Irbesartan

Pharmacologic Category

Angiotensin II Receptor Blocker; Antihypertensive

Dosing: Adult

Hypertension: Oral: 150 mg once daily; titrate as needed based on patient response up to 300 mg once daily (ACC/AHA [Whelton 2017]); maximum dose: 300 mg/day. Note: Starting dose in volume-depleted patients should be 75 mg.

Diabetic nephropathy: Oral: 300 mg once daily

* See Dosage and Administration in AHFS Essentials for additional information.

Dosing: Geriatric

Refer to adult dosing.

Dosing: Renal Impairment: Adult

Mild to severe impairment: No dosage adjustment necessary unless the patient is also volume depleted.

Hemodialysis: Not removed by hemodialysis

Dosing: Hepatic Impairment: Adult

No dosage adjustment necessary.

Dosing: Pediatric

Hypertension: Limited data available (AAP [Flynn 2017]; NHLBI 2011; Sakarcan 2001): Note: Use a lower starting dose of 50% of the recommended initial dose in volume- and salt-depleted patients.

Children ≥6 years: Oral: Initial: 75 mg once daily; may be titrated to a maximum dose of 150 mg once daily

Adolescents: Oral: Initial: 150 mg once daily; may be titrated to a maximum dose of 300 mg once daily

Proteinuria reduction in children with chronic kidney disease: Limited data available: Children ≥4 years and Adolescents: Oral: Studies utilized a fixed dosage based on weight categories (see the following); initial doses were approximately 2 mg/kg once daily; doses were increased after 3 to 5 weeks and again after 8 to 12 weeks if needed, according to specific blood pressure criteria; median final dose in the largest study (n=44; median age: 10 years): 4 mg/kg once daily (Franscini 2002; Gartenmann 2003; von Vigier 2000)

10 to 20 kg: Initial: 37.5 mg once daily

21 to 40 kg: Initial: 75 mg once daily

>40 kg: Initial: 150 mg once daily

Dosing: Renal Impairment: Pediatric

Children ≥6 years and Adolescents:

Mild to severe impairment: Hypertension: There are no pediatric specific recommendations; based on experience in adult patients, no dosage adjustment necessary unless the patient is also volume depleted.

Hemodialysis: Not removed by hemodialysis

Dosing: Hepatic Impairment: Pediatric

There are no pediatric specific recommendations; based on experience in adult patients, no dosage adjustment needed.

Use: Labeled Indications

Diabetic nephropathy: Treatment of diabetic nephropathy with an elevated serum creatinine and proteinuria (>300 mg/day) in patients with type 2 diabetes and hypertension

Hypertension: Management of hypertension

Guideline recommendations: The 2017 Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults recommends if monotherapy is warranted, in the absence of comorbidities (eg, cerebrovascular disease, chronic kidney disease, diabetes, heart failure, ischemic heart disease, etc.), that thiazide-like diuretics or dihydropyridine calcium channel blockers may be preferred options due to improved cardiovascular endpoints (eg, prevention of heart failure and stroke). ACE inhibitors and ARBs are also acceptable for monotherapy. Combination therapy may be required to achieve blood pressure goals and is initially preferred in patients at high risk (stage 2 hypertension or atherosclerotic cardiovascular disease [ASCVD] risk ≥10%) (ACC/AHA [Whelton 2017]).

* See Uses in AHFS Essentials for additional information.

Use: Off-Label: Adult

Acute coronary syndrome (secondary prevention of cardiovascular events)Level of Evidence [G]

Based on the American Heart Association/American College of Cardiology (AHA/ACC) guidelines for the management of patients with non-ST-elevation acute coronary syndromes (NSTE-ACS) and the American College of Cardiology Foundation/American Heart Association (ACC/AHA) guidelines for the management of patients with STE-ACS, an ARB is recommended and effective in patients with NSTE-ACS or STE-ACS who have indications for but are intolerant of ACE inhibitors; this includes patients with heart failure, MI, or anterior MI who have a left ventricular ejection fraction (LVEF) ≤40%. In post-STE-ACS patients, initiate within the first 24 hours.

Stable coronary artery diseaseLevel of Evidence [G]

Based on the American College of Cardiology/American Heart Association guideline for the diagnosis and management of patients with stable ischemic heart disease, an ACE inhibitor or ARB should be prescribed in all patients with stable ischemic heart disease who also have hypertension, diabetes mellitus, LVEF <40%, or CKD unless contraindicated.

Level of Evidence Definitions

Level of Evidence Scale

Class and Related Monographs

Angiotensin II Receptor Antagonists

Clinical Practice Guidelines

Atrial Fibrillation:

AHA/ACC/HRS, "2014 AHA/ACC/HRS Guideline for the Management of Patients with Atrial Fibrillation," March 2014

Chronic Kidney Disease:

KDIGO 2012 Clinical Practice Guidelines for the Evaluation and Management of Chronic Kidney Disease, January 2013

Coronary Artery Bypass Graft Surgery:

“2011 ACC/AHA Guideline for Coronary Artery Bypass Graft Surgery,” November 2011

AHA Scientific Statement, "Secondary Prevention After Coronary Artery Bypass Graft Surgery,” February 2015

Diabetes Mellitus:

American Diabetes Association, “Standards of Medical Care in Diabetes - 2019,” January 2019

Diabetes Canada, “Clinical Practice Guidelines for the Prevention and Management of Diabetes in Canada,” 2018

Hypertension:

"2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults," November 2017.

AHA/ACC/ASH, “Treatment of Hypertension in Patients with Coronary Artery Disease: A Scientific Statement by the American Heart Association, American College of Cardiology and American Society of Hypertension,” May 2015

"ACC/AHA Expert Consensus Document on Hypertension in the Elderly," 2011

AHA/ACC/CDC, “AHA/ACC/CDC Science Advisory: An Effective Approach to High Blood Pressure Control” November 2013

ASH/ISH, “Clinical Practice Guidelines for the Management of Hypertension in the Community: A Statement by the American Society of Hypertension and the International Society of Hypertension,” January 2014

Eighth Joint National Committee (JNC 8), "2014 Evidence-based Guideline for the Management of High Blood Pressure in Adults," December 2013

“National High Blood Pressure Education Program Working Group on High Blood Pressure in Children and Adolescents,” May 2005

Ischemic Heart Disease:

ACC/AHA/AATS/PCNA/SCAI/STS, "2014 Focused Update of the Guideline for the Diagnosis and Management of Patients with Stable Ischemic Heart Disease," July 2014

ACC/AHA/ACP/AATS/PCNA/SCAI/STS, “2012 Guideline for the Diagnosis and Management of Patients with Stable Ischemic Heart Disease,” November 2012

AHA/ACC, "2014 AHA/ACC Guideline for the Management of Patients with Non-ST-Elevation Acute Coronary Syndromes,” September 2014

ACC/AHA “2013 guideline for the management of ST-elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines”, January 2013

Peripheral Arterial Disease:

2011 ACC/AHA Focused Update of the Guideline for the Management of Patients with Peripheral Artery Disease (Updating the 2005 Guideline),” September 2011

Prevention:

“AHA/ACC Secondary Prevention and Risk Reduction Therapy for Patients with Coronary and Other Atherosclerotic Vascular Disease: 2011 Update,” November 2011

Surgery:

ACC/AHA, “2014 ACC/AHA Guideline on Perioperative Cardiovascular Evaluation and Management of Patients Undergoing Noncardiac Surgery,” August 2014

Valvular Heart Disease:

AHA/ACC, “2014 AHA/ACC Guideline for the Management of Patients with Valvular Heart Disease,” March 2014

Administration: Oral

Administer with or without food.

Administration: Pediatric

Oral: May be administered without regard to food. Capsules may be opened and mixed with small amount of applesauce prior to administration (Sakarcan 2001).

Storage/Stability

Store at 25°C (77°F); excursions are permitted between 15°C and 30°C (59°F and 86°F).

Medication Patient Education with HCAHPS Considerations

What is this drug used for?

• It is used to treat high blood pressure.

• It is used to protect kidney function in diabetic patients who have protein loss.

• It may be given to you for other reasons. Talk with the doctor.

Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:

• Kidney problems like unable to pass urine, blood in the urine, change in amount of urine passed, or weight gain.

• High potassium like abnormal heartbeat, confusion, dizziness, passing out, weakness, shortness of breath, or numbness or tingling feeling.

• Severe dizziness

• Passing out

• Signs of a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.

Medication Safety Issues

Sound-alike/look-alike issues:

Contraindications

Hypersensitivity to irbesartan or any component of the formulation; concomitant use with aliskiren in patients with diabetes mellitus

Documentation of allergenic cross-reactivity for angiotensin receptor blockers is limited. However, because of similarities in chemical structure and/or pharmacologic actions, the possibility of cross-sensitivity cannot be ruled out with certainty.

Canadian labeling: Additional contraindications (not in US labeling): Concomitant use with aliskiren in patients with moderate to severe renal impairment (GFR <60 mL/minute/1.73 m²); concomitant use with ACE inhibitors in patients with diabetic nephropathy; hereditary galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption; pregnancy; breastfeeding

Warnings/Precautions

Concerns related to adverse effects:

• Angioedema: Angioedema has been reported rarely with some angiotensin II receptor antagonists (ARBs) and may occur at any time during treatment (especially following first dose). It may involve the head and neck (potentially compromising airway) or the intestine (presenting with abdominal pain). Patients with idiopathic or hereditary angioedema or previous angioedema associated with ACE-inhibitor therapy may be at an increased risk. Prolonged frequent monitoring may be required, especially if tongue, glottis, or larynx are involved, as they are associated with airway obstruction. Patients with a history of airway surgery may have a higher risk of airway obstruction. Discontinue therapy immediately if angioedema occurs. Aggressive early management is critical. Intramuscular (IM) administration of epinephrine may be necessary. Do not readminister to patients who have had angioedema with ARBs.

• 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.

• Hypotension: Symptomatic hypotension may occur upon initiation in patients who are salt- or volume-depleted (eg, those treated with high-dose diuretics); correct volume depletion prior to administration. This transient hypotensive response is not a contraindication to further treatment with irbesartan.

• 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, chronic kidney disease, severe heart failure, volume depletion) 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.

• Ascites: Avoid use in patients with ascites due to cirrhosis or refractory ascites; if use cannot be avoided in patients with ascites due to cirrhosis, monitor blood pressure and renal function carefully to avoid rapid development of renal failure (AASLD [Runyon 2012]).

• Renal artery stenosis: Use 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 preexisting renal insufficiency.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Special populations:

• Pregnancy: [US Boxed Warning]: Drugs that act on the renin-angiotensin system can cause injury and death to the developing fetus. Discontinue as soon as possible once pregnancy is detected.

• Surgical patients: 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 (Hillis 2011). Based on current research and clinical guidelines in patients undergoing noncardiac surgery, continuing angiotensin-receptor blockers (ARB) is reasonable in the perioperative period. If ARBs are held before surgery, it is reasonable to restart postoperatively as soon as clinically feasible (ACC/AHA [Fleisher 2014]).

* See Cautions in AHFS Essentials for additional information.

Geriatric Considerations

No dosage adjustment is necessary when initiating angiotensin II receptor antagonists in the elderly. In clinical studies, no differences between younger adults and the elderly were demonstrated. Many elderly may be volume depleted due to diuretic use and/or blunted thirst reflex resulting in inadequate fluid intake.

The AHA/ACC/ASH 2015 scientific statement on the treatment of hypertension in patients with CAD warns to use caution to avoid decreases in DBP <60 mm Hg especially in patients >60 years of age since reduced coronary perfusion may occur. When lowering SBP in older hypertensive patients with wide pulse pressures, very low DBP values (<60 mm Hg) may result. In patients with obstructive CAD, clinicians should lower blood pressure slowly and carefully monitor for any untoward signs or symptoms, especially those resulting from myocardial ischemia and worsening heart failure (AHA/ACC/ASH [Rosendorff 2015]).

Pregnancy Risk Factor

D

Pregnancy Considerations

[US Boxed Warning]: Drugs that act on the renin-angiotensin system can cause injury and death to the developing fetus. When pregnancy is detected, discontinue as soon as possible. The use of drugs which act on the renin-angiotensin system are associated with oligohydramnios. Oligohydramnios, due to decreased fetal renal function, may lead to fetal lung hypoplasia and skeletal malformations. Oligohydramnios may not appear until after irreversible fetal injury has occurred. Use in pregnancy is also associated with anuria, hypotension, renal failure, skull hypoplasia, and death in the fetus/neonate. The exposed fetus should be monitored for fetal growth, amniotic fluid volume, and organ formation. Infants exposed in utero should be monitored for hyperkalemia, hypotension, and oliguria (exchange transfusions or dialysis may be needed). These adverse events are generally associated with maternal use in the second and third trimesters.

Chronic maternal hypertension itself is also associated with adverse events in the fetus/infant. The risk of birth defects, low birth weight, premature delivery, stillbirth, and neonatal death may be increased with chronic hypertension in pregnancy. Actual risks may be related to duration and severity of maternal hypertension (ACOG 203 2019).

The use of angiotensin II receptor blockers is generally not recommended to treat chronic hypertension in pregnant women and should generally be avoided in women planning a pregnancy (ACOG 203 2019).

Breast-Feeding Considerations

It is not known if irbesartan is present in breast milk.

Due to the potential for serious adverse reactions in the breastfeeding infant, the manufacturer recommends a decision be made whether to discontinue breastfeeding or to discontinue the drug, considering the importance of treatment to the mother.

Briggs' Drugs in Pregnancy & Lactation

• Irbesartan

Adverse Reactions

Unless otherwise indicated, incidences are reported for patients with hypertension.

>10%: Endocrine & metabolic: Hyperkalemia (diabetic nephropathy: 19%)

1% to 10%:

Cardiovascular: Orthostatic dizziness (diabetic nephropathy: 5%), orthostatic hypotension (diabetic nephropathy: 5%)

Central nervous system: Dizziness (diabetic nephropathy: 10%), fatigue (4%)

Gastrointestinal: Diarrhea (3%), dyspepsia (≤2%), heartburn (≤2%)

<1%, postmarketing, and/or case reports: Anaphylactic shock, anaphylaxis, anemia (case report; Simonetti 2007), angioedema, facial edema, hepatitis, increased creatine phosphokinase, increased liver enzymes, jaundice, lip edema, pharyngeal edema, thrombocytopenia, tinnitus, tongue edema, urticaria

* See Cautions in AHFS Essentials for additional information.

Allergy and Idiosyncratic Reactions

• Angiotensin Receptor Antagonist Allergy/Hypersensitivity

Toxicology

• Angiotensin II Receptor Blockers

Metabolism/Transport Effects

Substrate of CYP2C9 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential

Drug Interactions Open Interactions

Alfuzosin: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Aliskiren: May enhance the hyperkalemic effect of Angiotensin II Receptor Blockers. Aliskiren may enhance the hypotensive effect of Angiotensin II Receptor Blockers. Aliskiren may enhance the nephrotoxic effect of Angiotensin II Receptor Blockers. Management: Aliskiren use with ACEIs or ARBs in patients with diabetes is contraindicated. Combined use in other patients should be avoided, particularly when CrCl is less than 60 mL/min. If combined, monitor potassium, creatinine, and blood pressure closely. Risk D: Consider therapy modification

Amifostine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Amifostine. Management: When amifostine is used at chemotherapy doses, blood pressure lowering medications should be withheld for 24 hours prior to amifostine administration. If blood pressure lowering therapy cannot be withheld, amifostine should not be administered. Risk D: Consider therapy modification

Amphetamines: May diminish the antihypertensive effect of Antihypertensive Agents. Risk C: Monitor therapy

Angiotensin II: Receptor Blockers may diminish the therapeutic effect of Angiotensin II. Risk C: Monitor therapy

Angiotensin-Converting Enzyme Inhibitors: Angiotensin II Receptor Blockers may enhance the adverse/toxic effect of Angiotensin-Converting Enzyme Inhibitors. Angiotensin II Receptor Blockers may increase the serum concentration of Angiotensin-Converting Enzyme Inhibitors. Management: In US labeling, use of telmisartan and ramipril is not recommended. It is not clear if any other combination of an ACE inhibitor and an ARB would be any safer. Consider alternatives to the combination when possible. Risk D: Consider therapy modification

Antipsychotic Agents (Second Generation [Atypical]): Blood Pressure Lowering Agents may enhance the hypotensive effect of Antipsychotic Agents (Second Generation [Atypical]). Risk C: Monitor therapy

Barbiturates: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Benperidol: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Brigatinib: May diminish the antihypertensive effect of Antihypertensive Agents. Brigatinib may enhance the bradycardic effect of Antihypertensive Agents. Risk C: Monitor therapy

Brimonidine (Topical): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Bromperidol: Blood Pressure Lowering Agents may enhance the hypotensive effect of Bromperidol. Bromperidol may diminish the hypotensive effect of Blood Pressure Lowering Agents. Risk X: Avoid combination

CycloSPORINE (Systemic): Angiotensin II Receptor Blockers may enhance the hyperkalemic effect of CycloSPORINE (Systemic). Risk C: Monitor therapy

Dapoxetine: May enhance the orthostatic hypotensive effect of Angiotensin II Receptor Blockers. Risk C: Monitor therapy

Dexmethylphenidate: May diminish the therapeutic effect of Antihypertensive Agents. Risk C: Monitor therapy

Diazoxide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Drospirenone: Angiotensin II Receptor Blockers may enhance the hyperkalemic effect of Drospirenone. Risk C: Monitor therapy

DULoxetine: Blood Pressure Lowering Agents may enhance the hypotensive effect of DULoxetine. Risk C: Monitor therapy

Eplerenone: May enhance the hyperkalemic effect of Angiotensin II Receptor Blockers. Risk C: Monitor therapy

Heparin: May enhance the hyperkalemic effect of Angiotensin II Receptor Blockers. Risk C: Monitor therapy

Heparins (Low Molecular Weight): May enhance the hyperkalemic effect of Angiotensin II Receptor Blockers. Risk C: Monitor therapy

Herbs (Hypertensive Properties): May diminish the antihypertensive effect of Antihypertensive Agents. Risk C: Monitor therapy

Herbs (Hypotensive Properties): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Hypotension-Associated Agents: Blood Pressure Lowering Agents may enhance the hypotensive effect of Hypotension-Associated Agents. Risk C: Monitor therapy

Levodopa-Containing Products: Blood Pressure Lowering Agents may enhance the hypotensive effect of Levodopa-Containing Products. 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

Lormetazepam: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Methylphenidate: May diminish the antihypertensive effect of Antihypertensive Agents. Risk C: Monitor therapy

Molsidomine: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Naftopidil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Nicergoline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Nicorandil: May enhance the hyperkalemic effect of Angiotensin II Receptor Blockers. Risk C: Monitor therapy

Nicorandil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Nitroprusside: Blood Pressure Lowering Agents may enhance the hypotensive effect of Nitroprusside. Risk C: Monitor therapy

Nonsteroidal Anti-Inflammatory Agents: Angiotensin II Receptor Blockers may enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Specifically, the combination may result in a significant decrease in renal function. 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

Obinutuzumab: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Management: Consider temporarily withholding blood pressure lowering medications beginning 12 hours prior to obinutuzumab infusion and continuing until 1 hour after the end of the infusion. Risk D: Consider therapy modification

Pentoxifylline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Pholcodine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Pholcodine. Risk C: Monitor therapy

Phosphodiesterase 5 Inhibitors: May enhance the hypotensive effect of Blood Pressure Lowering Agents. 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 Blood Pressure Lowering Agents. Risk C: Monitor therapy

Quinagolide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Ranolazine: May enhance the adverse/toxic effect of Angiotensin II Receptor Blockers. Risk C: Monitor therapy

Sodium Phosphates: Angiotensin II Receptor Blockers may enhance the nephrotoxic effect of Sodium Phosphates. Specifically, the risk of acute phosphate nephropathy may be enhanced. Management: Consider avoiding this combination by temporarily suspending treatment with ARBs, or seeking alternatives to oral sodium phosphate bowel preparation. If the combination cannot be avoided, maintain adequate hydration and monitor renal function closely. Risk D: Consider therapy modification

Tacrolimus (Systemic): Angiotensin II Receptor Blockers may enhance the hyperkalemic effect of Tacrolimus (Systemic). Risk C: Monitor therapy

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 Antihypertensive Agents. Risk C: Monitor therapy

Test Interactions

May lead to false-negative aldosterone/renin ratio (ARR) (Funder 2016)

Genes of Interest

• Angiotensin I Converting Enzyme 1
• Angiotensin II Receptor, Type 1
• Angiotensinogen (Serpin Peptidase Inhibitor, Clade A, Member 8)
• Bradykinin Receptor B2
• Cytochrome P450 11B2
• Endoplasmic Reticulum Aminopeptidase 1

Monitoring Parameters

Blood pressure; electrolytes, serum creatinine, BUN, urinalysis

Hypertension: The 2017 Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults (ACC/AHA [Whelton 2017]):

Confirmed hypertension and known CVD or 10-year atherosclerotic cardiovascular disease (ASCVD) risk ≥10%: Target blood pressure <130/80 mm Hg is recommended

Confirmed hypertension without markers of increased ASCVD risk: Target blood pressure <130/80 mm Hg may be reasonable

Diabetes and hypertension: The American Diabetes Association (ADA) guidelines (ADA 2019):

Patients 18 to 65 years of age, without ASCVD, and 10-year ASCVD risk <15%: Target blood pressure <140/90 mm Hg is recommended

Patients 18 to 65 years of age and known ASCVD or 10-year ASCVD risk >15%: Target blood pressure <130/80 mm Hg may be appropriate if it can be safely attained

Patients >65 years of age (healthy or complex/intermediate health): Target blood pressure <140/90 mm Hg is recommended

Patients >65 years of age (very complex/poor health): Target blood pressure <150/90 mm Hg is recommended

Advanced Practitioners Physical Assessment/Monitoring

Obtain renal function tests, electrolytes, and urinalysis. Assess other medicines patient may be taking; alternate therapy or dosage adjustments may be needed. Monitor blood pressure on a regular basis during therapy. Assess for signs of angioedema.

Nursing Physical Assessment/Monitoring

Check ordered labs and report any abnormalities. Monitor blood pressure on a regular basis during therapy. Monitor for signs of angioedema.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral:

Avapro: 75 mg, 150 mg, 300 mg

Generic: 75 mg, 150 mg, 300 mg

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral:

Avapro: 75 mg, 150 mg, 300 mg

Generic: 75 mg, 150 mg, 300 mg

Anatomic Therapeutic Chemical (ATC) Classification

• C09CA04

Generic Available (US)

Yes

Pricing: US

Tablets (Avapro Oral)

75 mg (per each): $7.55

150 mg (per each): $7.95

300 mg (per each): $9.56

Tablets (Irbesartan Oral)

75 mg (per each): $0.44 - $2.92

150 mg (per each): $0.46 - $3.11

300 mg (per each): $0.55 - $3.69

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Mechanism of Action

Irbesartan is an angiotensin receptor antagonist. 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. Irbesartan binds to the AT1 angiotensin II receptor. This binding prevents angiotensin II from binding to the receptor thereby blocking the vasoconstriction and the aldosterone secreting effects of angiotensin II.

Pharmacodynamics/Kinetics

Onset of action: Peak effect: 1 to 2 hours

Maximum effect: 3-6 hours postdose; with chronic dosing maximum effect: ~2 weeks

Duration: >24 hours

Absorption: Rapid and complete

Distribution: V_d: 53 to 93 L

Protein binding, plasma: 90%, primarily to albumin and alpha-1 acid glycoprotein

Metabolism: Hepatic, via glucuronide conjugation and oxidation; oxidation occurs primarily by cytochrome P450 isoenzyme CYP2C9

Bioavailability: 60% to 80%

Half-life elimination: Terminal: 11 to 15 hours

Time to peak, serum: 1.5 to 2 hours

Excretion: Feces (80%); urine (20%)

Pharmacodynamics/Kinetics: Additional Considerations

Race: In healthy black patients, AUC values were approximately 25% greater than white patients.

Local Anesthetic/Vasoconstrictor Precautions

No information available to require special precautions

Effects on Dental Treatment

Key adverse event(s) related to dental treatment: Patients may experience orthostatic hypotension as they stand up after treatment; especially if lying in dental chair for extended periods of time. Use caution with sudden changes in position during and after dental treatment.

Effects on Bleeding

No information available to require special precautions

Related Information

• Angiotensin Agents

FDA Approval Date

September 30, 1997

References

American College of Obstetricians and Gynecologists (ACOG). ACOG practice bulletin no. 203: chronic hypertension in pregnancy. Obstet Gynecol. 2019;133(1):e26-e50.[PubMed 30575676]

American Diabetes Association (ADA). Diabetes Care. 2019;42(suppl 1):S1-S193. http://care.diabetesjournals.org/content/42/Supplement_1. Accessed January 10, 2019.

Amsterdam EA, Wenger NK, Brindis RG, et al; American College of Cardiology; American Heart Association Task Force on Practice Guidelines; Society for Cardiovascular Angiography and Interventions; Society of Thoracic Surgeons; American Association for Clinical Chemistry. 2014 AHA/ACC guideline for the management of patients with non-ST-elevation acute coronary syndromes: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines [published correction appears in J Am Coll Cardiol. 2014;64(24):2713-2714]. J Am Coll Cardiol. 2014;64(24):e139-e228. doi: 10.1016/j.jacc.2014.09.017.[PubMed 25260718]

Avapro (irbesartan) [prescribing information]. Bridgeton, NJ: Sanofi-Aventis; February 2016.

Avapro (irbesartan) [product monograph]. Laval, Quebec, Canada: Sanofi-Aventis Canada; June 2018.

Brooke BS, Habashi JP, Judge DP, et al, “Angiotensin II Blockade and Aortic-Root Dilation in Marfan's Syndrome,” N Engl J Med, 2008, 358(26):2787-95.[PubMed 18579813]

Canadian Diabetes Association Clinical Practice Guidelines Expert Committee, "Canadian Diabetes Association 2013 Clinical Practice Guidelines for the Prevention and Management of Diabetes in Canada," Can J Diabetes, 2013, 35(Suppl 1):1-212.

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):2560-72.[PubMed 12748199]

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.[PubMed 10988282]

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Brand Names: International

Agepin (NL); Andaran (LB, ZW); Angioblock MONO (EG); Aplorar (VN); Approvel (DE); Aprocare (PH); Aprovel (AE, AR, AT, BE, BH, BO, BR, BS, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DO, EC, EE, EG, ES, FI, FR, GB, GR, GT, HK, HN, HR, HU, ID, IE, IT, JM, JO, KR, KW, LB, LT, LU, LV, MT, MX, MY, NI, NL, NO, PA, PE, PH, PK, PL, PR, PT, PY, QA, RO, RU, SA, SE, SG, SI, SK, SV, TH, TR, TT, TW, UA, UY, VE, VN); Aprtan (KR); Arbit (BD); Arbitan (BD); Artibesan (NL); Atokken (RO); Avapro (AR, AU, BB, BM, BZ, GY, JP, MX, SR); Besanta (TH); Besartin (SG); Bestar (TH); Bewel 300 (TH); Bezart (PH); Converium (ET, SG, TR); Coravel (LK); Dynacard (LK); Elzar (ID); Fritens (ID); Gemot (TR); Gizlan (LB); Hypergold (VN); Ibefro (KR); Ibera (KR); Ibesaa (TW); Ibetan (KR); Ifirmasta (HR, IE); Iprestan (IE); Irbador (EG); Irbartan (ZW); Irbec (BG, NL); Irbedrin (EG); Irbee (BD); Irbegen (BH); Irbemed (PH); Irbenox (TH); Irbesan (HR, IE); Irbesel (PE); Irbesof (NL); Irbetan (JP, TW, UA); Irbeten (ID); Irbett (EC); Irbevell (MY); Irbevex (LK); Irbezyd (PH); Irbis (MY, ZW); Ircovas (VN); Irebeprex (CO); Iretensa (ID); Irovel (IN); Irprestan (HK); Irstran (MY); Irtan (ID); Irvebal (ID); Irvell (ID); Isart (BD); Izatan (KR); Karvea (AT, AU, CY, DK, ES, IE, MT, NL, PL, TR); Optima (TH); Presolin (HK, TH); Rycardon (MT); Tensiber (SG, VN); Virbez (PH); Zatrivir (DO, GT, HN, NI, PA, SV); Zatrivit (CR); Ziorel (LB)

Last Updated 2/16/20