IMPORTANT SAFETY INFORMATION
Post-Transplant Lymphoproliferative Disorder (PTLD)
- NULOJIX patients are at increased risk for developing PTLD, predominantly
involving the central nervous system (CNS)
- Recipients without immunity to EBV (ie, seronegative) are at particularly
increased risk; therefore, NULOJIX is contraindicated in transplant recipients
who are EBV seronegative or with unknown serostatus
- Monitor for new or worsening neurological, cognitive, or behavioral signs and
symptoms
- As the total burden of immunosuppression is a risk factor for PTLD, higher than
recommended doses or more frequent dosing of NULOJIX or concomitant
immunosuppressive agents are not recommended
- Other known risk factors for PTLD include cytomegalovirus (CMV) infection and
T cell-depleting therapy
- CMV prophylaxis is recommended for at least 3 months after transplantation
- Use
T cell-depleting therapy to treat acute
rejection cautiously
- Patients who are EBV seropositive and CMV seronegative may be at increased risk of
PTLD
- Since CMV seronegative patients are at increased risk for CMV disease (a
known risk factor for PTLD), the clinical significance of CMV serology for
PTLD remains to be determined; however, these findings should be considered
when prescribing NULOJIX
Management of Immunosuppression
- Only physicians experienced in immunosuppressive therapy and management of
kidney transplant patients should prescribe NULOJIX
- Patients should be managed in facilities with adequate laboratory
and supportive medical resources
- The physician responsible for maintenance therapy should have
complete information requisite for the follow-up of the patient
Progressive Multifocal Leukoencephalopathy (PML)
- NULOJIX patients are at increased risk for PML, often a rapidly progressive and
fatal opportunistic infection
- In clinical trials, two cases were reported in patients receiving NULOJIX at
higher cumulative doses and more frequently than the recommended regimen,
along with MMF and corticosteroids; one occurred in a kidney transplant
recipient and one occurred in a liver transplant recipient
- As PML has been associated with high levels of immunosuppression, higher than
recommended doses or more frequent dosing of NULOJIX and concomitant
immunosuppressive agents, including MMF, are not recommended
- Monitor for new or worsening neurological, cognitive, or behavioral signs and
symptoms
- PML is usually diagnosed by brain imaging, cerebrospinal fluid testing for
JC viral DNA by polymerase chain reaction, and/or brain biopsy
- Consultation with a specialist should be considered
- If PML is diagnosed, consider reduction or withdrawal of immunosuppression,
weighing risk to the allograft
Other Malignancies and Serious Infections
- Increased susceptibility to infection and possible development of
malignancies may result from immunosuppression
- Patients should avoid prolonged exposure to ultraviolet light and sunlight
- Patients receiving immunosuppressants, including NULOJIX, are at increased risk for
bacterial, viral, fungal, and protozoal infections, including opportunistic
infections and tuberculosis. Some infections were fatal
- Polyoma virus-associated nephropathy can lead to deteriorating renal
function and graft loss; consider reduction in immunosuppression, weighing
risk to the graft
- Tuberculosis was more frequently observed in patients receiving NULOJIX.
Evaluate for tuberculosis and initiate treatment for latent infection prior
to NULOJIX use
- CMV and Pneumocystis jiroveci prophylaxis is recommended after
transplantation
Liver Transplant: use in liver transplant patients is not
recommended due to increased risk of graft loss and death in a clinical
trial with more frequent administration of NULOJIX than studied in kidney transplant,
along with MMF and corticosteroids
Acute Rejection and Graft Loss with Corticosteroid
Minimization
- In NULOJIX postmarketing experience, corticosteroid minimization to 5 mg/day
between Day 3 and Week 6 post-transplant was associated with an increased rate and
grade of acute rejection, particularly Grade III
- These Grade III rejections occurred in patients with 4-6 human leukocyte
antigen (HLA) mismatches
- Graft loss was a consequence of Grade III rejection in some patients
- Corticosteroid utilization should be consistent with the NULOJIX clinical trial
experience
- Median (25th-75th percentile) corticosteroid doses were tapered to
about 15 mg (10-20 mg)/day by the first 6
weeks and remained at about 10 mg (5-10 mg)/day for the
first 6 months post-transplant
Immunizations: avoid use of live vaccines during NULOJIX
treatment
Coadministration with Anti-Thymocyte Globulin: in de
novo kidney transplant recipients, especially those with other predisposing risk factors
for venous thrombosis of the renal allograft, coadministration (at the same or
nearly the same time) with anti-thymocyte globulin may pose a risk for venous thrombosis
of the renal allograft. If anti-thymocyte globulin (or any other cell-depleting
induction treatment) and NULOJIX will be administered concomitantly, a 12-hour interval
between the two administrations is suggested
Risk of Rejection with Conversion From a Calcineurin Inhibitor
(CNI) Based Maintenance Regimen: conversion of patients from a CNI based
maintenance regimen increases the risk of acute rejection. Conversion of stable kidney
transplant recipients from a CNI based maintenance regimen to a NULOJIX based
maintenance regimen is not recommended unless the patient is CNI intolerant
Pregnancy: the data with NULOJIX use in pregnant women
are insufficient to inform on drug-associated risk. NULOJIX is known to cross the
placenta of animals. To monitor maternal-fetal outcomes of pregnant women who have
received NULOJIX, or whose partners have received NULOJIX, healthcare providers are
strongly encouraged to register pregnant patients in the Transplant Pregnancy Registry
International (TPR) by calling 1-877-955-6877
Lactation: there are no data on the presence of NULOJIX in human milk or
the effects on breastfed
infants or human milk production to inform risk of
NULOJIX to an infant during lactation. NULOJIX is excreted in rat milk and it is
possible that the drug will be present in human milk. The developmental and health
benefits of breastfeeding should be considered along with the mother’s clinical
need for NULOJIX, and any potential adverse effects on the breastfed
child from NULOJIX or from the underlying maternal
conditions
Most Common Adverse Reactions (≥20%) through 3 years:
anemia (45%), diarrhea (39%), urinary tract infection (37%),
peripheral edema (34%), constipation (33%), hypertension (32%),
pyrexia (28%), graft dysfunction (25%), cough (24%), nausea (24%),
vomiting (22%), headache (21%), hypokalemia (21%),
hyperkalemia (20%), and leukopenia (20%). No new adverse reactions were
observed in the long-term extension (years 4-7) studies
Please see Full Prescribing Information, including Boxed
WARNINGS.