Usage
- Enalapril + Hydrochlorothiazide is prescribed for the treatment of essential hypertension (high blood pressure) in patients whose blood pressure is not adequately controlled by enalapril alone. It is not suitable for initial therapy.
- Pharmacological Classification: Combined Angiotensin-Converting Enzyme (ACE) Inhibitor (enalapril) and Thiazide Diuretic (hydrochlorothiazide)
- Mechanism of Action: Enalapril blocks the conversion of angiotensin I to angiotensin II, a potent vasoconstrictor. This leads to vasodilation and reduced sodium retention. Hydrochlorothiazide increases the excretion of sodium and water by the kidneys, further contributing to lowering blood pressure.
Alternate Names
- The combination is often referred to as enalapril/hydrochlorothiazide or enalapril and hydrochlorothiazide.
- Brand Names: Vaseretic, Lexxel(when combined with felodipine), Lotensin HCT (when combined with benazepril), Capozide (when combined with captopril), Monopril HCT (when combined with fosinopril), Prinzide or Zestoretic(when combined with lisinopril), Uniretic(when combined with moexipril), Accuretic(when combined with quinapril)
How It Works
- Pharmacodynamics: Enalapril reduces peripheral vascular resistance and blood volume, leading to a decrease in blood pressure. Hydrochlorothiazide increases urine output, further reducing blood volume.
- Pharmacokinetics:
- Absorption: Both drugs are orally absorbed, enalapril as the maleate salt which is rapidly hydrolyzed to enalaprilat, the active form. Food does not significantly affect absorption.
- Metabolism: Enalapril is partially metabolized to enalaprilat. Hydrochlorothiazide is not extensively metabolized.
- Elimination: Enalapril and enalaprilat are primarily excreted by the kidneys. Hydrochlorothiazide is also excreted by the kidneys.
- Mode of Action: Enalapril competitively inhibits ACE, preventing the conversion of angiotensin I to angiotensin II. Hydrochlorothiazide inhibits sodium reabsorption in the distal convoluted tubule of the nephron.
- Receptor Binding, Enzyme Inhibition: Enalapril inhibits ACE. Hydrochlorothiazide inhibits sodium-chloride symporter.
- Elimination Pathways: Predominantly renal excretion for both drugs.
Dosage
Standard Dosage
Adults:
- Initial dose: Enalapril 5 to 10 mg + Hydrochlorothiazide 12.5 to 25 mg once daily.
- Maintenance dose: Up to Enalapril 20 mg + Hydrochlorothiazide 50 mg per day, which can be given as a single dose or in two divided doses.
- Dosage should be titrated based on blood pressure response.
Children:
- Use and dose must be determined by a doctor, but generally this medication is not recommended for use in children.
Special Cases:
- Elderly Patients: Initial dose should be lower (e.g., half a tablet daily) with careful titration based on renal function and blood pressure response.
- Patients with Renal Impairment: Dosage adjustment is required for patients with creatinine clearance less than 30 mL/min/1.73m². This medication is not recommended for patients with severe renal impairment.
- Patients with Hepatic Dysfunction: Use with caution. Dosage adjustments may be necessary.
- Patients with Comorbid Conditions: Careful monitoring is required in patients with diabetes, heart failure, and other cardiovascular diseases.
Clinical Use Cases The use of Enalapril+Hydrochlorothiazide for Intubation, Surgical Procedures, Mechanical Ventilation, Intensive Care Unit (ICU) Use, and Emergency Situations, such as Status Epilepticus or Cardiac Arrest has not been established and the manufacturer has not recommended its use in these situations. The standard dosage guidelines should be considered when such situations occur and dose modifications should be made as per the patient’s physiological condition.
Dosage Adjustments
- Dose adjustments are based on renal function, hepatic function, and the presence of other medical conditions.
- Close monitoring of serum electrolytes, renal function, and blood pressure is essential.
Side Effects
Common Side Effects
- Dizziness, lightheadedness, headache, cough, fatigue, muscle cramps.
Rare but Serious Side Effects
- Angioedema (swelling of the face, lips, tongue, throat, or extremities), hypotension, hyperkalemia, acute renal failure, hepatic dysfunction, severe skin reactions, pancreatitis, agranulocytosis.
Long-Term Effects
- Electrolyte imbalances, worsening of renal function, gout.
Adverse Drug Reactions (ADR)
- Angioedema, anaphylactoid reactions, severe hypotension.
Contraindications
- Hypersensitivity to enalapril, hydrochlorothiazide, or sulfonamides.
- History of ACE inhibitor-induced angioedema.
- Anuria, renal artery stenosis, pregnancy (second and third trimesters), severe hepatic impairment.
- Concomitant use with sacubitril/valsartan.
- Concomitant use of aliskiren in patients with diabetes or renal impairment.
Drug Interactions
- Other antihypertensives, potassium-sparing diuretics, potassium supplements, lithium, NSAIDs, alcohol, certain antineoplastic agents, gold injections, immunosuppressants, some antidepressants.
Pregnancy and Breastfeeding
- Pregnancy Safety Category: Category D (first trimester), Category X (second and third trimesters). Contraindicated during the second and third trimesters.
- Fetal risks: Fetal injury and death.
- Breastfeeding: Drug is excreted in breast milk and its use is not recommended.
- Safer alternative options: Other antihypertensive medications should be considered during pregnancy and breastfeeding.
Drug Profile Summary
- Mechanism of Action: ACE inhibitor (enalapril) and thiazide diuretic (hydrochlorothiazide) combination.
- Side Effects: Dizziness, lightheadedness, cough, angioedema, hypotension, hyperkalemia.
- Contraindications: Hypersensitivity, angioedema history, anuria, pregnancy (second and third trimesters), concomitant use with sacubitril/valsartan.
- Drug Interactions: Other antihypertensives, potassium supplements, lithium, NSAIDs.
- Pregnancy & Breastfeeding: Contraindicated in second and third trimesters of pregnancy; not recommended during breastfeeding.
- Dosage: Adults: Starting dose 5/12.5 mg to 10/25 mg once daily; maximum dose 20/50 mg per day.
- Monitoring Parameters: Blood pressure, serum electrolytes, renal function.
Popular Combinations
- Other antihypertensives such as beta-blockers (e.g., metoprolol) or calcium channel blockers (e.g., amlodipine) may be added if blood pressure is not adequately controlled with Enalapril+Hydrochlorothiazide alone.
Precautions
- Monitor renal function, electrolytes, and blood pressure regularly.
- Caution in patients with renal or hepatic impairment, collagen vascular disease, and diabetes.
- Avoid in pregnancy (especially second and third trimesters) and breastfeeding.
- Advise patients about potential for dizziness and hypotension.
- Alcohol can exacerbate side effects.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Enalapril + Hydrochlorothiazide?
A: The initial dose is typically Enalapril 5-10 mg + Hydrochlorothiazide 12.5-25 mg once daily. The maximum daily dose is Enalapril 20 mg + Hydrochlorothiazide 50 mg.
Q2: What are the common side effects?
A: Common side effects include dizziness, lightheadedness, cough, fatigue, and muscle cramps.
A: Serious side effects include angioedema, hypotension, hyperkalemia, acute renal failure, and severe skin reactions.
Q4: Is it safe to take Enalapril + Hydrochlorothiazide during pregnancy or breastfeeding?
A: No. It is contraindicated during the second and third trimesters of pregnancy and not recommended while breastfeeding.
Q5: What other medications should be avoided while taking Enalapril + Hydrochlorothiazide?
A: Avoid concomitant use of aliskiren (especially in patients with diabetes or renal impairment), potassium supplements, potassium-sparing diuretics, lithium, and NSAIDs. Consult a physician about any other medications being taken.
Q6: How does Enalapril + Hydrochlorothiazide work to lower blood pressure?
A: Enalapril blocks the formation of angiotensin II, a potent vasoconstrictor, leading to vasodilation. Hydrochlorothiazide promotes the excretion of sodium and water, reducing blood volume. These actions combined help lower blood pressure.
Q7: Can I take this medication with food?
A: Yes, Enalapril + Hydrochlorothiazide can be taken with or without food. However, if it upsets your stomach, it’s advisable to take it with food.
Q8: What should I do if I miss a dose?
A: If you miss a dose, take it as soon as you remember. However, if it is almost time for the next dose, skip the missed dose and continue with your regular schedule. Do not double the dose.
Q9: How should this medication be stored?
A: Store at room temperature away from moisture, heat, and direct light. Keep out of reach of children.
Q10: What monitoring parameters are essential when a patient is prescribed this medication?
A: Regular monitoring of blood pressure, serum creatinine and BUN, and serum electrolytes (especially potassium) is essential. If necessary, monitor CBC with differential periodically for patients with renal impairment and/or collagen vascular diseases.
