tacrolimus: clinical use

Prescribing considerations

• Initiation and changes in immunosuppression require an experienced transplant specialist.
• Review concurrent prescription, non-prescription, food and herbal exposures for CYP3A4, nephrotoxic, neurotoxic, QT-prolonging and potassium-raising effects.
• Severe hepatic impairment can reduce clearance; renal impairment increases concern because tacrolimus is nephrotoxic.
• Minimise ultraviolet exposure and maintain surveillance for infection and malignancy.

Contraindications and cautions

• Hypersensitivity to tacrolimus or other macrolides.
• Hypersensitivity to an excipient, particularly polyoxyethylene hydrogenated castor oil or structurally related compounds.

Monitoring

• Whole-blood tacrolimus concentrations, especially after formulation changes or interacting medicines.
• Renal and liver function, electrolytes—particularly potassium—and blood glucose.
• Blood pressure, full blood count and clinical evidence of infection, neurotoxicity or graft dysfunction.
• ECG, visual or neurological assessment when clinically indicated.

Clinical pharmacology

Tacrolimus binds FKBP12 and inhibits calcineurin-dependent T-cell signalling and cytokine transcription. It is metabolised predominantly through CYP3A4, accounting for many clinically significant interactions and the need for therapeutic drug monitoring.

Formulation and product differences

• The selected product is an intravenous concentrate requiring dilution and must not be administered undiluted or as a bolus.
• The infusion excipient polyoxyethylene hydrogenated castor oil can cause anaphylactoid reactions.
• Tacrolimus is absorbed by PVC, so compatible non-PVC preparation and administration equipment is required.
• Oral products vary in release characteristics. Prescribe and dispense oral products by brand; switching requires specialist supervision and therapeutic monitoring.

Solution for infusion

Route: Intravenous

Strengths: 5 mg/mL