Usage
Valsartan is prescribed for:
- Hypertension (high blood pressure)
- Heart failure (NYHA class II-IV)
- Post-myocardial infarction (heart attack) to reduce cardiovascular mortality in clinically stable patients with left ventricular failure or dysfunction.
Pharmacological Classification: Angiotensin II Receptor Blocker (ARB)
Mechanism of Action: Valsartan blocks the action of angiotensin II, a hormone that causes blood vessels to constrict, leading to increased blood pressure. By blocking angiotensin II receptors, valsartan causes vasodilation (widening of blood vessels), reducing blood pressure and improving heart function.
Alternate Names
- International Nonproprietary Name (INN): Valsartan
- No significant regional variations exist.
Brand Names: Diovan is a common brand name. Other brand names may exist depending on the region.
How It Works
Pharmacodynamics: Valsartan competitively binds to the angiotensin II type 1 (AT1) receptor, inhibiting the vasoconstrictor and aldosterone-secreting effects of angiotensin II. This results in decreased peripheral resistance and reduced blood volume, leading to lowered blood pressure.
Pharmacokinetics:
- Absorption: Well absorbed orally, though bioavailability is only about 23%. Food does not significantly affect absorption.
- Metabolism: Minimally metabolized in the liver, primarily by CYP2C9.
- Elimination: Primarily eliminated unchanged in the feces (approximately 83%) and urine (approximately 13%), with a half-life of about 6 hours.
Mode of Action: Valsartan competitively blocks AT1 receptors in vascular smooth muscle and the adrenal gland, thus blocking downstream effects including vasoconstriction, aldosterone synthesis, and cell growth and proliferation.
Receptor Binding: Selective for AT1 receptors.
Enzyme Inhibition/Neurotransmitter Modulation: Valsartan’s primary mechanism is receptor blockade, not enzyme inhibition or neurotransmitter modulation.
Elimination Pathways: Primarily biliary excretion (feces), with some renal excretion (urine).
Dosage
Standard Dosage
Adults:
- Hypertension: Starting dose is 80 mg or 160 mg once daily. The dosage can be titrated up to a maximum of 320 mg daily as needed.
- Heart Failure: Starting dose is 40 mg twice daily. The dosage can be increased to 80 mg and then 160 mg twice daily at intervals of at least two weeks, as tolerated, up to a maximum of 320 mg daily in divided doses.
- Post-MI: Starting dose is 20 mg twice daily. Titration to 40 mg twice daily within 7 days and then, as tolerated, to 160 mg twice daily.
Children (6-16 years):
- Hypertension: Starting dose is 1.3 mg/kg once daily (up to 40 mg total). The dosage can be adjusted according to blood pressure response, up to a maximum of 2.7 mg/kg or 160 mg once daily.
- Use in children younger than 6 years is not recommended.
Special Cases:
- Elderly Patients: No initial dosage adjustment is generally required. However, close monitoring is recommended.
- Patients with Renal Impairment: No specific dosage adjustment is recommended for creatinine clearance (CrCl) ≥ 30 mL/min. Use with caution if CrCl is less than 30 mL/min. Not significantly removed by dialysis.
- Patients with Hepatic Dysfunction: No specific dosage adjustment is needed for mild to moderate liver impairment. For severe liver impairment, dose should not exceed 80 mg.
- Patients with Comorbid Conditions: Close monitoring and potential dosage adjustment may be necessary for patients with diabetes, other cardiovascular diseases, or electrolyte imbalances.
Clinical Use Cases
Valsartan’s use in settings like intubation, surgical procedures, mechanical ventilation, ICU use, and emergency situations is primarily focused on its role in managing hypertension and heart failure within these contexts. It is not typically given as an acute intervention for these conditions.
Dosage Adjustments
Dosage adjustments may be required based on patient response, tolerability, and renal or hepatic function. Genetic polymorphism information related to CYP2C9 may be considered, although its clinical significance for valsartan dosing is not well-established.
Side Effects
Common Side Effects:
- Dizziness
- Headache
- Fatigue
- Upper respiratory tract infection
- Diarrhea
- Abdominal pain
Rare but Serious Side Effects:
- Angioedema (swelling of face, lips, tongue, throat, or extremities)
- Hypotension (low blood pressure)
- Renal dysfunction (kidney problems)
- Hyperkalemia (high potassium levels)
- Neutropenia (low white blood cell count)
Long-Term Effects:
Long-term use may lead to renal impairment, especially in patients with pre-existing renal disease.
Adverse Drug Reactions (ADR):
Angioedema and severe hypotension require immediate medical attention. Hyperkalemia and renal dysfunction may also warrant urgent intervention.
Contraindications
- Hypersensitivity to valsartan
- Pregnancy (especially second and third trimesters)
- Co-administration with aliskiren in patients with diabetes
- Bilateral renal artery stenosis or stenosis in a solitary kidney.
Drug Interactions
- Other ARBs, ACE inhibitors, and direct renin inhibitors: Increased risk of hypotension, hyperkalemia, and renal dysfunction.
- Potassium-sparing diuretics (e.g., spironolactone, triamterene, amiloride), potassium supplements: Increased risk of hyperkalemia.
- NSAIDs: Reduced antihypertensive effect and increased risk of renal impairment.
- Lithium: Increased lithium levels.
Pregnancy and Breastfeeding
- Pregnancy Safety Category: D (contraindicated)
- Fetal Risks: Oligohydramnios, fetal renal and lung damage, neonatal hypotension and death.
- Breastfeeding: Not recommended. Valsartan is excreted in breast milk, although levels are low. Potential for hypotension in infants. Safer alternatives should be considered.
Drug Profile Summary
- Mechanism of Action: Angiotensin II receptor blocker (ARB).
- Side Effects: Dizziness, headache, fatigue, upper respiratory infection, diarrhea, abdominal pain. Rare but serious: angioedema, hypotension, renal dysfunction, hyperkalemia.
- Contraindications: Hypersensitivity, pregnancy, bilateral renal artery stenosis, co-administration with aliskiren in patients with diabetes.
- Drug Interactions: Other ARBs, ACE inhibitors, direct renin inhibitors, potassium-sparing diuretics, potassium supplements, NSAIDs, lithium.
- Pregnancy & Breastfeeding: Contraindicated in pregnancy, not recommended during breastfeeding.
- Dosage: Varies depending on indication and patient factors. See detailed dosage guidelines above.
- Monitoring Parameters: Blood pressure, renal function (serum creatinine, BUN, potassium), signs of angioedema.
Popular Combinations
- Valsartan is often combined with hydrochlorothiazide (a thiazide diuretic) for enhanced antihypertensive effects.
Precautions
- General Precautions: Assess renal function, potassium levels, and blood pressure before and during treatment. Monitor for signs and symptoms of hypotension, angioedema, and hyperkalemia.
- Specific Populations: See dosage adjustments for elderly, renal impairment, and hepatic dysfunction.
- Pregnant Women: Contraindicated.
- Breastfeeding Mothers: Not recommended.
- Children & Elderly: See dosage guidelines.
- Lifestyle Considerations: Advise patients to avoid becoming dehydrated, especially during exercise or hot weather. Alcohol consumption may enhance the hypotensive effect.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Valsartan?
A: Dosage varies depending on the indication. See detailed dosage guidelines above.
Q2: What are the most common side effects of Valsartan?
A: Dizziness, headache, and fatigue are among the most common side effects.
Q3: Can Valsartan be used during pregnancy?
A: No, valsartan is contraindicated during pregnancy, especially in the second and third trimesters.
Q4: What if a patient on Valsartan becomes pregnant?
A: Discontinue valsartan immediately and consult with a healthcare professional.
Q5: How does Valsartan affect potassium levels?
A: Valsartan can increase potassium levels (hyperkalemia), especially when used with other drugs that also increase potassium. Monitoring potassium levels is important.
Q6: Can Valsartan be used with other antihypertensive medications?
A: Yes, valsartan can be combined with other antihypertensive agents. However, careful monitoring for hypotension is required, and dosage adjustments may be necessary.
Q7: What are the signs and symptoms of angioedema?
A: Angioedema is characterized by swelling of the face, lips, tongue, throat, or extremities. It can cause difficulty breathing and requires immediate medical attention.
Q8: What should be done if a patient experiences significant hypotension while on Valsartan?
A: The patient should lie down and elevate their legs. The healthcare professional should be notified immediately, and supportive measures may be necessary.
Q9: Are there any dietary restrictions while taking Valsartan?
A: Salt substitutes containing potassium should be avoided, especially in patients also taking potassium-sparing diuretics.
Q10: How should Valsartan be taken?
A: Valsartan tablets can be taken with or without food, preferably at the same time each day. Liquid formulations should be measured accurately using the provided syringe or spoon.
