Usage
- Chlorthalidone + Efonidipine is prescribed for the management of hypertension (high blood pressure), especially in cases where monotherapy is insufficient.
- Pharmacological Classification: Antihypertensive, combining a thiazide-like diuretic (Chlorthalidone) and a calcium channel blocker (Efonidipine).
- Mechanism of Action: Efonidipine inhibits calcium influx into vascular smooth muscle cells, leading to vasodilation. Chlorthalidone increases sodium and water excretion, reducing blood volume and further lowering blood pressure. The combination provides synergistic blood pressure control.
Alternate Names
- No widely recognized alternate names exist for the combination itself.
- Brand Names: Efnocar-CT is one of the brand names under which this combination is marketed.
How It Works
- Pharmacodynamics: Efonidipine primarily affects vascular smooth muscle, reducing peripheral vascular resistance. Chlorthalidone acts on the distal convoluted tubule in the kidneys, increasing sodium and chloride excretion, leading to diuresis. The combination produces a greater antihypertensive effect than either drug alone.
- Pharmacokinetics: Efonidipine is well-absorbed orally. It is metabolized by the liver, primarily by CYP3A4 enzymes. Chlorthalidone is also absorbed orally and has a long duration of action. It is primarily excreted unchanged by the kidneys.
- Mode of Action: Efonidipine selectively blocks L-type calcium channels, inhibiting calcium influx into vascular smooth muscle, leading to vasodilation and decreased blood pressure. Chlorthalidone inhibits the sodium-chloride cotransporter in the distal convoluted tubule, promoting natriuresis, diuresis, and reduced blood volume, contributing to lower blood pressure.
- Elimination Pathways: Efonidipine is primarily eliminated via hepatic metabolism (CYP3A4) followed by renal excretion. Chlorthalidone is primarily eliminated through renal excretion.
Dosage
Standard Dosage
Adults:
- One tablet daily, containing a fixed combination of Efonidipine (typically 40mg) and Chlorthalidone (typically 12.5mg).
Children:
- Not recommended for use in children as safety and efficacy haven’t been established in this population.
Special Cases:
- Elderly Patients: Efonidipine should be initiated at a lower dose (e.g., 20mg) with careful monitoring for hypotension. Chlorthalidone should also be started at the lower end of the dosing range due to potential age-related decline in hepatic, renal, or cardiac function.
- Patients with Renal Impairment: Caution is advised, and dose adjustment might be necessary based on creatinine clearance. For severe renal impairment (creatinine clearance <30 mL/min), the combination is contraindicated.
- Patients with Hepatic Dysfunction: Use with caution in patients with hepatic impairment. Dose adjustments may be necessary. For severe hepatic failure, the combination is contraindicated.
- Patients with Comorbid Conditions: Monitor closely in patients with conditions like diabetes, gout, and electrolyte imbalances (hypokalemia, hyponatremia, hypercalcemia). Adjustments may be necessary for those on a low-salt diet or with high cholesterol.
Clinical Use Cases
The provided sources mainly refer to the chronic management of hypertension. Specific dosage guidelines for scenarios like intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations are not detailed. Dosage adjustments must be based on clinical judgment and specific patient characteristics in these settings.
Dosage Adjustments
- Modify doses for renal/hepatic dysfunction.
- Consider electrolyte imbalances, gout, diabetes.
Side Effects
Common Side Effects
- Dizziness, headache, peripheral edema (swelling of ankles, feet, hands), flushing, gastrointestinal disturbances (nausea, constipation, abdominal discomfort).
Rare but Serious Side Effects
- Severe hypotension, syncope, electrolyte imbalances (hypokalemia, hyponatremia, hypomagnesemia, hypercalcemia), allergic reactions.
Long-Term Effects
- Potential for electrolyte imbalances and worsening of pre-existing metabolic or renal conditions with prolonged use.
Adverse Drug Reactions (ADR)
- Angioedema, severe hypotension requiring intervention, significant electrolyte derangements.
Contraindications
- Hypersensitivity to Efonidipine, Chlorthalidone, or sulfonamides.
- Anuria, severe renal failure (creatinine clearance <30 mL/min), severe hepatic failure.
- Refractory hypokalemia, hyponatremia, hypercalcemia.
- Symptomatic hyperuricemia (gout or uric acid calculi).
- Pregnancy.
Drug Interactions
- Other antihypertensive medications (additive hypotensive effects).
- Diuretics (enhanced electrolyte imbalances).
- NSAIDs (may reduce antihypertensive effect).
- Potassium supplements or potassium-sparing diuretics (increased risk of hyperkalemia).
- CYP3A4 inhibitors (may increase Efonidipine levels).
- Lithium (increased risk of lithium toxicity).
- Alcohol, grapefruit juice (may interact with Efonidipine metabolism).
Pregnancy and Breastfeeding
- Pregnancy Safety Category: Not recommended. Efonidipine’s safety in pregnancy hasn’t been established, and Chlorthalidone can cause fetal harm.
- Efonidipine’s excretion in breast milk is unknown; Chlorthalidone is excreted in breast milk. The combination is not recommended during breastfeeding.
Drug Profile Summary
- Mechanism of Action: Efonidipine: Calcium channel blocker, vasodilator. Chlorthalidone: Thiazide-like diuretic, reduces blood volume.
- Side Effects: Dizziness, headache, edema, flushing, GI issues. Rarely: hypotension, electrolyte imbalances.
- Contraindications: Hypersensitivity, anuria, severe renal/hepatic failure, electrolyte disturbances, gout, pregnancy.
- Drug Interactions: Other antihypertensives, diuretics, NSAIDs, potassium supplements, CYP3A4 inhibitors, lithium, alcohol.
- Pregnancy & Breastfeeding: Not recommended.
- Dosage: Adults: One tablet (Efonidipine 40mg/ Chlorthalidone 12.5mg) daily. Elderly: lower initial doses.
- Monitoring Parameters: Blood pressure, renal function, electrolytes (potassium, sodium, magnesium, calcium), blood glucose.
Popular Combinations
The combination of Efonidipine and Chlorthalidone is itself considered a popular and efficacious combination for hypertension management.
Precautions
- General Precautions: Screen for allergies, renal/hepatic dysfunction, electrolyte imbalances, gout, diabetes before initiating.
- Pregnant Women: Avoid.
- Breastfeeding Mothers: Avoid.
- Children & Elderly: Not recommended for children. Start elderly at lower doses.
- Lifestyle Considerations: Limit alcohol, avoid grapefruit juice, encourage lifestyle modifications (diet, exercise). Restrict driving or operating machinery if dizziness occurs.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Chlorthalidone + Efonidipine?
A: One tablet containing Efonidipine (typically 40mg) + Chlorthalidone (typically 12.5mg) once daily for adults. Lower initial doses are recommended for elderly patients.
Q2: What are the common side effects?
A: Dizziness, headache, peripheral edema, flushing, and gastrointestinal disturbances.
Q3: What are the contraindications?
A: Hypersensitivity, anuria, severe renal/hepatic failure, refractory electrolyte imbalances, symptomatic hyperuricemia, pregnancy.
Q4: How does this combination work?
A: Efonidipine is a calcium channel blocker causing vasodilation. Chlorthalidone is a diuretic reducing blood volume. Together, they have a synergistic antihypertensive effect.
Q5: Can it be used in pregnancy or breastfeeding?
A: No, it’s contraindicated in pregnancy and not recommended during breastfeeding.
Q6: What are the potential drug interactions?
A: Other antihypertensives, diuretics, NSAIDs, potassium supplements, CYP3A4 inhibitors, lithium, alcohol, grapefruit juice.
Q7: Are there any special considerations for elderly patients?
A: Start with lower doses of both Efonidipine and Chlorthalidone and monitor closely for hypotension.
Q8: What monitoring parameters are important?
A: Blood pressure, renal function, electrolytes (potassium, sodium, magnesium, calcium), and blood glucose should be monitored regularly.
Q9: What should a patient do if they miss a dose?
A: Take the missed dose as soon as remembered, unless it’s close to the next scheduled dose. Do not double the dose.
Q10: What should patients know about lifestyle modifications?
A: Lifestyle modifications such as following a low-sodium diet, regular exercise, limiting alcohol intake, and avoiding grapefruit juice can further improve blood pressure control.
