Introduction: Tacrolimus has formed the backbone of immunosuppressive therapy post liver transplantation since its introduction. The neurotoxicity of tacrolimus is one of the most common reasons for the need for discontinuation of this drug; and the incidence in liver transplant ranges from 10 to 30%, which is significantly higher than in kidney, lung or heart transplants. Switching to cyclosporine is an effective method to manage moderate to severe neurotoxicity. However, immunosuppression with cyclosporine is considered sub-optimal, with up to 10% higher rates of graft loss. Hence, the reintroduction of tacrolimus after the improvement of neurological symptoms, in a safe manner, is desirable.
Method: We did a retrospective study of all patients who underwent a liver transplant at our centre from 2019 to 2023, and were switched to cyclosporine secondary to tacrolimus-related toxicity.
Results: 61 patients were identified to have received cyclosporine from a total of 1353 liver transplant recipients, comprising predominantly of living donor liver transplants (only 2 deceased donor transplants). The reason for switching to cyclosporine was reviewed and 68.8% (n=42) were found to be secondary to neurotoxicity. Among the other causes, common were cardiotoxicity (n=7) and nephrotoxicity (n=4).  
In the case of neurotoxicity, a switch to cyclosporine had been made only in case of moderate to severe symptoms, as per institution protocol. Thus, mild manifestations such as headache and tremors had been managed conservatively without a change of medication. Excluding the patients with incomplete data, a detailed analysis was done for 35 patients with tacrolimus-related neurotoxicity necessitating the switch to cyclosporine.
The average duration of follow-up in this subset was 21 months. The switch to cyclosporine was done at a median of 20 days postoperatively (range, 0 to 385 days). The most common presentation of severe neurotoxicity was posterior reversible encephalopathy syndrome (PRES) with or without seizures (n=13), followed by psychosis and behavioural changes (n=11). Visual disturbances (n=2), peripheral neuropathy (n=2), debilitating tremors (n=2) and encephalopathy (n=3) were the other reasons for switching to cyclosporine.
On follow-up, 54.3% (n=19) of the patients could be switched back to tacrolimus. The median duration of cyclosporine for these patients was 108 days (range, 8 to 672 days). All patients tolerated the reintroduction of tacrolimus well, with only one patient showing continued mild behavioural changes, which were managed with medications.
Conclusion: Tacrolimus-related neurotoxicity is a major dose and drug-limiting adverse effect. However, most of the mild manifestations can be well managed with dose modifications. In case of severe symptoms, tacrolimus can be switched to cyclosporine till neurological improvement; following which it is feasible, safe and preferable to reintroduce tacrolimus for optimal long-term immunosuppression.