Intravenous Cyclosporine-Rifampin Interaction
A 10-year-old girl with chronic myelogenous leukemia began receiving cyclosporine the day before bone marrow transplant surgery. Three days after the transplant, she developed fever and neutropenia due to a Staphylococcus aureus bacteremia. Despite treatment with various antibiotics, the patient's fever persisted over the next 4 days. Intravenous rifampin was added to her antibiotic regimen of piperacillin, tobramycin, cloxacillin, and amphotericin. On day 12, the patient's blood cultures were negative and her fever had resolved; rifampin was discontinued. On day 16, the patient engrafted; she subsequently developed a grade II graft-versus-host disease of the skin and gastrointestinal tract, which responded to methylprednisolone. Her cyclosporine blood levels, which had been subtherapeutic since day 5 despite increasing intravenous dosages, were within the therapeutic range on day 21, and she was discharged 12 days later. To our knowledge, this is the first documented case of an intravenous cyclosporine-rifampin interaction that resulted in subtherapeutic cyclosporine concentrations in a child receiving a bone marrow transplant who subsequently developed acute graft-versus-host disease.
Cyclosporine is a key component of therapy to prevent acute graft-versus-host disease (GVHD) after a patient receives an allogeneic bone marrow transplant (BMT). This drug is given to all patients receiving an allogeneic BMT at our pediatric institution, starting on the day before transplantation.
During the period of neutropenia after a BMT, patients are susceptible to life-threatening infections, and a variety of antibiotics are used in prophylactic and treatment regimens. Rifampin -- an antibiotic with a broad spectrum of activity against gram-positive, gram-negative, and atypical pathogens -- is rarely used in our BMT unit, largely because it increases the hepatic and gut metabolism of cyclosporine, thus reducing its bioavailability. There are several reports of cyclosporine-rifampin drug interactions (leading to organ rejection 95% of the time) in adult kidney, liver, and heart transplant recipients.
To our knowledge, this is the first report of an intravenous cyclosporine-rifampin interaction that resulted in subtherapeutic cyclosporine concentrations in a pediatric BMT recipient who subsequently developed an acute GVHD episode.
A 10-year-old girl with chronic myelogenous leukemia began receiving cyclosporine the day before bone marrow transplant surgery. Three days after the transplant, she developed fever and neutropenia due to a Staphylococcus aureus bacteremia. Despite treatment with various antibiotics, the patient's fever persisted over the next 4 days. Intravenous rifampin was added to her antibiotic regimen of piperacillin, tobramycin, cloxacillin, and amphotericin. On day 12, the patient's blood cultures were negative and her fever had resolved; rifampin was discontinued. On day 16, the patient engrafted; she subsequently developed a grade II graft-versus-host disease of the skin and gastrointestinal tract, which responded to methylprednisolone. Her cyclosporine blood levels, which had been subtherapeutic since day 5 despite increasing intravenous dosages, were within the therapeutic range on day 21, and she was discharged 12 days later. To our knowledge, this is the first documented case of an intravenous cyclosporine-rifampin interaction that resulted in subtherapeutic cyclosporine concentrations in a child receiving a bone marrow transplant who subsequently developed acute graft-versus-host disease.
Cyclosporine is a key component of therapy to prevent acute graft-versus-host disease (GVHD) after a patient receives an allogeneic bone marrow transplant (BMT). This drug is given to all patients receiving an allogeneic BMT at our pediatric institution, starting on the day before transplantation.
During the period of neutropenia after a BMT, patients are susceptible to life-threatening infections, and a variety of antibiotics are used in prophylactic and treatment regimens. Rifampin -- an antibiotic with a broad spectrum of activity against gram-positive, gram-negative, and atypical pathogens -- is rarely used in our BMT unit, largely because it increases the hepatic and gut metabolism of cyclosporine, thus reducing its bioavailability. There are several reports of cyclosporine-rifampin drug interactions (leading to organ rejection 95% of the time) in adult kidney, liver, and heart transplant recipients.
To our knowledge, this is the first report of an intravenous cyclosporine-rifampin interaction that resulted in subtherapeutic cyclosporine concentrations in a pediatric BMT recipient who subsequently developed an acute GVHD episode.
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