Usage
- Medical Conditions: This combination drug is primarily prescribed for the treatment of hypertension (high blood pressure). It is used when monotherapy (treatment with a single drug) is insufficient to control blood pressure.
- Pharmacological Classification: Antihypertensive (combination of a calcium channel blocker and a thiazide diuretic).
- Mechanism of Action: This combination therapy addresses hypertension through two distinct mechanisms: S-amlodipine, a calcium channel blocker, relaxes and widens blood vessels, reducing vascular resistance. Hydrochlorothiazide, a thiazide diuretic, promotes the excretion of sodium and water by the kidneys, reducing blood volume. The combined effect lowers blood pressure.
Alternate Names
- There is no widely recognized alternate name for this specific fixed-dose combination, though it may sometimes be referred to as “S-amlodipine/hydrochlorothiazide”.
- Brand names vary depending on the manufacturer and region. Examples of brand names include Amtas-H, Amlopres-H and Amvazide.
How It Works
- Pharmacodynamics: S-amlodipine inhibits calcium influx into vascular smooth muscle and cardiac muscle, causing vasodilation and reducing cardiac workload. Hydrochlorothiazide inhibits sodium reabsorption in the distal convoluted tubule of the nephron, increasing sodium and water excretion, thereby lowering blood volume.
- Pharmacokinetics: S-amlodipine is well-absorbed orally, with peak plasma concentrations reached in 6-12 hours. It undergoes extensive hepatic metabolism, primarily by CYP3A4. Hydrochlorothiazide is also well-absorbed orally and is not extensively metabolized. It is primarily excreted unchanged by the kidneys.
- Mode of Action: S-amlodipine primarily acts by blocking L-type calcium channels in vascular smooth muscle, leading to vasodilation. Hydrochlorothiazide inhibits the sodium-chloride cotransporter in the distal convoluted tubule of the kidney, reducing sodium reabsorption and increasing water excretion.
- Elimination Pathways: S-amlodipine is extensively metabolized in the liver and its metabolites are excreted in urine and feces. Hydrochlorothiazide is mainly excreted unchanged in the urine.
Dosage
Standard Dosage
Adults:
- The initial dose is typically S-amlodipine 2.5 mg/Hydrochlorothiazide 12.5 mg once daily.
- The dosage may be increased to a maximum of S-amlodipine 5 mg/Hydrochlorothiazide 25 mg once daily, based on blood pressure response.
Children:
- The safety and effectiveness in children have not been well-established. The combination is generally not recommended for use in pediatric patients.
Special Cases:
- Elderly Patients: Initiate therapy with a low dose and titrate cautiously.
- Patients with Renal Impairment: Use with caution in patients with moderate to severe renal impairment. Dose adjustment may be necessary.
- Patients with Hepatic Dysfunction: Use with caution in patients with hepatic impairment. A lower starting dose and careful monitoring are recommended.
- Patients with Comorbid Conditions: Close monitoring is required in patients with heart failure, diabetes, or other comorbid conditions.
Clinical Use Cases
- The combination is not typically indicated for specific clinical scenarios like intubation, surgical procedures, mechanical ventilation, or emergency situations. Its primary use is in chronic hypertension management.
Dosage Adjustments
- Dose adjustments are based on individual patient response and tolerability, with consideration of renal and hepatic function.
Side Effects
Common Side Effects
- Peripheral edema (swelling of ankles and feet)
- Headache
- Dizziness
- Flushing
Rare but Serious Side Effects
- Severe hypotension (low blood pressure)
- Angioedema (swelling of face, lips, tongue, and throat)
- Hepatic dysfunction
- Electrolyte imbalances (hypokalemia, hyponatremia)
Long-Term Effects
- Electrolyte imbalances with chronic use
Adverse Drug Reactions (ADR)
- Stevens-Johnson syndrome (rare but serious skin reaction)
- Angioedema
Contraindications
- Hypersensitivity to amlodipine, hydrochlorothiazide, or sulfonamide-derived drugs.
- Anuria (inability to produce urine)
- Severe hepatic impairment
Drug Interactions
- Other antihypertensive medications (additive hypotensive effect)
- NSAIDs (may reduce antihypertensive effect and increase risk of renal impairment)
- Lithium (increased risk of lithium toxicity)
- CYP3A4 inhibitors or inducers (may alter amlodipine metabolism)
- Alcohol (may enhance hypotensive effect)
- Grapefruit juice (may increase amlodipine levels)
Pregnancy and Breastfeeding
- Pregnancy Safety Category: C (use with caution if benefits outweigh risks). ARB use during the second and third trimesters of pregnancy has been associated with fetotoxicity.
- Breastfeeding: Not recommended. Amlodipine and hydrochlorothiazide are excreted in breast milk.
Drug Profile Summary
- Mechanism of Action: S-amlodipine: Calcium channel blocker; Hydrochlorothiazide: Thiazide diuretic
- Side Effects: Peripheral edema, headache, dizziness, flushing, hypotension, angioedema, electrolyte imbalances.
- Contraindications: Hypersensitivity, anuria, severe hepatic impairment.
- Drug Interactions: Other antihypertensives, NSAIDs, lithium, CYP3A4 inhibitors/inducers, alcohol, grapefruit juice.
- Pregnancy & Breastfeeding: Use with caution during pregnancy (Category C); not recommended during breastfeeding.
- Dosage: Start with S-amlodipine 2.5 mg/Hydrochlorothiazide 12.5 mg once daily; titrate up to a maximum of 5 mg/25 mg once daily.
- Monitoring Parameters: Blood pressure, electrolytes (potassium, sodium, magnesium, calcium), renal function, hepatic function.
Popular Combinations
- Often prescribed alone as a two-drug combination. Other antihypertensives may be added if blood pressure remains uncontrolled.
Precautions
- Monitor for hypotension, electrolyte imbalances, and renal function.
- Use cautiously in patients with hepatic impairment, heart failure, or other comorbid conditions.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Hydrochlorothiazide + S-Amlodipine?
A: The initial dose is typically S-amlodipine 2.5 mg/Hydrochlorothiazide 12.5 mg once daily, with a maximum dose of S-amlodipine 5 mg/Hydrochlorothiazide 25 mg once daily.
Q2: What are the common side effects of this combination?
A: Common side effects include peripheral edema, headache, dizziness, and flushing.
Q3: Is this medication safe during pregnancy?
A: The combination should be used with caution during pregnancy, particularly during the second and third trimesters, due to potential fetal risks. Consult with a specialist.
Q4: Can this medication be used in patients with renal impairment?
A: It should be used cautiously in patients with moderate to severe renal impairment, with dose adjustments as needed.
Q5: What are the potential drug interactions with this combination?
A: It can interact with other antihypertensives, NSAIDs, lithium, CYP3A4 inhibitors/inducers, alcohol, and grapefruit juice.
Q6: What should be monitored in patients taking this medication?
A: Blood pressure, electrolytes (potassium, sodium, magnesium, calcium), renal function, and hepatic function should be monitored.
Q7: What is the mechanism of action of S-Amlodipine?
A: It acts by blocking calcium influx into vascular smooth muscle and cardiac muscle, causing vasodilation and reducing cardiac workload.
Q8: How does Hydrochlorothiazide work to lower blood pressure?
A: It inhibits sodium reabsorption in the kidneys, leading to increased excretion of sodium and water, thereby reducing blood volume and blood pressure.
Q9: Are there any dietary restrictions while taking this medication?
A: Patients should limit alcohol intake and avoid grapefruit juice, as they can interact with the medication.
Q10: Can this medication be stopped abruptly?
A: No, it should not be stopped abruptly. Dosage should be gradually tapered under the guidance of a physician.
