Telmisartan

Pronunciation: TEL-mi-SAR-tan
Class: Angiotensin II receptor antagonist

Trade Names

Micardis
- Tablets, oral 20 mg
- Tablets, oral 40 mg
- Tablets, oral 80 mg

Pharmacology

Antagonizes the effect of angiotensin II (vasoconstriction and aldosterone secretion) by blocking the angiotensin II (AT ₁ receptor) in vascular smooth muscle and the adrenal gland, producing decreased BP.

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Pharmacokinetics

Absorption

T _max is 0.5 to 1 h. Food slightly reduces bioavailability of telmisartan, with an AUC reduction of approximately 6% with a 40 mg dose and 20% with a 160 mg dose. At 40 and 160 mg, the bioavailability was 42% and 58%, respectively. Trough plasma concentrations with daily dosing are approximately 10% to 25% of C _max .

Distribution

Telmisartan is more than 99.5% protein bound. Vd is approximately 500 L.

Metabolism

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.

Elimination

Telmisartan half-life is approximately 24 h and total plasma Cl is more than 800 mL/min. After IV or oral administration, more than 97% is eliminated unchanged in feces via biliary excretion.

Special Populations

Telmisartan is not removed from blood by hemofiltration.

Plasma concentrations are increased and absolute bioavailability approaches 100%.

Pharmacokinetics do not differ between elderly patients and those younger than 65 y.

Pharmacokinetics have not been studied in patients younger than 18 y.

Plasma concentrations are generally 2 to 3 times higher in women than in men.

Indications and Usage

Treatment of hypertension; for the reduction of the risk of MI, stroke, or death from CV causes in patients 55 y and older who are at high risk of developing major CV events and are unable to take ACE inhibitors.

Contraindications

Known hypersensitivity (eg, anaphylaxis, angioedema) to telmisartan or any component of this product.

Dosage and Administration

PO 20 to 80 mg/day; usual starting dosage, 40 mg/day.

PO 80 mg once per day.

PO Initiate at low doses and uptitrate slowly in patients with biliary obstructive disorders or hepatic insufficiency.

General Advice

• May administer with or without food.
• May administer with other antihypertensive agents.

Storage/Stability

Store between 59° and 86°F.

Drug Interactions

Plasma concentrations of ramipril and the active metabolite, ramiprilat, may be increased, while plasma concentrations of telmisartan may be reduced. When coadministered, the hypotensive response may be increased because of possible additive pharmacodynamic effects, and because of the increased exposure to ramipril and ramiprilat. Coadministration of telmisartan and an ACE inhibitor is not recommended.

May increase plasma levels of digoxin, increasing the risk of toxicity. Monitor digoxin concentrations when starting, stopping, or changing the telmisartan dose. Adjust the digoxin dose as needed.

Plasma concentrations may be increased by telmisartan, resulting in an increase in the pharmacologic effects and adverse reactions of lithium. Monitor lithium serum concentrations. Adjust the lithium dose as needed.

The antihypertensive effect of telmisartan may be attenuated by NSAIDs. In patients who are elderly or volume-depleted, or have compromised renal function, coadministration of NSAIDs with telmisartan may result in deterioration of renal function, including possible acute renal failure.

The risk of hyperkalemia may be increased when a potassium-sparing diuretic is coadministered with telmisartan. Closely monitor serum potassium concentrations. Adjust treatment as needed.

Adverse Reactions

CNS

Asthenia, dizziness, fatigue, headache, weakness (postmarketing).

Cardiovascular

Atrial fibrillation, BP increased, bradycardia, CHF, hypertension aggravated, hypotension (including postural hypotension), MI, syncope (postmarketing)

Dermatologic

Skin ulcer (3%); erythema, sweating decreased, urticaria (postmarketing).

EENT

Sinusitis (3%); pharyngitis (1%).

GI

Diarrhea (3%); abdominal pain, dyspepsia, nausea (postmarketing).

Genitourinary

Erectile dysfunction, renal impairment including acute renal failure, UTI (postmarketing).

Hematologic-Lymphatic

Decreased hemoglobin (1%); anemia, eosinophilia, thrombocytopenia (postmarketing).

Metabolic

Edema, face edema, hyperkalemia, hypoglycemia (in diabetic patients), increased CPK, lower limb edema, uric acid increased (postmarketing).

Musculoskeletal

Back pain (3%); muscle cramps (including leg cramps), myalgia, rhabdomyolysis, tendon pain (including tendonitis), tenosynovitis (postmarketing).

Respiratory

Upper respiratory tract infection (7%); cough (2%).

Miscellaneous

Intermittent claudication (7%); abnormal hepatic function/liver disorder, anaphylactic reaction, angioedema (with fatal outcome), angioneurotic edema, chest pain, drug eruption (toxic skin eruption, mostly reported as toxicoderma, rash, and urticaria), hypersensitivity, pain (postmarketing).

Precautions

Pregnancy

Category D . May cause fetal harm.

Lactation

Undetermined.

Children

Safety and efficacy not established.

Renal Function

Treatment may be associated with oliguria and/or progressive azotemia, acute renal failure, and/or death in patients with renal dysfunction.

Hepatic Function

Use with caution.

Hyperkalemia

May occur, particularly in patients with advanced renal impairment, with heart failure, on renal replacement therapy, or on potassium supplements or other drugs that increase potassium levels.

Hypotension in volume-depleted patients

Symptomatic hypotension may occur after telmisartan initiation in intravascularly volume-depleted patients (eg, those treated with high-dose diuretics). Correct these conditions prior to administration or use a lower starting dose.

Renal effects

Use with caution in patients whose renal function may depend on the activity of the renin-angiotensin-aldosterone system (eg, patients with severe CHF or renal dysfunction); use may be associated with oliguria, progressive azotemia, acute renal failure, and/or death. Changes in renal function (including acute renal failure) have been reported when adding an ACE inhibitor to an angiotensin II receptor antagonist.

Overdosage

Symptoms

Bradycardia, dizziness, hypotension, tachycardia.

Patient Information

• Inform women of childbearing age about the consequences of exposure to drugs that act directly on the renin-angiotensin system. Discuss treatment options with women planning to become pregnant. Advise these patients to report pregnancies to their health care provider as soon as possible.

Copyright © 2009 Wolters Kluwer Health.