Usage
- Amlodipine + Valsartan is prescribed for the treatment of hypertension (high blood pressure). It is used when monotherapy with either drug alone is insufficient to control blood pressure. It may be used as initial therapy in some cases.
- Pharmacological Classification: Antihypertensive; Combination drug containing a calcium channel blocker (Amlodipine) and an angiotensin II receptor blocker (ARB) (Valsartan).
- Mechanism of Action: Amlodipine blocks calcium influx into vascular smooth muscle cells, leading to vasodilation. Valsartan blocks the angiotensin II receptor, preventing vasoconstriction and reducing aldosterone secretion. The combination of these mechanisms results in synergistic blood pressure lowering.
Alternate Names
- International variations may exist.
- Brand Name(s): Exforge is a common brand name. Other brand names are possible depending on the region.
How It Works
- Pharmacodynamics: Amlodipine and valsartan both work to lower blood pressure through different but complementary mechanisms. Amlodipine, a dihydropyridine calcium channel blocker, primarily affects the peripheral arterioles causing vasodilation and reducing peripheral resistance. Valsartan, an ARB, blocks the effects of angiotensin II, preventing vasoconstriction, reducing aldosterone secretion (reducing sodium and water retention), and decreasing sympathetic nervous system activity.
- Pharmacokinetics: Amlodipine is well absorbed orally and undergoes extensive hepatic metabolism via CYP3A4. It has a long half-life, allowing for once-daily dosing. Valsartan is also well absorbed orally but has lower bioavailability. It undergoes minimal metabolism and is primarily excreted unchanged in the feces, with a smaller portion eliminated renally. The pharmacokinetics of the combined formulation are similar to individual administration of the drugs.
- Mode of Action: Amlodipine acts on L-type calcium channels in vascular smooth muscle, inhibiting calcium influx and thus muscle contraction, leading to vasodilation. Valsartan competitively binds to the AT1 receptor, blocking angiotensin II from binding and initiating its downstream effects. The drugs have no direct effect on heart rate.
- Elimination Pathways: Amlodipine is primarily eliminated via hepatic metabolism (CYP3A4), with metabolites excreted in urine and feces. Valsartan is primarily excreted unchanged in feces and to a lesser extent in urine.
Dosage
Standard Dosage
Adults:
- Initial therapy: Amlodipine 5 mg + Valsartan 160 mg orally once daily.
- Add-on/Replacement therapy: Amlodipine 5 mg to 10 mg + Valsartan 160 mg to 320 mg orally once daily.
- The dose may be increased after 1 to 2 weeks as needed to control blood pressure, up to a maximum of Amlodipine 10 mg + Valsartan 320 mg once daily.
Children:
- Safety and efficacy not established in children.
Special Cases:
- Elderly Patients: Start with a low dose and titrate cautiously. Close blood pressure monitoring recommended.
- Patients with Renal Impairment: Monitor creatinine and potassium levels. Dose adjustment may be needed in moderate to severe impairment. Use with caution in patients with severe impairment. Contraindicated in patients with anuria or on dialysis.
- Patients with Hepatic Dysfunction: Use with caution. Reduced doses may be necessary. Contraindicated in severe hepatic impairment.
- Patients with Comorbid Conditions: Use with caution in heart failure, particularly after myocardial infarction. Closely monitor patients with diabetes, hyperkalemia, or other conditions.
Clinical Use Cases
- This medication is specifically indicated for hypertension. It is not typically used in emergency or acute situations, intubation, surgical procedures, mechanical ventilation or ICU settings, which require rapidly acting medications.
Dosage Adjustments
- Adjust based on blood pressure response and tolerability. Renal or hepatic dysfunction may necessitate dose reductions.
Side Effects
Common Side Effects
- Peripheral edema (swelling of ankles and feet)
- Dizziness, lightheadedness
- Headache
- Flushing
- Upper respiratory infections
- Fatigue
Rare but Serious Side Effects
- Hypotension (low blood pressure)
- Angioedema (swelling of face, lips, tongue, throat)
- Syncope
- Worsening angina or myocardial infarction
- Hyperkalemia (high potassium)
- Renal impairment
Long-Term Effects
- Renal function decline with prolonged use should be monitored.
Adverse Drug Reactions (ADR)
- Angioedema requires immediate medical attention.
Contraindications
- Hypersensitivity to amlodipine, valsartan, or any component of the formulation
- Pregnancy (especially second and third trimesters)
- Anuria
- Severe hepatic impairment
- Severe renal impairment (including patients on dialysis)
- Concomitant use of aliskiren in patients with diabetes
- Hypersensitivity to sulfonamide-derived drugs (due to hydrochlorothiazide component in combination products)
Drug Interactions
- Other antihypertensives (additive effects)
- Potassium-sparing diuretics or potassium supplements (increased risk of hyperkalemia)
- Lithium (increased lithium levels)
- Nonsteroidal anti-inflammatory drugs (NSAIDs) (reduced antihypertensive effect and increased risk of renal impairment)
- CYP3A4 inhibitors or inducers (may affect amlodipine levels)
- Alcohol (may increase risk of hypotension)
- Grapefruit juice (may affect amlodipine metabolism)
Pregnancy and Breastfeeding
- Pregnancy Safety Category: D (contraindicated). Causes fetal harm if administered during pregnancy, especially in the second and third trimesters. If pregnancy is detected, discontinue immediately.
- Breastfeeding: Not recommended. Amlodipine and valsartan are present in human breast milk and may affect infants. Discontinue breastfeeding or the drug, taking into account the importance of the drug to the mother.
Drug Profile Summary
- Mechanism of Action: Amlodipine: Calcium channel blocker, Valsartan: Angiotensin II receptor blocker.
- Side Effects: Edema, dizziness, headache, flushing, upper respiratory infections. Serious: hypotension, angioedema, hyperkalemia.
- Contraindications: Hypersensitivity, pregnancy, severe hepatic/renal impairment, concomitant use of aliskiren in patients with diabetes.
- Drug Interactions: Other antihypertensives, potassium supplements, lithium, NSAIDs, CYP3A4 inhibitors/inducers, alcohol.
- Pregnancy & Breastfeeding: Contraindicated in pregnancy. Not recommended during breastfeeding.
- Dosage: Start with 5/160 mg once daily, titrate up to 10/320 mg as needed.
- Monitoring Parameters: Blood pressure, renal function, electrolytes (especially potassium).
Popular Combinations
- Amlodipine + Valsartan is itself a popular combination. In some cases a thiazide diuretic, hydrochlorothiazide, can be added to create a triple combination for patients whose blood pressure is not controlled by two drugs.
Precautions
- General Precautions: Monitor blood pressure, renal function, and electrolytes. Assess for history of hypersensitivity or other contraindications.
- Specific Populations: Use with caution in elderly patients and those with hepatic or renal impairment. Contraindicated in pregnancy. Use during breastfeeding not recommended.
- Lifestyle Considerations: Limit alcohol intake. Advise patients about potential for dizziness and to avoid hazardous activities until effects are known. Counsel patients about the importance of adherence.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Amlodipine + Valsartan?
A: Initial dose: Amlodipine 5 mg + Valsartan 160 mg once daily. Titrate up to a maximum of 10 mg/320 mg as needed based on blood pressure response.
Q2: Can Amlodipine + Valsartan be used in patients with renal impairment?
A: Use cautiously, monitoring renal function and electrolytes. Avoid use in severe impairment or in patients on dialysis.
Q3: Is it safe to use this combination during pregnancy?
A: No, absolutely contraindicated. It can cause serious fetal harm.
Q4: What are the most common side effects?
A: Peripheral edema, dizziness, headache, flushing.
Q5: Are there any serious drug interactions to be aware of?
A: Yes, with other antihypertensives, potassium supplements, lithium, and NSAIDs, among others.
Q6: How does this combination work to lower blood pressure?
A: Amlodipine blocks calcium channels causing vasodilation, and valsartan blocks angiotensin II receptors preventing vasoconstriction and reducing aldosterone.
Q7: Can this medication be used in patients with liver disease?
A: Use cautiously in mild to moderate hepatic dysfunction with potential dose reduction. Contraindicated in severe liver impairment.
Q8: What should I do if my patient experiences angioedema?
A: Discontinue the medication immediately and provide appropriate medical care. Angioedema can be life-threatening.
Q9: What if the initial dose isn’t effective?
A: The dose can be increased after 1-2 weeks if blood pressure remains uncontrolled, up to the maximum dose.
Q10: Can Amlodipine + Valsartan be crushed or chewed?
A: Swallow tablets whole. Do not crush or chew.
