Hydrochlorothiazide + Metoprolol Succinate

Usage

Hydrochlorothiazide + Metoprolol Succinate is prescribed for the treatment of hypertension (high blood pressure) in patients who do not adequately respond to monotherapy with either drug. It combines two different mechanisms of action to achieve better blood pressure control.

• Pharmacological classification:

  • Hydrochlorothiazide: Thiazide diuretic
  • Metoprolol Succinate: Beta-1 selective adrenergic blocker (beta blocker)

• Mechanism of Action: Hydrochlorothiazide increases urine output, reducing blood volume and thus blood pressure. Metoprolol succinate blocks beta-1 receptors in the heart, reducing heart rate and cardiac output, which also lowers blood pressure. Additionally, it may cause vasodilation.

Alternate Names

No widely used alternate generic names exist.

• Brand Names: Lopressor HCT, Dutoprol

How It Works

• Pharmacodynamics: Hydrochlorothiazide lowers blood pressure by reducing blood volume through increased sodium and water excretion. Metoprolol lowers blood pressure by decreasing heart rate, cardiac output, and renin release, and may also cause vasodilation.

• Pharmacokinetics:

  • Absorption: Metoprolol succinate is well-absorbed orally. Hydrochlorothiazide is also well-absorbed orally. Food may increase metoprolol succinate bioavailability.
  • Metabolism: Metoprolol succinate is extensively metabolized by the liver, primarily by CYP2D6. Hydrochlorothiazide is not extensively metabolized.
  • Elimination: Metoprolol succinate metabolites are eliminated primarily in the urine. Hydrochlorothiazide is excreted unchanged in the urine.

• Mode of Action: Hydrochlorothiazide inhibits sodium reabsorption in the distal convoluted tubule of the nephron. Metoprolol succinate selectively blocks beta-1 adrenergic receptors in the heart.

• Receptor Binding, Enzyme Inhibition or Neurotransmitter Modulation: Metoprolol succinate is a beta-1 selective adrenergic antagonist. Hydrochlorothiazide does not directly interact with receptors or neurotransmitters.

• Elimination Pathways: Metoprolol succinate is primarily metabolized by CYP2D6 in the liver and its metabolites are excreted renally. Hydrochlorothiazide is primarily excreted unchanged in the urine via renal pathways.

Dosage

Standard Dosage

Adults:

• Initial dose: Hydrochlorothiazide 12.5 mg / Metoprolol Succinate 25 mg orally once daily.

• Titration: The dose may be titrated upwards every two weeks, as needed to control blood pressure, based on the patient’s response.

• Maximum dose: Hydrochlorothiazide 25 mg / Metoprolol Succinate 200 mg orally once daily.

• Administration: Once daily, with or without food. Can be administered with other antihypertensives if necessary.

Children: Use in children is not recommended. Safety and effectiveness have not been established in this population.

Special Cases:

• Elderly Patients: Initiate therapy with lower doses and titrate carefully, monitoring for side effects.

• Patients with Renal Impairment: Caution should be exercised in patients with renal impairment, as the cumulative effects of hydrochlorothiazide may develop. Dosage adjustments may be necessary.

• Patients with Hepatic Dysfunction: Use caution in patients with hepatic impairment. Initiate therapy with lower doses and titrate carefully, as metoprolol succinate is extensively metabolized by the liver.

• Patients with Comorbid Conditions: Use with caution in patients with diabetes, bradycardia, heart block, and other cardiovascular diseases. Individualized dosing may be necessary.

Clinical Use Cases

This combination is not indicated for use in emergency or acute settings such as intubation, surgical procedures, mechanical ventilation, or intensive care unit (ICU) use. It is intended for chronic management of hypertension.

Dosage Adjustments

Dosage adjustments should be made based on the individual patient’s response to therapy, renal function, and hepatic function. For patients with renal or hepatic impairment, a lower starting dose and careful titration are recommended.

Side Effects

Common Side Effects: Dizziness, fatigue, headache, nausea, diarrhea, dry mouth.

Rare but Serious Side Effects: Bradycardia, hypotension, bronchospasm, heart block, acute renal failure, angioedema, thrombocytopenia, agranulocytosis.

Long-Term Effects: Electrolyte imbalances (hypokalemia, hyponatremia, hypomagnesemia, hypercalcemia), gout, impaired glucose tolerance.

Adverse Drug Reactions (ADR): Severe bradycardia, hypotension, bronchospasm, heart failure exacerbation.

Contraindications

• Cardiogenic shock, heart block (second or third degree), sinus bradycardia, anuria, hypersensitivity to sulfonamides or metoprolol.
• Decompensated heart failure, sick sinus syndrome (unless paced), severe peripheral vascular disease.

Drug Interactions

• Clinically Significant Drug Interactions: Other antihypertensives (additive effect), calcium channel blockers (may exacerbate bradycardia or hypotension), insulin or oral hypoglycemic agents (may mask symptoms of hypoglycemia), NSAIDs (may reduce antihypertensive effect), digoxin (may increase risk of bradycardia), lithium (may increase lithium levels), CYP2D6 inhibitors (may increase metoprolol levels).

• CYP450 Interactions: Metoprolol is metabolized by CYP2D6. Inhibitors of CYP2D6 may increase metoprolol levels.

• Interactions with: Other antihypertensives, diuretics, NSAIDs, digoxin, lithium, alcohol, and CYP2D6 inhibitors/inducers. OTC medications should be reviewed for potential interactions.

Pregnancy and Breastfeeding

• Pregnancy Safety Category: C (Risk cannot be ruled out)

• Fetal Risks: May cause decreased placental perfusion, fetal bradycardia, and intrauterine growth retardation.

• Breastfeeding: Both drugs are excreted in breast milk. A decision should be made to discontinue breastfeeding or the drug, taking into account the importance of the drug to the mother.

Drug Profile Summary

• Mechanism of Action: Hydrochlorothiazide: reduces blood volume; Metoprolol: reduces cardiac output, heart rate, renin release.
• Side Effects: Dizziness, fatigue, headache, nausea, bradycardia, hypotension.
• Contraindications: Cardiogenic shock, heart block, sinus bradycardia, anuria, sulfonamide hypersensitivity.
• Drug Interactions: Other antihypertensives, digoxin, lithium, CYP2D6 inhibitors.
• Pregnancy & Breastfeeding: Use with caution if benefits outweigh risks. Both drugs are present in breast milk.
• Dosage: Start with 12.5/25 mg daily, titrate up to 25/200 mg as needed.
• Monitoring Parameters: Blood pressure, heart rate, electrolytes (potassium, sodium, magnesium, calcium), renal function, blood glucose.

Popular Combinations

Often used alone or in combination with other antihypertensives as needed to achieve target blood pressure.

Precautions

• General Precautions: Monitor blood pressure and heart rate regularly. Monitor electrolytes, particularly potassium. Assess renal and hepatic function. Caution patients about orthostatic hypotension.

• Specific Populations: As described above in Special Cases.

• Lifestyle Considerations: Restrict alcohol intake. Advise patients to avoid becoming overheated or dehydrated.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Hydrochlorothiazide + Metoprolol Succinate?

A: The starting dose is typically 12.5 mg Hydrochlorothiazide/25 mg Metoprolol Succinate once daily, with titration up to a maximum of 25 mg/200 mg daily as needed based on the patient’s blood pressure response.

Q2: What are the common side effects?

A: Common side effects include dizziness, fatigue, headache, nausea, and diarrhea.

Q3: Can this combination be used in patients with renal impairment?

A: It should be used with caution in patients with renal impairment due to the risk of hydrochlorothiazide accumulation. Dosage adjustments may be needed.

Q4: Is this combination safe during pregnancy?

A: It should be used during pregnancy only if the potential benefit outweighs the potential risk to the fetus. Discuss risks and benefits with the patient.

Q5: Can this combination be used with other antihypertensives?

A: Yes, it can be used with other antihypertensives if needed to achieve blood pressure control, but start with a lower dose of the additional antihypertensive to avoid excessive blood pressure reduction.

Q6: What are the contraindications to using this drug?

A: Contraindications include cardiogenic shock, severe bradycardia or heart block, severe heart failure, and hypersensitivity to sulfonamides or metoprolol.

Q7: What should patients be advised regarding lifestyle modifications?

A: Patients should be advised to limit alcohol intake, avoid becoming overheated or dehydrated, and to adhere to a healthy diet and exercise regimen.

Q8: How should this medication be discontinued?

A: Do not discontinue abruptly, especially in patients with ischemic heart disease. Taper the dose gradually over 1-2 weeks to avoid rebound hypertension or angina.

Q9: Should this medication be taken with food?

A: It can be taken with or without food, but if taken with food, it should be taken consistently with food to maintain consistent absorption.

Q10: How does this combination differ from using hydrochlorothiazide or metoprolol alone?

A: The combination provides additive blood pressure lowering effects through two different mechanisms of action, allowing for better control of blood pressure in patients who don’t respond adequately to monotherapy.