Usage
- This fixed-dose combination (FDC) medication is primarily prescribed for the treatment of Stage 2 hypertension (high blood pressure). It is indicated when monotherapy is insufficient to control blood pressure.
- Pharmacological Classification: Antihypertensive (combining a calcium channel blocker and a beta-blocker).
- Mechanism of Action: Azelnidipine, a dihydropyridine calcium channel blocker, inhibits calcium influx into vascular smooth muscle cells, causing vasodilation. Metoprolol succinate, a cardioselective beta-1 adrenergic receptor blocker, reduces heart rate and myocardial contractility. The combined action provides synergistic antihypertensive effects.
Alternate Names
- Azelnidipine/Metoprolol Succinate
- Brand names: Uniaz Beta (other brand names may exist)
How It Works
- Pharmacodynamics: Azelnidipine reduces blood pressure by decreasing systemic vascular resistance through vasodilation. Metoprolol decreases blood pressure by reducing cardiac output and inhibiting renin release.
- Pharmacokinetics: Azelnidipine is well-absorbed orally, metabolized in the liver (primarily via CYP3A4), and eliminated mainly in the feces. Metoprolol succinate undergoes extensive first-pass metabolism in the liver (CYP2D6) with renal elimination of metabolites.
- Mode of Action: Azelnidipine blocks L-type calcium channels in vascular smooth muscle, while metoprolol selectively antagonizes beta-1 adrenergic receptors in the heart.
- Receptor Binding/Enzyme Inhibition/Neurotransmitter Modulation: Metoprolol competitively blocks the binding of catecholamines to beta-1 receptors, leading to decreased heart rate and contractility. Azelnidipine is a calcium channel blocker, directly impacting smooth muscle.
- Elimination Pathways: Azelnidipine primarily undergoes hepatic metabolism by CYP3A4 and is excreted mainly in feces, with a small portion renally excreted. Metoprolol succinate is predominantly metabolized by CYP2D6 in the liver, and the metabolites are eliminated via the kidneys.
Dosage
Standard Dosage
Adults:
- Initial: Azelnidipine 8 mg + Metoprolol Succinate 25 mg or 50 mg once daily.
- Maintenance: Azelnidipine 16 mg + Metoprolol Succinate 25 mg or 50 mg once daily.
- Maximum: Azelnidipine 16 mg + Metoprolol Succinate 50 mg once daily.
Children:
- This FDC is not recommended for pediatric use. Safety and efficacy have not been established.
Special Cases:
- Elderly Patients: Start with a lower dose and titrate cautiously, considering renal function and patient response.
- Patients with Renal Impairment: Dose adjustment is recommended for moderate to severe impairment with close monitoring.
- Patients with Hepatic Dysfunction: Dose adjustment is usually required. Start with a lower dose and monitor liver function tests.
- Patients with Comorbid Conditions: Use cautiously in patients with diabetes, heart failure, or other cardiovascular diseases. Individualized dosing and monitoring are essential.
Clinical Use Cases
- The use of this combination in specialized settings like intubation, surgical procedures, mechanical ventilation, ICU, and emergency situations is not routinely indicated. Dosage in these scenarios should be determined based on the individual patient’s hemodynamic status and other clinical considerations. It is not specifically indicated for these uses and is primarily intended for chronic hypertension management.
Dosage Adjustments
- Dose adjustments are necessary for renal and hepatic dysfunction.
- Consider metabolic disorders and genetic polymorphisms affecting drug metabolism when adjusting the dose.
Side Effects
Common Side Effects
- Tiredness, dizziness, slow heart rate, low blood pressure, rash, diarrhea, nausea, breathlessness, flushing, palpitations.
Rare but Serious Side Effects
- Worsening heart failure (symptoms include chest pain, shortness of breath, swelling in legs/feet), severe allergic reactions, significant bradycardia, heart block.
Long-Term Effects
- Long-term effects specific to this combination are not well-established, but they may include metabolic changes, worsening of pre-existing cardiovascular conditions if not properly managed, and potential impacts on renal and liver function with prolonged use.
Adverse Drug Reactions (ADR)
- Angioedema, severe hypotension, bronchospasm (particularly in patients with underlying respiratory disease), marked bradycardia leading to syncope.
Contraindications
- Hypersensitivity to azelnidipine, metoprolol, or other components.
- Severe bradycardia, heart block greater than first degree, sick sinus syndrome (without a pacemaker).
- Cardiogenic shock, decompensated heart failure.
- Severe hepatic impairment.
Drug Interactions
- Other antihypertensives (additive effects).
- CYP3A4 inhibitors/inducers (may affect azelnidipine levels).
- CYP2D6 inhibitors/inducers (may affect metoprolol levels).
- Calcium channel blockers (additive effects).
- Beta-blockers (additive effects).
- Digoxin (increased risk of bradycardia).
- Clonidine (increased risk of rebound hypertension).
- Insulin or oral hypoglycemics (may mask signs of hypoglycemia).
Pregnancy and Breastfeeding
- Use with caution only if benefits outweigh risks. Consult with a specialist. Consider safer alternatives. Metoprolol is excreted in breast milk, and while considered low risk, potential effects on the neonate should be monitored. Azelnidipine’s effects during pregnancy and breastfeeding are less well-established, therefore caution is advised.
Drug Profile Summary
- Mechanism of Action: Azelnidipine: Calcium channel blocker (vasodilator). Metoprolol succinate: Beta-1 blocker (reduces heart rate, contractility).
- Side Effects: Common: Tiredness, dizziness, hypotension, bradycardia. Serious: Worsening heart failure, severe allergic reactions.
- Contraindications: Hypersensitivity, severe bradycardia, heart block, cardiogenic shock, decompensated heart failure, severe hepatic impairment.
- Drug Interactions: Other antihypertensives, CYP3A4 and CYP2D6 inhibitors/inducers.
- Pregnancy & Breastfeeding: Use with caution if benefits outweigh risks. Consult a specialist.
- Dosage: Adults: Azelnidipine 8-16 mg + Metoprolol Succinate 25-50 mg once daily. Not recommended for children.
- Monitoring Parameters: Blood pressure, heart rate, renal function, liver function, electrolytes.
Popular Combinations
This FDC is a popular combination. Additional antihypertensives (thiazide diuretics, ACE inhibitors) may be added in resistant cases with cautious titration and monitoring.
Precautions
- Monitor for hypotension, bradycardia, and worsening heart failure.
- Assess renal and hepatic function before and during treatment.
- Caution in patients with diabetes, peripheral artery disease, or other cardiovascular diseases.
- Avoid abrupt discontinuation; taper dose gradually under medical supervision.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Azelnidipine + Metoprolol Succinate?
A: The initial dose is Azelnidipine 8 mg + Metoprolol Succinate 25 or 50 mg once daily, which can be increased to a maximum of Azelnidipine 16 mg + Metoprolol Succinate 50 mg once daily as needed to control blood pressure.
Q2: What are the common side effects?
A: Common side effects include tiredness, dizziness, slow heart rate (bradycardia), low blood pressure (hypotension), diarrhea, nausea, and rash.
Q3: Is it safe to use during pregnancy or breastfeeding?
A: It should be used cautiously during pregnancy and breastfeeding only if the potential benefits outweigh the risks. Consult a specialist.
Q4: Are there any contraindications for this medication?
A: Yes, contraindications include hypersensitivity to the components, severe bradycardia, heart block, cardiogenic shock, decompensated heart failure, and severe hepatic impairment.
Q5: What are the major drug interactions I should be aware of?
A: Significant interactions can occur with other antihypertensives, CYP3A4 inhibitors/inducers, and CYP2D6 inhibitors/inducers. Inform your patients to provide a complete medication list.
Q6: What should I monitor in patients taking this combination?
A: Monitor blood pressure, heart rate, renal function, liver function, and electrolytes.
Q7: Can I abruptly stop this medication?
A: No, abrupt discontinuation can exacerbate myocardial ischemia and other adverse events. Taper the dose gradually under medical supervision.
Q8: How does this combination work at the cellular level?
A: Azelnidipine blocks calcium channels in vascular smooth muscle, causing vasodilation. Metoprolol blocks beta-1 receptors in the heart, decreasing heart rate and contractility.
Q9: What patient education points are important?
A: Advise patients about potential side effects, drug interactions, the importance of adherence to therapy, and to report any unusual symptoms to their healthcare provider. Emphasize the importance of lifestyle modifications (diet, exercise).
Q10: Are there any dietary restrictions while taking this medication?
A: Patients should limit alcohol intake and follow a healthy diet recommended for hypertension management. Grapefruit juice may interact with azelnidipine, so it’s generally advised to avoid it.
