Makindo Medical Notes

⚠️ Important Safety: - Tacrolimus must be prescribed and dispensed by brand name only to avoid inadvertent switching → risk of toxicity or graft rejection. - Do not give clarithromycin with tacrolimus → risk of dangerous toxicity. Always check the BNF link here.

📖 About

• Potent immunosuppressant used in solid organ transplantation and autoimmune diseases.
• Belongs to the macrolide lactone group (similar origin to ciclosporin but more potent).

⚙️ Mode of Action

• Binds to FK-binding protein (FKBP12).
• Inhibits calcineurin → prevents transcription of interleukin-2 and other cytokines.
• Result: ↓ T-cell activation and proliferation.

💊 Indications & Dose

• Prevention of organ rejection in liver, kidney, heart transplantation.
• Dose is formulation-specific → check BNF and monitor drug levels closely.
• Other uses: Ulcerative colitis, T-cell mediated diseases.
• Topical use: Severe eczema and other dermatological conditions.

🔗 Interactions

• Tacrolimus is metabolised by CYP3A4 and highly protein-bound.
• Toxicity more likely in anaemia or hypoalbuminaemia (↑ free drug).

⬆️ Drugs that Increase Tacrolimus Levels

• Macrolides: Clarithromycin, Erythromycin.
• Azole antifungals: Itraconazole, Ketoconazole, Fluconazole (>200 mg/day).
• Calcium channel blockers: Diltiazem, Nicardipine.
• Antivirals: HIV protease inhibitors, Telaprevir, Boceprevir.
• Other: Amiodarone, Danazol, Progestogens.

⬇️ Drugs that Reduce Tacrolimus Levels

• Anticonvulsants: Carbamazepine, Phenytoin, Phenobarbital, Primidone.
• Antimicrobials: Rifampicin, Griseofulvin, Caspofungin.

⚠️ Cautions

• Monitor renal function, electrolytes (K⁺, Mg²⁺), and blood pressure.
• Monitor trough blood levels to avoid toxicity/rejection.
• Increased risk of infections and malignancy (esp. skin cancers, lymphoproliferative disease).

🚫 Contraindications

• See BNF (e.g. hypersensitivity, uncontrolled infections).

❗ Side Effects

• Nephrotoxicity: renal impairment, hyperkalaemia, hypomagnesaemia.
• Neurotoxicity: tremor, headache, paraesthesia, seizures.
• GI: nausea, vomiting, diarrhoea.
• Cardio-metabolic: hypertension, diabetes mellitus.
• Arthralgia, skin reactions.

📚 References

• BNF – Tacrolimus