Azilsartan for the management of Hypertension.

Azilsartan is an angiotensin receptor blocker that primarily inhibits angiotensin I receptors resulting in vasodilation and inhibiting sodium and water retention.

It is used in the management of hypertension.

It is also used as off-label medicine to treat patients with stable coronary artery disease and for the secondary prevention of cardiovascular events in patients with the acute coronary syndrome.

 

Adult dose :

Dose in the treatment of Hypertension:

  • 40 mg orally once a day.
  • The dose may be titrated upwards upto 80 mg once a day.

Dose in children:

Not recommended

 

Pregnancy Risk Factor D

 

  • [US Boxed Warning]
    • Azilsartan can, just like other drugs that act on the RAAS, cause injury or death for the developing fetus.
    • Once pregnancy is confirmed, it should be stopped immediately.
    • It crosses the placental boundary and is associated with oligohydramnios, which can cause fetal lung hypoplasia or skeletal malformations.
    • Additionally, oligohydramnios might not be present until irreversible fetal injuries have occurred.
    • It can also lead to hypotension, anuria and skull hypoplasia in infants/neonates.
    • ACE-Inhibitors and ARBs should generally be avoided in hypertensive patients of child-bearing ages.
    • Alternative therapies should be considered if necessary.

Use Azilsartan during lactation

  •  
    • It is unknown if the drug can be absorbed into breastmilk.
    • The manufacturer suggests that you stop using the drug and discontinue breastfeeding because of possible adverse effects.

 

 Renal dose:

Adjustment in the dose has not been recommended. Renal functions should be monitored.

 

Dose in liver disease :

Adjustment in the dose has not been provided in the manufacturer's labeling, however, it should be used with caution especially in advanced liver disease and those with ascites. 

 

Side effects :

Common Side Effects of Azilsartan Include:

  • Gastrointestinal:
    • Diarrhea

Frequency not defined:

  • Cardiovascular:
    • Hypotension
    • Orthostatic Hypotension
  • Central Nervous System:
    • Dizziness
    • Fatigue
    • Orthostatic Dizziness
  • Gastrointestinal:
    • Nausea
  • Neuromuscular & Skeletal:
    • Asthenia
    • Muscle Spasm
  • Renal:
    • Increased Serum Creatinine
  • Respiratory:
    • Cough

 

Contraindication to Azilsartan Include:

 

  • Avoid using azilsartan with aliskiren-containing products.
  • Allergy to azilsartan medoxomil, or any component of this formulation
  • Pregnancy
  • Breastfeeding

Warnings and Precautions

  • Angioedema
    • Zilsartan has been associated with angioedema. This can occur at any stage of treatment.
    • Patients with a history of angioedema associated with ACE-inhibitors, idiopathic, or hereditary angioedema may be at higher risks.
    • If patients experience swelling in the larynx, glottis or face, it is important to monitor them.
    • The drug should be stopped immediately and not be restarted.
    • Aggressive management of the airway and Intramuscular epinephrine should be part of the resuscitation.
  • Hyperkalemia:
    • Patients with impaired renal function, Diabetes mellitus, Patients taking potassium-sparing diuretics and patients who take potassium-containing salts or potassium supplements are at increased risk of hyperkalemia.
  • Hypotension
    • Hypotension is a risk factor for patients who are salt- and volume-depleted (e.g. patients on high-dose diuretics).
    • The patient must be well hydrated before initiating therapy.
    • Zilsartan therapy is safe for transient hypotension.
  • Renal function deterioration:
    • Angiotensin receptor blocking drugs may cause deterioration in renal function, as evidenced by an increase of serum creatinine.
    • Patients with volume-depleted, heart disease, and renal artery stenosis are at highest risk for renal function decline.
    • Treatment may cause a slight increase in serum creatinine. However, it is important to continue treatment and monitor your renal function.
  • Mitral and aortic stenosis:
    • Patients suffering from mitral or aortic blockage should be cautious when taking the drug.
  • Ascites:
    • Patients suffering from cirrhosis and refractory ascites must be cautious about taking the drug.
    • To avoid rapid decline in renal function, it is important to monitor blood pressure and renal functions.
  • Renal artery stenosis
    • This should be avoided in bilateral renal arterial stenosis, and it should only be used in unilateral renal artery narrowing.
  • Renal impairment
    • Preexisting renal impairments should be avoided.

 

Azilsartan: Drug Interaction

Note: Drug Interaction Categories:

  • Risk Factor C: Monitor When Using Combination
  • Risk Factor D: Consider Treatment Modification
  • Risk Factor X: Avoid Concomitant Use

    Risk Factor C (Monitor therapy).

    Alfuzosin Might increase the hypotensive effects of Blood Pressure Lowering Agents.
    Amphetamines May decrease the antihypertensive effects of Antihypertensive Drugs.
    Angiotensin II Angiotensin II's therapeutic effects may be diminished by receptor blockers.
    Antipsychotic Agents, Second Generation (Atypical) Blood Pressure Lowering Agents can increase the hypotensive effects of Antipsychotic Agents (Second Gen [Atypical]).
    Barbiturates Might increase the hypotensive effects of Blood Pressure Lowering Agents.
    Benperidol Might increase the hypotensive effects of Blood Pressure Lowering Agents.
    Brigatinib May decrease the antihypertensive effects of Antihypertensive Drugs. Brigatinib could increase the bradycardic effects of Antihypertensive Drugs.
    Brimonidine (Topical) Might increase the hypotensive effects of Blood Pressure Lowering Agents.
    CycloSPORINE Systemic Angiotensin II Receptor-Blockers could increase the hyperkalemic effects of CycloSPORINE Systemic.
    Dapoxetine May increase the orthostatic hypotensive effects of Angiotensin II receptor Blockers.
    Dexmethylphenidate Antihypertensive agents may have a less therapeutic effect.
    Diazoxide Might increase the hypotensive effects of Blood Pressure Lowering Agents.
    Drospirenone Angiotensin II receptor blockers could increase the hyperkalemic effects of Drospirenone.
    DULoxetine DULoxetine may increase hypotensive effects by lowering blood pressure.
    Eplerenone May increase the hyperkalemic effects of Angiotensin-2 Receptor Blockers.
    Heparin May increase the hyperkalemic effects of Angiotensin-2 Receptor Blockers.
    Heparins (Low Molecular Weight) May increase the hyperkalemic effects of Angiotensin-2 Receptor Blockers.
    Herbs (Hypertensive Properties) May decrease the antihypertensive effects of Antihypertensive Drugs.
    Herbs (Hypotensive properties) Might increase the hypotensive effects of Blood Pressure Lowering Agents.
    Hypotension-Associated Agents Blood Pressure Lowering Agents may enhance the hypotensive effect of Hypotension-Associated Agents.
    Levodopa-Containing Products Blood Pressure Lowering Agents can increase the hypotensive effects of Levodopa -Containing Products.
    Lormetazepam Might increase the hypotensive effects of Blood Pressure Lowering Agents.
    Methylphenidate May decrease the antihypertensive effects of Antihypertensive Drugs.
    Molsidomine Might increase the hypotensive effects of Blood Pressure Lowering Agents.
    Naftopidil Might increase the hypotensive effects of Blood Pressure Lowering Agents.
    Nicergoline Might increase the hypotensive effects of Blood Pressure Lowering Agents.
    Nicorandil May increase the hyperkalemic effects of Angiotensin-2 Receptor Blockers.
    Nicorandil Might increase the hypotensive effects of Blood Pressure Lowering Agents.
    Nitroprusside The hypotensive effects of Nitroprusside may be enhanced by blood pressure lowering agents.
    Nonsteroidal Anti-Inflammatory Drugs Angiotensin II receptor blockers can increase the toxic/adverse effects of Nonsteroidal Anti-Inflammatory Agents. The combination could result in a significant decrease of renal function. Nonsteroidal anti-inflammatory agents may decrease the therapeutic effects of Angiotensin II Receptor Blockers. Combining these two agents can also reduce glomerular filtration, and may even improve renal function.
    Pentoxifylline Might increase the hypotensive effects of Blood Pressure Lowering Agents.
    Pholcodine Pholcodine may increase hypotensive effects by lowering blood pressure.
    Phosphodiesterase 5 Inhibitors Might increase the hypotensive effects of Blood Pressure Lowering Agents.
    Potassium Salts May increase the hyperkalemic effects of Angiotensin-2 Receptor Blockers.
    Potassium-Sparing Diuretics Angiotensin II Receptor Blockers could increase the hyperkalemic effects of Potassium–Sparing Diuretics.
    Prostacyclin Analogues Might increase the hypotensive effects of Blood Pressure Lowering Agents.
    Quinagolide Might increase the hypotensive effects of Blood Pressure Lowering Agents.
    Ranolazine May increase the toxic/adverse effects of Angiotensin II Receptor-Blockers.
    Tacrolimus (Systemic) Angiotensin II Receptor Blockers could increase the hyperkalemic effects of Tacrolimus.
    Tolvaptan May increase the hyperkalemic effects of Angiotensin-2 Receptor Blockers.
    Trimethoprim May increase the hyperkalemic effects of Angiotensin-2 Receptor Blockers.
    Yohimbine May decrease the antihypertensive effects of Antihypertensive Drugs.

    Risk Factor D (Consider therapy modifications)

     
    Aliskiren May increase the hyperkalemic effects of Angiotensin-2 Receptor Blockers. Aliskiren could increase the hypotensive effects of Angiotensin Receptor Blockers. Aliskiren could increase the nephrotoxic effects of Angiotensin-2 Receptor Blockers. Patients with diabetes should not use Aliskiren in combination with ACEIs and ARBs. Combining Aliskiren with ACEIs or ARBs in patients with diabetes should be avoided, especially if CrCl is below 60 mL/min. Monitor potassium, creatinine and blood pressure carefully if combined.
    Amifostine Amifostine's hypotensive effects may be enhanced by blood pressure lowering agents. Treatment: Blood pressure lowering drugs should be stopped 24 hours before amifostine is administered to chemotherapy patients. Amifostine should be avoided if blood pressure lowering medication cannot be withheld.
    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: Telmisartan/ramipril are not recommended for US labeling. It is unclear if any other combination of ACE inhibitors and ARBs would be safer. If possible, consider alternatives to the combination.
    Lithium Angiotensin II receptor antagonists may increase serum levels of Lithium. Management: After adding an antagonist to the angiotensin II receptor, Lithium dosage reductions may be necessary.
    Obinutuzumab This may increase the hypotensive effects of Blood Pressure Lowering Agents. Management: You may temporarily withhold blood pressure lowering medication beginning 12 hours before obinutuzumab injection and continuing for 1 hour after infusion.
    Sodium Phosphates Angiotensin II receptor blockers could increase the nephrotoxic effects of Sodium Phosphates. In particular, acute phosphate-nephropathy risk may be increased. Management: You can avoid this combination by temporarily stopping treatment with ARBs or looking for alternatives to oral sodium-phosphate bowel preparation. Maintain adequate hydration, and closely monitor your renal function if the combination is not possible.

    Risk Factor X (Avoid Combination)

     
    Bromperidol Bromperidol's hypotensive effects may be enhanced by Blood Pressure Lowering agents. Bromperidol could decrease the hypotensive effects of Blood Pressure Lowering agents.

 

Monitoring parameters:

 Monitor Blood pressure, serum electrolytes, serum creatinine, and BUN.

Target Blood pressure:

  • Target blood pressure of less than 130/80 mmHg in patients with hypertension and known cardiovascular disease or the 10-year ASCVD risk is greater than 10%.
  • The target blood pressure of less than 130/80 mmHg may be reasonable in patients with ASCVD risk.
  • Target blood pressure of less than 140/90 mmHg in patients aged 18 – 65 years with Diabetes and hypertension without cardiovascular disease and the 10-year ASCVD risk is less than 15%.
  • Target blood pressure of less than 130/80 mmHg in patients aged 18 – 65 years with Diabetes, hypertension, cardiovascular disease, or the 10-year ASCVD risk is greater than 15%.
  • Target blood pressure of less than 140/90 mmHg in patients aged more than 65 years and without major comorbid conditions.
  • Target blood pressure of less than 150/90 mmHg in patients aged more than 65 years and poor health or comorbid conditions.

 

How to take Azilsartan?

It may be administered orally without regard to food.

 

Mechanism of action of Azilsartan:

Azilsartan blocks the binding of angiotensin I to its receptors. It is highly attracted to angiotensin I receptors as well as angiotensin I receptors. Angiotensin II can cause vasoconstriction and stimulate the synthesis of aldosterone. It also stimulates the heart and causes sodium reabsorption.

Azilsartan inhibits the angiotensin receptors only in the vascular smooth muscle and adrenal glands, with very little effect on the cardiovascular system or bradykinin More than 99% are covered by the drugprotein-bound. It is then hydrolyzed in your stomach to make it an active metabolite.MetabolizedTo inactive metabolites, use CYP2C9.

It has been abioavailability60% and morehalf-life eliminationA total of 11 hours. The time it takes topeak serum concentrationIt takes 1.5-3 hours. It is excreted primarily via feces (55%) and urine (42%).

 

 

International Brands:

  • Azildac
  • Azilispire
  • Azilsar
  • Azilva
  • Edarbi
  • Ipreziv
  • Lan Sha

 

Brands in pakistan:

No brands available in Pakistan 

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