Usage
- Azilsartan medoxomil is prescribed for the treatment of essential hypertension (high blood pressure) in adults. It can be used alone or in combination with other antihypertensive medications. Lowering blood pressure reduces the risk of cardiovascular events, primarily strokes and myocardial infarctions.
- Pharmacological classification: Angiotensin II Receptor Blocker (ARB)
- Mechanism of Action: Azilsartan medoxomil is a prodrug that is converted to azilsartan in the body. Azilsartan blocks the action of angiotensin II, a hormone that causes blood vessels to constrict, by selectively binding to the angiotensin II type 1 (AT1) receptor. This blockade prevents angiotensin II from binding to the AT1 receptors in vascular smooth muscle, leading to vasodilation and a reduction in blood pressure.
Alternate Names
- International Nonproprietary Name (INN): Azilsartan medoxomil
- Brand names: Edarbi, Edarbyclor (in combination with chlorthalidone)
How It Works
- Pharmacodynamics: Azilsartan’s primary effect is the reduction of blood pressure. It does not affect bradykinin levels, nor does it bind to ion channels involved in cardiovascular regulation.
- Pharmacokinetics: Azilsartan medoxomil is rapidly hydrolyzed to azilsartan in the gastrointestinal tract during absorption. It has an elimination half-life of approximately 11 hours, achieves steady-state levels within 5 days, and does not accumulate in plasma with once-daily dosing.
- Mode of Action: Azilsartan selectively binds to AT1 receptors, preventing angiotensin II from binding. The action of angiotensin II at AT1 receptors results in vasoconstriction and increased blood pressure. By blocking this binding, azilsartan promotes vasodilation, and along with fluid and sodium excretion, reduces blood pressure.
- Receptor Binding, Enzyme Inhibition, or Neurotransmitter Modulation: Selective AT1 receptor antagonist. It shows high selectivity for AT1 receptors over other receptors. The binding is slow, and the dissociation from the AT1 receptor is also slow, which may contribute to its long duration of action.
- Elimination Pathways: Primarily eliminated via biliary/fecal excretion (approximately 55%). Renal excretion accounts for about 42% of elimination, primarily as unchanged azilsartan. Metabolism plays a minor role in azilsartan elimination. It is not significantly metabolized by CYP450 enzymes.
Dosage
Standard Dosage
Adults:
- The recommended starting dose is 40 mg orally once daily.
- The dose may be increased to a maximum of 80 mg orally once daily for patients whose blood pressure is not adequately controlled by the lower dose.
- For patients taking high doses of diuretics, a 40 mg starting dose should be considered.
Children:
- The safety and efficacy of azilsartan medoxomil in children and adolescents aged 0 to < 18 years have not yet been established. No data are available.
Special Cases:
- Elderly Patients: No initial dose adjustment is generally necessary, but a lower starting dose (e.g., 20 mg) can be considered for patients over 75 years old due to a potential increased risk of hypotension.
- Patients with Renal Impairment: No dose adjustment is needed for mild or moderate renal impairment. Caution should be exercised in patients with severe renal impairment and end-stage renal disease, as there is limited experience in these patients. Hemodialysis does not effectively remove azilsartan.
- Patients with Hepatic Dysfunction: For mild to moderate hepatic impairment, a lower starting dose (e.g., 20 mg) should be considered, and the maximum dose should not exceed 80 mg. Use is not recommended in patients with severe hepatic impairment.
- Patients with Comorbid Conditions: In patients with volume or salt depletion (e.g., due to vomiting, diarrhea, or high-dose diuretics), initiate azilsartan under close medical supervision. A lower starting dose (e.g., 20 mg) may be considered. For patients with diabetes, avoid concomitant use with aliskiren. Black patients may require higher doses or concomitant therapy to achieve adequate blood pressure control.
Clinical Use Cases
- Azilsartan medoxomil’s use is specifically for chronic hypertension management. It is not indicated for acute blood pressure control in settings like intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations (e.g., cardiac arrest).
Dosage Adjustments
- Dosage adjustments may be necessary based on individual patient responses and tolerability. If blood pressure is not adequately controlled with azilsartan alone, additional antihypertensive medications may be added.
- Renal and hepatic function should be assessed prior to and periodically during treatment. Serum electrolytes, particularly potassium, should also be monitored.
Side Effects
Common Side Effects
- Dizziness
- Diarrhea
- Fatigue
- Cough
- Nausea
- Muscle spasms
Rare but Serious Side Effects
- Angioedema (swelling of face, lips, tongue, throat, or extremities)
- Hypotension (low blood pressure)
- Renal impairment (worsening of kidney function)
- Hyperkalemia (high blood potassium)
- Liver dysfunction
Long-Term Effects
- Long-term data on the effects of azilsartan are limited. Regular monitoring of renal function, electrolytes, and blood pressure is essential during prolonged use.
Adverse Drug Reactions (ADR)
- Angioedema requires immediate discontinuation of azilsartan and appropriate medical intervention.
- Symptoms of hyperkalemia (muscle weakness, slow or irregular heartbeat) require prompt medical attention.
- Signs of severe hypotension (dizziness, lightheadedness, fainting) necessitate immediate evaluation and supportive care.
Contraindications
- Hypersensitivity to azilsartan medoxomil
- Second and third trimesters of pregnancy
- Concomitant use with aliskiren in patients with diabetes or moderate to severe renal impairment
- Anuria
Drug Interactions
- Nonsteroidal anti-inflammatory drugs (NSAIDs): May reduce the antihypertensive effect of azilsartan and increase the risk of renal impairment, especially in elderly, volume-depleted, or renally compromised patients.
- Aliskiren: Concomitant use with azilsartan is contraindicated in patients with diabetes or moderate to severe renal impairment due to an increased risk of hypotension, hyperkalemia, and renal impairment.
- Potassium-sparing diuretics and potassium supplements: May increase the risk of hyperkalemia.
- Other antihypertensive agents: May have additive blood pressure-lowering effects. Close monitoring of blood pressure is needed.
- Lithium: Azilsartan may increase lithium levels, leading to lithium toxicity.
Pregnancy and Breastfeeding
- Pregnancy Safety Category: Category D (second and third trimesters). Use during pregnancy can cause fetal harm and death. Discontinue azilsartan as soon as possible if pregnancy is detected.
- Breastfeeding: Azilsartan is not recommended during breastfeeding due to the potential for neonatal exposure. A decision should be made to discontinue breastfeeding or discontinue the drug, taking into account the importance of the drug to the mother.
Drug Profile Summary
- Mechanism of Action: Angiotensin II receptor blocker (ARB) that selectively binds to the AT1 receptor, causing vasodilation and lowering blood pressure.
- Side Effects: Common: Dizziness, diarrhea, fatigue, cough, nausea, muscle spasms. Serious: Angioedema, hypotension, renal impairment, hyperkalemia.
- Contraindications: Hypersensitivity, second/third trimester pregnancy, concomitant use with aliskiren in patients with diabetes or renal impairment.
- Drug Interactions: NSAIDs, aliskiren, potassium-sparing diuretics, other antihypertensives.
- Pregnancy & Breastfeeding: Contraindicated in second/third trimester pregnancy, not recommended while breastfeeding.
- Dosage: Adults: 40-80 mg once daily.
- Monitoring Parameters: Blood pressure, renal function, serum electrolytes (especially potassium).
Popular Combinations
- Azilsartan + Chlorthalidone (Edarbyclor): This combination combines the ARB action of azilsartan with the diuretic effect of chlorthalidone, providing enhanced blood pressure control.
- Azilsartan + other antihypertensives (e.g., thiazide diuretics, calcium channel blockers): Can provide additional blood pressure lowering in patients not adequately controlled with azilsartan alone.
Precautions
- General Precautions: Assess renal function and serum electrolytes before initiating therapy and periodically during treatment. Monitor blood pressure regularly.
- Specific Populations:
- Pregnant Women: Contraindicated during the second and third trimesters. Discontinue as soon as pregnancy is detected.
- Breastfeeding Mothers: Not recommended. Choose alternative antihypertensives with established safety profiles.
- Children & Elderly: Not recommended in children under 18. Use with caution in the elderly, especially those over 75, due to the risk of hypotension.
- Lifestyle Considerations: Advise patients on lifestyle modifications such as diet, exercise, and stress reduction to help manage blood pressure. Excessive perspiration, vomiting, or diarrhea may lead to volume depletion and exacerbate hypotension, so patients should be advised to report these symptoms.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Azilsartan medoxomil?
A: The recommended starting dose is 40 mg once daily, which can be increased to a maximum of 80 mg once daily if needed. A lower starting dose (e.g., 20 mg) should be considered for elderly patients over 75 years and patients with mild to moderate hepatic impairment.
Q2: What is the mechanism of action of Azilsartan Medoxomil?
A: It selectively blocks the angiotensin II type 1 (AT1) receptor, leading to vasodilation and a reduction in blood pressure.
Q3: What are the common side effects of Azilsartan Medoxomil?
A: Common side effects include dizziness, diarrhea, fatigue, cough, nausea, and muscle spasms.
Q4: Is Azilsartan Medoxomil safe to use during pregnancy or breastfeeding?
A: No, it is contraindicated during the second and third trimesters of pregnancy and is not recommended during breastfeeding.
Q5: How should Azilsartan Medoxomil be administered?
A: It should be taken orally once daily, with or without food.
Q6: What should I do if I miss a dose of Azilsartan Medoxomil?
A: Take the missed dose as soon as possible, unless it is almost time for your next dose. Do not take a double dose to make up for a missed dose.
Q7: Does Azilsartan Medoxomil interact with other medications?
A: Yes, it can interact with NSAIDs, aliskiren, potassium-sparing diuretics, and other antihypertensive medications. It’s crucial to inform your doctor about all other medications you are taking.
Q8: Are there any specific monitoring parameters for patients taking Azilsartan Medoxomil?
A: Yes, blood pressure, renal function, and serum electrolytes (especially potassium) should be monitored regularly.
Q9: What are the contraindications for Azilsartan Medoxomil?
A: Contraindications include hypersensitivity to azilsartan medoxomil, second and third-trimester pregnancy, and concomitant use with aliskiren in patients with diabetes or moderate to severe renal impairment.
