Azilsartan Kamedoxomil

Name: Azilsartan Kamedoxomil

Azilsartan Kamedoxomil Dosage and Administration

General

BP Monitoring and Treatment Goals

  • Carefully monitor BP during initial titration or subsequent upward adjustment in dosage.500 501

  • When available, use evidence-based dosing information (i.e., dosages shown in randomized controlled trials to reduce complications of hypertension) to determine target dosages; target dosages usually can be achieved within 2–4 weeks but may take up to several months.501

  • If adequate BP response not achieved with a single antihypertensive agent, add a second drug with demonstrated benefit; if goal BP still not achieved with optimal dosages of 2 antihypertensive agents, add a third drug.501 May maximize dosage of the first drug before adding a second drug, or add a second drug before maximizing dosage of the initial drug.501

  • Consider initiating antihypertensive therapy with a combination of drugs if patient's BP exceeds goal BP by >20/10 mm Hg.500 501 503 504

  • Goal is to achieve and maintain optimal control of BP; individualize specific target BP based on consideration of multiple factors, including patient age and comorbidities, and currently available evidence from clinical studies.500 501 (See Hypertension under Uses.)

Administration

Oral Administration

Administer orally once daily without regard to meals.1

Must be dispensed and stored in the original manufacturer's container.1

Dosage

Available as azilsartan kamedoxomil (the potassium salt of azilsartan medoxomil); dosage expressed in terms of azilsartan medoxomil.1

Adults

Hypertension Oral

Usual dosage: 80 mg once daily.1 Consider a reduced initial dosage of 40 mg once daily in patients receiving high dosages of diuretics.1

If BP is not adequately controlled, may add other antihypertensive agents.1

If intolerable adverse effects occur, consider dosage reduction; if adverse effects worsen or fail to resolve, may need to discontinue and switch to another antihypertensive drug class.501

Special Populations

Hepatic Impairment

No adjustment of initial azilsartan medoxomil dosage necessary in patients with mild to moderate hepatic impairment.1 Not studied in patients with severe hepatic impairment.1

Renal Impairment

No adjustment of initial azilsartan medoxomil dosage necessary in patients with mild to severe renal impairment or end-stage renal disease.1

Geriatric Patients

No adjustment of initial azilsartan medoxomil dosage is necessary.1

Volume- and/or Salt-depleted Patients

Correct volume and/or salt depletion prior to initiation of azilsartan therapy or initiate therapy using lower initial dosage (40 mg once daily).1

Interactions for Azilsartan Kamedoxomil

Metabolized principally by CYP2C9.1

Specific Drugs

Drug

Interaction

Comments

ACE inhibitors

Increased risk of renal impairment, hyperkalemia, and hypotension1

Generally, avoid concomitant use; monitor BP, renal function, and electrolytes if used concomitantly1

Aliskiren

Increased risk of renal impairment, hyperkalemia, and hypotension1 550

Generally, avoid concomitant use; monitor BP, renal function, and electrolytes if used concomitantly1 550

Concomitant use contraindicated in patients with diabetes mellitus1 550

Avoid concomitant use in patients with GFR <60 mL/minute1 550

Amlodipine

Pharmacokinetic interactions unlikely1

Angiotensin II receptor antagonists

Increased risk of renal impairment, hyperkalemia, and hypotension1

Generally, avoid concomitant use; monitor BP, renal function, and electrolytes if used concomitantly1

Antacids

Pharmacokinetic interactions unlikely1

Chlorthalidone

Pharmacokinetic interactions unlikely1

Greater reversible increases in SCr possible1

Digoxin

Pharmacokinetic interactions unlikely1

Diuretics, potassium-sparing

Possible increase in serum potassium concentrations9

Avoid concomitant administration9

Fluconazole

Pharmacokinetic interactions unlikely1

Glyburide

Pharmacokinetic interactions unlikely1

Hydrochlorothiazide

Greater reversible increases in SCr possible1

Ketoconazole

Pharmacokinetic interactions unlikely1

Lithium

Increased serum lithium concentrations and lithium toxicity reported with concomitant angiotensin II receptor antagonist therapy1

Monitor serum lithium concentrations during concomitant therapy1

Metformin

Pharmacokinetic interactions unlikely1

NSAIAs, including selective cyclooxygenase-2 (COX-2) inhibitors

Possible deterioration of renal function, including possible acute renal failure, in patients who are geriatric, volume-depleted, or have compromised renal function; effects usually reversible1

Possible attenuation of azilsartan antihypertensive effect1

Periodically monitor renal function1

Pioglitazone

Pharmacokinetic interactions unlikely1

Potassium supplements and potassium-containing salt substitutes

Possible increase in serum potassium concentrations9

Avoid concomitant administration9

Warfarin

Pharmacokinetic interactions unlikely1

Azilsartan Kamedoxomil Pharmacokinetics

Absorption

Bioavailability

Azilsartan medoxomil (prodrug) is rapidly and completely hydrolyzed to azilsartan during absorption in the GI tract.1

Absolute bioavailability of azilsartan is about 60%.1

Peak plasma azilsartan concentration generally reached 1.5–3 hours following oral administration.1

Increases in AUC are dose proportional following single or multiple doses of azilsartan medoxomil in the range of 20–320 mg.1

Steady-state concentrations of azilsartan are achieved within 5 days.1

Onset

Most of the antihypertensive effect of azilsartan occurs within 2 weeks.1

Food

Food does not affect bioavailability of azilsartan.1

Special Populations

Modest increases in peak plasma azilsartan concentration and AUC reported in geriatric patients and in patients with mild to severe renal impairment or mild to moderate hepatic impairment; no dosage adjustment required.1 Not studied in patients with severe hepatic impairment.1

Distribution

Extent

Azilsartan crosses the placenta and is distributed in the fetus in rats.1

A minimal amount of azilsartan-associated radioactivity crosses the blood-brain barrier in rats.1

Azilsartan is distributed into milk in rats; not known whether azilsartan is distributed into human milk.1

Plasma Protein Binding

>99%.1

Elimination

Metabolism

Azilsartan medoxomil undergoes rapid and complete hydrolysis to azilsartan.1

Azilsartan is metabolized primarily by CYP2C9.1

Azilsartan is metabolized to 2 primary metabolites, both of which are inactive; metabolite M-II (the major metabolite) is formed by O-dealkylation, and metabolite M-I (the minor metabolite) is formed by decarboxylation.1

Systemic exposures to M-II and M-I are approximately 50% and <1%, respectively, that of azilsartan.1

Elimination Route

Radiolabeled azilsartan medoxomil is eliminated mainly in feces (55%) and urine (42%, with 15% as azilsartan).1

Half-life

Approximately 11 hours.1

Stability

Storage

Oral

Tablets

25ºC (may be exposed to 15–30ºC).1 Dispense and store in tightly closed original container; protect from light and moisture.1

Advice to Patients

  • Risk of hypotension.2 Importance of lying down and informing clinician immediately if lightheadedness or dizziness occurs.2

  • Importance of storing azilsartan medoxomil in the original container, tightly closed and protected from light and moisture.2

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed; importance of discussing other options for hypertension treatment if pregnancy occurs.2 Importance of informing women of childbearing potential of risk of serious harm or death in the fetus and infant if azilsartan is used during the second or third trimester of pregnancy.1 2 (See Fetal/Neonatal Morbidity and Mortality under Cautions.) All women of childbearing potential should be advised to report pregnancy to their clinician as soon as possible.1

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, vitamins, and herbal supplements.2

  • Importance of informing patients of other important precautionary information.1 (See Cautions.)

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