Presentation Authors: Nagendra Nath Mishra*, Anand, India
Introduction: Interstitial Cystitis/ Bladder Pain Syndrome (IC/BPS)is a chronic condition in which the effectiveness of current treatments is limited with no cure available. Cyclosporine A is emerging as a treatment modality in intractable cases of IC/BPS but use is limited due to side effects. Tacrolimus also is calcineurin inhibitor as Cyclosporine A and is very toxic. Thinking that tacrolimus is insoluble in water we used tacrolimus dissolved in DMSO in patients of intractable IC/BPS and found it to be effective in 50 percent patients but the solution thus prepared caused irritation to the urinary bladder making it difficult for the patients to retain the solution in bladder for 30 minutes. This led to poor patient compliance. To increase the compliance we went on decreasing concentration of DMSO to 2% and found that there is no decrease in the absorption of DMSO confirmed by serum level. To further decrease the irritability of the solution we decided to use only sterile water to dissolve tacrolimus. The aim of this study was to see if tacrolimus dissolved in water was absorbed through bladder mucosa in blood, and was safe effective and acceptable to the patient.
Methods: From Jun 17 to Oct 18 tacrolimus powder (1mg/kg) dissolved in sterile water was instilled in bladder of 9 patients(6 females and 3 males) of intractable BPS/IC. 6 of these patients had hunners lesion(HL) and 3 did not have hunners lesion(NHL).Patients received three cycles of therapy at interval of 14 days. Base line complete blood count, blood glucose, renal and liver function test were done and repeated after third instillation. Serum tacrolimus level was also measured in first 2 patients after 30 minutes of instillation. Primary study endpoint was Global Response Assessment (GRA) score. For the sake of comparison in first patient first and second instillation was done with tacrolimus dissolved in 2% DMSO and third instillation was with sterile water.
Results: 4 out of 9 patients improved symptomatically( follow up extending from 1 to 13 month-mean 11 month and median 13 month). 3 HL and one NHL patient improved(50% versus 33). Except for post- instillation flare in one patient no side effects were observed in the patients during follow-up. Patients were able to retain the solution easily for 30 minutes. Blood levels of tacrolimus reached same safe level(8.73-9.98ng) irrespective of using either DMSO or water for preparing the solution.2 patients dropped after one instillation, one due to flare up and second due to personal reason.
Conclusions: This study proved that tacrolimus dissolved in water is absorbed in blood through bladder mucosa in IC/BPS patients and is safe effective and acceptable. The positive response is maintained long term. Patient compliance is good when tacrolimus is dissolved in sterile water. Solution in sterile water is acceptable to the patients without compromising safety and effect. This is a very effective formulation as improvement is seen in 43% patients with severe disease and unpredictable surgery can be avoided. Result is better in HL patient than NHL. First time in the world we have demonstrated that tacrolimus powder dissolved in sterile water is absorbed in blood via bladder mucosa