Usage
- This combination is prescribed for the management of heart failure, especially in patients with reduced ejection fraction (HFrEF), with or without type 2 diabetes. It’s specifically indicated for heart failure post-myocardial infarction. It’s also being explored for use in other cardiovascular conditions.
- Pharmacological Classification: This combination includes a sodium-glucose cotransporter-2 (SGLT2) inhibitor (dapagliflozin) and a beta-blocker (metoprolol succinate).
Alternate Names
- Natribeta 10/50 Tablet SR (brand name in some regions)
How It Works
- Pharmacodynamics: Dapagliflozin increases urinary glucose excretion, leading to decreased blood glucose levels, diuresis, and natriuresis. Metoprolol succinate blocks beta-1 adrenergic receptors, reducing heart rate, contractility, and blood pressure.
- Pharmacokinetics: Dapagliflozin is well-absorbed orally and primarily eliminated renally. Metoprolol succinate is extensively metabolized by CYP2D6, with some renal elimination.
- Mode of Action: Dapagliflozin inhibits SGLT2 in the kidneys, increasing glucose excretion in the urine and lowering blood glucose levels. It also promotes diuresis and natriuresis, reducing blood volume and preload. Metoprolol succinate blocks beta-1 adrenergic receptors in the heart, reducing heart rate and myocardial contractility, thus lowering blood pressure and myocardial oxygen demand.
- Elimination Pathways: Dapagliflozin is mainly eliminated renally. Metoprolol succinate is metabolized by CYP2D6 with hepatic and renal excretion of metabolites.
Dosage
Standard Dosage
Adults:
- Dapagliflozin: 10 mg orally once daily.
- Metoprolol Succinate: Dosage needs to be individualized based on blood pressure, heart rate, and overall clinical condition. The starting dose may range from 12.5 mg to 100 mg per day, titrated up as needed. The maximum dose is usually 400 mg/day. Dosage and titration schedules may vary based on the formulation (immediate-release or extended-release).
Children: The safety and efficacy of this combination have not been established in the pediatric population.
Special Cases:
- Elderly Patients: Start with lower doses and titrate cautiously, monitoring renal function.
- Patients with Renal Impairment: Dose adjustments are necessary for both drugs based on the degree of impairment. Consult specific guidelines for each medication.
- Patients with Hepatic Dysfunction: Caution is advised with metoprolol succinate.
- Patients with Comorbid Conditions (e.g., Diabetes, Cardiovascular Disease): Careful monitoring and dose adjustment may be required.
Clinical Use Cases
The combination of dapagliflozin and metoprolol succinate is not typically used in clinical scenarios like intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations. Its primary indication is for chronic heart failure management. Metoprolol tartrate, the immediate release form of metoprolol, is more suitable for intravenous administration in acute settings.
Side Effects
Common Side Effects:
Headache, diarrhea, nausea, vomiting, runny nose, sore throat, dizziness, lightheadedness, and hypotension.
Rare but Serious Side Effects:
Angioedema, anaphylaxis, worsening heart failure, severe hypotension, lactic acidosis (with metformin if used concurrently), Fournier’s gangrene.
Long-Term Effects: Chronic kidney disease progression is possible, especially in those with pre-existing renal impairment.
Adverse Drug Reactions (ADR): Hypersensitivity reactions, symptomatic hypotension, worsening renal function.
Contraindications
- Hypersensitivity to either drug.
- Severe bradycardia, sick sinus syndrome, second- or third-degree heart block (without a pacemaker).
- Decompensated heart failure.
- Severe hypotension.
- Severe renal impairment.
Drug Interactions
- Insulin and other antidiabetic medications: Increased risk of hypoglycemia.
- Diuretics: Enhanced hypotensive effects.
- Calcium channel blockers: Additive effects on heart rate and blood pressure.
- CYP2D6 inhibitors/inducers: Can alter metoprolol metabolism.
- Alcohol: Increased risk of dizziness and hypotension.
Pregnancy and Breastfeeding
- Pregnancy: Dapagliflozin is generally not recommended during pregnancy. Metoprolol succinate should be used cautiously only if the potential benefit outweighs the risk to the fetus.
- Breastfeeding: Dapagliflozin should be avoided during breastfeeding. Metoprolol succinate is excreted in breast milk and caution is advised.
Drug Profile Summary
- Mechanism of Action: Dapagliflozin increases urinary glucose excretion; metoprolol succinate blocks beta-1 adrenergic receptors.
- Side Effects: Common: Headache, dizziness, hypotension. Serious: Angioedema, worsening heart failure.
- Contraindications: Hypersensitivity, severe bradycardia, decompensated heart failure.
- Drug Interactions: Insulin, diuretics, calcium channel blockers, CYP2D6 inhibitors/inducers.
- Pregnancy & Breastfeeding: Not recommended during pregnancy or breastfeeding.
- Dosage: Dapagliflozin: 10mg daily; Metoprolol Succinate: individualized, up to 400 mg/day.
- Monitoring Parameters: Blood glucose, blood pressure, heart rate, renal function, electrolytes.
Popular Combinations
Dapagliflozin is often combined with other antidiabetic agents like metformin. Metoprolol succinate may be combined with other antihypertensives or heart failure medications. The specific combinations depend on patient needs and comorbidities.
Precautions
- General Precautions: Pre-screening for allergies, metabolic disorders, organ dysfunction. Renal function should be assessed before starting dapagliflozin.
- Pregnant Women: Avoid dapagliflozin. Metoprolol succinate use with caution.
- Breastfeeding Mothers: Avoid dapagliflozin. Caution with metoprolol succinate.
- Children & Elderly: Not recommended for pediatric use. Use cautiously in the elderly.
- Lifestyle Considerations: Limit alcohol intake due to increased risk of hypotension and dizziness.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Dapagliflozin + Metoprolol Succinate?
A: Dapagliflozin: 10 mg once daily. Metoprolol succinate: individualized based on patient’s condition, starting from 12.5 mg to 100 mg daily, up to a maximum of 400 mg.
Q2: What are the primary uses of this combination?
A: Management of heart failure (HFrEF), particularly post-myocardial infarction, with or without type 2 diabetes.
Q3: What are the key drug interactions to consider?
A: Interactions can occur with insulin, other antidiabetic drugs, diuretics, calcium channel blockers, and CYP2D6 inhibitors/inducers.
Q4: Are there any contraindications to using this combination?
A: Yes. Contraindications include hypersensitivity, severe bradycardia, decompensated heart failure, severe hypotension, and severe renal impairment.
Q5: What are the common side effects patients may experience?
A: Common side effects include headache, dizziness, hypotension, gastrointestinal issues (diarrhea, nausea, vomiting), and upper respiratory symptoms.
Q6: What monitoring parameters are essential during treatment?
A: Monitor blood glucose, blood pressure, heart rate, renal function, and electrolytes.
Q7: Can this combination be used in pregnant or breastfeeding women?
A: It’s generally not recommended during pregnancy or breastfeeding due to potential risks.
Q8: What are the potential long-term effects of this combination?
A: Chronic kidney disease progression is a potential long-term effect, especially in patients with pre-existing renal impairment.
Q9: What should patients be advised regarding lifestyle modifications?
A: Patients should be advised to limit alcohol intake due to increased risk of hypotension and dizziness. They should also be counseled on the importance of medication adherence and regular follow-up appointments.
