Usage
- Azilsartan medoxomil + Chlorthalidone is prescribed for the treatment of hypertension (high blood pressure) in patients whose blood pressure is not adequately controlled on monotherapy or as initial therapy in patients likely to require multiple antihypertensive agents to achieve their blood pressure goals.
- Pharmacological Classification: Angiotensin II Receptor Blocker (ARB) + Thiazide-like Diuretic combination.
- Mechanism of Action: Azilsartan medoxomil blocks the action of angiotensin II, a hormone that causes blood vessels to constrict. This blockade leads to vasodilation and a decrease in blood pressure. Chlorthalidone increases the excretion of sodium and water by the kidneys, further reducing blood volume and blood pressure.
Alternate Names
- No widely used alternate names for the combination exist.
- Brand Name(s): Edarbyclor
How It Works
- Pharmacodynamics: Azilsartan medoxomil, a prodrug, is rapidly converted to azilsartan, its active metabolite. Azilsartan selectively blocks the AT1 subtype angiotensin II receptor, preventing angiotensin II-mediated vasoconstriction and aldosterone secretion. Chlorthalidone inhibits sodium reabsorption in the distal convoluted tubule of the nephron, leading to increased excretion of sodium, chloride, and water.
- Pharmacokinetics: Azilsartan medoxomil is orally administered and hydrolyzed to azilsartan during absorption in the gastrointestinal tract. Peak plasma concentrations of azilsartan are reached within 1.5 to 3 hours. Chlorthalidone is also administered orally and is well-absorbed. It has a long half-life of around 40-60 hours, allowing for once-daily dosing. Both drugs are primarily excreted via the kidneys, though a significant portion of azilsartan is also excreted in bile.
- Receptor Binding/Enzyme Inhibition: Azilsartan acts by selectively binding to and blocking the AT1 angiotensin II receptor. Chlorthalidone inhibits the sodium-chloride cotransporter in the distal tubule of the kidney.
- Elimination Pathways: Primarily renal excretion for both drugs, with biliary excretion playing a substantial role for azilsartan.
Dosage
Standard Dosage
Adults:
- Initial dose: 40 mg azilsartan medoxomil/12.5 mg chlorthalidone once daily.
- Maintenance dose: May be increased to 40 mg azilsartan medoxomil/25 mg chlorthalidone once daily after 2-4 weeks if blood pressure goals are not met.
- Maximum dose: 40 mg azilsartan medoxomil/25 mg chlorthalidone once daily.
Children:
- The safety and efficacy of this combination have not been established in pediatric patients.
Special Cases:
- Elderly Patients: No specific dose adjustments are required for elderly patients, but monitoring for hypotension and renal function is advised.
- Patients with Renal Impairment: No dose adjustment is necessary for mild to moderate renal impairment. Use with caution in patients with severe renal impairment.
- Patients with Hepatic Dysfunction: No dose adjustment is necessary for mild to moderate hepatic impairment. Use with caution and consider a lower starting dose in patients with hepatic impairment.
- Patients with Comorbid Conditions: Careful monitoring and dose adjustments may be necessary for patients with congestive heart failure, diabetes, and other comorbid conditions.
Clinical Use Cases
The drug is indicated for chronic hypertension management and is not typically used in acute settings like intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations.
Dosage Adjustments
Dose adjustments may be needed based on the patient’s response to therapy and tolerability. Consider lower starting doses in patients with hepatic or renal impairment.
Side Effects
Common Side Effects:
- Dizziness
- Fatigue
- Diarrhea
- Nausea
- Upper respiratory tract infections
Rare but Serious Side Effects:
- Angioedema
- Hypotension
- Syncope
- Renal failure
- Electrolyte imbalances (hypokalemia, hyponatremia)
Long-Term Effects:
- Long-term effects can include electrolyte disturbances, and potential impact on renal function and blood glucose levels, particularly with chronic chlorthalidone use.
Adverse Drug Reactions (ADR):
- Serious ADRs include angioedema, severe hypotension, acute renal failure, and potentially life-threatening electrolyte imbalances.
Contraindications
- Hypersensitivity to azilsartan medoxomil, chlorthalidone, or any component of the formulation.
- Pregnancy (especially second and third trimesters)
- Anuria
Drug Interactions
- Other antihypertensive medications (additive hypotensive effect).
- Nonsteroidal anti-inflammatory drugs (NSAIDs) (may reduce antihypertensive efficacy and increase risk of renal impairment)
- Lithium (increased lithium levels)
- Aliskiren (increased risk of hypotension, hyperkalemia, and renal impairment)
- Potassium supplements or potassium-sparing diuretics (increased risk of hyperkalemia)
Pregnancy and Breastfeeding
- Pregnancy Safety Category: D (contraindicated during the second and third trimesters)
- Fetal Risks: May cause fetal harm or death, particularly during the second and third trimesters due to effects on the renin-angiotensin system.
- Breastfeeding: Azilsartan’s presence in breast milk is unknown, but chlorthalidone is excreted in breast milk. Breastfeeding while taking Edarbyclor is not recommended due to potential adverse effects on the nursing infant.
Drug Profile Summary
- Mechanism of Action: ARB + thiazide-like diuretic. Blocks angiotensin II receptors and increases sodium and water excretion.
- Side Effects: Dizziness, fatigue, diarrhea, nausea, upper respiratory tract infections; rarely: angioedema, hypotension, renal failure.
- Contraindications: Hypersensitivity, pregnancy, anuria.
- Drug Interactions: Other antihypertensives, NSAIDs, lithium, aliskiren, potassium supplements.
- Pregnancy & Breastfeeding: Contraindicated in pregnancy (especially second and third trimesters); breastfeeding not recommended.
- Dosage: 40/12.5 mg once daily initially, may increase to 40/25 mg once daily.
- Monitoring Parameters: Blood pressure, renal function, electrolytes (potassium, sodium), uric acid.
Popular Combinations
- May be used in combination with other antihypertensive agents like calcium channel blockers or beta-blockers if blood pressure goals are not met with Edarbyclor alone.
Precautions
- Monitor renal function, particularly in patients with renal impairment.
- Monitor electrolytes, especially potassium and sodium.
- Monitor for signs of hypotension, particularly in volume-depleted patients or those on other antihypertensive medications.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Azilsartan medoxomil + Chlorthalidone?
A: Initial dose is 40/12.5 mg once daily; may be increased to 40/25 mg once daily if needed.
Q2: How long does it take for Edarbyclor to work?
A: Most of the antihypertensive effect is usually seen within 1-2 weeks.
Q3: Can I take this medication if I have kidney problems?
A: Use with caution in severe renal impairment; dose adjustment may be needed.
Q4: What are the serious side effects of Edarbyclor?
A: Angioedema, hypotension, syncope, renal failure, and electrolyte imbalances.
Q5: Can I take this medication during pregnancy?
A: No, it is contraindicated, especially during the second and third trimesters.
Q6: What should I do if I miss a dose?
A: Take the missed dose as soon as you remember. If it is almost time for your next dose, skip the missed dose and take the next dose at your regularly scheduled time. Do not double the dose.
Q7: What are the common drug interactions with Edarbyclor?
A: Other antihypertensives, NSAIDs, lithium, aliskiren, potassium-sparing diuretics.
Q8: Can this medication be used in children?
A: The safety and efficacy have not been established in children.
Q9: What if I experience dizziness while taking this medication?
A: Report dizziness to your doctor. It is a common side effect, and caution should be exercised when performing tasks requiring alertness, such as driving.
Q10: How should Edarbyclor be stored?
A: Store at room temperature away from moisture, heat, and light.
