Modigraf (Tacrolimus)

• Tacrolimus is used in immunosuppressive therapy to manage conditions where immune modulation is required.
• Organ transplant rejection: prevents graft rejection by inhibiting T‑cell activation and cytokine production.
• Atopic dermatitis: reduces severe skin inflammation and lesion formation in patients unresponsive to topical agents.
• Autoimmune skin disorders: controls disease activity in conditions such as psoriasis when conventional therapies have failed.

• Tacrolimus binds to the intracellular protein FKBP‑12, forming a complex that inhibits the phosphatase activity of calcineurin. This blockade prevents dephosphorylation of nuclear factor of activated T‑cells (NF‑AT), thereby suppressing interleukin‑2 transcription and subsequent T‑cell activation, leading to reduced immune response.

Adverse reactions may occur with tacrolimus therapy and are categorized by frequency and severity.

Common Side Effects

• Headache: mild to moderate intensity.
• Nausea: occasional gastrointestinal upset.
• Tremor: fine shaking of hands or limbs.
• Elevated blood glucose: transient hyperglycaemia.
• Hypertension: increase in blood pressure readings.
• Diarrhoea: loose stools without infection.

Serious or Rare Side Effects

• Nephrotoxicity: impaired kidney function requiring monitoring.
• Neurotoxicity: seizures or severe confusion.
• Infections: opportunistic infections due to immunosuppression.
• Malignancy: increased risk of lymphomas and skin cancers.
• Hepatotoxicity: abnormal liver enzymes indicating liver injury.

• Patients should be monitored closely for safety and efficacy when using tacrolimus.
• Therapeutic drug monitoring: regular blood level checks to maintain target concentrations.
• Renal function assessment: baseline and periodic creatinine measurements.
• Infection vigilance: screen for viral, bacterial, and fungal infections before and during therapy.
• Pregnancy counseling: discuss potential risks with a healthcare professional.
• Drug interaction review: evaluate concomitant medications for possible interactions.
• Store at ambient temperature: keep below 25 °C, retain in original packaging, protect from moisture and direct sunlight.

Tacrolimus has a notable interaction profile that requires careful management.

Major Interactions (Avoid)

• Strong CYP3A4 inhibitors (e.g., ketoconazole, clarithromycin): can markedly increase tacrolimus levels.
• CYP3A4 inducers (e.g., rifampicin, carbamazepine): may reduce drug exposure and risk of rejection.
• Antacids containing aluminium or magnesium: decrease absorption when taken simultaneously.

Moderate Interactions (Monitor Closely)

• Calcium channel blockers (e.g., diltiazem): may modestly raise tacrolimus concentrations.
• Macrolide antibiotics (e.g., erythromycin): require dose adjustment and monitoring.
• Antifungal agents (e.g., fluconazole): can increase levels, necessitating periodic blood tests.