Nonabsorbable corticosteroids use in the treatment of gastrointestinal graft-versus-host disease.

For over a decade, nonabsorbable corticosteroids have been employed in the treatment of gastrointestinal graft-versus-host-disease (GVHD) in hematopoietic stem cell transplant (HSCT), as monotherapy or in combination with systemic corticosteroids. The majority of the evidence showing a favorable outcome consisted of case series, small phase II trials and a large randomized phase III trial. The 2 most commonly studied molecules were oral budesonide and beclomethasone diproprionate. Although these reports hint at some benefit with the local treatment strategy, their methodologic inconsistencies preclude meaningful adoption to everyday clinical practice. This review evaluates the current evidence of nonabsorbable corticosteroids in HSCT and sets forth recommendations for future trials with these agents.

Influence of plasma exchange on the disposition of the fourth generation cephalosporin cefepime.

Cefepime, a fourth generation cephalosporin, is widely used in hematology and oncology patients. These patients may require plasma exchange (PE) for indications such as chemotherapy- or cancer-induced thromobotic thrombocytopenic purpura to name a few. To date, no pharmacokinetic evaluation has been conducted assessing cefepime's disposition during PE. A 2 g IV cefepime single dose was given to patients undergoing therapeutic PE. Two hours from cefepime dose administration, plasma concentration was measured. PE was then instituted and cefepime plasmapheresate concentration was measured at the completion of the PE session. Cefepime levels were measured using HPLC. The percentage removed by PE was calculated as: amount removed/2 g dose. Ten adult patients were analyzed: median age (range): 52 years (33-67) and median weight (range); 82.85 kg (47-120). PE indications were: myasthenia gravis (n = 3), transverse myelitis (n = 2), multiple sclerosis (n = 1), chronic inflammatory demyelinating polyneuropathy (n = 1), idiopathic thrombocytopenic purpura (n = 1), thrombotic thrombocytopenic purpura (n = 1), and humoral rejection post cadaveric renal allograft (n = 1). All patients except one had a creatinine clearance >60 mL/min. One patient was excluded from the pharmacokinetic analysis owing to loss of venous access during PE. For the remaining nine patients, total plasma volume removed was 3.5 L (range: 2.5-3.5) and duration of PE was 120 min (range: 94-209). The cefepime removed by PE was 3.7% (range: 2.1-6.7). A strong correlation was found between cefepime plasma concentration prior to PE and the amount of drug removed (r = 0.96, r(2) = 0.92; p<0.05). The above results suggest that, under the studied conditions, cefepime removal by PE is clinically insignificant (approximately 4% of total 2 g dose).

Immediate cross-hypersensitivity between micafungin and caspofungin: a case report.

A hematopoietic stem cell transplant patient with a history of immediate drug hypersensitivity reaction to micafungin was considered for a caspofungin trial. A caspofungin intradermal skin test was performed. The result was positive, suggesting the presence of cross-reactivity and that the cyclic peptide nucleus chemical structure shared between echinocandins is the site of IgE recognition. It is recommended to avoid challenging patients with history of immediate hypersensitivity to one echinocandin with another.

Effect of aprepitant on intravenous tacrolimus disposition in reduced intensity hematopoietic stem cell transplantation.

Aprepitant (AP) is a known inhibitor of cytochrome P450 3A4 which may affect tacrolimus metabolism. We retrospectively examined the effect of oral AP on intravenous tacrolimus concentrations in 26 patients undergoing reduced intensity transplantation from 09/2005 to 09/2006. Oral AP 125 mg daily was administered on transplant day +1 and 80 mg on days +2 and +3. Intravenous tacrolimus was administered as a 0.03 mg/kg/day continuous infusion on day -6 through day +1 (pre-AP), during-AP (days +2 to +7), and post-AP starting on day +8. Tacrolimus doses were adjusted to achieve concentrations of 5-20 ng/mL. Dose-corrected tacrolimus concentrations (ng/mL/mg per dose) in the pre-AP, during-AP, and post-AP time periods were: 8.12 (95% CI: 7.3-9.1), 11.63 (95% CI: 9.63-13.63), and 11.42 (95% CI: 8.12-14.7), respectively (P<0.01 between pre-AP and during-AP, P<0.01 between during-AP and post-AP, P = 0.01 between pre-AP and post-AP time periods). Although statistically significant, the observed rise was not clinically significant between during-AP and post-AP time periods. Previous work has shown that AP is not expected to exert an inhibitory effect within 48 h of AP discontinuation. Collectively, these data suggest that AP effect on tacrolimus metabolism is of minor clinical significance. A controlled trial is needed to confirm these findings.

Drug removal by plasmapheresis: an evidence-based review.

Contrary to the literature about drug removal during hemodialysis, data regarding drug removal during plasmapheresis are sparse. Over the last 40 years, approximately 70 publications-mostly case reports of overdoses-have described the effects of plasmapheresis on pharmaceutical agents. Important issues are drug extraction during plasma exchange with chemotherapy, as well as drug classes such as antiinfectives, anticoagulants, antiepileptics, cardiovascular agents, and immunosuppressants. Other considerations are the merits and pitfalls of the different methods used in published reports and recommendations for future pharmacokinetic studies in this field.

Palifermin in a hematopoietic stem cell transplant patient with osteonecrosis of the jaw.

This case report describes the use of palifermin in a multiple myeloma patient with a history of osteonecrosis of the jaw (ONJ) for the prevention of high-dose chemotherapy-induced mucositis. Following the day of autologous stem cell infusion, palifermin was discontinued secondary to adverse events. Specifically, palifermin-associated macroglossia seemed to exacerbate the pain localized in the oral cavity area affected by ONJ, necessitating escalated doses of narcotic analgesics. When contemplating palifermin as a mucosal protectant in a hematopoietic stem cell transplant patient with ONJ, a careful benefit-to-risk assessment is in order to ensure optimal effectiveness without undue harm.