Envarsus XR Drug Interactions: A Complete Guide

Envarsus XR (Tacrolimus extended-release) is a medication where drug interactions aren't just inconvenient — they can be dangerous. Because Tacrolimus has a narrow therapeutic index (meaning the difference between an effective dose and a toxic dose is small), even minor changes in blood levels can cause serious problems.

This guide covers the major interactions you need to know about, including prescription drugs, supplements, over-the-counter products, and food.

How Drug Interactions Work With Envarsus XR

Tacrolimus is primarily processed by your liver through an enzyme system called CYP3A4. Anything that speeds up or slows down CYP3A4 will change how much Tacrolimus stays in your blood:

• CYP3A4 inhibitors slow down the enzyme → Tacrolimus levels go up → higher risk of toxicity (kidney damage, neurotoxicity)
• CYP3A4 inducers speed up the enzyme → Tacrolimus levels go down → higher risk of organ rejection

Your doctor manages this through regular trough level blood tests, but knowing what to avoid can help you stay safe between appointments.

Major Drug Interactions

These interactions are considered the most clinically significant. Your doctor will either avoid these combinations entirely or monitor you very closely:

Cyclosporine

Never take Cyclosporine (Neoral, Gengraf, Sandimmune) and Envarsus XR at the same time. Both are calcineurin inhibitors, and combining them dramatically increases the risk of kidney damage. If switching between them, you must wait at least 24 hours after the last dose of one before starting the other.

Strong CYP3A4 Inhibitors (Increase Tacrolimus Levels)

These drugs slow down how your liver processes Tacrolimus, causing dangerous buildups:

• Ketoconazole (antifungal)
• Itraconazole (antifungal)
• Voriconazole (antifungal)
• Posaconazole (antifungal)
• Clarithromycin (antibiotic — brand name Biaxin)

If any of these are medically necessary, your doctor will likely reduce your Envarsus XR dose and monitor your levels more frequently.

Strong CYP3A4 Inducers (Decrease Tacrolimus Levels)

These drugs speed up Tacrolimus metabolism, potentially dropping your levels below what's needed to protect your transplant:

• Rifampin (antibiotic used for tuberculosis)
• Phenytoin (seizure medication — brand name Dilantin)
• Carbamazepine (seizure medication — brand name Tegretol)
• St. John's Wort (herbal supplement for depression)

These are particularly dangerous because dropping Tacrolimus levels can lead to acute organ rejection, which may be irreversible.

Cannabidiol (CBD)

CBD products — including CBD oil, gummies, and topicals — can increase Tacrolimus levels. This is an interaction many patients don't know about, especially since CBD products are widely available over the counter. If you use any CBD products, tell your transplant team immediately.

Live Vaccines

Because Envarsus XR suppresses your immune system, live vaccines should be avoided. Your weakened immune system may not be able to handle even the weakened virus in a live vaccine. Examples include MMR, varicella (chickenpox), and the nasal flu spray (FluMist). Inactivated vaccines are generally safe — check with your doctor before any vaccination.

Moderate Drug Interactions

These interactions are less severe but still important to manage:

• Antacids with magnesium or aluminum hydroxide — can affect absorption
• Proton pump inhibitors (PPIs) like Lansoprazole (Prevacid) and Omeprazole (Prilosec) — may alter Tacrolimus levels
• Cimetidine (Tagamet) — an older heartburn medication that can affect drug metabolism
• Nephrotoxic drugs — medications that can also damage the kidneys, including:
  • Aminoglycoside antibiotics (Gentamicin, Tobramycin)
  • Amphotericin B (antifungal)
  • NSAIDs (Ibuprofen/Advil, Naproxen/Aleve) — this is a big one because many people take these without thinking
• Schisandra sphenanthera extracts — a traditional Chinese medicine supplement

Supplements and OTC Products to Watch

Just because something is "natural" or available without a prescription doesn't mean it's safe with Envarsus XR:

• St. John's Wort — seriously decreases Tacrolimus levels (listed above as a major interaction)
• CBD products — increases Tacrolimus levels
• NSAIDs (Ibuprofen, Naproxen, Aspirin in high doses) — increases kidney toxicity risk when combined with Tacrolimus
• Magnesium supplements — may affect absorption
• Potassium supplements — Envarsus XR can cause hyperkalemia (high potassium), so adding potassium supplements can make this worse

Always check with your transplant team before starting any new supplement, vitamin, or over-the-counter medication.

Food and Drink Interactions

Grapefruit and Grapefruit Juice

Grapefruit inhibits CYP3A4 in your gut, increasing Tacrolimus absorption and blood levels. Avoid grapefruit and grapefruit juice entirely while on Envarsus XR. This includes Seville oranges and pomelos, which contain similar compounds.

Alcohol

Alcohol can worsen many Envarsus XR side effects, including liver stress and gastrointestinal issues. While an occasional drink may not cause a crisis, discuss alcohol use honestly with your doctor.

High-Fat Meals

Envarsus XR should be taken on an empty stomach (1 hour before or 2 hours after eating) because high-fat meals change how the drug is absorbed. Taking it with food can lead to unpredictable blood levels.

What to Tell Your Doctor

Before starting Envarsus XR — and at every follow-up visit — give your transplant team a complete picture:

• All prescription medications you take, including those prescribed by other doctors
• Over-the-counter drugs — especially pain relievers, antacids, and cold medicines
• Supplements and vitamins — including herbal products, CBD, and traditional remedies
• Recreational substances — including marijuana and CBD edibles
• Changes to any medication — even stopping something can affect Tacrolimus levels
• Planned vaccinations — so they can advise on which are safe

Keep a written list and update it regularly. Your life depends on this medication working correctly, and interactions are one of the biggest preventable risks.

Final Thoughts

Envarsus XR has a narrow therapeutic window, which makes drug interactions especially dangerous. The good news is that most interactions are well-documented and manageable — as long as your transplant team knows about everything you're taking.

When in doubt, ask before you take it. And if cost or availability is making it hard to stay consistent with Envarsus XR, explore savings options or use Medfinder to find it in stock near you.