tacrolimus monohydrate: clinical use

Prescribing considerations

• Systemic therapy and any formulation conversion require clinicians experienced in transplantation and access to therapeutic drug monitoring.
• Prescribe and dispense oral tacrolimus by brand. Confirm the formulation at transitions of care and investigate unexpected concentration changes, toxicity or rejection.
• Review interacting medicines promptly; diarrhoea can substantially alter tacrolimus exposure.
• For ointment, exclude infection and suspicious, premalignant or malignant lesions before application; reassess persistent lymphadenopathy or inadequate response.

Contraindications and cautions

• Hypersensitivity to tacrolimus, formulation excipients or macrolides.
• Product-specific excipients require review, including lactose and, in some capsules, soya lecithin.
• Protopic should not be used in congenital or acquired immunodeficiency or alongside systemic immunosuppressive therapy; avoid use on clinically infected sites until treated.

Monitoring

• Tacrolimus whole-blood trough concentration, particularly after initiation, formulation change, interaction changes, diarrhoea or suspected rejection or toxicity.
• Renal and hepatic function, blood pressure, glucose, potassium, magnesium, blood count and relevant lipids.
• ECG and QT-risk factors where clinically indicated; assess neurological symptoms, infection, malignancy and graft function.
• For topical treatment, monitor response, local infection, lymphadenopathy and continued need for treatment.

Clinical pharmacology

Tacrolimus is a narrow-therapeutic-index calcineurin inhibitor metabolised mainly by CYP3A4 and transported by P-glycoprotein. Formulation, food and interacting substances can materially alter systemic exposure.

Formulation and product differences

• Prograf hard capsules are immediate-release oral tacrolimus.
• Dailiport prolonged-release capsules and Envarsus prolonged-release tablets have modified-release profiles and are not automatically interchangeable with each other or immediate-release products.
• Modigraf is supplied as granules for freshly prepared oral suspension and requires non-PVC preparation and administration equipment.
• Protopic is a topical ointment with low systemic exposure under usual conditions; its indications, precautions and monitoring differ from oral tacrolimus.

Ointment

Route: Cutaneous

Strengths: 0.03%, 0.1%

Capsule

Route: Oral

Strengths: 0.5 mg, 0.75 mg, 1 mg, 2 mg, 3 mg, 5 mg