may be appropriate for patients ≥80 years of age,502 504 505 530 application of this goal to those ≥60 years of age is controversial, especially for those at higher cardiovascular risk.501 502 505 506 508 511 515

In the past, initial antihypertensive drug therapy was recommended for patients with diabetes mellitus or chronic kidney disease who had BP ≥130/80 mm Hg;500 503 current hypertension management guidelines generally recommend a BP threshold of 140/90 mm Hg for these individuals (same as for the general population of patients without these conditions), although a goal of <130/80 mm Hg may still be considered.501 502 503 504 520 530 535 536 541

Diabetic Nephropathy

A recommended agent in the management of patients with diabetes mellitus and persistent albuminuria who have modestly elevated (30–300 mg/24 hours) or higher (>300 mg/24 hours) levels of urinary albumin excretion; slows rate of progression of renal disease in such patients.26 27 28 30 33 34 35 36 37 520 535 536

Heart Failure

Angiotensin II receptor antagonists are considered a reasonable alternative for inhibition of the renin-angiotensin system in patients with heart failure and reduced left ventricular ejection fraction (LVEF) who are intolerant of ACE inhibitors; because of their established benefits, ACE inhibitors are preferred.524 528

Micardis Dosage and Administration

General

BP Monitoring and Treatment Goals

  • Carefully monitor BP during initial titration or subsequent upward adjustment in dosage.500 501

  • When available, use evidence-based dosing information (i.e., dosages shown in randomized controlled trials to reduce complications of hypertension) to determine target dosages; target dosages usually can be achieved within 2–4 weeks but may take up to several months.501

  • If adequate BP response not achieved with a single antihypertensive agent, add a second drug with demonstrated benefit; if goal BP still not achieved with optimal dosages of 2 antihypertensive agents, add a third drug.501 May maximize dosage of the first drug before adding a second drug, or add a second drug before maximizing dosage of the initial drug.501

  • Consider initiating antihypertensive therapy with a combination of drugs if patient's BP exceeds goal BP by >20/10 mm Hg.500 501 503 504

  • Goal is to achieve and maintain optimal control of BP; individualize specific target BP based on consideration of multiple factors, including patient age and comorbidities, and currently available evidence from clinical studies.500 501 (See Hypertension under Uses.)

Administration

Oral Administration

Administer orally once daily without regard to meals.1 2

Dosage

Adults

Hypertension
Telmisartan Therapy
Oral

Initially, 40 mg once daily in adults without intravascular volume depletion.1

Usual dosage: 20–80 mg once daily;1 2 5 500 no additional therapeutic benefit with higher dosages.1 2

If intolerable adverse effects occur, consider dosage reduction; if adverse effects worsen or fail to resolve, may need to discontinue and switch to another antihypertensive drug class.501

Telmisartan/Hydrochlorothiazide Fixed-combination Therapy
Oral

Manufacturer states fixed-combination preparation should not be used for initial antihypertensive therapy.2

If BP is not adequately controlled by monotherapy with telmisartan 80 mg daily, can switch to fixed-combination tablets (telmisartan 80 mg and hydrochlorothiazide 12.5 mg; then telmisartan 160 mg and hydrochlorothiazide 25 mg), administered once daily.2

If BP is not adequately controlled by monotherapy with hydrochlorothiazide 25 mg or if BP is controlled but hypokalemia is problematic at this dosage, can use fixed-combination tablets containing telmisartan 80 mg and hydrochlorothiazide 12.5 mg, administered once daily.2 Can increase dosage to telmisartan 160 mg and hydrochlorothiazide 25 mg, if needed, to control BP.2

Special Populations

Hepatic Impairment

Initiate therapy under close medical supervision in patients with obstructive biliary disease or hepatic impairment.1

If fixed-combination tablets are used in patients with obstructive biliary disease or hepatic impairment, recommended initial dosage is telmisartan 40 mg and hydrochlorothiazide 12.5 mg daily.2 Use of fixed combination not recommended in those with severe hepatic impairment.2

Renal Impairment

No initial dosage adjustments necessary in patients with Clcr >30 mL/minute.1 2 Manufacturer makes no specific recommendations regarding telmisartan monotherapy in those with Clcr ≤30 mL/minute.1

Telmisartan/hydrochlorothiazide fixed combination not recommended in patients with Clcr <30 mL/minute.2

Geriatric Patients

No initial dosage adjustments necessary.1 2

Volume- and/or Salt-Depleted Patients

Correct volume and/or salt depletion prior to initiation of therapy or initiate therapy under close medical supervision using lower initial dosage.1 2

Cautions for Micardis

Contraindications

  • Known hypersensitivity to telmisartan or any ingredient in the formulation.1 2 7

Warnings/Precautions

Warnings

Hypotension

Possible symptomatic hypotension, particularly in volume- and/or salt-depleted patients (e.g., those treated with diuretics or undergoing dialysis).1 2 (See Volume- and/or Salt-Depleted Patients under Dosage and Administration.)

Transient hypotension is not a contraindication to additional doses; may reinstate therapy cautiously after BP is stabilized (e.g., with volume expansion).1 2

Fetal/Neonatal Morbidity and Mortality

Possible fetal and neonatal morbidity and mortality when used during pregnancy.1 2 50 (See Boxed Warning.) Such potential risks occur throughout pregnancy, especially during the second and third trimesters.50

Also may increase the risk of major congenital malformations when administered during the first trimester of pregnancy.49 50

Discontinue as soon as possible when pregnancy is detected, unless continued use is considered lifesaving.49 50 Nearly all women can be transferred successfully to alternative therapy for the remainder of their pregnancy.13

Malignancies

In July 2010, FDA initiated a safety review of angiotensin II receptor antagonists after a published meta-analysis found a modest but statistically significant increase in risk of new cancer occurrence in patients receiving an angiotensin II receptor antagonist compared with control.120 121 123 126 However, subsequent studies, including a larger meta-analysis conducted by FDA, have not shown such risk.126 127 128 129 Based on currently available data, FDA has concluded that angiotensin II receptor antagonists do not increase the risk of cancer.126

Sensitivity Reactions

Anaphylactoid reactions and/or angioedema possible;1 2 7 14 not recommended in patients with a history of angioedema associated with or unrelated to ACE inhibitor or angiotensin II receptor antagonist therapy.b

General Precautions

Renal Effects

Possible oliguria, progressive azotemia and, rarely, acute renal failure and/or death in patients with severe heart failure.1 2

Increases in BUN and Scr possible in patients with unilateral or bilateral renal artery stenosis.1 2

Use of Fixed Combinations

When used in fixed combination with hydrochlorothiazide, consider the cautions, precautions, and contraindications associated with hydrochlorothiazide.2

Specific Populations

Pregnancy

Category C (1st trimester); Category D (2nd and 3rd trimesters).1 2 (See Boxed Warning.)

Lactation

Distributed into milk in rats; not known whether distributed into human milk.1 2 Discontinue nursing or the drug.1 2

Pediatric Use

Safety and efficacy not established in children <18 years of age.1 2 21

Geriatric Use

No substantial differences in safety or efficacy relative to younger adults, but increased sensitivity cannot be ruled out.1 2

Hepatic Impairment

Plasma telmisartan concentrations may be increased in patients with obstructive biliary disease or hepatic impairment.1 2 (See Special Populations under Absorption, in Pharmacokinetics.) Dosage adjustments may be necessary.2 (See Hepatic Impairment under Dosage and Administration.)

Use of telmisartan in fixed combination with hydrochlorothiazide is not recommended in patients with severe hepatic impairment.2

Renal Impairment

Deterioration of renal function may occur.1 2 (See Renal Effects under Cautions.)

Use of telmisartan in fixed combination with hydrochlorothiazide is not recommended in patients with Clcr <30 mL/minute.2

Black Patients

BP reduction may be smaller in black patients compared with nonblack patients.1 (See Hypertension under Uses.)

Common Adverse Effects

Upper respiratory tract infection, sinusitis, pharyngitis, back pain, diarrhea.1

Interactions for Micardis

Not metabolized by CYP isoenzymes; has no effect on CYP isoenzymes except for some inhibition of CYP2C19 in vitro.1 2

Specific Drugs

Drug

Interaction

Comment

Acetaminophen

Interactions unlikely1 2

Amlodipine

Interactions unlikely1 2

Digoxin

Increased plasma digoxin concentrations1 2

Monitor serum digoxin concentrations when telmisartan therapy is initiated, adjusted, or discontinued in patients stabilized on digoxin1 2 3 21

Glyburide

Interactions unlikely1 2

Hydrochlorothiazide

Additive hypotensive effects1 2

Ibuprofen

Interactions unlikely1 2

Simvastatin

Interactions unlikely1 2

Warfarin

Possible decreased plasma warfarin concentrations; INR not affected1 2

Micardis Pharmacokinetics

Absorption

Bioavailability

Absolute bioavailability is dose dependent: 42% at 40 mg, 58% at 160 mg.1 2

Peak plasma concentration generally reached at 0.5–1 hour following oral administration.1 2

Onset

Antihypertensive effect evident within 2 weeks, with maximum BP reduction after 4 weeks.1

Food

Food slightly reduces bioavailability.1 2

Special Populations

In patients with hepatic insufficiency, plasma telmisartan concentrations are increased and absolute bioavailability approaches 100%.1 2

Distribution

Extent

Crosses the placenta and is distributed in the fetus in animals.1 2

Distributed into milk in rats; not known whether distributed into human milk.1 2

Plasma Protein Binding

>99.5% (principally albumin and α1-acid glycoprotein).1 2

Elimination

Metabolism

Metabolized in liver (via conjugation) to inactive metabolite.1 2

Not metabolized by CYP isoenzymes.1 2

Elimination Route

Eliminated mainly (>97%) as unchanged drug in feces (via bile); small amounts (<1%) eliminated in urine.1 2

Half-life

Biphasic; terminal half-life is approximately 24 hours.1 2

Special Populations

Not removed from blood by hemofiltration.1 2

Stability

Storage

Oral

Tablets

25°C (may be exposed to 15–30°C).1 2 Do not remove tablets from blisters until immediately before administration.1 2

Actions

  • Blocks the physiologic actions of angiotensin II, including vasoconstrictor and aldosterone-secreting effects.1 2

  • Does not interfere with response to bradykinins and substance P.1 2

  • Does not share the ACE inhibitor common adverse effect of dry cough.1 2 33

Advice to Patients

  • Risks of use during pregnancy.1 2 49 50

  • Importance of women informing their clinician if they are or plan to become pregnant or plan to breast-feed.1 2

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs.1 2

  • Importance of informing patients of other important precautionary information.1 2 (See Cautions.)

Preparations

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

Telmisartan

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets

20 mg

Micardis

Boehringer Ingelheim

40 mg

Micardis

Boehringer Ingelheim

80 mg

Micardis

Boehringer Ingelheim

Telmisartan Combinations

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets

40 mg with Hydrochlorothiazide 12.5 mg

Micardis HCT

Boehringer Ingelheim

80 mg with Hydrochlorothiazide 12.5 mg

Micardis HCT

Boehringer Ingelheim

80 mg with Hydrochlorothiazide 25 mg

Micardis HCT

Boehringer Ingelheim

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 02/2015. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Micardis 20MG Tablets (BOEHRINGER INGELHEIM): 30/$123.19 or 90/$337.09

Micardis 40MG Tablets (BOEHRINGER INGELHEIM): 30/$123.99 or 90/$355.97

Micardis 80MG Tablets (BOEHRINGER INGELHEIM): 30/$122.99 or 90/$325.95

Micardis HCT 40-12.5MG Tablets (BOEHRINGER INGELHEIM): 30/$123.99 or 90/$339.96

Micardis HCT 80-12.5MG Tablets (BOEHRINGER INGELHEIM): 30/$122.00 or 90/$335.97

Micardis HCT 80-25MG Tablets (BOEHRINGER INGELHEIM): 30/$123.99 or 90/$349.97

Twynsta 80-5MG Tablets (BOEHRINGER INGELHEIM): 30/$129.99 or 90/$365.98

AHFS DI Essentials. © Copyright, 2004-2015, Selected Revisions February 6, 2015. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

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2. Boehringer Ingelheim. Micardis HCT (telmisartan and hydrochlorothiazide) tablets prescribing information. Ridgefield, CT; 2004 Apr 19.

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