Use of low-dose tacrolimus and associated hypomagnesemia in the prevention of erectile dysfunction following prostatectomy for prostate cancer.
BACKGROUND
Hypomagnesemia with urinary magnesium wasting is a well described adverse event with calcineurin inhibitor therapy. Prostate cancer is the most prevalent cancer in men in the United States. Injury to the cavernous nerves during radical prostatectomy frequently results in erectile dysfunction. Tacrolimus has been shown to be neuroprotective in the rat cavernous nerve injury model, an animal model representative of the neural injury that occurs in humans at the time of radical prostatectomy.


METHODS
In a randomized, double-blind, placebo-controlled trial, the utility of tacrolimus was assessed for prevention of erectile dysfunction following bilateral nerve-sparing radical prostatectomy.


RESULTS
Low dose tacrolimus, associated with low trough levels, resulted in mild hypomagnesemia, which was an early and persistent finding. As early as one week after institution of therapy, mean and median serum magnesium levels were significantly lower in the tacrolimus arm as compared to the placebo arm (p<0.001 for both). While the mean and median levels were within the normal range at Week 1, 10.9% of tacrolimus-treated patients had levels <1.8mg/dL, compared to none in the placebo arm (p=0.017). Median and mean levels remained significantly different at Week 5, Month 3 and Month 6. No clinical manifestations of hypomagnesemia were noted and no subject required treatment with magnesium. Changes in serum magnesium occurred earlier than other potential metabolic adverse events described with tacrolimus (changes in serum glucose, creatinine or potassium).


CONCLUSIONS
These data indicate that mild hypomagnesemia is an early and sensitive biomarker for the effect of tacrolimus on the kidney.
Transplant Genomics Inc., Brookline, MA, USA. Electronic address: roy@transplantgenomics.com.
Martin R
MR
First
The EMMES Corporation, Rockville, MD, USA.
Alice K
AK
Henning
Astellas Pharma Global Development, Northbrook, IL, USA.
William E
WE
Fitzsimmons
D065095:Calcineurin Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D004311:Double-Blind Method; D007172:Erectile Dysfunction / Q000097:blood* / Q000175:diagnosis / Q000517:prevention & control; D006801:Humans; D008274:Magnesium / Q000097:blood*; D008297:Male; D008875:Middle Aged; D011468:Prostatectomy / Q000009:adverse effects* / Q000639:trends; D011471:Prostatic Neoplasms / Q000097:blood* / Q000175:diagnosis / Q000628:therapy; D016559:Tacrolimus / Q000008:administration & dosage* / Q000009:adverse effects
D065095:Calcineurin Inhibitors; D008274:Magnesium; D016559:Tacrolimus
Serum magnesium; Tacrolimus; Tacrolimus blood levels