ENVARSUS XR

Envarsus XR is the brand name for tacrolimus and is available as an extended-release tablet formulation.

Envarsus XR is available in the strengths 0.75 mg, 1 mg, and 4 mg oral extended-release tablets. It is created with proprietary MeltDose® technology to improve the release and absorption of tacrolimus over 24 hours.

ENVARSUS XR is indicated for the prophylaxis of organ rejection in de novo kidney transplant patients in combination with other immunosuppressants.

ENVARSUS XR is also indicated for the prophylaxis of organ rejection in kidney transplant patients converted from tacrolimus immediate-release formulations in combination with other immunosuppressants.

Envarsus XR is a once-daily, extended-release version of tacrolimus, a medication used to prevent organ rejection in kidney transplant patients. It belongs to a class of drugs called calcineurin inhibitors, which work by suppressing the immune system. It contains the active ingredient tacrolimus.

Mechanism of Action

Tacrolimus blocks an enzyme called calcineurin, which is essential for activating T-cells, the white blood cells that can attack a transplanted organ. It does this by binding to a protein called FKBP12, forming a complex that stops calcineurin from working. This reduces the production of interleukin-2 and other signals needed for T-cell activity, lowering the risk of rejection.

Unique Technology

Envarsus XR uses MeltDose® technology to improve how tacrolimus is absorbed in the body. This helps the drug dissolve better in the gut, providing smoother, more consistent levels of the drug in the bloodstream over time.

Envarsus XR is taken once daily, usually in the morning, and should be taken at the same time each day to maintain steady levels in the bloodstream. It must be taken on an empty stomach, either at least one hour before or two hours after a meal, since food can affect how the medication is absorbed. The tablet should be swallowed whole with a glass of water and should never be crushed, chewed, or split, as this would interfere with its extended-release properties.

Patients taking Envarsus XR should avoid grapefruit and grapefruit juice, which can alter how the drug is processed in the body and increase the risk of side effects. It’s important not to miss doses, but if a dose is missed and it’s close to the time for the next one, the missed dose should be skipped, never doubled. Regular blood tests are necessary to monitor tacrolimus levels and adjust the dose as needed. Doctors may also check kidney function, liver enzymes, and other lab values to ensure the medication remains safe and effective.

Envarsus XR is not interchangeable with other forms of tacrolimus, such as Prograf or Astagraf XL. If switching from another formulation, the healthcare provider will carefully determine a new dose. Always follow your doctor’s instructions closely and do not make any changes without medical advice.

Envarsus XR is generally safe when used exactly as prescribed and closely monitored by a healthcare provider. It is an FDA-approved medication commonly used to prevent organ rejection in kidney transplant patients.

However, it has a narrow therapeutic range, meaning the difference between an effective dose and a harmful one is small. Because of this, patients need regular blood tests to monitor tacrolimus levels, as well as kidney, liver, and other health markers. While effective, Envarsus can cause side effects such as kidney toxicity, high blood pressure, high blood sugar or new-onset diabetes, increased risk of infections due to immune suppression, tremors, headaches, or in rare cases, increased risk of certain cancers like skin cancer and lymphoma.

It may not be suitable for individuals with severe liver problems, a history of tacrolimus intolerance, or those taking certain interacting medications. Despite these risks, when taken under strict medical supervision with proper follow-up, Envarsus XR can be a safe and vital part of transplant care.

Common side effects of Envarsus XR (tacrolimus extended-release) can affect several body systems, particularly because the drug suppresses the immune system. While not everyone experiences them, the following are frequently reported:

General & Metabolic

• Headache
• Fatigue or weakness
• Fever
• Insomnia

Kidney-Related

• Increased creatinine levels (a sign of reduced kidney function)
• Decreased urine output
• Swelling (edema)

Cardiovascular

• High blood pressure (hypertension)
• Fast heart rate (tachycardia)

Blood Sugar & Metabolism

• High blood sugar (hyperglycemia)
• New-onset diabetes after transplant (NODAT)

Neurological

• Tremors (shakiness)
• Numbness or tingling
• Dizziness

Gastrointestinal

• Diarrhea
• Nausea or vomiting
• Abdominal pain
• Constipation

Immune & Infections

• Increased risk of infections due to immune suppression
• Upper respiratory infections
• Urinary tract infections (UTIs)

Lab Abnormalities

• Elevated potassium (hyperkalemia)
• Low magnesium (hypomagnesemia)
• Abnormal liver enzymes

If you experience any of these side effects, especially tremors, sleep disturbances, or signs of kidney issues, it’s important to contact your doctor.

Serious side effects of Envarsus XR (tacrolimus extended-release) are less common but potentially life-threatening. These effects often require immediate medical attention and may lead to hospitalization or changes in treatment. Here are the most important ones to be aware of:

Kidney Damage (Nephrotoxicity)
Tacrolimus can cause significant damage to the kidneys, especially at high levels. Signs include reduced urine output, swelling, elevated creatinine, or electrolyte imbalances.

Serious Infections
Because Envarsus suppresses the immune system, it increases the risk of severe infections, including:

• Opportunistic infections (e.g., CMV, BK virus)
• Fungal infections (e.g., aspergillosis)
• Bacterial sepsis

Symptoms may include fever, chills, cough, or confusion.

Neurotoxicity
High tacrolimus levels can cause:

• Seizures
• Severe tremors
• Confusion or delirium
• Speech or coordination problems

New-Onset Diabetes After Transplant (NODAT)
Envarsus can impair blood sugar control, leading to diabetes, especially in those with risk factors.

High Blood Pressure and Heart Issues
It can cause severe hypertension, arrhythmias, or even heart failure in some patients.

Liver Damage (Hepatotoxicity)
May result in elevated liver enzymes or liver dysfunction. Symptoms include jaundice (yellowing of the skin/eyes), dark urine, or abdominal pain.

Cancer Risk
Long-term use increases the risk of certain cancers, particularly:

• Lymphoma (Post-transplant lymphoproliferative disorder, or PTLD)
• Skin cancer (especially with sun exposure)

Anaphylaxis or Allergic Reactions
Rare but serious allergic responses can occur, including rash, swelling, difficulty breathing, or anaphylactic shock.

Important:

These risks are why regular blood monitoring, kidney and liver function tests, and clinical evaluations are critical while taking Envarsus XR. If you experience symptoms like severe fatigue, mental changes, unusual bruising, persistent fever, or difficulty breathing, seek medical attention immediately.

Envarsus XR (tacrolimus extended-release) has many potential drug and food interactions that can significantly affect its levels in the body. Because it has a narrow therapeutic window, even small changes in absorption or metabolism can lead to serious side effects or reduced effectiveness.

1. Drugs That Increase Tacrolimus Levels, which in turn increase the risk of toxicity. The following drug classes inhibit CYP3A enzymes, which slows the breakdown of tacrolimus:

• Antifungals: ketoconazole, itraconazole, fluconazole, voriconazole
• Macrolide antibiotics: erythromycin, clarithromycin
• HIV protease inhibitors: ritonavir, lopinavir
• Calcium channel blockers: diltiazem, verapamil
• Grapefruit and grapefruit juice (a strong CYP3A4 inhibitor)

2. Drugs That Decrease Tacrolimus Levels. The following drug classes induce CYP3A enzymes, speeding up tacrolimus metabolism:

• Anticonvulsants: phenytoin, carbamazepine, phenobarbital
• Rifampin (an antibiotic used for tuberculosis)
• St. John’s Wort (an herbal antidepressant)

3. Drugs That Increase Risk of Side Effects:

• NSAIDs (like ibuprofen, naproxen): increase kidney risk
• Other nephrotoxic drugs: aminoglycosides, amphotericin B, cisplatin
• Diuretics: may worsen electrolyte disturbances (especially potassium and magnesium)
• ACE inhibitors/ARBs: may increase risk of high potassium and kidney issues
• Statins: increase risk of muscle toxicity (rhabdomyolysis) when used with tacrolimus

4. Vaccines
Live vaccines (like MMR, varicella, or yellow fever) should be avoided during treatment, as the immune system is suppressed and response may be inadequate or dangerous.

5. Food Interactions
Grapefruit and grapefruit juice should be completely avoided.

High-fat meals can affect absorption and may delay or reduce drug levels.

Always take Envarsus XR on an empty stomach (1 hour before or 2 hours after a meal).

Veloxis Pharmaceuticals, Inc.

If you are able to become pregnant, you should use effective birth control before and during treatment with ENVARSUS XR.

• tacrolimus