Usage
- Azelnidipine + Olmesartan Medoxomil is prescribed for the treatment of essential hypertension (high blood pressure). It is also used to reduce cardiovascular risk, such as the risk of stroke and heart attack, in hypertensive patients.
- Pharmacological Classification: Antihypertensive (combination of a calcium channel blocker and an angiotensin II receptor blocker).
- Mechanism of Action: This combination drug works through two distinct mechanisms:
- Azelnidipine (Calcium Channel Blocker): Inhibits calcium influx into vascular smooth muscle cells, leading to vasodilation and reduced blood pressure. It also exhibits anti-atherosclerotic and antioxidant properties. Notably, it does not typically cause reflex tachycardia.
- Olmesartan Medoxomil (Angiotensin II Receptor Blocker): Blocks the action of angiotensin II, a hormone that causes vasoconstriction. This leads to vasodilation and a reduction in blood pressure.
Alternate Names
- Olmesartan medoxomil/azelnidipine
- Rezaltas (brand name in Japan, containing 10/8 mg and 20/16 mg dosages)
- Olmezest-AZ (brand name)
- Olmesar Plus (brand name)
How It Works
- Pharmacodynamics:
- Azelnidipine primarily acts on L-type calcium channels in vascular smooth muscle, causing vasodilation and reducing peripheral resistance. Olmesartan medoxomil blocks angiotensin II type 1 receptors, inhibiting vasoconstriction and reducing blood pressure. The combined effect of both drugs leads to a synergistic reduction in blood pressure.
- Pharmacokinetics:
- Azelnidipine: Rapidly absorbed after oral administration. It is extensively metabolized by the liver via the CYP3A4 enzyme system. Primarily excreted in the feces, with some renal excretion. High plasma protein binding (approximately 90%).
- Olmesartan Medoxomil: Rapidly converted to its active metabolite, olmesartan, during absorption from the gastrointestinal tract. Undergoes minimal hepatic metabolism and is primarily excreted unchanged in the urine and feces.
- Mode of Action: Azelnidipine blocks the influx of calcium ions into vascular smooth muscle cells by inhibiting L-type calcium channels. This inhibits smooth muscle contraction and leads to vasodilation, lowering blood pressure. Olmesartan blocks the binding of angiotensin II to its type 1 receptors (AT1 receptors) on vascular smooth muscle. This inhibits the vasoconstricting effects of angiotensin II, resulting in vasodilation.
- Elimination Pathways: Azelnidipine is primarily eliminated through hepatic metabolism, with a small portion excreted in the urine. Olmesartan is primarily eliminated unchanged through both renal and biliary excretion.
Dosage
Standard Dosage
Adults:
- Initial dose: Olmesartan Medoxomil 20 mg + Azelnidipine 8 mg once daily.
- Maintenance dose: May be increased to Olmesartan Medoxomil 40 mg + Azelnidipine 16 mg once daily if needed.
Children:
- Safety and efficacy not established in children younger than 18 years.
Special Cases:
- Elderly Patients: Initiate at a lower dose and monitor closely.
- Patients with Renal Impairment: No dosage adjustment recommended for mild to moderate renal impairment; use with caution in severe renal impairment.
- Patients with Hepatic Dysfunction: Use with caution; initiate at a lower dose and monitor closely.
- Patients with Comorbid Conditions: Monitor for potential drug interactions and adjust dosage as needed.
Clinical Use Cases
- Dosage adjustments are not specifically indicated for intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations. However, close monitoring of blood pressure is crucial in these settings, and dosage adjustments may be needed based on individual patient response.
Dosage Adjustments
- Dose adjustments may be required based on patient response, renal or hepatic function, and other factors. Close monitoring of blood pressure and other clinical parameters is essential.
Side Effects
Common Side Effects:
- Dizziness, headache, peripheral edema (swelling in the ankles and feet), fatigue, nausea.
Rare but Serious Side Effects:
- Angioedema (swelling of the face, lips, tongue, or throat), hypotension (low blood pressure), renal failure, hepatic dysfunction, hyperkalemia (high potassium levels).
Long-Term Effects:
- Long-term effects are still being studied, but potential concerns include renal dysfunction and cardiovascular events.
Adverse Drug Reactions (ADR):
- Angioedema, severe hypotension, acute renal failure, hepatic injury, hyperkalemia.
Contraindications
- Hypersensitivity to azelnidipine, olmesartan medoxomil, or any component of the formulation.
- Pregnancy (especially second and third trimesters).
- Biliary obstruction.
- Concomitant use with strong CYP3A4 inhibitors (such as itraconazole, ketoconazole, clarithromycin, ritonavir).
Drug Interactions
- CYP3A4 Inhibitors: Increase azelnidipine levels.
- Potassium supplements or salt substitutes: May lead to hyperkalemia.
- Nonsteroidal anti-inflammatory drugs (NSAIDs): May reduce the antihypertensive effect.
- Lithium: Olmesartan can increase lithium levels.
- Diuretics: May enhance the hypotensive effect.
- Grapefruit juice: May increase azelnidipine levels.
Pregnancy and Breastfeeding
- Pregnancy Safety Category: D (contraindicated). Olmesartan can cause fetal harm, especially during the second and third trimesters.
- Breastfeeding: Not recommended. Olmesartan may be excreted in breast milk.
Drug Profile Summary
- Mechanism of Action: Azelnidipine: Calcium channel blocker. Olmesartan: Angiotensin II receptor blocker.
- Side Effects: Dizziness, headache, peripheral edema, fatigue, nausea.
- Contraindications: Hypersensitivity, pregnancy, biliary obstruction, strong CYP3A4 inhibitors.
- Drug Interactions: CYP3A4 inhibitors, potassium supplements, NSAIDs, lithium.
- Pregnancy & Breastfeeding: Contraindicated in pregnancy. Not recommended during breastfeeding.
- Dosage: Adult: Start with Olmesartan Medoxomil 20 mg + Azelnidipine 8 mg once daily, adjustable to 40/16 mg.
- Monitoring Parameters: Blood pressure, renal function, potassium levels, liver function tests.
Popular Combinations
- This combination itself is a popular and effective treatment for hypertension. It is sometimes combined with other antihypertensive agents, such as thiazide diuretics or beta-blockers, if further blood pressure control is needed.
Precautions
- Monitor renal function, potassium levels, and blood pressure.
- Caution in patients with hepatic impairment.
- Avoid grapefruit juice.
- Use with caution in elderly patients.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Azelnidipine + Olmesartan Medoxomil?
A: The initial dose is typically Olmesartan Medoxomil 20 mg + Azelnidipine 8 mg once daily, which may be increased to 40/16 mg if needed.
Q2: What are the common side effects?
A: Dizziness, headache, peripheral edema, fatigue, and nausea are common side effects.
Q3: Is it safe during pregnancy?
A: No, it is contraindicated during pregnancy, especially in the second and third trimesters.
Q4: What if I miss a dose?
A: Take the missed dose as soon as you remember, unless it’s close to the time for your next dose. Do not double the dose.
Q5: Can I drink alcohol while taking this medication?
A: Limit alcohol consumption as it may enhance the hypotensive effect.
Q6: Are there any dietary restrictions?
A: A low-sodium diet is recommended for managing hypertension. Avoid grapefruit juice.
Q7: What should I do if I experience side effects?
A: Contact your physician to discuss managing or adjusting the medication.
Q8: How does this combination work differently than taking azelnidipine or olmesartan alone?
A: The combination provides a synergistic effect, lowering blood pressure more effectively than either drug alone. It addresses multiple mechanisms involved in hypertension.
Q9: How long does it take to see the full effects of the medication?
A: It may take several weeks to achieve the full antihypertensive effect.
Q10: Can I stop taking this medication if my blood pressure returns to normal?
A: No, do not stop taking the medication without consulting your doctor. Abrupt discontinuation can lead to rebound hypertension. Your physician will advise on the appropriate course of action.
