Usage
- Medical Conditions: This combination medication is primarily prescribed for the management of hypertension (high blood pressure) in patients whose blood pressure is not adequately controlled by monotherapy.
- Pharmacological Classification: This is a combination of two antihypertensive drug classes:
- Nebivolol: Beta-1 adrenergic receptor blocker (beta-blocker).
- Indapamide: Thiazide-like diuretic.
- Mechanism of Action: Nebivolol reduces blood pressure by blocking beta-1 receptors in the heart, leading to decreased heart rate and cardiac output. It also appears to cause vasodilation via nitric oxide release. Indapamide lowers blood pressure by increasing the excretion of sodium, chloride, and water from the body through the kidneys.
Alternate Names
- No widely recognized alternate names for this specific combination exist. However, the individual drugs have various names internationally.
- Brand Names: Numerous brand names exist depending on the manufacturer and region, including but not limited to Nebula D, and other regional variations.
How It Works
- Pharmacodynamics: Nebivolol exhibits cardioselectivity, predominantly affecting beta-1 receptors with minimal impact on beta-2 receptors at therapeutic doses. It reduces heart rate, cardiac output, and peripheral vascular resistance. Indapamide inhibits sodium reabsorption in the distal convoluted tubule of the nephron, increasing urine output and reducing plasma volume.
- Pharmacokinetics:
- Nebivolol: Well absorbed orally, reaching peak plasma concentrations in 1.5 to 4 hours. Food does not significantly affect absorption. It is highly protein-bound (98%), primarily to albumin. Metabolized in the liver, primarily via glucuronidation and secondarily by CYP2D6. Both parent drug and metabolites contribute to beta-blocking activity. Elimination half-life is variable, influenced by CYP2D6 metabolism.
- Indapamide: Almost completely absorbed from the gastrointestinal tract. Peak plasma concentrations reached in about 1 to 2 hours for immediate-release and 12 hours for extended-release formulations. Highly protein-bound (71% to 79%). Extensively metabolized in the liver. Excreted primarily in urine (60% to 70%) and feces (20% to 30%). Half-life ranges from 14 to 18 hours.
- Mode of Action: Nebivolol selectively antagonizes beta-1 adrenergic receptors, reducing sympathetic stimulation of the heart. Indapamide inhibits sodium reabsorption by blocking the sodium-chloride symporter in the distal tubule.
- Receptor Binding/Enzyme Inhibition: Nebivolol exhibits high affinity for beta-1 adrenergic receptors. Indapamide interacts with the sodium-chloride symporter.
- Elimination Pathways: Nebivolol is mainly eliminated via hepatic metabolism, with some renal excretion. Indapamide is primarily excreted in the urine, with some fecal elimination.
Dosage
Standard Dosage
Adults:
- Nebivolol: Initial 5 mg orally once daily, adjusted as needed at 1-2 week intervals up to a maximum of 40 mg/day.
- Indapamide: Initial 1.25 mg orally once daily, may be increased to 2.5 mg after 4 weeks, and then to 5 mg after another 4 weeks if needed.
- Combination: A common starting dose is nebivolol 5 mg/indapamide 1.25 mg once daily, with adjustments made based on the individual patient response. It is typically taken in the morning.
Children: This combination is not recommended for children under 18 years of age as safety and efficacy have not been established.
Special Cases:
- Elderly Patients: Start with lower doses of both medications and titrate cautiously, considering potential age-related decline in organ function. For nebivolol, a maximum of 5mg per day is recommended for patients older than 65.
- Patients with Renal Impairment: For nebivolol, the initial dose is 2.5 mg once daily for creatinine clearance <30 mL/min. Indapamide should be used with caution, and dose reduction might be necessary. Close monitoring of renal function is advised.
- Patients with Hepatic Dysfunction: For nebivolol, the initial dose is 2.5 mg once daily for moderate impairment. It is contraindicated in severe hepatic impairment. Indapamide should be used with caution, as dose reduction may be required.
- Patients with Comorbid Conditions: Careful monitoring is essential for individuals with diabetes, gout, or systemic lupus erythematosus. Adjust dosages and monitor closely.
Clinical Use Cases
This particular combination is not typically used in acute settings like intubation, surgical procedures, mechanical ventilation, ICU care, or emergency situations. Its primary indication is the long-term management of hypertension.
Dosage Adjustments
Dosages need to be modified based on individual patient factors like renal or hepatic impairment, metabolic disorders, or genetic polymorphisms affecting drug metabolism. Careful monitoring of blood pressure, electrolytes, and renal function is necessary.
Side Effects
Common Side Effects:
- Dizziness
- Headache
- Fatigue
- Fluid retention
- Peripheral edema
- Slow heart rate (bradycardia)
Rare but Serious Side Effects:
- Severe allergic reactions
- Worsening of heart failure
- Severe hypotension
- Heart block
- Bronchospasm (in susceptible individuals)
Long-Term Effects:
- Electrolyte imbalances (e.g., hypokalemia, hyponatremia)
- Impaired glucose tolerance
- Increased uric acid levels
Adverse Drug Reactions (ADR):
- Angioedema (rare)
- Stevens-Johnson syndrome (rare)
- Toxic epidermal necrolysis (rare)
- Severe bradycardia or hypotension
Contraindications
- Hypersensitivity to nebivolol, indapamide, or any component of the formulation
- Severe hepatic impairment (Child-Pugh Class C)
- Severe bradycardia
- Second- or third-degree heart block (without a pacemaker)
- Cardiogenic shock
- Decompensated heart failure
- Severe hypotension
Drug Interactions
- Other antihypertensive medications (additive effect)
- Calcium channel blockers (increased risk of bradycardia and hypotension)
- Class I antiarrhythmic drugs (increased risk of bradycardia and heart block)
- Nonsteroidal anti-inflammatory drugs (NSAIDs) (may reduce the antihypertensive effect)
- Insulin or oral antidiabetic agents (may mask symptoms of hypoglycemia)
Pregnancy and Breastfeeding
- Pregnancy: Category C. Use only if the potential benefit justifies the potential risk to the fetus.
- Breastfeeding: Indapamide is excreted in breast milk. Nebivolol’s excretion is uncertain. Use with caution or choose an alternative if possible.
Drug Profile Summary
- Mechanism of Action: Nebivolol: Beta-1 blocker, vasodilator. Indapamide: Thiazide-like diuretic.
- Side Effects: Dizziness, headache, fatigue, fluid retention, bradycardia, electrolyte imbalances.
- Contraindications: Severe hepatic impairment, bradycardia, heart block, cardiogenic shock, decompensated heart failure.
- Drug Interactions: Other antihypertensives, calcium channel blockers, NSAIDs, insulin/oral antidiabetics.
- Pregnancy & Breastfeeding: Use with caution. Consider risks and benefits.
- Dosage: Nebivolol: 5 mg/day initially, titrated up to 40 mg/day. Indapamide: 1.25 mg/day initially, titrated up to 5 mg/day.
- Monitoring Parameters: Blood pressure, heart rate, electrolytes (potassium, sodium, chloride), renal function, blood glucose, uric acid.
Popular Combinations
While this combination itself is popular, sometimes additional antihypertensives are added if blood pressure goals are not met. This should be done under close medical supervision.
Precautions
- General Precautions: Evaluate for allergies, metabolic disorders, and organ dysfunction.
- Specific Populations: Discussed in the “Special Cases” section of Dosage.
- Lifestyle Considerations: Limit alcohol, avoid smoking. May impair ability to drive or operate machinery due to potential dizziness.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Indapamide + Nebivolol?
A: The typical starting dose is nebivolol 5 mg/indapamide 1.25 mg once daily, taken orally. Dosage adjustments depend on individual response and patient specific factors such as age, renal function, and hepatic function.
Q2: How should this combination be taken?
A: Orally, once daily, typically in the morning, with or without food.
Q3: What are the common side effects?
A: Dizziness, headache, fatigue, and peripheral edema are common side effects.
Q4: What are the contraindications to this combination?
A: Contraindications include severe hepatic impairment, severe bradycardia, second- or third-degree heart block (without pacemaker), cardiogenic shock, and decompensated heart failure.
Q5: Are there any significant drug interactions?
A: Yes. It can interact with other antihypertensives, calcium channel blockers, NSAIDs, and insulin or oral antidiabetic agents.
Q6: Can this combination be used in pregnancy or while breastfeeding?
A: It should be used with caution. The potential benefits must outweigh the risks. Consult specialist advice.
Q7: What monitoring parameters are important while a patient is on this combination?
A: Monitor blood pressure, heart rate, electrolytes (especially potassium), renal function, blood glucose, and uric acid levels.
Q8: How should the medication be discontinued?
A: It should be tapered gradually under medical supervision to avoid rebound hypertension or other withdrawal effects.
Q9: What should be done if a dose is missed?
A: Take the missed dose as soon as remembered unless it is close to the time for the next dose. Do not double the dose.
Q10: How long does it take for Indapamide + Nebivolol to start working?
A: It may take several weeks for the full blood pressure-lowering effect to be achieved.
