Usage
Hydrochlorothiazide + Valsartan is prescribed for the treatment of hypertension (high blood pressure). It is used in patients whose blood pressure is not adequately controlled by monotherapy or as initial therapy in patients likely to require multiple medications to achieve their blood pressure goals. Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions. It belongs to the pharmacological class of antihypertensives, combining a thiazide diuretic (hydrochlorothiazide) with an angiotensin II receptor blocker (ARB) (valsartan).
The mechanism of action involves two components: valsartan blocks the action of angiotensin II, a hormone that causes blood vessels to constrict, leading to vasodilation. Hydrochlorothiazide increases the excretion of sodium and water by the kidneys, further reducing blood volume and pressure.
Alternate Names
This combination is often referred to as Valsartan-Hydrochlorothiazide or Valsartan/HCTZ. Brand names under which this drug is marketed include Diovan HCT and Co-Diovan.
How It Works
Pharmacodynamics: Valsartan exerts its antihypertensive effect by selectively blocking the AT1 receptor, preventing angiotensin II from binding and causing vasoconstriction. Hydrochlorothiazide acts on the distal convoluted tubule in the kidneys, inhibiting sodium and chloride reabsorption, leading to increased water excretion and a decrease in blood volume.
Pharmacokinetics:
Valsartan is well absorbed orally but has low bioavailability (around 23%) due to extensive first-pass metabolism. It is highly bound to plasma proteins (over 90%) and is primarily metabolized in the liver, though a substantial portion is excreted unchanged in the bile. Elimination half-life is approximately 6 hours.
Hydrochlorothiazide is also well-absorbed orally with a bioavailability of around 70%. Peak plasma concentrations are reached within 2-5 hours. It is moderately bound to plasma proteins (40-70%) and is excreted primarily unchanged by the kidneys. Its elimination half-life varies, averaging 6-15 hours.
Mode of Action: At the molecular level, valsartan acts as a competitive antagonist at the AT1 receptor, preventing the downstream effects of angiotensin II, including vasoconstriction, aldosterone release, and sympathetic nervous system activation. Hydrochlorothiazide inhibits the sodium-chloride symporter in the distal convoluted tubule of the kidneys, disrupting the reabsorption process and leading to diuresis.
Elimination Pathways: Valsartan is primarily eliminated through biliary excretion, while hydrochlorothiazide is eliminated via renal excretion.
Dosage
Standard Dosage
Adults:
The usual starting dose is 160 mg valsartan/12.5 mg hydrochlorothiazide once daily. The dose can be increased after 1–2 weeks to a maximum of 320 mg valsartan/25 mg hydrochlorothiazide once daily as needed to control blood pressure.
Children:
The safety and efficacy of valsartan/hydrochlorothiazide have not been established in pediatric patients under 18 years of age, and its use in this age group is not recommended.
Special Cases:
- Elderly Patients: No specific dose adjustments are recommended, though elderly patients are generally more susceptible to side effects and may require close monitoring. Start at the low end of the dosage range, and monitor the response.
- Patients with Renal Impairment: Use with caution in patients with mild to moderate renal impairment; not recommended in those with severe renal impairment (creatinine clearance ≤ 30 mL/min).
- Patients with Hepatic Dysfunction: Use with caution in patients with mild to moderate hepatic impairment without cholestasis; contraindicated in patients with severe hepatic impairment.
- Patients with Comorbid Conditions: Caution is advised in patients with conditions like diabetes, congestive heart failure, and history of gout.
Clinical Use Cases
The specific dosages for specialized clinical use cases like intubation, surgical procedures, mechanical ventilation, ICU use, and emergency situations are not explicitly outlined in this context, as this combination is primarily prescribed for chronic hypertension management. Dosage adjustments in such situations should be made based on the patient’s overall clinical status and blood pressure control needs under the guidance of a physician.
Dosage Adjustments
Dose modifications may be needed depending on the individual patient’s response to treatment, renal function, hepatic function, and the presence of comorbid conditions.
Side Effects
Common Side Effects
Dizziness, headache, fatigue, upper respiratory tract infections, and viral infections.
Rare but Serious Side Effects
Hypotension, kidney impairment, angioedema (swelling of face, lips, tongue, or throat), liver dysfunction, electrolyte imbalances (hypokalemia, hyponatremia), and allergic reactions.
Long-Term Effects
Long-term use of hydrochlorothiazide can lead to electrolyte imbalances, particularly hypokalemia, and may contribute to increased uric acid levels, potentially worsening gout. Valsartan can impact renal function, especially in patients with pre-existing kidney disease.
Adverse Drug Reactions (ADR)
Clinically significant ADRs include angioedema, symptomatic hypotension, acute renal failure, hepatotoxicity, and severe electrolyte disturbances. These require immediate intervention.
Contraindications
Absolute contraindications: Anuria, hypersensitivity to sulfonamide-derived drugs, severe renal impairment, severe hepatic impairment, pregnancy (second and third trimesters), and concomitant use of aliskiren in patients with diabetes or moderate-to-severe renal impairment.
Relative contraindications: Volume depletion, hyponatremia, hypercalcemia, symptomatic hyperuricemia, and conditions involving enhanced potassium loss.
Drug Interactions
Hydrochlorothiazide + Valsartan interacts with various drugs including:
- Other antihypertensive medications (additive hypotensive effect)
- NSAIDs (may reduce antihypertensive efficacy and worsen renal function)
- Potassium supplements and potassium-sparing diuretics (increased risk of hyperkalemia)
- Lithium (increased lithium toxicity)
- Alcohol (may increase hypotension)
- Diabetes medications (may require dosage adjustment)
Pregnancy and Breastfeeding
This drug is contraindicated during the second and third trimesters of pregnancy due to the risk of fetal harm. Use during breastfeeding is not recommended; a decision should be made to discontinue breastfeeding or the drug, considering the importance of the drug to the mother.
Drug Profile Summary
- Mechanism of Action: Valsartan blocks AT1 receptors causing vasodilation; Hydrochlorothiazide increases urinary excretion of sodium and water.
- Side Effects: Dizziness, headache, hypotension, electrolyte imbalances, angioedema, and kidney problems.
- Contraindications: Anuria, hypersensitivity to sulfonamides, pregnancy, severe renal/hepatic impairment.
- Drug Interactions: Other antihypertensives, NSAIDs, potassium supplements, lithium, alcohol.
- Pregnancy & Breastfeeding: Contraindicated in the 2nd and 3rd trimesters of pregnancy; not recommended during breastfeeding.
- Dosage: Initial: 160/12.5 mg once daily; Max: 320/25 mg once daily.
- Monitoring Parameters: Blood pressure, renal function (BUN, creatinine), serum electrolytes (potassium, sodium, magnesium), and uric acid.
Popular Combinations
This drug is commonly used as itself, a combination of valsartan and hydrochlorothiazide, offering both ARB and diuretic effects. This is often preferred over combining separate valsartan and hydrochlorothiazide tablets due to patient adherence.
Precautions
- Monitor patients for hypotension, especially at initiation and dose increase.
- Regularly assess renal function and electrolytes, especially potassium and sodium levels.
- Monitor for signs of angioedema, such as swelling of the face, lips, or throat.
- Caution is advised in patients with renal or hepatic impairment, heart failure, or diabetes.
- Advise patients to avoid alcohol while taking this medication.
FAQs (Frequently Asked Questions)
Q1: What is the recommended starting dosage for Hydrochlorothiazide + Valsartan?
A: The recommended starting dosage for adults is typically 160 mg valsartan / 12.5 mg hydrochlorothiazide once daily.
Q2: What is the maximum dose of Hydrochlorothiazide + Valsartan?
A: The maximum dose is 320 mg valsartan / 25 mg hydrochlorothiazide once daily.
Q3: Can Hydrochlorothiazide + Valsartan be used in children?
A: No, it is not recommended for use in patients under 18 years old.
Q4: What are the most common side effects of Hydrochlorothiazide + Valsartan?
A: The most common side effects are dizziness, headache, and fatigue.
Q5: What should be done if a patient experiences angioedema while taking this medication?
A: Discontinue the medication immediately and provide appropriate medical support as angioedema can be life-threatening.
Q6: How does renal impairment affect the dosing of Hydrochlorothiazide + Valsartan?
A: Use with caution in patients with mild to moderate renal impairment. It’s not recommended for patients with severe renal impairment (creatinine clearance ≤ 30 mL/min).
Q7: Can Hydrochlorothiazide + Valsartan be used during pregnancy?
A: No, it is contraindicated during the second and third trimesters of pregnancy due to potential harm to the fetus.
Q8: Are there any interactions with NSAIDs?
A: Yes, NSAIDs can reduce the antihypertensive effect of this medication and may worsen renal function. Concurrent use should be monitored carefully.
Q9: How should hyperkalemia be managed in patients taking this combination?
A: Discontinue Hydrochlorothiazide + Valsartan and initiate measures to reduce potassium levels, such as dietary restrictions or potassium-lowering agents, as indicated by the severity of hyperkalemia. Closely monitor serum potassium levels.
