Infusion-related events

Alemtuzumab is a recombinant DNA-derived humanized monoclonal antibody used in the treatment of chronic lymphocytic leukemia and T-cell lymphoma. It targets CD52, a protein present on the surface of mature lymphocytes. Alemtuzumab has been associated with infusion-related events including hypotension, rigors, fever, shortness of breath, bron-chospasm, chills, and/or rash. Also reported were syncope, pulmonary infiltrates, cardiac arrhythmias, myocardial infarction and cardiac arrest. 

Quinupristin-dalfopristin is approved for treatment of infections caused by staphylococci or by vancomycin-resistant strains of E faecium, but not E faecalis, which is intrinsically resistant probably because of an efflux-type resistance mechanism. The principal toxicities are infusion-related events, such as pain at the infusion site, and an arthralgia-myalgia syndrome. 

Amphotericin colloidal dispersion has been compared with amphotericin deoxycholate in a prospective, randomized, double-blind study in the empirical treatment of fever and neutropenia in 213 patients (25). Patients were stratified by age and concomitant use of ciclosporin or tacrolimus and then randomized to receive ABCD (4 mg/kg/day) or amphotericin deoxycholate (0.8 mg/ kg/day) for 14 days. Renal dysfunction was less likely to develop and occurred later with ABCD than with amphotericin deoxycholate. Likewise, the absolute and percentage fall in the serum potassium concentration from baseline to the end of therapy was greater with amphotericin deoxycholate than ABCD. However, probable or possible infusion-related hypoxia and chills were more common with ABCD than amphotericin deoxycholate. There was a therapeutic response in 50% of the patients who received ABCD and 43% of those who received amphotericin deoxycholate. Thus, ABCD was of comparable efficacy and less nephrotoxic than amphotericin deoxycholate, but infusion-related events were more common with ABCD. 

Vancomycin is highly associated with adverse infusion-related events. These are especially prevalent with higher doses and a rapid infusion rate. A rapid infusion rate has been shown to cause anaphylactoid reactions, including hypotension, wheezing, dyspnea, urticaria, and pruritus. A significant drug rash (the so-called red man syndrome) also can occur. These events are much less frequent with a slower infusion rate. 

Caspofimgin 50 mg/m /day has been studied in a multicenter, prospective, open study in children aged 3 months to 17 years with invasive aspergillosis, invasive candidiasis, or esophageal candidiasis [88 ]. There were adverse events in seven patients, but none was considered drug related. There were laboratory adverse events in five patients, which were considered to be drug related in three. There were no infusion-related events or withdrawals because of... 

The most common reasons for discontinuation of treatment were infusion-related reactions (ie, dyspnea, flushing, headache, rash). Adverse events have been reported in a higher proportion of RA patients receiving the 10 mg/kg dose than the 3 mg/kg dose however, no differences were observed in the frequency of adverse events between the 5 and 10 mg/kg doses in patients with Crohn disease. 

In the clinical studies the most common adverse events observed with lar-onidase treatment were upper respiratory tract infection, rash, and injection site reaction. The most common adverse reactions requiring intervention were infusion-related reactions (IRRs), particularly flushing. Those requiring intervention were offset by slowing the infusion rate, temporarily stopping the infusion, and/or administering additional antipyretics and/or antihistamines. 

Docetaxel should be administered the day after trastuzumab for the first cycle because of the potential for infusion-related reactions to trastuzumab, particularly during or after the first administration. Serious adverse reactions to trastuzumab infusion that have been reported infrequently include dyspnoea (shortness of breath), hypotension, wheezing, hypertension, bronchospasm, supraventricular tachyarrhythmia, reduced oxygen saturation, anaphylaxis, respiratory distress and urticaria (itching). The majority of these events occur during or within 2.5 hours of the start of the first infusion. Should an infusion reaction occur, the infusion should be discontinued and the patient monitored until resolution of any observed symptoms - the infusion may be resumed when symptoms abate. If the first cycle is well tolerated then dosing of the drugs in future cycles may occur on the same day. 

The safety and efficacy of ABCD have been stndied in 220 bone marrow transplant recipients enrolled in the same five phase I or phase II stndies (23). The median dose in this population was 4 (range 0.4—8.0) mg/kg, and the median duration of treatment was 16 (range 1-409) days. Overall, 37 (19%) of the patients had nephrotoxicity, defined as a doubling of serum creatinine from baseline, an increase of 88 pmol/l from baseline, or at least a 50% fall in calculated creatinine clearance. There were no significant changes in hepatic transaminases, alkaline phosphatase, or total bilirubin. Fever and chills were reported by 12 and 11% of patients respectively. Other acute, severe, infusion-related adverse events were hypoxia (4.1%), hypertension (2.7%), and hypotension (2.7%). 

The safety and efficacy of ABLC 5 mg/kg/day in patients with neutropenia and intolerance or refractoriness to amphotericin deoxycholate have been reported in two smaller series of 25 treatment courses from the UK. In one, the mean serum creatinine at the start of therapy was 139 pmol/l and at the end of therapy 132 pmol/l there were no infusion-related adverse events (27). There was an increase in alanine transaminase activity in 12 of the 22 analysed treatment courses. In the other, there was an increase in serum creatinine in 5 of 18 courses (28%), and hypokalemia (less than 2.5 mmol/1) in two courses (11%) premedication for infusion-associated reactions was required in three courses (17%) (28). There were modest increases in serum alanine transaminase activities in five patients (30%). 

Safety data have been published in a retrospective analysis of 551 patients with invasive fungal infections intolerant of or refractory to conventional antifungal therapy, 73 of whom received ABLC initially at 3 mg/kg/day instead of 5 mg/kg/day, as recommended in the protocol (30). There were no notable differences in adverse events (increased semm creatinine, infusion-related chills) between the two gronps. Serum creatinine values were improved or stable at the end of therapy in 78 and 70% of patients respectively. 

The safety and efficacy of low dose ABLC (1 mg/kg/day) for empirical treatment of fever and nentropenia have been studied in 69 episodes in 61 patients with hematological malignancies (35). The median duration of therapy was 8 (range 2-19) days and 13 patients had mUd to moderate infusion-related adverse events. Creatinine concentrations remained stable in 42 cases, improved in 9, and deteriorated in 18. There were no other toxic effects. The response rate (resolution of fever dnring neutropenia and absence of invasive fungal infection) was 67%. 

Liposomal amphotericin and ABLC have been compared in an open randomized study in 75 adults with leukemia and 82 episodes of suspected or documented mycosis (48). The median durations of treatment and dosages were 15 days at 4 mg/kg/day for liposomal amphotericin and 10 days at 3 mg/kg/day for ABLC. Acute but not dose-limiting infusion-related adverse events occurred in 36 versus 70%. Bilirubin increased to over 1.5 times baseline in 59 versus 38%. There was no difference in the effects of either agent on renal function and drug-related withdrawals. The overall response rate to therapy in documented fungal infections (29 and 30% respectively) was not different between the two drugs. 

Anaphylaxis after ABCD occurred in a patient who had previously been treated with both amphotericin deoxycholate and ABLC without infusion-related adverse effects (65). During the first infusion of ABCD he developed spontaneously reversible severe back pain and then swelling of his lips, respiratory distress, and left-sided hemipar-esis, which resolved after 24 hours. An MRI scan suggested an ischemic event in the right putamen, lending support to the hypothesis that he had had an anaphylactic reaction to ABCD, hypoperfusion, and a subsequent stroke. 

In an open, dose-escalating study, 24 patients were allocated to five consecutive daily doses of a humanized IgGl anti-CD4 monoclonal antibody (4162W94) (4). There was at least one predefined infusion-related adverse effect (for example fever, chills/rigors, headache, nausea, vomiting, diarrhea, dyspnea, or hypotension) in 17 patients. Most of these events were mild or moderate in intensity, occurred on the first day of dosing, and resolved within 8 hours. In some patients the adverse events were associated with the... 

Infusion-related adverse effects of gemtuzumab ozogamicin can be treated with a brief course of an intravenous glucocorticoid. Of 143 patients with refractory myeloid leukemia treated with gemtuzumab ozogamicin, 110 received paracetamol 650 mg orally with diphenhydramine 50 mg intravenously and 33 received the same premeditations plus methylprednisolone sodium succinate 50 mg intravenously before the infusion and repeated 1 hour later (1). There were grade 2 or worse infusion-related adverse events in 32 (29%) of the former, but in only one of the latter (3%). 

A Japanese study compared the efficacy and safety of zoledronic acid 4 mg, administered as a 15-minute infusion every month for 1 year, versus placebo in 228 women with bone metastases from breast cancer [21]. Zoledronic acid reduced skeletal-related events by 39% and was well tolerated with a safety profile similar to that of placebo. Only 1 patient in the zoledronic acid group had a notable serum creatinine increase (2.0 mg/ dl) from a baseline of 1.3 mg/ dl compared with 7 patients in the placebo group. Moreover, no patient treated with zoledronic acid developed a grade 3 or 4 serum creatinine increase according to the National Cancer Institute common toxicity criteria, whereas... 

No serious adverse events related to rAHF-PFM were reported in the Pivotal study. In total, 19 non-serious adverse events in seven patients were judged to be product-related these included taste perversion, headache, fever, diarrhea, dizziness, hot flashes, pain in upper abdomen, pain in lower chest, shortness of breath, sweating, nausea, rigors, and itching in the arm used for the infusion [8]. Five non-serious drag-related events were mild, 12 were moderate, and two (one high fever and one severe headache, reported concurrently in one patient) were severe. No patient withdrew from the study because of any study-drag-related adverse event [8, 25, 27-29],... 

Observational studies In a pooled analysis of data from patients with rheumatoid arthritis treated with rituximab in combination with methotrexate safety analyses were based on 5013 patient-years of rituximab exposure [146 ]. The most frequent adverse event was infusion-related reactions, which occurred in 25% of patients during the first infusion under 1% of infusion-related reactions were considered serious. The overall serious infection rate was 4.31 per 100 patient-years. Infections and serious infections remained stable over time across five courses. Compared with other patients with rheumatoid arthritis and with the general US population, there was no increased risk of malignancy. 

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