Rapid intravenous infusion of amphotericin B: A pilot study

Cruz, Julia M.; Peacock, James E.; Loomer, Lance; Holder, Lawrence E.; Evans, Gregory W.; Powell, Bayard L.; Lyerly, Evan; Capizzi, Robert L.

doi:10.1016/0002-9343(92)90040-i

Cited by 41 publications

(9 citation statements)

References 21 publications

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“…They observed an increase of serum creatinine in 47% of patients, and the doubling time was 19 days. Cruz et al tested various AmB infusion rates in 25 patients [6]. A serum creatinine increase of 44 µmol/l (0.5 mg/dl) was observed in 68% of patients.…”

Section: Discussionmentioning

confidence: 96%

Must we really fear toxicity of conventional amphotericin B in oncological patients?

Mayer

Doubek

Vorlíček

1999

Support Care Cancer

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Fungal infections are an important cause of morbidity and mortality in patients with malignancies. Therefore, the use of amphotericin B (AmB) is essential for these patients. Results from the literature to date show that renal toxicity is the most serious adverse effect of AmB. Renal impairment manifests as a decrease in glomerular filtration and damage to tubular function. Currently, there is no reliable method of preventing nephrotoxicity. We have observed that sodium supplementation alone may not prevent nephrotoxicity. We noted that a large decrease in serum potassium and magnesium was followed by a significant reduction in creatinine clearance and an increase in both serum urea and creatinine. Therefore, we surmised that potassium and magnesium supplements corresponding to the amounts lost by the kidneys, as well as sufficient hydration, are necessary to prevent renal function damage. We decided to test our hypothesis in 32 cancer patients. During AmB therapy, serum electrolyte concentrations and biochemical parameters of renal function and fluid balance were monitored frequently. The daily ion supplementation corresponded to the amount lost through the kidneys. The total duration of administration ranged from 4 to 39 days, with a mean of 13.7 days (median 11.0 days). The mean daily AmB dose was 0.89 mg/kg (median 0.88 mg/kg). The average diuresis was 3863 ml/day, and the median 4000 ml/day. The daily mean i.v.-administered sodium dose was 195.9 mmol, the daily mean dose of i.v. potassium was 103.7 mmol, and the daily mean dose of i.v. magnesium was 9.0 mmol. The frequency of infusion-related side-effects was only 10.0%. These reactions were treated with hydrocortisone. We observed a significant increase in potassium and magnesium lost through the kidneys, and a significant increase in fractional sodium and potassium excretion through the renal tubuli. We did not observe a significant increase in serum creatinine and ion imbalances. Interestingly, the average creatinine clearance did not decrease, but actually increased slightly, though to a statistically insignificant degree, from 1.425 ml/s at the beginning of treatment to 1.589 ml/s on the 20th day of AmB use. Sufficient hydration of patients and ion supplementation corresponding to the amount lost by the kidneys is an effective prophylaxis for prevention of AmB-induced decrease in renal function and for countering imbalances of serum electrolyte concentrations during use of AmB. The frequency of infusion-related side-effects is minimal relative to other reports.

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Section: Discussionmentioning

confidence: 96%

Must we really fear toxicity of conventional amphotericin B in oncological patients?

Mayer

Doubek

Vorlíček

1999

Support Care Cancer

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“…Although these toxicities are also associated with conventional amphotericin B therapy, it is difficult to compare actual incidence rates since the reported incidence of infusion-related toxicity in BMT patients treated with amphotericin B varies according to the report. 8,27,28 Despite the hepatic metabolism of ABCD, there were no significant liver toxicities observed.…”

mentioning

confidence: 98%

Treatment of invasive fungal infections with amphotericin B colloidal dispersion in bone marrow transplant recipients

Noskin

Pietrelli

Gurwith

et al. 1999

Bone Marrow Transplant

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Summary:Amphotericin B colloidal dispersion (ABCD, AMPHO-TEC, AMPHOCIL), a lipid complex of amphotericin B, was developed to reduce the nephrotoxicity of amphotericin B while retaining its antifungal efficacy. In this retrospective review, the efficacy and safety of ABCD were evaluated in 220 BMT recipients (167 allogeneic; 53 autologous) with suspected or documented lifethreatening fungal infections (primarily Candida or Aspergillus species). Patients were treated in five openlabel clinical trials of ABCD therapy. ABCD was administered intravenously once daily, median dose of 4 mg/kg, for up to 409 days (mean 23 days, median 16 days). Successful therapeutic response to treatment (complete or partial) was reported in 52% of the 99 evaluable patients with proven infection, and in 40% of all 220 patients. In the evaluable population, the response and mortality rates were 51% and 73%, respectively, in the allogeneic BMT patients, compared to 52% and 48% in the autologous BMT patients. The response rate for evaluable patients with Candida spp was 65%, 38% for patients with Aspergillus spp, and 42% for patients with other or multiple fungal infections. In this patient population at high risk of nephrotoxicity due to concomitant cyclosporine and/or other nephrotoxic agents, ABCD did not cause renal dysfunction. Although the majority of patients had pre-existing renal impairment (median baseline serum creatinine 1.8 mg/dl), there was no trend towards increasing serum creatinine. No unexpected toxicities were observed. In conclusion, ABCD appears to be safe and effective for the treatment of severe fungal infections in BMT patients. Keywords: ABCD; amphotericin B cholesteryl sulfate for injection; amphotericin B colloidal dispersion; marrow transplant; fungal infection; nephrotoxicity Opportunistic fungal infections are an increasing cause of morbidity and mortality in bone marrow transplant (BMT) patients. evolved, the problem of invasive fungal infection has assumed increased significance. In reports from marrow transplant centers 1-3 the incidence of systemic fungal infections ranges from 4 to 30% with a mortality rate approaching 100%. 4 The administration of prophylactic fluconazole may decrease the incidence of documented systemic fungal infection following high-dose chemotherapy and BMT. 5,6 However, despite fluconazole prophylaxis, over half of patients still require empiric therapy with amphotericin B for prolonged unexplained febrile episodes. 5 Additionally, fluconazole is not effective against Aspergillus spp infections and certain species of Candida, such as C. krusei and most strains of C. glabrata.Amphotericin B, a polyene antibiotic that has been used to treat fungal infections for four decades, is still considered the most reliable agent for therapy of mycoses in immunosuppressed patients. However, its well known adverse effects, particularly dose-limiting nephrotoxicity, often complicate and limit its effective use. 7 Although the reported incidence is quite variable, two recent reviews estimate that 6...

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“…24' 49, 50 In a randomized, double-blind trial rapid infusions were associated with increased clinical toxicity, including shaking chills, fever, nausea, and vomiting, compared with slow (4-hr) infusions.49 However,' when patients were premedicated with agents such as diphenhydramine, hydrocortisone, and acetaminophen, rapid infusions were well tolerated. 24,50 Neither chest discomfort nor pulmonary function abnormalities were reported with rapid infusions in these trials.…”

Section: Discussionmentioning

confidence: 81%

“…24 Acute reactions usually occur 1-3 hours into the infusion and may be related to the release of interleukin-1 , PGE2, and tumor necrosis factor.'. [24][25][26][27][28] Allergic reactions and anaphylaxis have been reported with amphotericin B deoxycholate as well as lipid products, thus justifying the recommendation of a l-mg test dose. ', 3 , '', 12, [29][30][31][32][33][34] Allergic reactions to amphotericin B are typically characterized by tachypnea, dyspnea, and acute bronchospasm manifested by wheezing, and may also include flushing, facial edema, and rash.'.…”

Section: Discussionmentioning

confidence: 99%

Chest Discomfort Associated with Liposomal Amphotericin B: Report of Three Cases and Review of the Literature

Johnson,

Drew,

Perfect

1998

Pharmacotherapy

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Liposomal formulations of amphotericin B are designed to maintain therapeutic efficacy of amphotericin B deoxycholate while reducing its associated toxicities. In three patients chest discomfort occurred during planned 1‐hour infusions of liposomal amphotericin B (AmBisome) 3 mg/kg/day during an open‐label trial. The first patient experienced chest tightness and difficulty breathing and the second had dyspnea and acute hypoxia, both within 10 minutes of the start of the infusion. The third patient complained of chest pain 5 minutes after the start of two infusions. All symptoms resolved on terminating therapy. Two patients were later rechallenged with slower infusions and tolerated the drug well. A review of the English‐language literature revealed only two other case reports of infusion‐related chest or pulmonary reactions with the drug, although similar reactions were noted in several reports of clinical trials. Further review of the literature revealed reports of chest and pulmonary adverse events with other liposomal formulations of amphotericin B, liposomal daunorubicin, liposomal doxorubicin, and liposomes. The pathophysiology of such reactions remains unclear, and premedication with diphenhydramine did not completely prevent this reaction in one of our patients. We recommend infusing liposomal amphotericin B over at least 2 hours with careful monitoring for adverse reactions.

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Rapid intravenous infusion of amphotericin B: A pilot study

Cited by 41 publications

References 21 publications

Must we really fear toxicity of conventional amphotericin B in oncological patients?

Must we really fear toxicity of conventional amphotericin B in oncological patients?

Treatment of invasive fungal infections with amphotericin B colloidal dispersion in bone marrow transplant recipients

Chest Discomfort Associated with Liposomal Amphotericin B: Report of Three Cases and Review of the Literature

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