Usage
- Amlodipine + Chlorthalidone is primarily prescribed for the treatment of hypertension (high blood pressure). It may also be used to treat edema (fluid retention).
- Pharmacological Classification: Antihypertensive (combination drug containing a calcium channel blocker and a thiazide diuretic).
- Mechanism of Action: This combination therapy lowers blood pressure through two distinct mechanisms. Amlodipine, a calcium channel blocker, inhibits calcium influx into vascular smooth muscle cells, causing vasodilation. Chlorthalidone, a thiazide diuretic, promotes diuresis by inhibiting sodium reabsorption in the distal convoluted tubule of the nephron, reducing blood volume.
Alternate Names
- No widely recognized alternate names exist for this specific combination.
- Brand Names: Numerous brand names exist depending on the manufacturer and region (e.g., Amlodac CH).
How It Works
- Pharmacodynamics: Amlodipine reduces peripheral vascular resistance, lowering blood pressure. Chlorthalidone reduces blood volume through its diuretic action, further contributing to blood pressure reduction. The combination offers a synergistic effect.
- Pharmacokinetics:
- Amlodipine: Well absorbed orally, peak plasma concentrations reached in 6-12 hours. Extensively metabolized by the liver (CYP3A4 substrate), primarily excreted in the urine and feces. Long half-life (30-50 hours).
- Chlorthalidone: Well absorbed orally, peak plasma concentrations in 2-4 hours. Not extensively metabolized, primarily excreted unchanged in the urine. Long half-life (40-60 hours).
- Mode of Action: Amlodipine blocks L-type calcium channels in vascular smooth muscle, preventing calcium influx, which leads to vasodilation. Chlorthalidone inhibits sodium reabsorption in the distal convoluted tubule of the nephron, increasing sodium and water excretion.
- Elimination Pathways: Amlodipine is primarily eliminated via hepatic metabolism (CYP3A4) and subsequent excretion in urine and feces. Chlorthalidone is primarily eliminated unchanged by renal excretion.
Dosage
Standard Dosage
Adults:
- Initial dose: Amlodipine 2.5-5 mg + Chlorthalidone 12.5-25 mg once daily.
- Titration: Dosage can be adjusted based on individual patient response, typically over 7-14 days.
- Maximum dose: Amlodipine 10 mg + Chlorthalidone 25 mg once daily.
Children:
- Not typically recommended for pediatric use. Safety and efficacy not well established.
Special Cases:
- Elderly Patients: Start with lower doses and titrate cautiously due to increased sensitivity.
- Patients with Renal Impairment: Adjust dose based on renal function. Close monitoring is necessary.
- Patients with Hepatic Dysfunction: Use with caution. Dose adjustments may be needed.
- Patients with Comorbid Conditions: Monitor closely, especially in patients with diabetes, heart failure, or other cardiovascular diseases.
Clinical Use Cases
- Intubation, Surgical Procedures, Mechanical Ventilation, ICU Use, Emergency Situations: Dosage adjustments are determined on a case-by-case basis depending on the specific clinical context and patient status. This combination is not typically adjusted for these situations.
Dosage Adjustments
- Dose modification may be necessary based on renal/hepatic function, patient response, and concomitant medications.
Side Effects
Common Side Effects
- Dizziness, headache, peripheral edema (swelling of ankles and feet), fatigue, flushing, palpitations.
Rare but Serious Side Effects
- Hypotension, syncope, angioedema, hepatotoxicity, Stevens-Johnson syndrome.
Long-Term Effects
- Electrolyte imbalances (hypokalemia, hyponatremia, hypomagnesemia), hyperglycemia, hyperuricemia.
Adverse Drug Reactions (ADR)
- Severe hypotension, allergic reactions, reflex tachycardia.
Contraindications
- Hypersensitivity to amlodipine, chlorthalidone, or sulfonamides.
- Anuria, severe hepatic impairment, hypersensitivity.
Drug Interactions
- Other antihypertensives (additive effects), NSAIDs, lithium, digoxin, CYP3A4 inhibitors/inducers (affect amlodipine metabolism), alcohol (additive hypotensive effect), potassium-sparing diuretics.
Pregnancy and Breastfeeding
- Pregnancy: Use only if clearly needed, potential fetal harm.
- Breastfeeding: Not recommended, excreted in breast milk.
Drug Profile Summary
- Mechanism of Action: Amlodipine: Calcium channel blocker causing vasodilation. Chlorthalidone: Thiazide diuretic reducing blood volume.
- Side Effects: Dizziness, headache, edema, fatigue. Serious: Hypotension, angioedema.
- Contraindications: Hypersensitivity, anuria, severe hepatic impairment.
- Drug Interactions: Other antihypertensives, NSAIDs, lithium, CYP3A4 inhibitors/inducers.
- Pregnancy & Breastfeeding: Not recommended.
- Dosage: Adults: 2.5-10 mg amlodipine + 12.5-25 mg chlorthalidone once daily.
- Monitoring Parameters: Blood pressure, electrolyte levels, renal function, blood glucose.
Popular Combinations
- Often used with other antihypertensives (ACE inhibitors, ARBs, beta-blockers) for synergistic blood pressure control in resistant hypertension.
Precautions
- General Precautions: Monitor blood pressure, electrolytes, and renal function.
- Pregnant Women: Avoid unless absolutely necessary.
- Breastfeeding Mothers: Not recommended.
- Children & Elderly: Use with caution, lower initial doses.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Amlodipine + Chlorthalidone?
A: The initial dose is typically Amlodipine 2.5-5 mg + Chlorthalidone 12.5-25 mg once daily, titrated based on patient response up to a maximum of Amlodipine 10 mg + Chlorthalidone 25 mg once daily.
Q2: How does this combination lower blood pressure?
A: It combines the vasodilating effects of amlodipine with the diuretic action of chlorthalidone, resulting in synergistic blood pressure lowering.
Q3: What are the common side effects?
A: Common side effects include dizziness, headache, peripheral edema, fatigue, and flushing.
Q4: Are there any serious side effects?
A: Rare but serious side effects include severe hypotension, angioedema, and hepatotoxicity.
Q5: Can this medication be used during pregnancy or breastfeeding?
A: It’s generally not recommended during pregnancy or breastfeeding due to potential risks to the fetus or infant.
Q6: What are the contraindications for this combination?
A: Contraindications include hypersensitivity to amlodipine, chlorthalidone, or sulfonamides, anuria, and severe hepatic impairment.
Q7: What other medications should be avoided while taking Amlodipine + Chlorthalidone?
A: Avoid concomitant use with other antihypertensives unless carefully monitored, NSAIDs, lithium, digoxin, and CYP3A4 inhibitors/inducers.
Q8: What should patients be monitored for during treatment?
A: Monitor blood pressure, electrolyte levels (especially potassium, sodium, and magnesium), renal function, and blood glucose levels.
Q9: Can this combination be used in elderly patients?
A: It can be used but with caution and at lower initial doses due to increased sensitivity to side effects.
Q10: What should I do if a patient misses a dose?
A: Take the missed dose as soon as remembered, unless it’s close to the time for the next dose. Do not double the dose.
