What You Should Know About Tolvaptan Side Effects

If you've been prescribed Tolvaptan — sold as Samsca for hyponatremia or Jynarque for autosomal dominant polycystic kidney disease (ADPKD) — understanding the side effects is an important part of managing your treatment. Some side effects are common and manageable, while others are serious and require immediate medical attention. Here's what to expect.

What Is Tolvaptan?

Tolvaptan is a vasopressin V2-receptor antagonist made by Otsuka Pharmaceutical. It works by blocking a hormone called vasopressin, which causes your kidneys to hold onto water. By blocking this signal, Tolvaptan helps your body excrete excess water. For a full overview of the medication, see our guide on what Tolvaptan is and how it's used.

Common Side Effects

These side effects are experienced by many patients taking Tolvaptan. They're usually manageable and may improve over time:

• Thirst and dry mouth — This is the most common side effect, especially with Jynarque. Because the drug causes your body to excrete more water, you'll feel thirstier than usual. Drinking plenty of water throughout the day is essential.
• Polyuria (increased urine output) — You'll urinate more frequently and produce larger volumes. This is a direct result of how the drug works.
• Nocturia — Waking up at night to urinate is very common. Many patients take their last dose earlier in the day to minimize nighttime disruptions.
• Pollakiuria (urinary frequency) — Even beyond increased volume, you may feel the need to urinate more often.
• Fatigue — Some patients feel tired, especially in the first few weeks of treatment.
• Hyperglycemia — Elevated blood sugar levels have been reported. If you have diabetes, monitor your glucose more closely.
• Decreased appetite — Some patients experience reduced hunger or anorexia.
• Constipation — This may occur as the body adjusts to changes in fluid balance.

Serious Side Effects

These side effects are less common but can be dangerous. Contact your doctor immediately — or go to the emergency room — if you experience any of the following:

Hepatotoxicity (Liver Injury) — Jynarque Boxed Warning

Jynarque carries a boxed warning for serious and potentially fatal liver injury. Symptoms of liver problems include:

• Yellowing of the skin or eyes (jaundice)
• Dark urine
• Nausea or vomiting that doesn't go away
• Unusual fatigue
• Upper right abdominal pain

This is why Jynarque requires monthly liver function tests (ALT, AST, bilirubin) for the first 18 months, then every 3 months after that. The drug is only available through the Jynarque REMS program because of this risk.

Osmotic Demyelination Syndrome (ODS) — Samsca Boxed Warning

Samsca carries a boxed warning for osmotic demyelination syndrome, a rare but devastating neurological condition that can occur if sodium levels are corrected too rapidly. Symptoms may include:

• Difficulty speaking or swallowing
• Drowsiness or confusion
• Mood changes
• Involuntary movements or weakness
• Seizures

This is why Samsca must be started in a hospital where sodium levels can be monitored closely.

Other Serious Side Effects

• Hypernatremia — Sodium levels that climb too high can cause confusion, muscle twitching, and seizures.
• Dehydration and hypovolemia — Excessive fluid loss can lead to dizziness, rapid heartbeat, and dangerously low blood pressure.
• Gastrointestinal bleeding — Particularly in patients with liver cirrhosis.
• Hyperkalemia — Elevated potassium levels, which can affect heart rhythm.

Special Populations

Certain groups should be especially careful with Tolvaptan:

• Patients with liver disease — Samsca should not be used for more than 30 days in patients with underlying liver disease. Jynarque requires rigorous liver monitoring.
• Pregnant women — Tolvaptan is pregnancy Category C. Use only if the potential benefit justifies the risk to the fetus.
• Breastfeeding mothers — Tolvaptan is not recommended during breastfeeding.
• Elderly patients — Those who cannot sense or respond to thirst should not take Tolvaptan, as dehydration risk is significant.
• Patients taking CYP3A4 inhibitors — Certain medications can dangerously increase Tolvaptan levels in your body.

How to Manage Common Side Effects

While you can't eliminate all side effects, there are practical strategies to make them more tolerable:

• Stay hydrated — Drink water throughout the day and keep a water bottle nearby at all times. With Jynarque, you should drink water whenever you're thirsty and before bed.
• Plan your doses — If nocturia is disruptive, talk to your doctor about timing your doses earlier in the day.
• Monitor your weight — Sudden weight loss can indicate excessive fluid loss. Weigh yourself daily and report significant changes.
• Keep up with lab work — Don't skip your scheduled blood tests. Liver function monitoring for Jynarque and sodium monitoring for Samsca are non-negotiable safety requirements.
• Track your symptoms — Keep a simple log of side effects to discuss with your doctor. Note when they occur, how severe they are, and whether they're improving or worsening.

Final Thoughts

Tolvaptan is a powerful medication that helps manage serious conditions, but it comes with real side effects that you should be prepared for. Thirst and frequent urination are nearly universal — plan for them. More importantly, know the warning signs of liver injury and osmotic demyelination syndrome so you can act quickly if they occur. Stay on top of your lab monitoring schedule, and don't hesitate to call your doctor if something doesn't feel right. For help finding Tolvaptan at an affordable price, visit Medfinder or check out our savings guide.