Usage
- Hydrochlorothiazide + Nebivolol is primarily indicated for the treatment of essential hypertension (high blood pressure) in adults. This combination therapy is typically initiated when monotherapy with either drug fails to achieve adequate blood pressure control. By lowering blood pressure, this medication helps reduce the risk of serious cardiovascular complications like stroke, heart attack, and kidney problems. In certain instances, it might also be utilized as part of a treatment regimen for heart failure, given Nebivolol’s positive impact on cardiac function and Hydrochlorothiazide’s role in reducing fluid buildup.
- Pharmacological Classification: This combination drug belongs to the class of antihypertensive agents. Specifically, it combines a beta-blocker (Nebivolol) and a thiazide diuretic (Hydrochlorothiazide).
- Mechanism of Action: Hydrochlorothiazide acts by inhibiting sodium reabsorption in the distal convoluted tubule of the nephron, promoting increased excretion of sodium, chloride, and water. This leads to a decrease in blood volume and, consequently, lower blood pressure. Nebivolol, a highly selective β1-adrenergic receptor blocker, reduces heart rate and myocardial contractility, leading to decreased cardiac output and blood pressure. It also exhibits vasodilatory properties. This combined effect of reducing cardiac output and peripheral resistance effectively controls high blood pressure.
Alternate Names
- There is no officially recognized alternate name for the combination product itself. However, the individual components have other names. Hydrochlorothiazide is sometimes referred to as HCTZ or Microzide. Nebivolol is available as Nebilet or Bystolic. The combination is marketed under various brand names like Nebilet Plus, Nebilong-H, and Nebivalve H, among others.
How It Works
- Pharmacodynamics: Hydrochlorothiazide exerts its antihypertensive effect primarily by reducing blood volume through diuresis (increased urine production). It also has some direct vasodilatory effects. Nebivolol selectively blocks β1-adrenergic receptors in the heart, leading to reduced heart rate, contractility, and cardiac output. It also has some vasodilatory effects, potentially mediated by nitric oxide release. The two drugs work synergistically to lower blood pressure.
- Pharmacokinetics: Both drugs are administered orally. Nebivolol is rapidly absorbed with variable bioavailability due to extensive first-pass metabolism. It is metabolized primarily by CYP2D6, with some contribution from other CYP enzymes. Hydrochlorothiazide is well absorbed and not extensively metabolized. It is primarily excreted unchanged in the urine. Nebivolol is eliminated through both hepatic and renal pathways, while Hydrochlorothiazide is predominantly excreted renally.
- Mode of Action: At the molecular level, Hydrochlorothiazide inhibits the sodium-chloride symporter in the distal convoluted tubule, preventing sodium reabsorption. Nebivolol binds to and blocks β1-adrenergic receptors in the heart, preventing the binding of catecholamines like norepinephrine and epinephrine, thereby reducing their effects on heart rate and contractility.
- Receptor Binding, Enzyme Inhibition, or Neurotransmitter Modulation: Nebivolol primarily involves receptor binding (β1-adrenergic receptors). Hydrochlorothiazide acts by inhibiting the sodium-chloride symporter.
- Elimination Pathways: Hydrochlorothiazide is primarily eliminated through renal excretion, with a small amount excreted in the feces. Nebivolol is eliminated via hepatic and renal routes.
Dosage
Standard Dosage
Adults:
- The usual starting dose is one tablet containing 5 mg nebivolol and 12.5 mg hydrochlorothiazide once daily. The dose may be increased to one tablet containing 5 mg nebivolol and 25 mg hydrochlorothiazide once daily, as needed. It’s preferable to take the medication at the same time each day, with or without food.
Children:
- The safety and efficacy of Hydrochlorothiazide + Nebivolol have not been established in children. Its use is not recommended in pediatric patients.
Special Cases:
- Elderly Patients: Generally, the same starting dose is used as in younger adults, but dose titration should be done cautiously, considering age-related decline in renal function.
- Patients with Renal Impairment: In patients with severe renal impairment (creatinine clearance < 30 mL/min), the use of Hydrochlorothiazide + Nebivolol is contraindicated. For moderate renal impairment, dosage adjustments may be necessary.
- Patients with Hepatic Dysfunction: The use of this combination is contraindicated in patients with severe hepatic impairment.
- Patients with Comorbid Conditions: Caution should be exercised in patients with diabetes, as Nebivolol can mask symptoms of hypoglycemia. In patients with asthma or COPD, Nebivolol can exacerbate bronchospasm, and close monitoring is necessary.
Clinical Use Cases
- The provided sources do not specify dosage recommendations for this combination in specific clinical settings like intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations.
Dosage Adjustments
- Dose adjustments should be based on individual patient response and tolerability. Careful monitoring of blood pressure is crucial during titration. In patients with renal or hepatic impairment, lower starting doses and cautious titration are necessary.
Side Effects
Common Side Effects
- Dizziness
- Lightheadedness
- Fatigue
- Headache
- Nausea
- Constipation
- Diarrhea
- Increased urination
Rare but Serious Side Effects
- Slow heart rate (bradycardia)
- Severe low blood pressure (hypotension)
- Worsening of heart failure
- Bronchospasm (in patients with asthma or COPD)
- Electrolyte imbalances (hypokalemia, hyponatremia, hypomagnesemia, hypercalcemia)
- Allergic reactions
Long-Term Effects
- Potential long-term effects may include electrolyte imbalances, gout, and increased risk of certain skin cancers with chronic hydrochlorothiazide use.
Adverse Drug Reactions (ADR)
- Clinically significant ADRs include severe hypotension, bradycardia, bronchospasm, and electrolyte imbalances. These require immediate medical attention.
Contraindications
- Hypersensitivity to Nebivolol, Hydrochlorothiazide, or sulfa drugs
- Severe bradycardia (<60 bpm)
- Second or third-degree heart block (without a pacemaker)
- Sick sinus syndrome
- Cardiogenic shock
- Decompensated heart failure
- Severe hepatic impairment
- Severe renal impairment (creatinine clearance < 30 mL/min)
- Anuria
- Severe peripheral arterial circulatory disorders
- Untreated pheochromocytoma
- Metabolic acidosis
- Refractory hypokalemia, hypercalcemia, or hyponatremia
- Symptomatic hyperuricemia
Drug Interactions
- Other antihypertensive medications: Additive hypotensive effects
- Alcohol: Increased risk of dizziness and drowsiness
- Antipsychotics, tricyclic antidepressants, barbiturates, and narcotic drugs: Enhanced hypotensive effect
- Sympathomimetics: Counteraction of Nebivolol’s effects
- Digoxin: Increased risk of bradycardia
- Lithium: Increased lithium levels
- NSAIDs: Decreased antihypertensive effect of Nebivolol
- Insulin and oral antidiabetic drugs: Masking of hypoglycemia symptoms
- Corticosteroids: Hypokalemia
Pregnancy and Breastfeeding
- Pregnancy Safety Category: Hydrochlorothiazide + Nebivolol is generally contraindicated during pregnancy, especially in the third trimester, due to potential risks to the fetus, including fetal growth restriction, bradycardia, hypoglycemia, and respiratory problems.
- Breastfeeding: Nebivolol and Hydrochlorothiazide can be excreted in breast milk and potentially harm the nursing infant. Breastfeeding is not recommended while taking this combination.
Drug Profile Summary
- Mechanism of Action: Combines beta-blocker and diuretic actions to lower blood pressure
- Side Effects: Dizziness, lightheadedness, fatigue, headache, nausea, electrolyte imbalances
- Contraindications: Severe bradycardia, heart block, heart failure, hepatic/renal impairment, pregnancy
- Drug Interactions: Other antihypertensives, alcohol, antipsychotics, digoxin, lithium, NSAIDs
- Pregnancy & Breastfeeding: Contraindicated
- Dosage: 5mg/12.5mg or 5mg/25mg once daily
- Monitoring Parameters: Blood pressure, heart rate, electrolytes, renal function
Popular Combinations
The provided sources don’t mention any other popular combinations besides nebivolol and hydrochlorothiazide.
Precautions
- General Precautions: Monitor blood pressure and heart rate regularly. Assess renal and hepatic function before starting therapy. Check electrolyte levels periodically, especially potassium.
- Specific Populations: Pregnant women (contraindicated), breastfeeding mothers (contraindicated), children (not recommended), elderly (dose adjustment may be needed)
- Lifestyle Considerations: Limit alcohol intake. Advise patients about potential dizziness and to avoid driving or operating machinery until effects are known.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Hydrochlorothiazide + Nebivolol?
A: The usual starting dose for adults is one tablet containing 5 mg nebivolol and 12.5 mg hydrochlorothiazide once daily. The dose may be increased as needed to 5 mg nebivolol and 25 mg hydrochlorothiazide once daily.
Q2: How should Hydrochlorothiazide + Nebivolol be taken?
A: Take one tablet daily, preferably at the same time each day, with or without food.
Q3: What are the most common side effects of Hydrochlorothiazide + Nebivolol?
A: Common side effects include dizziness, lightheadedness, fatigue, headache, nausea, constipation, diarrhea, and increased urination.
Q4: Who should not take Hydrochlorothiazide + Nebivolol?
A: Patients with severe bradycardia, heart block, heart failure, severe hepatic or renal impairment, hypersensitivity to sulfa drugs, and pregnant or breastfeeding women should not take this combination.
Q5: Can Hydrochlorothiazide + Nebivolol be used during pregnancy?
A: No, it’s contraindicated during pregnancy, especially during the third trimester.
Q6: Can I drink alcohol while taking Hydrochlorothiazide + Nebivolol?
A: Alcohol should be limited as it can increase the risk of dizziness and drowsiness.
Q7: What should I do if I miss a dose?
A: Take the missed dose as soon as you remember. However, if it is nearly time for your next dose, skip the missed dose and continue with your regular schedule. Do not double the dose.
Q8: Does Hydrochlorothiazide + Nebivolol interact with other medications?
A: Yes, it can interact with other antihypertensives, alcohol, antipsychotics, digoxin, lithium, and NSAIDs, among others. It’s crucial to inform your doctor about all other medications you are taking.
Q9: How does Hydrochlorothiazide + Nebivolol affect patients with diabetes?
A: Nebivolol can mask symptoms of hypoglycemia in patients with diabetes, requiring careful blood glucose monitoring.
Q10: What are the long-term effects of Hydrochlorothiazide + Nebivolol?
A: Potential long-term effects include electrolyte imbalances, gout, and increased risk of non-melanoma skin cancer with chronic hydrochlorothiazide use.
