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ALERT: U.S. Boxed Warning
The FDA-approved labeling includes a boxed warning. See Warnings/Precautions section for a concise summary of this information. For verbatim wording of the boxed warning, consult the product labeling or www.fda.gov.
Pronunciation
(tel mi SAR tan)
U.S. Brand Names
Generic Available
No
Canadian Brand Names
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
Treatment of hypertension (may be used alone or in combination with other antihypertensive agents); cardiovascular risk reduction in patients ?55 years of age unable to take ACE inhibitors and who are at high risk of major cardiovascular events (eg, MI, stroke, death)
Pregnancy Risk Factor
C (1st trimester); D (2nd and 3rd trimesters)
Pregnancy Considerations
Medications which act on the renin-angiotensin system are reported to have the following fetal/neonatal effects: Hypotension, neonatal skull hypoplasia, anuria, renal failure, and death; oligohydramnios is also reported. These effects are reported to occur with exposure during the second and third trimesters. There are no adequate and well-controlled studies in pregnant women. [U.S. Boxed Warning]: Based on human data, drugs that act on the angiotensin system can cause injury and death to the developing fetus when used in the second and third trimesters. Angiotensin receptor blockers should be discontinued as soon as possible once pregnancy is detected.
Lactation
Excretion in breast milk unknown/not recommended
Contraindications
There are no contraindications listed in manufacturer's labeling.
Warnings/Precautions
Boxed warnings:
• Pregnancy: See “Special populations” below.
Concerns related to adverse effects:
• Hyperkalemia: May occur; risk factors include renal dysfunction, diabetes mellitus, concomitant use of potassium-sparing diuretics, potassium supplements and/or potassium containing salts. Use cautiously, if at all, with these agents and monitor potassium closely.
• Renal function deterioration: May be associated with deterioration of renal function and/or increases in serum creatinine, particularly in patients with low renal blood flow (eg, renal artery stenosis, heart failure) whose glomerular filtration rate (GFR) is dependent on efferent arteriolar vasoconstriction by angiotensin II; deterioration may result in oliguria, acute renal failure, and progressive azotemia. Small increases in serum creatinine may occur following initiation; consider discontinuation only in patients with progressive and/or significant deterioration in renal function.
Disease-related concerns:
• Aortic/mitral stenosis: Use with caution in patients with significant aortic/mitral stenosis.
• Hepatic impairment: Use with caution in patients who have biliary obstructive disorders or hepatic dysfunction.
• Hypovolemia: Avoid use or use a smaller dose in patients who are volume depleted; correct depletion first.
• Renal artery stenosis: Use telmisartan with caution in patients with unstented unilateral/bilateral renal artery stenosis. When unstented bilateral renal artery stenosis is present, use is generally avoided due to the elevated risk of deterioration in renal function unless possible benefits outweigh risks.
• Renal impairment: Use with caution with pre-existing renal insufficiency and severe renal impairment.
Special populations:
• Pregnancy: [U.S. Boxed Warning]: Based on human data, drugs that act on the angiotensin system can cause injury and death to the developing fetus when used in the second and third trimesters. Angiotensin receptor blockers should be discontinued as soon as possible once pregnancy is detected.
Adverse Reactions
May be associated with worsening of renal function in patients dependent on renin-angiotensin-aldosterone system.
1% to 10%:
Cardiovascular: Intermittent claudication (7%; placebo 6%), chest pain (?1%), hypertension (?1%), peripheral edema (?1%)
Central nervous system: Dizziness (?1%), fatigue (?1%), headache (?1%), pain (?1%)
Dermatologic: Skin ulcer (3%; placebo 2%)
Gastrointestinal: Diarrhea (3%), abdominal pain (?1%), dyspepsia (?1%), nausea (?1%)
Genitourinary: Urinary tract infection (?1%)
Neuromuscular & skeletal: Back pain (3%), myalgia (?1%)
Respiratory: Upper respiratory infection (7%), sinusitis (3%), cough (?1%), pharyngitis (1%)
<1%, postmarketing, and/or case reports (limited to important or life-threatening): Abnormal ECG, abnormal vision, abscess, allergic reaction, anemia, angina, angioedema, angioneurotic edema, anxiety, arthralgia, arthritis, asthma, atrial fibrillation, bradycardia, bronchitis, BUN increased, cerebrovascular disorder, CHF, conjunctivitis, constipation, cramps, creatinine kinase increased, cystitis, depression, dermatitis, diabetes mellitus, diaphoresis, dyspnea, earache, eczema, edema, enteritis, epistaxis, eosinophilia, erectile dysfunction, erythema, facial edema, fever, flatulence, flushing, frequent urination, fungal infection, gastroenteritis, gout, hemoglobin decreased, hemorrhoids, hepatic dysfunction, hypercholesterolemia, hyperkalemia, hypersensitivity, hypotension, impotence, insomnia, liver enzymes increased, malaise, MI, migraine, muscle cramps, nervousness, orthostatic hypotension (more frequent in dialysis patients), otitis media, palpitation, paresthesia, pruritus, renal dysfunction, renal failure, rhabdomyolysis, rash, reflux, rhinitis, serum creatinine increased, somnolence, syncope, tachycardia, tendon pain, tendonitis, tenosynovitis, thrombocytopenia, tinnitus, toothache, uric acid increased, urticaria, vertigo, vomiting, weakness, xerostomia
Metabolism/Transport Effects
Inhibits CYP2C19 (weak)
Drug Interactions
ACE Inhibitors: Angiotensin II Receptor Blockers may enhance the adverse/toxic effect of ACE Inhibitors. Risk C: Monitor therapy
Amifostine: Antihypertensives may enhance the hypotensive effect of Amifostine. Management: When amifostine is used at chemotherapy doses, antihypertensive medications should be withheld for 24 hours prior to amifostine administration. If antihypertensive therapy can not be withheld, amifostine should not be administered. Risk D: Consider therapy modification
Antihypertensives: May enhance the hypotensive effect of other Antihypertensives. Risk C: Monitor therapy
Cardiac Glycosides: Telmisartan may increase the serum concentration of Cardiac Glycosides. Risk C: Monitor therapy
Diazoxide: May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
Eplerenone: May enhance the hyperkalemic effect of Angiotensin II Receptor Blockers. Risk C: Monitor therapy
Herbs (Hypertensive Properties): May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
Herbs (Hypotensive Properties): May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
Hypotensive Agents: May enhance the adverse/toxic effect of other Hypotensive Agents. Risk C: Monitor therapy
Lithium: Angiotensin II Receptor Blockers may increase the serum concentration of Lithium. Management: Lithium dosage reductions will likely be needed following the addition of an angiotensin II receptor antagonist. Risk D: Consider therapy modification
MAO Inhibitors: May enhance the orthostatic effect of Orthostasis Producing Agents. Risk C: Monitor therapy
Methylphenidate: May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
Nonsteroidal Anti-Inflammatory Agents: May diminish the therapeutic effect of Angiotensin II Receptor Blockers. The combination of these two agents may also significantly decrease glomerular filtration and renal function. Risk C: Monitor therapy
Pentoxifylline: May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
Phosphodiesterase 5 Inhibitors: May enhance the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
Potassium Salts: May enhance the hyperkalemic effect of Angiotensin II Receptor Blockers. Risk C: Monitor therapy
Potassium-Sparing Diuretics: Angiotensin II Receptor Blockers may enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Risk C: Monitor therapy
Prostacyclin Analogues: May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
Ramipril: Telmisartan may increase the serum concentration of Ramipril. Concentrations of the active metabolite, ramiprilat, may also be increased. Risk C: Monitor therapy
RiTUXimab: Antihypertensives may enhance the hypotensive effect of RiTUXimab. Risk D: Consider therapy modification
Tolvaptan: May enhance the hyperkalemic effect of Angiotensin II Receptor Blockers. Risk C: Monitor therapy
Trimethoprim: May enhance the hyperkalemic effect of Angiotensin II Receptor Blockers. Risk C: Monitor therapy
Yohimbine: May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
Ethanol/Nutrition/Herb Interactions
Herb/Nutraceutical: Avoid herbs with hypertensive properties (bayberry, blue cohosh, cayenne, ephedra, ginger, ginseng [American], kola, licorice); may diminish the antihypertensive effect of telmisartan. Avoid herbs with hypotensive properties (black cohosh, California poppy, coleus, golden seal, hawthorn, mistletoe, periwinkle, quinine, shepherd's purse); may enhance the hypotensive effect of telmisartan.
Storage
Store at 25°C (77°F); excursions between 15°C to 30°C (59°F to 86°F) permitted. Protect from moisture and do not remove from blister pack until immediately before use.
Mechanism of Action
Angiotensin II acts as a vasoconstrictor. In addition to causing direct vasoconstriction, angiotensin II also stimulates the release of aldosterone. Once aldosterone is released, sodium as well as water are reabsorbed. The end result is an elevation in blood pressure. Telmisartan is a nonpeptide AT1 angiotensin II receptor antagonist. This binding prevents angiotensin II from binding to the receptor thereby blocking the vasoconstriction and the aldosterone secreting effects of angiotensin II.
Pharmacodynamics/Kinetics
Orally active, not a prodrug
Onset of action: 1-2 hours
Duration: Up to 24 hours
Distribution: Vd: 500 L
Protein binding: >99.5%; primarily to albumin and alpha1-acid glycoprotein
Metabolism: Hepatic via conjugation to inactive metabolites; not metabolized via CYP
Bioavailability (dose dependent): 42% to 58%; Hepatic impairment: Approaches 100%
Half-life elimination: Terminal: 24 hours
Time to peak, plasma: 0.5-1 hours
Excretion: Feces (97%)
Clearance: Total body: 800 mL/minute
Dosage
Oral:
Adults:
Hypertension: Initial: 40 mg once daily; usual maintenance dose range: 20-80 mg/day. Patients with volume depletion should be initiated on the lower dosage with close supervision.
Cardiovascular risk reduction: Initial: 80 mg once daily. Note: It is unknown whether doses <80 mg/day are associated with a reduction in risk of cardiovascular morbidity or mortality.
Elderly:
Hypertension: Initial: 20 mg/day; usual maintenance dose range: 20-80 mg/day
Cardiovascular risk reduction: Initial 80 mg once daily
Dosage adjustment in renal impairment: No adjustment required; hemodialysis patients are more susceptible to orthostatic hypotension
Dosage adjustment in hepatic impairment: Initiate therapy with low dose; titrate slowly and monitor closely.
Administration: Oral
May be administered without regard to meals.
Monitoring Parameters
Blood pressure; electrolytes, serum creatinine, BUN
Dietary Considerations
May be taken without regard to meals.
Patient Education
Do not take any new medication during therapy unless approved by prescriber. Take exactly as directed and do not alter dose or discontinue without consulting prescriber. Monitor blood pressure on a regular basis at same time of day, as advised by prescriber. This drug does not eliminate need for diet or exercise regimen as recommended by prescriber. May cause dizziness, fainting, or lightheadedness (use caution when driving or engaging in tasks that require alertness until response to drug is known); or postural hypotension (use caution when rising from lying or sitting position or climbing stairs). Report unusual weight gain and swelling of ankles, hands, face, lips, throat, or tongue; persistent fatigue; dry cough or respiratory difficulty; palpitations or chest pain; CNS changes; GI disturbances; muscle or bone pain, cramping, or tremors; change in urinary pattern; changes in hearing or vision; or other adverse response. Pregnancy/breast-feeding precautions: Inform prescriber if you are or intend to become pregnant. This drug should not be used in the 2nd or 3rd trimester of pregnancy. Consult prescriber for appropriate contraceptive measures if necessary or if you suspect you might be pregnant. Breast-feeding is not recommended.
Geriatric Considerations
No initial dose adjustment is required. There appear to be no significant differences in response between the elderly and younger adults (limited data available). Monitor closely during initiation phase. Many elderly may be volume depleted due to diuretics and/or blunted thirst reflex resulting in inadequate fluid intake.
Anesthesia and Critical Care Concerns/Other Considerations
Clinical Pearls/Comments: In patients on chronic angiotensin receptor blocker (ARB) therapy, intraoperative hypotension may occur with induction and maintenance of general anesthesia; however, discontinuation of therapy prior to surgery is controversial. If continued preoperatively, avoidance of hypotensive agents during surgery is prudent. Episodes of intraoperative hypotension may be managed by fluid administration and/or modest doses of alpha-adrenergic agents. Severe hypotension may occur in patients who are sodium- and/or volume-depleted; initiate lower doses and monitor closely when starting therapy in these patients. ARB therapy may elicit an increase in potassium and creatinine, especially when used in patients with bilateral renal artery stenosis. Concomitant NSAID therapy may attenuate blood pressure control; use of NSAIDs should be avoided or limited, with monitoring of blood pressure control. In the setting of heart failure, NSAID use may be associated with an increased risk for fluid accumulation and edema and therefore should be avoided.
Evidence-Based Information: The angiotensin II receptor antagonists have similar indications as ACE inhibitors. In heart failure, the angiotensin II antagonists are especially useful in providing an alternative therapy in those patients who have intractable cough due to ACE inhibitor therapy. Candesartan has been studied as an alternative therapy in chronic heart failure patients who cannot tolerate an ACE-I (CHARM-Alternative) and as an added therapy in heart failure patients who are maintained on an ACE-I (CHARM-Added). In both studies, the combined endpoint of cardiovascular death or heart failure hospitalizations was significantly improved over the placebo-treated group.
Cardiovascular Considerations
Hypertension: According to the 2003 JNC 7 guidelines for the treatment of hypertension, most patients with hypertension will require treatment with at least 2 antihypertensives. First-line therapy for hypertension is a diuretic (eg, hydrochlorothiazide or chlorthalidone). When a diuretic cannot be used or when a compelling indication exists for another drug, other types of antihypertensives may be used (eg, ACEIs, ARBs, beta-blockers, CCBs). Angiotensin II receptor blockers are among the multiple choices of agents that have shown benefit in a number of different patient subtypes. Compelling indications for an ARB include patients with heart failure, diabetes, or chronic kidney disease. The LIFE trial (Dahlof, 2002) confirmed that ARB (losartan 50-100 mg daily) was better tolerated than a beta-blocker (atenolol), and resulted in significant reduction in mortality, angina, or HF hospitalization (primary endpoint). Stroke and new-onset diabetes were significantly reduced in the losartan treatment group.
Treatment should be targeted to a goal blood pressure of <140/90 mm Hg. If diabetes or renal disease coexists, the blood pressure goal should be <130/80 mm Hg.
Cardiovascular risk reduction: The Telmisartan Randomised Assessment Study in ACE Intolerant Subjects with Cardiovascular Disease (TRANSCEND) trial evaluated the use of telmisartan versus placebo in 5926 patients (mean age: 67 years) who were ACE inhibitor intolerant [cough (88.2%), symptomatic hypotension (4.1%), angioedema/anaphylaxis (1.3%), renal dysfunction (1%) and other reasons (8.3%)]. The primary endpoint of the study, a composite of cardiovascular death, MI, stroke, or hospitalization for heart failure, was found not to be statistically different between the two groups. However, a statistically significant difference was found with the secondary outcome – a composite of cardiovascular death, myocardial infarction, or stroke (telmisartan: 384 [13%] vs. placebo: 440 [14.8%], p=0.048). Patients receiving telmisartan were hospitalized less for cardiovascular reasons.
Cautions: Similar to ACE inhibitors, pre-existing volume depletion caused by diuretic therapy may potentiate hypotension in response to angiotensin II antagonists. Concomitant NSAID therapy may attenuate blood pressure control; use of NSAIDs should be avoided or limited, with monitoring of blood pressure control. In the setting of heart failure, NSAID use may be associated with an increased risk for fluid accumulation and edema. Because of the lack of effect on the response to bradykinin, angiotensin receptor blockers are less likely to be associated with nonrenin-angiotensin effects such as cough and angioedema. The angiotensin II antagonists do not cause increases in levels of bradykinin as the ACEIs do.
Dental Health: Effects on Dental Treatment
No significant effects or complications reported
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Mental Health: Effects on Mental Status
May cause dizziness or fatigue, may rarely cause insomnia, anxiety, nervousness, depression, or sedation
Mental Health: Effects on Psychiatric Treatment
May decrease lithium clearance, resulting in an increase in serum lithium levels and potential lithium toxicity; monitor serum lithium levels
Nursing: Physical Assessment/Monitoring
Assess potential for interactions with other pharmacological agents and herbal products patient may be taking (eg, increased risk of hypercalcemia or increased hypotensive effects). Assess results of laboratory tests, therapeutic effectiveness (reduced hypertension), and adverse response (eg, hypotension, diarrhea, URI, cough) on a regular basis during therapy. Teach patient proper use, need for regular blood pressure monitoring, possible side effects/appropriate interventions, and adverse symptoms to report.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet: 20 mg, 40 mg, 80 mg
Pricing: U.S. (www.drugstore.com)
Tablets (Micardis)
20 mg (28): $52.99
20 mg (30): $90.96
40 mg (7): $20.99
40 mg (30): $100.47
80 mg (30): $94.82
References
Chobanian AV, Bakris GL, Black HR, et al, “The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: The JNC 7 Report,” JAMA, 2003, 289(19):2560-71.
Cohn JN and Tognoni G, “Valsartan Heart Failure Trial Investigators. A Randomized Trial of the Angiotensin-Receptor Blocker Valsartan in Chronic Heart Failure,” N Engl J Med, 2001, 345(23):1667-75.
Conlin P, Moore T, Swartz S, et al, “Effect of Indomethacin on Blood Pressure Lowering by Captopril and Losartan in Hypertensive Patients,” Hypertension, 2000, 36(3):461-5.
“Consensus Recommendations for the Management of Chronic Heart Failure. On Behalf of the Membership of the Advisory Council to Improve Outcomes Nationwide in Heart Failure,” Am J Cardiol, 1999, 83(2A):1A-38A.
Dahlof B, Devereux RB, Kjeldsen SE, et al, “Cardiovascular Morbidity and Mortality in the Losartan Intervention For Endpoint Reduction in Hypertension Study (LIFE): A Randomised Trial Against Atenolol,” Lancet, 2002, 359(9311):995-1003.
Dickstein K, Kjekshus J, et al, “Effects of Losartan and Captopril on Mortality and Morbidity in High-Risk Patients After Acute Myocardial Infarction: The OPTIMAAL Randomised Trial. Optimal Trial in Myocardial Infarction with Angiotensin II Antagonist Losartan,” Lancet , 2002, 360(9335):752-60.
Epstein BJ and Gums JG, “Angiotensin Receptor Blockers Versus ACE Inhibitors: Prevention of Death and Myocardial Infarction in High-Risk Populations,” Ann Pharmacother, 2005, 39(3):470-80.
Granger CB, McMurray JJ, Yusuf S, et al, “Effects of Candesartan in Patients With Chronic Heart Failure and Reduced Left-Ventricular Systolic Function Intolerant to Angiotensin-Converting-Enzyme Inhibitors: The CHARM-Alternative Trial,” Lancet, 2003, 362(9386):772-6.
Hunt SA, Baker DW, Chin MH, et al, “ACC/AHA Guidelines for the Evaluation and Management of Chronic Heart Failure in the Adult: Executive Summary. A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Revise the 1995 Guidelines for the Evaluation and Management of Heart Failure),” J Am Coll Cardiol, 2001, 38(7):2101-13.
Karlberg BE, Lins LE, and Hermansson K, “Efficacy and Safety of Telmisartan, a Selective AT1 Receptor Antagonist, Compared With Enalapril in Elderly Patients With Primary Hypertension. TEES Study Group,” J Hypertens, 1999, 17(2):293-302.
“K/DOQI Clinical Practice Guidelines for Chronic Kidney Disease: Evaluation, Classification, and Stratification. Kidney Disease Outcome Quality Initiative,” Am J Kidney Dis, 2002, 39(2 Suppl 2):1-246. Available at: http://www.kidney.org/professionals/doqi/kdoqi/toc.htm. Accessed August 1, 2003.
McMurray JJ, Ostergren J, Swedberg K, et al, “Effects of Candesartan in Patients With Chronic Heart Failure and Reduced Left-Ventricular Systolic Function Taking Angiotensin-Converting-Enzyme Inhibitors: The CHARM-Added Trial,” Lancet, 2003, 362(9386):767-71.
Pfeffer MA, McMurray JJ, Velazquez EJ, et al, “Valsartan, Captopril, or Both in Myocardial Infarction Complicated by Heart Failure, Left Ventricular Dysfunction, or Both,” N Engl J Med, 2004, 350(2):203.
Pitt B, Poole-Wilson PA, Segal R, et al, “Effect of Losartan Compared With Captopril on Mortality in Patients With Symptomatic Heart Failure: Randomised Trial - The Losartan Heart Failure Survival Study ELITE II,” Lancet, 2000, 355(9215):1582-7.
The Telmisartan Randomised Assessment Study in ACE Intolerant Subjects with Cardiovascular Disease (TRANSCEND) Investigators, “Effects of the Angiotensin-Receptor Blocker Telmisartan on Cardiovascular Events in High-risk Patients Intolerant to Angiotensin-Converting Enzyme Inhibitors: A Randomized Controlled Trial,” Lancet, 2008, 372(9644):1174-83.
International Brand Names
Lexi-Comp.com
Last full review/revision December 2009
Content last modified December 2009
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