Valsartan

The dosage of Valsartan is highly individualized based on the condition being treated and the patient's response to the medication. Healthcare providers typically start with a lower dose and titrate upward.

• Hypertension: The usual starting dose is 80 mg or 160 mg once daily. If blood pressure is not adequately controlled, the dose may be increased to a maximum of 320 mg once daily. The full blood pressure-lowering effect is usually attained within 2 to 4 weeks.
• Heart Failure: The recommended starting dose is 40 mg twice daily. The dose is typically titrated to 80 mg and then to 160 mg twice daily, as tolerated by the patient. The goal is to reach the highest dose tolerated by the patient to maximize cardiovascular benefits.
• Post-Myocardial Infarction: Treatment may be initiated as early as 12 hours after a heart attack. The starting dose is usually 20 mg twice daily. Providers may double the dose within 7 days to 40 mg twice daily, with a target maintenance dose of 160 mg twice daily as tolerated.

Valsartan is approved for the treatment of hypertension in children aged 6 to 16 years.

• Dosing by Weight: For children who can swallow tablets, the starting dose is usually 1.3 mg/kg once daily (up to 40 mg total). The dose is adjusted based on blood pressure response, up to a maximum of 2.7 mg/kg (up to 160 mg total) once daily.
• Pediatric Use Limitation: Valsartan has not been studied and is not recommended for children under the age of 1 year due to potential risks to developing kidneys.

Renal Impairment

No initial dosage adjustment is required for patients with mild to moderate renal impairment. However, in patients with severe renal impairment (Creatinine Clearance < 10 mL/min), Valsartan should be used with extreme caution as there is limited clinical data. Use in patients on dialysis is generally not recommended unless deemed necessary by a specialist.

Hepatic Impairment

No initial dosage adjustment is typically required for patients with mild to moderate liver disease. However, since Valsartan is primarily eliminated through the bile, patients with obstructive biliary disorders or severe hepatic impairment should use the drug with caution and may require lower doses.

Elderly Patients

While no specific starting dose adjustment is required for the elderly, healthcare providers often monitor older adults more closely for symptoms of hypotension (low blood pressure) or changes in kidney function, especially if they are also taking diuretics.

Valsartan should be taken exactly as prescribed by your healthcare provider.

• Consistency: It can be taken with or without food, but it should be taken the same way each day to maintain consistent blood levels.
• Administration: Tablets should be swallowed whole with a glass of water. If using the oral solution, use a calibrated measuring device rather than a household spoon to ensure accurate dosing.
• Timing: For hypertension, taking the dose at the same time each day (e.g., every morning) helps maintain blood pressure control. For heart failure or post-MI, doses are usually split into morning and evening administrations.
• Storage: Store at room temperature (20°C to 25°C or 68°F to 77°F) in a dry place away from moisture and heat.

If you miss a dose, take it as soon as you remember. However, if it is almost time for your next scheduled dose, skip the missed dose and resume your regular dosing schedule. Do not take two doses at once to make up for a missed one, as this increases the risk of severe low blood pressure.

An overdose of Valsartan can lead to severe hypotension (extremely low blood pressure), which may cause dizziness, fainting, or a rapid or slow heart rate (tachycardia or bradycardia). In severe cases, circulatory collapse or shock can occur. If an overdose is suspected, contact emergency medical services or a poison control center immediately. Treatment usually involves supportive care, such as intravenous fluids to raise blood pressure.

> Important: Follow your healthcare provider's dosing instructions precisely. Do not adjust your dose or stop taking the medication without medical guidance, as stopping suddenly can cause a rapid increase in blood pressure.

While many people tolerate Valsartan well, some may experience side effects as their body adjusts to the medication. The most common side effects reported in clinical trials include:

• Dizziness: This is the most frequent complaint, often occurring when moving from a sitting or lying position to standing (orthostatic hypotension). It typically feels like a brief lightheadedness.
• Fatigue: A general feeling of tiredness or low energy.
• Headache: Mild to moderate head pain that usually diminishes over time.
• Increased Blood Potassium (Hyperkalemia): This is often asymptomatic but is detected through blood tests. It is more common in patients with heart failure or kidney disease.

• Cough: While much less common than with ACE inhibitors, some patients still develop a dry, persistent cough.
• Abdominal Pain: Discomfort or cramping in the stomach area.
• Diarrhea: Loose or frequent stools.
• Back Pain: General muscle aches in the lower or upper back.
• Viral Infections: Such as the common cold or flu-like symptoms.

• Angioedema: Swelling of the deeper layers of the skin, often around the face, lips, tongue, or throat. This is a medical emergency.
• Rhabdomyolysis: A rare condition where muscle tissue breaks down, releasing a damaging protein into the blood. Symptoms include unexplained muscle pain, tenderness, or weakness, and dark-colored urine.
• Impaired Renal Function: In susceptible individuals, Valsartan can cause a decline in kidney function, especially if the patient is dehydrated or taking other medications that affect the kidneys.

> Warning: Stop taking Valsartan and call your doctor immediately if you experience any of the following:

• Signs of an Allergic Reaction: Hives, difficulty breathing, or swelling of your face, lips, tongue, or throat.
• Fainting or Severe Lightheadedness: This may indicate that your blood pressure has dropped too low.
• Signs of High Potassium: Nausea, weakness, tingly feeling, chest pain, irregular heartbeats, or loss of movement.
• Kidney Problems: Little or no urination, painful or difficult urination, swelling in your feet or ankles, or feeling tired or short of breath.
• Liver Problems: Loss of appetite, stomach pain (upper right side), tiredness, itching, dark urine, or jaundice (yellowing of the skin or eyes).

Long-term use of Valsartan is generally considered safe and is often necessary for the chronic management of hypertension and heart failure. However, prolonged use requires regular monitoring of kidney function and electrolyte levels (especially potassium). In some patients, long-term use may lead to a gradual increase in serum creatinine levels, signifying changes in renal filtration. There is no evidence to suggest that Valsartan causes cumulative toxicity or dependency over several years of use.

Fetal Toxicity: Valsartan carries a prominent FDA Black Box Warning regarding its use during pregnancy. Drugs that act directly on the renin-angiotensin system can cause injury and even death to the developing fetus. When pregnancy is detected, Valsartan should be discontinued as soon as possible. Exposure to ARBs during the second and third trimesters has been associated with fetal lung hypoplasia (underdeveloped lungs), skeletal deformations, and neonatal skull hypoplasia. It can also lead to oligohydramnios (decreased amniotic fluid), which is a sign of decreased fetal renal function.

Report any unusual symptoms to your healthcare provider immediately. Side effects can often be managed by adjusting the dose or switching to a different medication within the same class.

Valsartan is a potent medication that requires careful medical supervision. Patients must be aware that while the drug effectively manages high blood pressure and heart failure, it does not cure these conditions. Treatment is typically lifelong. Patients should not stop taking Valsartan even if they feel well, as high blood pressure often has no noticeable symptoms. It is also vital to stay hydrated, as excessive sweating, vomiting, or diarrhea can lead to a significant drop in blood pressure, potentially causing fainting or kidney issues.

WARNING: FETAL TOXICITY

• When pregnancy is detected, discontinue Valsartan as soon as possible.
• Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus.
• Use of these drugs during the second and third trimesters of pregnancy reduces fetal renal function and increases fetal and neonatal morbidity and death.
• Potential neonatal adverse effects include skull hypoplasia, anuria, hypotension, renal failure, and death.

• Anaphylaxis and Angioedema: Patients with a history of angioedema (swelling of the face, lips, or throat) while taking other medications (especially ACE inhibitors like Lisinopril) should use Valsartan with extreme caution. If swelling occurs, the drug must be stopped immediately and emergency care sought.
• Hypotension (Low Blood Pressure): Patients who are volume- or salt-depleted (e.g., those on high-dose diuretics) may experience excessive hypotension. Blood pressure should be monitored closely during the initiation of therapy.
• Impaired Renal Function: Valsartan can cause changes in kidney function, including acute renal failure, particularly in patients with pre-existing kidney disease or those with renal artery stenosis (narrowing of the arteries to the kidneys).
• Hyperkalemia: Because Valsartan can increase potassium levels, patients should avoid using potassium supplements or salt substitutes containing potassium without consulting their doctor.

To ensure the safe use of Valsartan, healthcare providers will require regular laboratory tests:

• Blood Pressure: Frequent monitoring, especially when starting or changing doses, to ensure the target range is met without causing hypotension.
• Serum Potassium: Periodic checks to ensure potassium levels do not become dangerously high (hyperkalemia).
• Serum Creatinine and BUN: Tests to monitor kidney function, particularly in patients with known renal impairment or heart failure.

Valsartan may cause dizziness or lightheadedness, especially during the first few days of treatment or after a dose increase. Patients should observe how they react to the medication before driving, operating heavy machinery, or performing tasks that require alertness.

Alcohol can enhance the blood pressure-lowering effect of Valsartan, which may lead to increased dizziness, lightheadedness, or fainting. It is generally advised to limit alcohol consumption while taking this medication.

Do not stop taking Valsartan abruptly. While it does not typically cause a "withdrawal syndrome" in the traditional sense, stopping the medication can lead to a rapid rebound in blood pressure, which increases the risk of heart attack or stroke. If discontinuation is necessary, your doctor will provide a tapering schedule.

> Important: Discuss all your medical conditions, including any history of liver disease, kidney disease, or heart valve problems, with your healthcare provider before starting Valsartan.

• Aliskiren: The use of Valsartan in combination with Aliskiren (a direct renin inhibitor) is strictly contraindicated in patients with diabetes mellitus. This combination significantly increases the risk of renal impairment, hyperkalemia, and hypotension. In patients with moderate to severe renal impairment (GFR < 60 mL/min), this combination should also be avoided.

• Lithium: Valsartan can increase the blood levels of lithium, a medication used for bipolar disorder. This can lead to lithium toxicity, characterized by tremors, confusion, and seizures. If used together, lithium levels must be monitored very frequently.
• Potassium-Sparing Diuretics: Medications such as Spironolactone, Triamterene, or Amiloride can cause additive increases in blood potassium levels. Using these with Valsartan requires frequent electrolyte monitoring to prevent life-threatening hyperkalemia.
• ACE Inhibitors: Combining Valsartan with an ACE inhibitor (like Enalapril or Ramipril) is generally not recommended as it increases the risk of side effects (hypotension, hyperkalemia, and kidney failure) without providing significant additional benefit for most patients.

• Non-Steroidal Anti-Inflammatory Drugs (NSAIDs): Drugs like Ibuprofen, Naproxen, and Celecoxib can reduce the antihypertensive effect of Valsartan. More importantly, in patients who are elderly, volume-depleted, or have compromised kidney function, the combination can lead to a further deterioration of renal function, including possible acute renal failure.
• Other Antihypertensives: Taking Valsartan with other blood pressure medications (calcium channel blockers, beta-blockers) will have an additive effect. While often intended, it requires careful monitoring to prevent blood pressure from dropping too low.

• Potassium-Rich Foods: While a healthy diet is encouraged, patients on Valsartan should avoid excessive consumption of high-potassium foods (like bananas, spinach, and potatoes) or salt substitutes that use potassium chloride instead of sodium chloride, as this can lead to hyperkalemia.
• Grapefruit: Unlike some other heart medications, Valsartan does not have a significant interaction with grapefruit juice.
• High-Fat Meals: As noted in the pharmacokinetics section, food can reduce the absorption rate of Valsartan, but this is usually not clinically significant. It is best to be consistent—either always take it with food or always without.

• St. John's Wort: May potentially reduce the effectiveness of Valsartan by inducing certain metabolic pathways, though the clinical impact is usually minimal.
• Natural Licorice: Can cause the body to retain salt and water, which counteracts the blood pressure-lowering effects of Valsartan.
• Hawthorn: This herb may have mild blood pressure-lowering properties and could theoretically increase the effects of Valsartan, leading to hypotension.

Valsartan does not typically interfere with common laboratory tests, but it will directly affect results for:

• Plasma Renin Activity: Levels may increase as a compensatory mechanism for AT1 receptor blockade.
• Serum Potassium and Creatinine: These levels may be elevated due to the drug's pharmacological action.

For each major interaction, the management strategy usually involves dose adjustment, more frequent monitoring of lab values, or selecting an alternative medication.

> Important: Tell your doctor about ALL medications, supplements, and herbal products you are taking, including over-the-counter pain relievers and cold medicines.

Valsartan must NEVER be used in the following circumstances:

• Pregnancy: Due to the high risk of fetal injury and death (Black Box Warning), Valsartan is strictly contraindicated during the second and third trimesters and should be avoided in the first trimester if possible.
• Hypersensitivity: Patients with a known allergy to Valsartan or any of the inactive ingredients in the tablet (such as lactose, magnesium stearate, or microcrystalline cellulose) must not take the drug. Symptoms of hypersensitivity include rash, itching, and anaphylaxis.
• Concomitant Aliskiren in Diabetes: Using Valsartan with Aliskiren in patients who have diabetes is prohibited due to the severe risk of kidney failure and hyperkalemia.

In these conditions, the risks and benefits must be carefully weighed by a healthcare professional:

• Bilateral Renal Artery Stenosis: In patients with narrowing of the arteries to both kidneys, Valsartan can cause a rapid decline in renal function and acute kidney failure because these patients rely on the renin-angiotensin system to maintain glomerular filtration.
• Severe Hepatic Impairment: Since the liver and biliary system are the primary routes of elimination for Valsartan, patients with severe liver disease or biliary obstruction may experience dangerously high levels of the drug.
• Severe Congestive Heart Failure: While Valsartan is used to treat heart failure, in very severe cases where renal function depends on the RAAS, ARBs can cause oliguria (low urine output) or progressive azotemia (high nitrogen levels in the blood).
• Volume Depletion: Patients who are severely dehydrated or have low salt levels should have their condition corrected before starting Valsartan to prevent severe hypotension.

While Valsartan is chemically distinct from ACE inhibitors, patients who have experienced angioedema while taking an ACE inhibitor (like Lisinopril or Benazepril) may have a slightly higher risk of experiencing the same reaction with Valsartan. This is not a strict contraindication, but it requires extreme vigilance during the start of therapy.

> Important: Your healthcare provider will evaluate your complete medical history, including any history of kidney or liver issues, before prescribing Valsartan.

Valsartan is classified as Pregnancy Category D. It is known to be teratogenic (causes birth defects) in humans. Exposure to drugs that act on the renin-angiotensin system during the second and third trimesters can cause injury and death to the developing fetus. Specific risks include neonatal skull hypoplasia, anuria (failure of kidneys to produce urine), reversible or irreversible renal failure, and death. If a patient becomes pregnant while taking Valsartan, the medication must be stopped immediately, and an alternative treatment for blood pressure should be established under the guidance of an obstetrician and cardiologist.

It is not known whether Valsartan is excreted in human breast milk. However, animal studies have shown that Valsartan is present in the milk of lactating rats. Because of the potential for serious adverse reactions in the nursing infant (such as effects on kidney development), a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.

Valsartan is approved for hypertension in children aged 6 to 16. The safety and effectiveness in children younger than 6 years old have not been established. Furthermore, Valsartan is contraindicated in infants under 1 year of age because of the critical role the renin-angiotensin system plays in organ development, particularly the kidneys, during the first year of life.

Clinical studies did not identify overall differences in the safety or effectiveness of Valsartan between elderly patients (65 and older) and younger patients. However, older adults are more likely to have decreased renal or hepatic function and are more susceptible to hypotension. Therefore, healthcare providers may start with lower doses and monitor blood pressure and kidney function more frequently in this population.

For patients with mild to moderate renal impairment, no initial dose adjustment is needed. However, in patients with severe renal impairment (Creatinine Clearance < 10 mL/min) or those on dialysis, Valsartan should be used with caution. The drug is not removed by hemodialysis because it is highly bound to plasma proteins.

In patients with mild to moderate chronic liver disease, the exposure (AUC) to Valsartan is approximately twice that of healthy volunteers. While no specific starting dose adjustment is mandated, providers should use the lowest effective dose and monitor the patient closely. Valsartan should be avoided or used with extreme caution in patients with severe hepatic impairment or biliary cirrhosis.

> Important: Special populations require individualized medical assessment to ensure the benefits of Valsartan therapy outweigh the potential risks.

Valsartan is a potent and highly selective antagonist of the Angiotensin II Type 1 (AT1) receptor. Angiotensin II is the primary vasoactive hormone of the renin-angiotensin-aldosterone system (RAAS). It binds to two main receptors: AT1 and AT2. The AT1 receptor mediates the well-known cardiovascular effects of Angiotensin II, including vasoconstriction, aldosterone synthesis and release, cardiac stimulation, and renal reabsorption of sodium.

By selectively blocking the AT1 receptor, Valsartan inhibits these effects, leading to vasodilation and reduced blood pressure. Unlike ACE inhibitors, Valsartan does not inhibit the enzyme that breaks down bradykinin. Therefore, it does not lead to the accumulation of bradykinin, which is thought to be the primary cause of the persistent dry cough and angioedema associated with ACE inhibitor therapy. Furthermore, by blocking the AT1 receptor, Valsartan causes a feedback increase in Angiotensin II levels; this excess Angiotensin II can then stimulate the AT2 receptors, which are believed to have counter-regulatory effects like vasodilation and anti-proliferation.

• Onset of Action: The antihypertensive effect usually begins within 2 hours of oral administration.
• Peak Effect: The maximum reduction in blood pressure is typically reached 4 to 6 hours after a dose.
• Duration: The effects last for at least 24 hours, supporting once-daily dosing for hypertension.
• Tolerance: There is no evidence of tachyphylaxis (rapidly diminishing response) or rebound hypertension after sudden withdrawal of the drug.

| Parameter | Value |

|---|---|

| Bioavailability | ~25% (Oral) |

| Protein Binding | 95% (Mainly Albumin) |

| Half-life | 6 to 9 hours |

| Tmax | 2 to 4 hours |

| Metabolism | Minimal (~20%), inactive metabolites |

| Excretion | Fecal 83%, Renal 13% |

• Molecular Formula: C24H29N5O3
• Molecular Weight: 435.5 g/mol
• Solubility: Soluble in ethanol and methanol; slightly soluble in water.
• Structure: Valsartan is a tetrazole derivative and a non-peptide molecule. Its structure allows it to mimic the C-terminal end of Angiotensin II, enabling competitive inhibition at the receptor site.

Valsartan is classified as an Angiotensin II Receptor Blocker (ARB). Other drugs in this class include Losartan, Candesartan, and Olmesartan. Within the broader therapeutic area of cardiovascular medicine, it is considered a first-line agent for hypertension management and a core component of Guideline-Directed Medical Therapy (GDMT) for heart failure.