Azilsartan
medicaldialogues.in/generics/azilsartan-2721677
Indications, Uses, Dosage, Drugs Interactions, Side effects
Azilsartan
Drug Related WarningAzilsartan
It is known to cause fetal toxicity or teratogenicity.
Fetal Toxicity: Use of drugs that act on the renin-angiotensin system during the second and third trimesters of pregnancy reduces fetal renal function and increases fetal and neonatal morbidity and death. The resulting oligohydramnios can be associated with fetal lung hypoplasia and skeletal deformities. Potential neonatal adverse effects include skull hypoplasia, anuria, hypotension, renal failure, and death. When pregnancy is detected, discontinue Azilsartan as soon as possible.
Medicine Type :
Allopathy
Prescription Type:
Prescription Required
Approval :
DCGI (Drugs Controller General of India)
Schedule
Schedule H
Pharmacological Class:
Angiotensin II Receptor Blocker (ARBs), Therapy Class:
Antihypertensive, Azilsartan is an antihypertensive agent belonging to Angiotensin II Receptor Blocker.
Azilsartan is approved for the treatment of Hypertension. It is also used for Heart failure and prevention of heart attack and stroke.
The estimated absolute bioavailability of the Azilsartan following administration of azilsartan medoxomil is approximately 60%. After oral administration of azilsartan medoxomil, the peak plasma concentrations (Cmax) of Azilsartan are reached within 1.5 to 3 hours. The volume of distribution of the Azilsartan is approximately 16L. Azilsartan is metabolized to two primary metabolites. The major enzyme responsible for azilsartan metabolism is CYP2C9. In the oral dose of 14C-labeled azilsartan medoxomil, approximately 55% of the radioactivity was recovered in feces and it is approximately 42% in urine, with 15% of the dose excreted in urine as Azilsartan.
Azilsartan shows common side effects like nausea, fatigue, diarrhea, etc
Azilsartan is available in the form of a Tablet.
Azilsartan is available in India, Europe, the US, and Mexico.
Azilsartan, belonging to the Angiotensin II Receptor Blocker, acts as an antihypertensive agent. Azilsartan works by relaxing blood vessels by blocking the action of a chemical that usually makes blood vessels tighter. This lowers blood pressure, allowing the blood to flow more smoothly to different organs and the heart to pump more efficiently.
Azilsartan blocks the action of vasoconstrictor and aldosterone-secreting effects of angiotensin II by selectively blocking the binding of the angiotensin II to the AT1 receptor in many tissues, such as vascular smooth muscle and the adrenal gland. Its action is independent of the pathway for angiotensin II synthesis.
The time taken for Azilsartan to show its effect is not clinically established.
Azilsartan may remain in your body for approximately 2-3 days.
The Tmax was found within 1.5-3 hours following the administration of Azilsartan, and the Cmax was about 888.3 and 831.3 ng/mL.
Azilsartan is available in the form of a Tablet.
Azilsartan tablet is taken as directed by a physician, and the regular tablet is often taken once a day, swallowed with plenty of water, with or without Food.
Azilsartan is approved for the treatment of Hypertension. It is used alone or in combination with other medications for the treatment of hypertension, also known as high blood pressure. This medicine improves blood flow by blood vessel relaxation.
Azilsartan works by blocking the action of a natural chemical in the body that causes the narrowing of the blood vessels. Thus, Azilsartan promotes a smooth flow of blood. It blocks the vasoconstrictor and aldosterone-secreting effects of angiotensin II by selectively blocking the binding of angiotensin II to the AT1 receptor in many tissues, like vascular smooth muscle and adrenal gland. Its action is independent of the pathway for angiotensin II synthesis.
Azilsartan is approved for the treatment of Hypertension. It is also used for Heart failure and prevention of heart attack and stroke. It may be used alone or in combination with other antihypertensive agents.
Hypertension
Azilsartan is useful for antihypertensive treatment as monotherapy or in combination therapy with other antihypertensive agents in patients aged 18 years or older. It is also commercially available as a combination therapy with chlorthalidone. Azilsartan is recommended as a first-line agent when initiating antihypertensive therapy.
Although not approved, there have been certain off-label indications. These include:
Myocardial Infarction
Azilsartan has been shown to decrease blood pressure levels more than its precursors, Olmesartan, and valsartan, and is theorized to lower mortality rates and the onset of cardiovascular disease. The benefits could be especially pertinent in the patients that have heart failure and have a myocardial infarction and may have potential off-label uses for these patients.
Delay progression of proteinuria in Diabetes mellitus
In patients with diabetes mellitus and hypertension, ARBs are effective in reducing blood pressure compared to the other first-line agents. ARBs and ACE inhibitors are considered the most efficacious in reducing the progression of moderate-to-severe albuminuria, and they may be used in an off-label fashion.
Azilsartan is available in the form of a tablet.
Hypertension
Azilsartan is available in an oral tablet form with 40 and 80 mg strength that is to be taken once a day, and it can be administered with or without Food. Although 80 mg is recommended as a starting dose for patients with hypertension. 40 mg may be the beginning dose for patients with concomitant high-dose diuretic therapy, as well as patients that are volume- or salt-deprived. For patients having a renal or mild-to-moderate hepatic impairment, dose adjustments are not necessary; the same applies to elderly patients.
The duration and dosage of the treatment should be according to the clinical judgment of the treating physician.
Myocardial Infarction
Azilsartan 20 and 40 mg once daily was more effective than is to be taken once a day, and it can be administered with or without Food. Azilsartan can stabilize atherosclerotic plaque and reduce cardiac fibrosis formation following myocardial infarction
Delay progression of proteinuria in Diabetes mellitus
In patients with diabetes mellitus and hypertension, ARBs are effective in reducing blood pressure in addition to the other first-line agents. 20 mg daily dose of Azilsartan significantly decreased proteinuria and blood pressure. These significant reductions in proteinuria and blood pressure during azilsartan treatment were not associated with significant increases in side effects, this is the first study of azilsartan in which the primary outcome is proteinuria.
Azilsartan is available in dosage strengths of 40 mg and 80 mg.
Azilsartan is available in the dosage form of Tablets.
Hypertension:
Potassium Rich Foods: Azilsartan may cause high blood potassium levels. Hence, avoid potassium-rich Food while taking this medication.
The dietary restriction should be individualized as per patient requirements.
Azilsartan is contraindicated in patients with
Hypersensitivity
Do not coadminister with aliskiren in patients has diabetes
Fetal Toxicity
The use of drugs that act on the renin-angiotensin system during the second and third trimesters of pregnancy reduces fetal renal function and increases fetal and neonatal morbidity and death. The resulting oligohydramnios can be associated with fetal lung hypoplasia and skeletal deformities. Potential neonatal adverse effects include skull hypoplasia, anuria, hypotension, renal failure, and death. When pregnancy is detected, discontinue Azilsartan as soon as possible.
Hypotension In Volume- Or Salt-Depleted Patients
In patients with an activated renin-angiotensin system, such as volume- and/or saltdepleted patients (e.g., those being treated with high doses of diuretics), symptomatic hypotension may occur after initiation of treatment with Azilsartan. Correct volume or salt depletion prior to administration of Azilsartan, or start treatment at 40 mg. If hypotension does occur, the patient should be placed in the supine position and, if necessary, given an
intravenous infusion of normal saline. The transient hypotensive response is not a contraindication to further treatment, which usually can be continued without difficulty once the blood pressure has stabilized.
Impaired Renal Function
As a consequence of inhibiting the renin-angiotensin system, changes in renal function may be anticipated in susceptible individuals treated with Azilsartan. In patients whose renal function may depend on the activity of the renin-angiotensin system (e.g., patients with severe congestive heart failure, renal artery stenosis, or volume depletion), treatment with angiotensin-converting enzyme inhibitors and angiotensin receptor blockers has been associated with oliguria or progressive azotemia and rarely with acute renal failure and death. Similar results may be anticipated in patients treated with Azilsartan.
Alcohol Warning
During the treatment with Azilsartan, the consumption of alcohol is not recommended as it may lower blood pressure and can cause headache, dizziness, lightheadedness, and/or changes in the heart rate.
Breast Feeding Warning
It is not known if the Azilsartan is excreted in human milk, but low concentrations of Azilsartan are excreted in the milk of lactating rats. Because of the possible adverse effects on the nursing infant, a decision should be made whether to discontinue the drug, taking into account the importance of the drug to the mother.
Pregnancy Warning
Pregnancy Category C: (1st trimester); D (2nd and 3rd trimesters)
Avoid use in pregnancy. When pregnancy is detected, discontinue the use of Azilsartan as soon as possible. It acts directly on the renin-angiotensin system and can cause injury and death to the developing fetus.
Food Warning
The food warning while consuming Azilsartan is that it should be taken in concentrations during its consumption
Potassium Rich Foods: Azilsartan may cause high blood potassium levels. Hence, avoid potassium-rich Food while taking this medicine.
The adverse reactions related to Losartan can be categorized as
Common Adverse effects:
Diarrhea
Dizziness
Fatigue
Less Common Adverse effects:
Nausea
Muscle spasm
Cough
Asthenia
Postural hypotension
Rare adverse effects:
Skin rash
Pruritus
Angioedema
The clinically relevant drug interactions of the molecule Azilsartan is briefly summarized here.
Non-steroidal Anti-Inflammatory Agents, Including Selective Cyclooxygenase-2 Inhibitors (COX-2 Inhibitors)
In patients who are elderly, volume-depleted (including those on diuretic therapy), or who have compromised renal function, coadministration of NSAIDs, including selective COX-2 inhibitors, with angiotensin II receptor antagonists, including Azilsartan, may result in deterioration of renal function, including possible acute renal failure. These effects are usually reversible. Monitor renal function periodically in patients receiving Azilsartan and NSAID therapy.
The antihypertensive effect of angiotensin II receptor antagonists, including azilsartan, may be attenuated by NSAIDs, including selective COX-2 inhibitors.
Dual Blockade of The Renin-Angiotensin System (RAS)
Dual blockade of the RAS with angiotensin receptor blockers, ACE inhibitors, or aliskiren is associated with increased risks of hypotension, hyperkalemia, and changes in renal function (including acute renal failure) compared to monotherapy. Most patients receiving the combination of two RAS inhibitors do not obtain any additional benefit compared to monotherapy. In general, avoid the combined use of RAS inhibitors. Closely monitor blood pressure, renal function, and electrolytes in patients on Azilsartan and other agents that affect the RAS.
Do not coadminister aliskiren with Azilsartan in patients with diabetes. Avoid the use of aliskiren with Azilsartan in patients with renal impairment (GFR < 60 mL/min).
Lithium
Increases in serum lithium concentrations and lithium toxicity have been reported during concomitant administration of lithium with angiotensin II receptor agonists. Monitor serum lithium levels during concomitant use.
The common side of Azilsartan includes the following
Major side effects
Diarrhea
Dizziness
Nausea
Fatigue
Minor side effects
Cough
Sweating
Blurred vision
Muscle spasm
The use of Azilsartan should be prudent in the following group of special populations.
Pregnancy
Pregnancy Category D
The use of Azilsartan affects the renin-angiotensin system during the second and third trimesters of pregnancy, decreases fetal renal function, and increases fetal and neonatal morbidity and death. The resulting oligohydramnios can be associated with fetal lung hypoplasia and skeletal deformations. The neonatal adverse effect includes skull hypoplasia, anuria, hypotension, renal failure, and death. When pregnancy is detected, discontinue the use of Azilsartan as soon as possible. Most epidemiologic studies that examined fetal abnormalities after exposure to antihypertensive use in the first trimester have not distinguished the drugs affecting the renin-angiotensin system from other antihypertensive agents. Proper management of maternal hypertension during pregnancy is important to optimize for both mother and the fetus.
In the unusual case, there is no appropriate alternative to therapy with drugs affecting the renin-angiotensin system for a particular patient, apprising the mother of the potential risk to the fetus. Serial ultrasound examinations perform to assess the intra-amniotic environment. If oligohydramnios is observed, discontinue the use of Azilsartan unless it is considered lifesaving for the mother. Fetal testing may be appropriate during the week of pregnancy. Patients and physicians should be aware that oligohydramnios may not appear until after the fetus has sustained irreversible injury. Closely observe infants with histories of in utero exposure to the Azilsartan for hypotension, hyperkalemia, and oliguria.
Nursing Mothers
It is not known if the Azilsartan is excreted in human milk, but low concentrations of Azilsartan are excreted in the milk of lactating rats. Because of the possible adverse effects on the nursing infant, a decision should be made whether to discontinue the drug, taking into account the importance of the drug to the mother.
Pediatric Use
Neonates with a history of in-utero exposure to the Azilsartan
If oliguria or hypotension occurs, support the blood pressure and renal function in that exchange; transfusions or dialysis may be required.
Safety and effectiveness in pediatric patients under the age of 18 years have not been established.
Geriatric Use
No dose adjustment with the Azilsartan is necessary for elderly patients. Out of the total patients in clinical studies with Azilsartan, 26% were elderly (65 years of age and older); 5% were 75 years of age and older. Abnormally high serum creatinine levels were more likely to be reported for patients aged 75 or older. There are no other differences in safety or effectiveness were observed between both elderly and younger patients, but the greater sensitivity of some older individuals cannot be ruled out.
Renal Impairment
Dose adjustment is not required in patients has a mild-to-severe renal impairment or endstage renal disease. Patients having moderate to severe renal impairment are more likely to report abnormally high serum creatinine values.
Hepatic Impairment
No dose adjustment is necessary for a patient with mild or moderate hepatic impairment. Azilsartan has not been studied in patients having severe hepatic impairment.
Limited data are available related to the overdosage of Azilsartan in humans. During clinical trials in healthy subjects, once-daily doses of up to 320 mg of Azilsartan were administered to subjects for seven days and were well tolerated. In the trials of an overdose, supportive therapy should be instituted as dictated by the patient's clinical status. Azilsartan is not dialyzable.
Pharmacodynamics:
The pressor effects of an angiotensin II infusion in a dose-related manner are inhibited by Azilsartan. Azilsartan single dose is equivalent to 32 mg azilsartan medoxomil, which inhibited the maximal pressor effect at peak by approximately 90% and approximately 60% at 24 hours. The plasma angiotensin I and II concentrations and plasma renin activity increased while plasma aldosterone concentrations reduced after single and repeated administration of the Azilsartan to healthy subjects; no significant clinical effects in the
serum potassium or sodium were observed. The effect on Cardiac Repolarization: A thorough QT/QTc study was conducted to assess the potential of the Azilsartan to prolong the QT/QTc interval in healthy volunteers. There was no evidence of QT/QTc prolongation at 320 mg dose of Azilsartan.
Pharmacokinetics:
Absorption: In the gastrointestinal tract during absorption, Azilsartan medoxomil is hydrolyzed to Azilsartan, the active metabolite. Azilsartan medoxomil is not traced in plasma after oral administration. The dose proportionality in exposure was established for Azilsartan in azilsartan medoxomil dose range of 20 mg to 320 mg after the single or multiple administration. The absolute bioavailability of Azilsartan following administration of azilsartan medoxomil is approximately 60%. After the oral administration of azilsartan medoxomil, peak plasma concentrations (Cmax) of Azilsartan are reached within 1.5 to 3 hours. The bioavailability of Azilsartan is not affected by Food.
Distribution: The volume of distribution of the Azilsartan is approximately 16L. Azilsartan is highly bound about >99% to the human plasma proteins, mainly serum albumin. In rats, the minimal azilsartan-associated radioactivity crossed the bloodbrain barrier. Azilsartan passed across the placental barrier in the pregnant rats and was distributed to the fetus.
Metabolism and Elimination: Azilsartan is metabolized into two primary metabolites. The major metabolite in the plasma is formed by O-dealkylation, referred to as M-II, and the minor metabolite is formed by decarboxylation, which is referred to as M-I. The systemic exposures to the major and minor metabolites in humans were approximately 50% and less than 1% of Azilsartan, respectively. Both M-I and MII do not contribute to the pharmacologic activity of Azilsartan. The major enzyme responsible for azilsartan metabolism is CYP2C9.
Following an oral dose of 14C-labeled azilsartan medoxomil, approximately 55% of the radioactivity was recovered in feces and about 42% in urine, with 15% of the dose excreted in urine as Azilsartan. The elimination half-life and renal clearance of Azilsartan are approximately 11 hours and 2.3 mL/min respectively. Steady-state levels of Azilsartan are achieved within 5 days and there is no accumulation in plasma that occurs with repeated once-daily dosing.
There are some clinical studies of the azilsartan drug which are mentioned below:
1. Angeli F, Verdecchia P, et al. Pharmacokinetic evaluation and clinical utility of azilsartan medoxomil for the treatment of hypertension. Expert opinion on drug metabolism & toxicology. 2013 Mar 1;9(3):379-85.
2. Perry CM. Azilsartan medoxomil. Clinical drug investigation. 2012 Sep;32(9):621-39.
3. Pradhan A, Tiwari A, et al. Azilsartan: current evidence and perspectives in the management of hypertension. International Journal of Hypertension. 2019 Nov 3;2019.
4. De Caterina AR, Harper AR, et al. Critical evaluation of the efficacy and tolerability of azilsartan. Vascular Health and Risk Management. 2012;8:299.
https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/200796s000lbl.pdf
https://www.rxlist.com/edarbi-drug.htm#warnings
https://go.drugbank.com/drugs/DB08822
https://www.practo.com/medicine-info/azilsartan-1593-api
https://www.1mg.com/generics/azilsartan-medoxomil-404950#:~:text=You should take Azilsartan medoxomil,the same time every day
Jyoti Suthar
Jyoti is a Post graduate in Pharmaceutics ( M Pharm) She did her graduation ( B Pharm) From SSR COLLEGE OF PHARMACY And thereafter did her M Pharm specialized in Pharmaceutics from SSR COLLEGE OF PHARMACY
Dr JUHI SINGLA
Dr JUHI SINGLA has completed her MBBS from Era’s Lucknow Medical college and done MD pharmacology from SGT UNIVERSITY Gurgaon. She can be contacted at editorial@medicaldialogues.in. Contact no. 01143720751
