Introduction
Telmisartan is an angiotensin II receptor blocker (ARB) used primarily in the management of hypertension and cardiovascular risk reduction. As a non-peptide antagonist of the angiotensin II type 1 (AT1) receptor, it represents a cornerstone therapy in modern cardiovascular medicine with additional metabolic benefits that distinguish it from other ARBs.
Mechanism of Action
Telmisartan selectively and competitively blocks the binding of angiotensin II to the AT1 receptor, which is responsible for the majority of angiotensin II's physiological effects. By inhibiting angiotensin II-mediated vasoconstriction, aldosterone secretion, sympathetic nervous system activation, and renal sodium reabsorption, telmisartan produces potent antihypertensive effects. Additionally, telmisartan demonstrates partial peroxisome proliferator-activated receptor-gamma (PPAR-γ) activation, which may contribute to its insulin-sensitizing and metabolic effects.
Indications
- Hypertension: First-line treatment for essential hypertension
- Cardiovascular risk reduction: Reduction of cardiovascular morbidity in patients 55 years or older at high risk of cardiovascular events who cannot tolerate ACE inhibitors
- Off-label uses may include diabetic nephropathy, heart failure, and metabolic syndrome (though not FDA-approved for these indications)
Dosage and Administration
Hypertension:- Initial dose: 40 mg once daily
- Maintenance dose: 20-80 mg once daily
- Maximum dose: 80 mg daily
- Recommended dose: 80 mg once daily
- Renal impairment: No initial dosage adjustment necessary
- Hepatic impairment: Use with caution in patients with biliary obstructive disorders or hepatic impairment
- Elderly: No dosage adjustment necessary
- Pediatric: Safety and effectiveness not established
Pharmacokinetics
Absorption: Bioavailability is 42-58%, with peak concentrations achieved in 0.5-1 hour. Food slightly reduces bioavailability. Distribution: Volume of distribution is approximately 500 L, with >99.5% plasma protein binding. Metabolism: Minimally metabolized by conjugation to the acyl glucuronide; no cytochrome P450-mediated metabolism. Elimination: Primarily excreted unchanged in feces (97%), with terminal elimination half-life of approximately 24 hours.Contraindications
- Hypersensitivity to telmisartan or any component of the formulation
- Concomitant use with aliskiren in patients with diabetes
- Pregnancy (second and third trimesters)
Warnings and Precautions
Pregnancy: Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus when used during the second and third trimesters. Hypotension: Symptomatic hypotension may occur in volume-depleted patients. Renal impairment: Monitor renal function in patients with renal artery stenosis, heart failure, or volume depletion. Hyperkalemia: May occur, particularly in patients with renal impairment, diabetes, or those taking potassium-sparing diuretics. Hepatic impairment: Use caution in patients with hepatic impairment or biliary obstruction.Drug Interactions
- ACE inhibitors: Increased risk of hyperkalemia, hypotension, and renal impairment
- Aliskiren: Contraindicated in diabetic patients due to increased risk of renal impairment, hyperkalemia, and hypotension
- NSAIDs: May diminish antihypertensive effect and increase risk of renal impairment
- Potassium-sparing diuretics/potassium supplements: Increased risk of hyperkalemia
- Lithium: Increased lithium concentrations
- Digoxin: Increased digoxin concentrations (monitor levels)
Adverse Effects
Common (≥1%):- Upper respiratory infection (7%)
- Back pain (3%)
- Sinusitis (3%)
- Diarrhea (3%)
- Pharyngitis (2%)
- Angioedema (<0.1%)
- Hypotension
- Hyperkalemia
- Acute renal failure
- Elevated liver enzymes
Monitoring Parameters
- Blood pressure (regular measurements)
- Renal function (serum creatinine, BUN) at baseline and periodically
- Serum electrolytes (particularly potassium) at baseline and periodically
- Liver function tests in patients with pre-existing hepatic disease
- Pregnancy testing in women of childbearing potential
Patient Education
- Take medication exactly as prescribed, usually once daily with or without food
- Do not stop taking abruptly without consulting your healthcare provider
- Report any signs of allergic reaction (swelling of face, lips, tongue, or throat)
- Notify your doctor if you experience dizziness, lightheadedness, or fainting
- Inform all healthcare providers about all medications you are taking
- Use effective contraception if you are of childbearing potential
- Report any pregnancy to your healthcare provider immediately
- Regular blood pressure monitoring is important
- Maintain adequate hydration, especially during hot weather or illness
References
1. White WB, et al. Cardiovascular morbidity and mortality in patients with diabetes in the ONTARGET and TRANSCEND studies. Lancet. 2008;372(9638):117-124. 2. Yusuf S, et al. Telmisartan, ramipril, or both in patients at high risk for vascular events. N Engl J Med. 2008;358(15):1547-1559. 3. Micardis® (telmisartan) prescribing information. FDA-approved labeling. 4. Wienen W, et al. A review on the pharmacokinetics and pharmacodynamics of telmisartan. Clin Pharmacokinet. 2000;38(3):257-270. 5. Benson SC, et al. Identification of telmisartan as a unique angiotensin II receptor antagonist with selective PPARγ-modulating activity. Hypertension. 2004;43(5):993-1002. 6. Mancia G, et al. 2013 ESH/ESC guidelines for the management of arterial hypertension. J Hypertens. 2013;31(7):1281-1357.