Posaconazole, a prophylactic therapy in patients with haematological cancer: drug use evaluation study

Abstract

Background Posaconazole (PSZ), is an antifungal prophylactic therapy that is used in haematological cancer patients. In 2010, PSZ was added to the formulary of the National Centre for Cancer Care & Research (NCCCR), the only adult cancer hospital in Qatar. Objective To conduct a drug use evaluation (DUE) study of PSZ at NCCCR. Method A retrospective, single centred, observational DUE study was conducted to include a convenient sample of haematological cancer patients who used PSZ prophylactically in 2010. All 31 patients were nominated; 20 patients profiles were reviewed. Data were collected using a pre-prepared collection sheet and descriptive analysis was performed. Results One patient was excluded as he was not a haematological cancer patient. All remaining 19 patients received PSZ for prophylaxis and were compliant. More than 50% of patients received proton pump inhibitors concurrently with PSZ. Only 1 case had a recorded recommendation regarding the administration of PSZ with food. Five patients received a vincristine based chemotherapy protocol, one of which developed seizures. Two patients developed mild breakthrough fungal infection while on PSZ. Conclusions The PSZ practice in NCCCR abides by its regulations of use. However, clear recommendations regarding administration of PSZ with meals is essential. PSZ co-administration with proton pump inhibitors should be either stopped or managed by PSZ therapeutic drug monitoring to avoid PSZ sub-therapeutic levels. Possible serious drug interactions in patients treated with vincristine based chemotherapy should be highlighted and monitored.

Hyperlipidemia Alters the Pharmacokinetics of Posaconazole and Vincristine Upon Co-Administration in Rats

“…Owing to their immunocompromised state and intensive chemotherapy, the ALL patient population is highly susceptible to invasive fungal infections. Triazole antifungals including fluconazole, voriconazole, itraconazole, and posaconazole (PSZ) are among the common measures taken for the prophylaxis and treatment of invasive fungal infections [ 18 , 40 ]. Posaconazole is widely used as prophylactic therapy in hematopoietic stem cell transplant recipients with graft-vs.-host disease, or in individuals with hematological malignancies experiencing prolonged neutropenia as a result of intensive chemotherapy [ 3 , 18 , 22 ].…”

“…After oral administration in humans, PSZ is erratically absorbed and follows linear pharmacokinetics. Posaconazole has a large V d (1774 L), and is considerably bound to plasma proteins with a proportion of 98% to albumin [ 18 , 22 , 25 ]. Posaconazole has a median t 1/2 between 15 and 35 h [ 7 ].…”

“…The time reported to reach maximum plasma concentration is between 6 and 8 h [ 33 ]. Posaconazole is excreted unchanged in feces, with only 16% undergoing glucuronidation through UGT1A4 and recovered in urine [ 10 , 18 ]. It was also reported that PSZ undergoes enterohepatic circulation, presenting a second peak after 24 h [ 24 , 33 ].…”

High Performance Liquid Chromatographic Assay for the Simultaneous Determination of Posaconazole and Vincristine in Rat Plasma

“…Posaconazole (PSZ) is an oral triazole antifungal used in the treatment of severe oropharyngeal candidiasis, invasive aspergillosis, and other fungal infections in patients who are resistant to, or intolerant of, other antifungal drugs. PSZ is also given for prophylaxis in patients who are at high risk for invasive fungal disease due to immunosuppression, such as haematopoietic stem cell transplant recipients with graft-versus-host disease, or those with haematological malignancies with prolonged neutropenia as a result of chemotherapy [ 1 , 2 ]. The coadministration of azoles (as prophylaxis or treatment of fungal infections) and VCR has been shown to increase VCR neurotoxic effects due to the inhibition of cytochrome P450 (CYP) isoform 3A4, for which VCR is a substrate [ 2 ].…”

“…PSZ is also given for prophylaxis in patients who are at high risk for invasive fungal disease due to immunosuppression, such as haematopoietic stem cell transplant recipients with graft-versus-host disease, or those with haematological malignancies with prolonged neutropenia as a result of chemotherapy [ 1 , 2 ]. The coadministration of azoles (as prophylaxis or treatment of fungal infections) and VCR has been shown to increase VCR neurotoxic effects due to the inhibition of cytochrome P450 (CYP) isoform 3A4, for which VCR is a substrate [ 2 ]. Those neurotoxic symptoms usually appear as constipation and peripheral neurotoxicity [ 3 ].…”