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CASE REPORTS resolve. Sirolimus was switched to prednisolone (serum creatinine level 356 |imol/L). About 7 months later, his serum creatinine level had increased to 449 |imol/L. Prednisolone was tapered and replaced with everolimus. His serum creatinine improved to 360 |J.mol/L, and there was no recurrence of his pulmonary symptoms. A 51-year-old woman was switched from ciclosporinbased treatment to sirolimus [dosage not stated] because of calcineurin inhibitor toxicity; mycophenolate was continued. She had a serum creatinine level of 291 |imol/L. The next year, she was admitted with fever and cough [time to reaction onset not clearly stated]. Bronchoscopic biopsy revealed allergic interstitial pneumonia. Sirolimus was switched to everolimus. Her pulmonary findings and symptoms resolved. At last follow-up, her serum creatinine level was stable at 223 lO-mol/L. A 65-year-old man was switched to sirolimus 2mg [frequency not stated] and mycophenolate because of cutaneous spinocellular cancers. An unspecified time later, he was hospitalised due to lymphocytic alveolitis, revealed by bronchoscopic lung biopsy. Sirolimus was switched to everolimus. His serum creatinine level was 212 |xmol/L and he had no pulmonary infiltration on a chest x-ray or subjective complaints. However, he subsequently had relapsing allergic pneumonitis; everolimus was to be withdrawn and replaced with prednisolone. A sixth patient, aged 62 years, developed sirolimusinduced pneumonitis and was switched to everolimus. [Patient sex, therapeutic indication, dosage and duration of therapy, and patient outcome not stated].
Rehm B, Keller F, Mayer J, Stracke S. Resolution of sirolimus-induced pneumonitis after conversion to everolimus. Transplantation Proceedings 38: 711 -713, No. 3, Apr 2006 - Germany 801064376

haemopoiesis. He continued to receive antibacterials and supportive treatment. The absence of haemopoietic-cell progenitors was confirmed by a repeat bone-marrow biopsy 2 weeks later, and he was diagnosed with aplastic anaemia. Three months after the last temozolomide treatment, he underwent a T-cell depleted allogeneic stem cell transplantation. He recovered well, received immunosuppressive therapy and continued antibacterial prophylaxis. On day 60 after transplantation, he was diagnosed with cytomegalovirus viraemia, followed by paraplegia from transverse myelitis. He received IV ganciclovir and foscarnet, but had progressive malaise and weight loss, and did not recover his neurological function. A decision was made to receive comfort care, and he died 4 months after transplantation. Author comment: "This patient received two antiepileptic drugs associated with aplastic anaemia phenytoin and carbamazepine. . . The patient presented here gives further evidence for a causative role of temozolomide in irreversible bone-marrow failure. Although other causes cannot be ruled out, the timeline of temozolomide treatment and the haematological recovery between cycles are consistent with chemotherapeutic effects."
Villano JL, Collins CA, Manasanch EE, Ramaprasad C, V a n Besien K. Aplastic anaemia in patient with glioblastoma multiforme treated with temozolomide. Lancet Oncology 7; 436-438, N o . 5, M a y 2006 - USA oiO64394

Topiramate see Oxcarbazepine/topiramate

Warfarin interaction



Aplastic anaemia: case report A 45-year-old man developed aplastic anaemia after treatment with temozolomide for glioblastoma. The man received radiotherapy and temozolomide 75 mg/mVday, for 6 weeks. After the treatment, he had a WBC count of 4.7 x lO'cells/L, an absolute neutrophil count of 3610 x 10cells/L, a platelet level of 180 x lO'/L and a haemoglobin level of 128 g/L. Four weeks later, he started temozolomide 200 mg/mVday, for 5 days of a 28-day cycle. His nadir absolute neutrophil count was 1070 X 10* cells/L and his WBC count was 1.6 X 10'cells/L, during the third cycle. Temozolomide was reduced to 150 mg/m^, and the fourth cycle was initiated when his blood counts recovered adequately. After the fourth cycle, he developed persistent and profound pancytopenia, with a WBC count of 1.7 X 10 cells/L, a neutrophil count of 740 x 10* cells/L, a platelet level of 23 x lO'/L and a haemoglobin level of 84 g/L. All drugs including the man's concomitant phenytoin and carbamazepine were discontinued and he received prophylactic antibacterials, epoetin alfa,filgrastimand platelet transfusions. Eight weeks after temozolomide treatment, his pancytopenia worsened. He had a WBC count of 0.3 X 10' cells/L, a neutrophil count of < 100 X 10* cells/L, a platelet level of 9 x lO'/L and a haemoglobin level of 73 g/L. A bone-marrow biopsy revealed hypocellular bone marrow with nearly absent

Interaction with concomitant herbal medicine leading to retroperitoneal and rectus sheath haematomas in an elderly patient: case report A 70-year-old woman receiving warfarin after a mechanical mitral valve placement developed retroperitoneal and rectus sheath haematomas during concomitant treatment with Matricaria chamomilla [chamomile; dosage not stated]. The woman, who had been receiving warfarin (4mg 3 days a week and 6mg 4 days a week), presented with a cough, difficulty sleeping and expectoration of yellow sputum; her concomitant medications included amiodarone. She had a haemoglobin level of 117 g/L and an INR of 3.6 (therapeutic range 2.5-3.5). She was diagnosed with an upper respiratory tract infection and was discharged without antibacterial treatment. After 5 days, she presented again with similar symptoms and was feeling weaker. She had bilateral pedal oederna, dyspnoea on exertion and ecchymoses in her perineal area, over her left hip and across her lower abdomen. Her haemoglobin level and INR were 80 g/L and 7.9, respectively. The woman received packed RBCs and fresh frozen plasma. An abdominal CT scan showed a retroperitoneal haematoma (12 x 7 x 6cm) in her pelvis, medial to her left obturator internus muscle. She also had bilateral recti muscle haemorrhage that measured 4.7 x 2.9cm on her right and 4.2 x 7.7cm on her left. She was hospitalised and received IV heparin. Her haemorrhages subsequently self-occluded. Her warfarin dose was adjusted to achieve a stable INR and heparin was discontinued. She was then

Reactions 3 Jun 2006 No. 1104

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discharged with an INR of 2.5 and a stable haemoglobin level. Further questioning revealed that after her initial discharge, she had started applying a teaspoon-sized dollop of chamomile-based skin lotion to each of her leg 4-5 times a day for pedal oedema. She had also started receiving 4-5 cups per day of chamomile tea for pharyngitis and a camphor-based lotion for chest congestion. Author comment: "It is highly likely that an herb-drug pharmacodynamic interaction accounted for the increased [haemorrhage] observed. Specifically, the coumarin constituent of chamomile may have worked in synergy with warfarin and resulted in supratherapeutic anticoagulation, which would explain her increased INR."
Segal R, Pilote L. Warfarin interaction with Matricaria chamomilla. CMAJ: Canadian Medical Association Journal 174: 1281-1282, No. 9, 25 Apr 2006 Canada 8OIOM37I


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Reactions 3 Jun 2006 No. 1104