Docetaxel/lopinavir/ritonavir interaction
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Myelosuppression, mucositis and rash: case report A 30-year-old woman developed prolonged myelosuppression, grade 4 mucositis and desquamating rash during concomitant treatment with docetaxel and lopinavir/ritonavir (Kaletra). The woman underwent wide local excision and sentinel lymph node biopsy for grade 2 invasive ductal breast cancer. She then received fluorouracil, epirubicin and cyclophosphamide every 21 days for three cycles, followed by sequential three-cycle docetaxel therapy of 100 mg/m2 every 21 days. She tolerated her first two cycles of docetaxel with minimal toxicity of grade 1–2 nausea, grade 1 neuropathy and grade 2 fatigue. After her fifth chemotherapy cycle (second cycle of docetaxel), she had a low-risk needlestick injury from her HIV-positive partner. A week before her third docetaxel cycle, she started receiving post-exposure prophylaxis (PEP) with Kaletra, which contains lopinavir 400mg and ritonavir 100mg twice daily, and lamivudine/zidovudine (Combivir). She received her third docetaxel cycle uneventfully with dexamethasone prophylaxis. However, she was admitted on day 6 of the cycle (after 13 days of PEP) with grade 2 mucositis, febrile neutropenia and grade 2 arthralgia and myalgia. On admission, she had a total WBC count of 1.3 × 109/L and a neutrophil count of 0.6 × 109/L. The next day, her neutrophil count decreased to 0.005 × 109/L. The woman received piperacillin/tazobactam, gentamicin and fluconazole. Blood cultures revealed Cellumonas species. Over the following few days, her mucositis deteriorated to grade 4 and her swinging fevers continued with persistent neutropenia (grade 4). She received teicoplanin, followed by meropenem. She received granulocyte colony-stimulating factors and her fluconazole dosage was increased. On day 7, her neutrophil count increased to 2.1 × 109/L. However, she then developed diarrhoea and, on day 10, she developed erythema and facial swelling. Combivir was replaced by another antiretroviral because of ongoing myelosuppression. However, she decided to discontinue all antiretrovirals. She developed a florid rash on her feet and hands. Fluconazole was replaced by caspofungin. After 2 weeks’ hospitalisation, her condition did not improve and she started receiving ganciclovir for possible CMV-related mucositis. She received parenteral nutrition. Further investigation revealed widespread ulceration of her oesophagus and gastric antrum. Her condition started to improve on day 16 with an improvement in her WBC count and mucositis resolution. On day 20, she experienced a mild gastrointestinal bleed that was managed conservatively. However, despite this her recovery continued. Twenty-six days after admission, she was well and was discharged home. Author comment: "In order to quantify the strength of the association, the authors used the Drug Interaction Probability Scale . . . Using the data presented above, a score of 5 classified this as a probable causal relationship." Hewish M, et al. Severe synergistic toxicity from docetaxel in a patient treated conc
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