Usage
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Amlodipine + Hydrochlorothiazide is prescribed for the treatment of hypertension (high blood pressure). It can be used as initial therapy in patients who likely require multiple drugs to achieve blood pressure goals. The combination may also be appropriate as replacement therapy for patients already receiving amlodipine and hydrochlorothiazide from separate tablets using the same doses.
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Pharmacological Classification:
- Amlodipine: Calcium Channel Blocker (Dihydropyridine type)
- Hydrochlorothiazide: Thiazide Diuretic
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Mechanism of Action: This combination therapy utilizes two distinct mechanisms to control blood pressure. Amlodipine blocks calcium influx into vascular smooth muscle, leading to vasodilation. Hydrochlorothiazide promotes diuresis by inhibiting sodium reabsorption in the distal convoluted tubule of the nephron, thereby reducing blood volume.
Alternate Names
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There is no single international nonproprietary name (INN) for this combination. It is usually referred to as amlodipine/hydrochlorothiazide.
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Brand Names: Numerous brand names exist worldwide. Some common brand names include Caduet, Exforge HCT, Amturnide.
How It Works
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Pharmacodynamics: Amlodipine causes peripheral vasodilation, reducing systemic vascular resistance and blood pressure. Hydrochlorothiazide reduces blood volume by increasing the excretion of sodium, chloride, and water. The combination has a synergistic effect on lowering blood pressure.
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Pharmacokinetics:
- Absorption: Amlodipine is well absorbed orally, reaching peak plasma concentration in 6-12 hours. Hydrochlorothiazide is also well absorbed orally.
- Metabolism: Amlodipine is extensively metabolized by the liver via CYP3A4. Hydrochlorothiazide is not extensively metabolized.
- Elimination: Amlodipine metabolites are primarily excreted in the urine and feces. Hydrochlorothiazide is primarily excreted unchanged in the urine.
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Mode of Action: Amlodipine binds to L-type calcium channels in vascular smooth muscle, inhibiting calcium influx and promoting vasodilation. Hydrochlorothiazide inhibits the sodium-chloride symporter in the distal convoluted tubule, impairing sodium reabsorption and promoting natriuresis and diuresis.
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Receptor Binding/Enzyme Inhibition/Neurotransmitter Modulation: Amlodipine: L-type calcium channel blocker. Hydrochlorothiazide: Sodium-chloride symporter inhibitor.
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Elimination Pathways: Amlodipine: Hepatic metabolism (CYP3A4), renal and fecal excretion. Hydrochlorothiazide: Primarily renal excretion.
Dosage
Standard Dosage
Adults:
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Initial dose: Amlodipine 2.5 mg/Hydrochlorothiazide 12.5 mg or Amlodipine 5 mg/Hydrochlorothiazide 12.5 mg orally once daily.
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Maintenance dose: Titrate upward according to blood pressure response, usually within 7-14 days. Maximum dose is Amlodipine 10 mg/Hydrochlorothiazide 25 mg once daily.
Children:
- Not typically recommended for pediatric patients. Safety and efficacy have not been well established.
Special Cases:
- Elderly Patients: Initiate at lower amlodipine doses (2.5 mg) and titrate cautiously as they might be more sensitive to blood pressure changes.
- Patients with Renal Impairment: Dose adjustments may be required in patients with creatinine clearance less than 30 mL/min. Hydrochlorothiazide is ineffective in patients with severe renal impairment.
- Patients with Hepatic Dysfunction: Start with a lower amlodipine dose (2.5 mg) and titrate slowly. Closely monitor liver function tests.
- Patients with Comorbid Conditions: Careful consideration should be given to patients with heart failure or coronary artery disease.
Clinical Use Cases
- This medication is primarily indicated for chronic hypertension management and is not typically used in acute clinical settings like intubation, surgical procedures, mechanical ventilation, or emergency situations.
Dosage Adjustments
- Based on blood pressure response and tolerability, the dose can be titrated upward after 7–14 days.
- In patients with hepatic impairment, a lower initial dose of amlodipine is recommended.
Side Effects
Common Side Effects:
- Peripheral edema (swelling of ankles and feet), dizziness, headache, flushing, fatigue.
Rare but Serious Side Effects:
- Hypotension (low blood pressure), angioedema (swelling of face, lips, tongue), hepatic dysfunction, severe electrolyte imbalances (hypokalemia).
Long-Term Effects:
- Electrolyte disturbances, particularly hypokalemia.
Adverse Drug Reactions (ADR):
- Angioedema, severe hypotension, hepatotoxicity.
Contraindications
- Hypersensitivity to amlodipine, hydrochlorothiazide, other sulfonamide-derived drugs, or other dihydropyridines.
- Anuria (absence of urine formation).
- Pregnancy (second and third trimesters).
- Severe hepatic impairment or biliary obstructive disorders.
Drug Interactions
- Amlodipine: CYP3A4 inhibitors (e.g., azole antifungals, some macrolide antibiotics) may increase amlodipine concentrations. CYP3A4 inducers (e.g., rifampin) may decrease amlodipine concentrations.
- Hydrochlorothiazide: May interact with other antihypertensives, lithium, digoxin, corticosteroids, NSAIDs.
- Alcohol can potentiate the hypotensive effects of both drugs.
Pregnancy and Breastfeeding
- Pregnancy Category: D (second and third trimesters). Contraindicated due to risk of fetal harm.
- Breastfeeding: Amlodipine and hydrochlorothiazide are excreted in breast milk. Not recommended during breastfeeding due to potential for adverse effects in infants. Choose alternative antihypertensives.
Drug Profile Summary
- Mechanism of Action: Amlodipine: Calcium channel blockade; Hydrochlorothiazide: Thiazide diuretic.
- Side Effects: Peripheral edema, dizziness, headache, flushing, hypotension.
- Contraindications: Hypersensitivity, anuria, pregnancy, severe hepatic impairment.
- Drug Interactions: CYP3A4 inhibitors/inducers (amlodipine), other antihypertensives, lithium, digoxin.
- Pregnancy & Breastfeeding: Contraindicated in pregnancy (2nd/3rd trimesters), not recommended during breastfeeding.
- Dosage: Adults: Start 2.5/12.5 mg or 5/12.5 mg once daily, titrate to max 10/25 mg.
- Monitoring Parameters: Blood pressure, heart rate, electrolytes (potassium, sodium, magnesium), renal function, liver function tests.
Popular Combinations
- This combination itself is commonly used. Other antihypertensives may be added, such as ACE inhibitors, ARBs, or beta-blockers if blood pressure control is not achieved with amlodipine/hydrochlorothiazide alone.
Precautions
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Amlodipine + Hydrochlorothiazide?
A: Initial dose: 2.5/12.5 mg or 5/12.5 mg orally once daily; Maximum dose: 10/25 mg once daily
Q2: What are the common side effects?
A: Peripheral edema, dizziness, headache, flushing, and fatigue.
Q3: Is it safe to use during pregnancy?
A: Contraindicated during the second and third trimesters of pregnancy due to potential for fetal harm.
Q4: Can it be used in patients with renal impairment?
A: Use cautiously. Adjust dose based on creatinine clearance. Avoid in severe renal failure or anuria.
Q5: What are the significant drug interactions?
A: CYP3A4 inhibitors/inducers, other antihypertensives, lithium, digoxin, NSAIDs, alcohol.
Q6: What monitoring is necessary during treatment?
A: Blood pressure, electrolytes, renal function, liver function.
Q7: Can this medication be crushed or chewed?
A: Swallow tablets whole. Do not crush or chew.
Q8: What if a dose is missed?
A: Take the missed dose as soon as remembered, unless it is almost time for the next dose. Do not double the dose.
Q9: What is the mechanism of the hypotensive effect?
A: Amlodipine causes vasodilation, reducing peripheral vascular resistance. Hydrochlorothiazide promotes diuresis, reducing blood volume. The combination produces a synergistic blood pressure lowering effect.
Q10: How should the drug be stored?
A: Store at room temperature away from moisture, heat, and light.
