Azilsartan

Black Box Warnings

Discontinue as soon as possible when pregnancy is detected; affects renin-angiotensin system causing oligohydramnios, which may result in fetal injury and/or death

Contraindications

Hypersensitivity

Do not coadminister with aliskiren in patients with diabetes

Cautions

Correct volume or salt depletion before administration (risk for excessive hypotension)

Abnormally high serum creatinine values more likely reported in patients aged 75 or older

Caution with hyperkalemia

Increased risk for renal failure in patients with risk factors (eg, renal artery stenosis); monitor for worsening renal function in patients with renal impairment

Dual blockade of the renin angiotensin system with ARBs, ACE inhibitors, or aliskiren associated with increased risk for hypotension, hyperkalemia, and renal function changes (including acute renal failure) compared to monotherapy

NSAIDs may attenuate antihypertensive response

Coadministration with NSAIDs increase risk of renal impairment including acute renal failure

Azilsartan is a prescription medication used to treat high blood pressure in adults.

This medication may be prescribed for other uses. Ask your doctor or pharmacist for more information.

Azilsartan is part of the drug class:

• ANGIOTENSIN II ANTAGONISTS, PLAIN

Azilsartan may cause side effects, including:

• Harm or death to your unborn fetus if taken in the second or third trimester. See "FDA Warning" and "Pregnancy" sections.
• Low blood pressure (hypotension) and dizziness is most likely to happen if you also:
  • take water pills (diuretics)
  • are on a low-salt diet
  • take other medicines that affect your blood pressure
  • get sick with vomiting or diarrhea
  • do not drink enough fluids

If you feel faint or dizzy, lie down and call your doctor right away.

The most common side effect in clinical trials was diarrhea, occurring in 2 percent of the people taking azilsartan. Other reported side effects included:

• nausea
• weakness
• fatigue 
• muscle spasms
• dizziness
• dizziness when standing from a lying position
• cough

These are not all the possible side effects with azilsartan. Tell your doctor if you have any side effect that bothers you or that does not go away.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Tell your doctor about all the medicines you take including prescription and non-prescription medicines, vitamins, and herbal supplements. Especially tell your doctor if you take:

• aliskiren (Tekturna, in Amturnide, Tekamlo, Tekturna HCT)
• aspirin
• other nonsteroidal anti-inflammatory medications (NSAIDs) such as ibuprofen (Advil, Motrin) and naproxen (Aleve, Naprosyn)
• selective COX-2 inhibitors such as celecoxib (Celebrex)
• diuretics ('water pills') such as amiloride, spironolactone, and triamterene
• other medications to treat high blood pressure or heart problems
• potassium supplements

This is not a complete list of azilsartan drug interactions. Ask your doctor or pharmacist for more information.

Tell your doctor if you are breastfeeding or plan to breastfeed. It is not known if azilsartan is excreted in human breast milk or if it will harm your nursing baby. 

You and your doctor should decide if you will take azilsartan or breastfeed. You should not do both. Talk with your doctor about the best way to feed your baby if you take azilsartan.

If you take too much azilsartan call your healthcare provider or local Poison Control Center, or seek emergency medical attention right away.

If azilsartan is administered by a healthcare provider in a medical setting, it is unlikely that an overdose will occur. However, if overdose is suspected, seek emergency medical attention.

Usual Adult Dose for Hypertension:

80 mg orally once a day

Comments: Consider a starting dose of 40 mg orally once a day for patients on high diuretic doses.

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

Tablet, Oral, as medoxomil:

Edarbi: 40 mg, 80 mg

Hypertension: Treatment of hypertension; may be used alone or in combination with other antihypertensives

Guideline recommendations:

Hypertension: The 2014 guideline for the management of high blood pressure in adults (Eighth Joint National Committee [JNC 8]) recommends initiation of pharmacologic treatment to lower blood pressure for the following patients:

• Patients ≥60 years with systolic blood pressure (SBP) ≥150 mm Hg or diastolic blood pressure (DBP) ≥90 mm Hg.

• Patients <60 years with SBP ≥140 mm Hg or DBP is ≥90 mm Hg.

• Patients ≥18 years with diabetes and SBP ≥140 mm Hg or DBP ≥90 mm Hg.

• Patients ≥18 years with chronic kidney disease (CKD) and SBP ≥140 mm Hg or DBP ≥90 mm Hg.

Coronary artery disease and hypertension: The American Heart Association, American College of Cardiology and American Society of Hypertension (AHA/ACC/ASH) 2015 scientific statement for the treatment of hypertension in patients with coronary artery disease (CAD) recommends the use of an ARB (or ACE inhibitor) as part of a regimen in patients with hypertension and chronic stable angina if there is prior MI, LV systolic dysfunction, diabetes mellitus, or CKD. A BP target of <140/90 mm Hg is reasonable for the secondary prevention of cardiovascular events. A lower target BP (<130/80 mm Hg) may be appropriate in some individuals with CAD, previous MI, stroke or transient ischemic attack, or CAD risk equivalents (AHA/ACC/ASH [Rosendorff 2015]).

Diabetes and hypertension: The American Diabetes Association (ADA) guidelines recommend an ARB (or an ACE inhibitor) for patients with HTN and diabetes with albuminuria (urinary albumin-to-creatinine ratio [UACR] ≥30 mg/g). For patients with hypertension and diabetes without albuminuria, any of the 4 classes of blood pressure medications (eg, ACE inhibitors, ARBs, thiazide-like diuretics, dihydropyridine calcium channel blockers) may be used and have shown beneficial cardiovascular outcomes (ADA 2017a).

Mild to moderate impairment: No dosage adjustment necessary; however, carefully monitor the patient.

Severe impairment: No dosage adjustment provided in manufacturer’s labeling (has not been studied).

Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Protect from moisture and light. Dispense and store in original container.

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 in patients taking angiotensin II receptor blockers ; 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 azilsartan.

• 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, 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.

• 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 in 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).

Applies to azilsartan medoxomil: oral tablet

General

The most common side effects were diarrhea, dizziness, headache, dyslipidemia, cough, and increased blood creatine phosphokinase.[Ref]

Gastrointestinal

Common (1% to 10%): Diarrhea
Uncommon (0.1% to 1%): Nausea[Ref]

Nervous system

Common (1% to 10%): Dizziness, headache
Frequency not reported: Dizziness postural[Ref]

Metabolic

Common (1% to 10%): Dyslipidemia
Uncommon (0.1% to 1%): Blood uric acid increased, hyperuricemia[Ref]

Respiratory

Common (1% to 10%): Cough[Ref]

Musculoskeletal

Common (1% to 10%): Blood creatine phosphokinase increased
Uncommon (0.1% to 1%): Muscle spasm[Ref]

Dermatologic

Uncommon (0.1% to 1%): Rash, pruritus
Rare (less than 0.1%): Angioedema[Ref]

Other

Uncommon (0.1% to 1%): Fatigue, peripheral edema
Frequency not reported: Asthenia[Ref]

Hematologic

Uncommon (0.1% to 1%): Low hemoglobin, low hematocrit, low RBC counts[Ref]

Renal

Uncommon (0.1% to 1%): Blood creatinine increased[Ref]

Cardiovascular

Uncommon (0.1% to 1%): Hypotension[Ref]

Some side effects of azilsartan medoxomil may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

No adjustment recommended

Mild to moderate liver dysfunction: No adjustment recommended
Severe liver dysfunction: Unknown