Tacrolimus
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: 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**.
Routes of administration
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
Drug interactions
- Ketoconazole · Inhibits CYP3A metabolism, significantly increasing systemic tacrolimus levels · major
- Erythromycin · Inhibits metabolism, increasing tacrolimus levels · major
- Grapefruit juice · Increases systemic absorption and blood levels of tacrolimus · moderate
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)
Overdose
Systemic overdose can lead to severe nephrotoxicity, neurotoxicity (tremors, seizures), and profound immunosuppression. Treatment is supportive and symptomatic. No specific antidote exists.
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.