Tacrolimus
FK-506
Also known as: Protopic · Prograf · Advagraf · FK-506 · fujimycin
Reviewed by the VetSheet Veterinary TeamUpdated Apr 5, 2026Evidence-based veterinary reference
Dosing by species
Dosing data for this drug is not yet available in the VetSheet formulary. Every other section below is complete. Consult the current product label before prescribing.
Overview
Tacrolimus (FK 506) is a potent macrolide immunosuppressant. In veterinary medicine, it is primarily used topically for immune-mediated dermatoses (such as perianal fistulas and atopic dermatitis) and ophthalmically for keratoconjunctivitis sicca (KCS). Systemic use is less common due to potential toxicity but may be utilized for severe immune-mediated diseases.
Clinical Pearl: Tacrolimus is often effective in KCS cases that are refractory to cyclosporine.
Mechanism of action
Binds to the intracellular protein FKBP-12 (FK506 binding protein) → forms a complex that inhibits calcineurin (a calcium-dependent phosphatase) → prevents dephosphorylation of NF-AT (nuclear factor of activated T-cells) → inhibits transcription of IL-2 and other cytokines → profound T-lymphocyte inhibition.
Safety & warnings
Contraindications
- Hypersensitivity to macrolides
- Active systemic infections
- Malignancy (for systemic use)
Adverse effects
- Topical: local irritation, erythema, pruritus
- Ophthalmic: mild ocular irritation
- Systemic: GI upset (vomiting, diarrhea), nephrotoxicity, neurotoxicity, secondary infections
Precautions
Warning: Avoid switching between oral brands due to narrow therapeutic index and variable bioavailability. Wear gloves when applying topical formulations to avoid inadvertent human exposure. Monitor blood levels if used systemically.
Drug interactions
Inhibits CYP3A metabolism, significantly increasing systemic tacrolimus levels
Inhibits metabolism, increasing tacrolimus levels
Increases systemic absorption and blood levels of tacrolimus
Monitoring
- Tear production (Schirmer Tear Test) for KCS
- Resolution of skin lesions
- Whole blood trough levels (if used orally)
- Renal and hepatic function (if used orally)
Pharmacokinetics
Half-life
Absorption
Poor and variable oral absorption. Minimal systemic absorption from intact skin, but absorption increases significantly when applied to inflamed or damaged skin.
Distribution
Highly protein bound, primarily to erythrocytes and plasma proteins.
Metabolism
Extensively metabolized in the liver and intestines by CYP3A enzymes.
Elimination
Primarily excreted via the biliary/fecal route.
Overdose
Systemic overdose can lead to severe nephrotoxicity, neurotoxicity (tremors, seizures), and profound immunosuppression. Treatment is supportive and symptomatic. No specific antidote exists.
Available products
Formulations
- Topical: 0.03% skin ointment
- Topical: 0.1% skin ointment
- Ophthalmic: 0.02% eye drop (solution)
- Oral: various preparations
Veterinary
- Tacrolimus 0.02% eye drops (often compounded or specific veterinary brands)
Human-labeled
- Protopic 0.03% ointment
- Protopic 0.1% ointment
- Prograf capsules
- Advagraf capsules
Regulatory status
POM (Prescription Only Medicine). Often used off-label under the cascade.
POM (Prescription Only Medicine). Often used off-label under the cascade.
No regulatory data for: 🇺🇸 US · 🇭🇰 HK · 🇹🇼 TW · 🇯🇵 JP · 🇰🇷 KR · 🇦🇺 AU
Storage & stability
Store at room temperature away from moisture and heat. Keep tubes and bottles tightly closed.
Client information
Wear gloves when applying the ointment to your pet's skin or eyes. Wash hands thoroughly after use. Do not allow other pets to lick the treated area.
Warning: If using oral medication, do not switch brands without consulting your veterinarian, as different brands are absorbed differently. Pregnant women should avoid handling this medication if possible.
VetSheet drug reference is intended for licensed veterinary professionals as a clinical decision-support aid, not a substitute for professional judgement or the manufacturer’s current label.