Updated: April 9, 2026

Astagraf XL Drug Interactions: What to Avoid and What to Tell Your Doctor

Author

Peter Daggett

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Why Astagraf XL Has So Many Drug Interactions
Drugs That INCREASE Tacrolimus Blood Levels (CYP3A4 Inhibitors)
Drugs That DECREASE Tacrolimus Blood Levels (CYP3A4 Inducers)
Drugs That Increase Risk of Kidney Damage (Nephrotoxic Combinations)
Other Important Drug Interactions
Food Interactions: Grapefruit and Alcohol
Supplement Interactions
What to Tell Your Doctor

Astagraf XL (tacrolimus) has numerous serious drug interactions. Here's what kidney transplant patients need to know about which drugs, foods, and supplements to avoid in 2026.

Astagraf XL (tacrolimus extended-release capsules) has an extensive list of potential drug interactions -- more than most medications. Because tacrolimus has a narrow therapeutic index (a small gap between the effective dose and the toxic dose), even modest changes in tacrolimus blood levels caused by drug interactions can lead to organ rejection or dangerous toxicity.

This guide covers the most important drug, food, and supplement interactions with Astagraf XL that every kidney transplant patient and caregiver needs to know in 2026.

Why Astagraf XL Has So Many Drug Interactions

Tacrolimus is primarily metabolized by the CYP3A4 and CYP3A5 enzymes in your liver and intestines. Any drug, food, or supplement that inhibits these enzymes (slows them down) will cause tacrolimus blood levels to rise -- potentially causing toxicity. Any drug that induces (speeds up) these enzymes will cause tacrolimus levels to fall -- potentially causing rejection.

Additionally, some drugs interact with Astagraf XL not through CYP3A4 but through shared side effects -- for example, combining Astagraf XL with other nephrotoxic drugs increases the risk of kidney damage.

Drugs That INCREASE Tacrolimus Blood Levels (CYP3A4 Inhibitors)

These drugs slow the breakdown of tacrolimus, causing levels to rise. Higher levels increase the risk of nephrotoxicity, neurotoxicity, and other toxicities:

Antifungals: Fluconazole, itraconazole, voriconazole, posaconazole -- commonly used in transplant patients for fungal infection prevention; major interaction
Macrolide antibiotics: Erythromycin, clarithromycin -- use azithromycin when possible (less interaction)
HIV antiretrovirals: Ritonavir-boosted protease inhibitors (lopinavir/ritonavir, atazanavir, indinavir, nelfinavir) -- major inhibitors
Calcium channel blockers: Diltiazem, verapamil (also used for hypertension in transplant patients) -- increase tacrolimus levels moderately
Other medications: Danazol, ethinyl estradiol, methylprednisolone, nefazodone, cimetidine

Drugs That DECREASE Tacrolimus Blood Levels (CYP3A4 Inducers)

These drugs speed up tacrolimus metabolism, causing levels to fall dangerously low -- increasing rejection risk:

Antibiotics: Rifampin (rifampicin), rifabutin -- strong inducers; avoid if possible
Anti-seizure medications: Phenobarbital, phenytoin, carbamazepine -- significant inducers; requires dose monitoring
Targeted cancer therapies: Lorlatinib -- strongly decreases tacrolimus levels; avoid combination

Drugs That Increase Risk of Kidney Damage (Nephrotoxic Combinations)

Since Astagraf XL can cause nephrotoxicity on its own, combining it with other nephrotoxic drugs is particularly dangerous:

Aminoglycoside antibiotics (gentamicin, tobramycin, amikacin)
Amphotericin B (antifungal)
Ganciclovir and valganciclovir (used for CMV prevention/treatment in transplant)
Cisplatin and certain chemotherapy agents
NSAIDs (ibuprofen, naproxen) -- reduce blood flow to kidneys; use acetaminophen instead when possible
Piroxicam (NSAID) -- also increases tacrolimus toxicity through an additional mechanism

Other Important Drug Interactions

Cyclosporine: Avoid using Astagraf XL together with cyclosporine; additive nephrotoxicity and interaction risk
Sirolimus/Temsirolimus: Not generally used together with full-dose tacrolimus due to additive toxicity
QT-prolonging drugs: Ziprasidone, certain antiarrhythmics, macimorelin -- combined use increases risk of life-threatening heart arrhythmia (Torsades de pointes)
Potassium-sparing diuretics: Amiloride, spironolactone -- increased hyperkalemia risk
Cannabidiol (CBD): Can affect tacrolimus metabolism via CYP3A4; tacrolimus levels should be monitored if CBD is used

Food Interactions: Grapefruit and Alcohol

Grapefruit and grapefruit juice: Inhibit intestinal CYP3A4, causing tacrolimus levels to rise significantly. Avoid completely.
Alcohol: Causes the extended-release capsule to release tacrolimus too quickly, producing a spike in blood levels and increased risk of toxicity. Avoid alcohol while taking Astagraf XL.

Supplement Interactions

St. John's Wort: A strong CYP3A4 inducer; can dramatically decrease tacrolimus levels. Avoid completely.
Magnesium, calcium, potassium supplements: Astagraf XL causes electrolyte disturbances; supplementation should be guided by labs

What to Tell Your Doctor

Before starting any new medication, supplement, or herbal product, tell your transplant team. Never start or stop any medication without checking with your transplant physician or pharmacist first. Keep a complete, up-to-date medication list and share it with every healthcare provider you see.

For a full understanding of Astagraf XL risks, read our guides on Astagraf XL side effects and how Astagraf XL works.

Frequently Asked Questions

Astagraf XL has numerous drug interactions through CYP3A4 metabolism. Drugs that increase tacrolimus levels include azole antifungals (fluconazole, voriconazole), macrolide antibiotics (erythromycin), HIV protease inhibitors, and diltiazem/verapamil. Drugs that decrease levels include rifampin, phenytoin, phenobarbital, carbamazepine, and St. John's Wort. Additional interactions increase nephrotoxicity (NSAIDs, aminoglycosides) or heart arrhythmia risk (QT-prolonging drugs).

Use NSAIDs like ibuprofen or naproxen with extreme caution on Astagraf XL. NSAIDs can decrease blood flow to the kidneys, compounding Astagraf XL's own nephrotoxicity. Use acetaminophen (Tylenol) for pain relief instead, unless your transplant team advises otherwise. Always check with your transplant physician or pharmacist before taking any over-the-counter pain medication.

No. Alcohol causes Astagraf XL's extended-release mechanism to break down, causing the drug to release too quickly and producing a dangerous spike in tacrolimus blood levels. This dramatically increases the risk of toxicity. Avoid alcohol entirely while taking Astagraf XL.

No. St. John's Wort is a potent inducer of CYP3A4 and can cause a dramatic decrease in tacrolimus blood levels, potentially falling below the threshold needed to prevent organ rejection. The Astagraf XL prescribing information specifically lists St. John's Wort as an interaction to avoid. Herbal supplements are not regulated like medications, so always tell your transplant team about any supplements you take.

Most commonly used azole antifungals (fluconazole, itraconazole, voriconazole, posaconazole) significantly inhibit CYP3A4 and raise tacrolimus levels, often requiring a dose reduction. If antifungal therapy is needed, your transplant pharmacist will typically recommend reducing the tacrolimus dose preemptively and monitoring levels closely. Some antifungals like nystatin (topical or oral) and micafungin have less CYP3A4 interaction. Always consult your transplant team before starting any antifungal.

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