a Department of Pharmacy Practice, Albany College of Pharmacy, 106 New Scotland Avenue, Albany, NY 12208; b University of Utah Hospitals and Clinics, Salt Lake City, UT 84132, USA
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Abstract |
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Introduction |
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Materials and methods |
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Results |
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Amphotericin B was dosed at 0.67 ± 0.30 mg/kg for a mean of 21.9 days (range 757 days). Amiloride 5 mg bd was started on day 6.2 ± 5.3 of amphotericin B therapy. Amiloride doses were subsequently increased to 10 mg bd in six patients. The duration of amiloride therapy was 14.7 ± 12.6 days.
Serum potassium concentrations before initiation of amphotericin B were 3.8 ± 0.5 mmol/L. After amphotericin B administration, serum potassium concentrations declined to 3.3 ± 0.6 mmol/L, corresponding to the day of amiloride initiation. Daily mean potassium concentrations are shown in Figure 1. The mean serum concentrations for the 5 days preceding and following the initiation of amiloride were 3.4 ± 0.5 and 3.9 ± 0.8 mmol/L (P = 0.002), respectively.
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No significant differences were seen before and after amiloride addition in magnesium serum concentrations (0.97 ± 0.12 versus 0.99 ± 0.13 mmol/L, P > 0.05), total magnesium intake (14.6 ± 18.2 versus 14.4 ± 8.7 mmol/day, P > 0.05), or supplemental magnesium (0.6 ± 2.5 versus 0.9 ± 3.8 mmol/day, P > 0.05).
Hyperkalaemia was observed in two patients receiving amiloride. Case 1 occurred after an increase in amiloride to 10 mg bd. Increases in potassium content of the total parenteral nutrition had been made for the 2 days before the incident, and potassium intake totalled nearly 200 mmol/ day. The serum potassium increased to 6.9 mmol/L. Amiloride was discontinued and kayexelate administered. The patient was restarted on amiloride 10 days later when the serum potassium level was continually measured near 3.0 mmol/L. Case 2 occurred while the patient was receiving amiloride 10 mg bd. The serum potassium reached 6.2 mmol/L, and amiloride was discontinued. The potassium concentration quickly fell and the patient required 40 mmol/day of intravenous potassium for the 2 days immediately following discontinuation.
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Discussion |
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In the present report, amiloride was added to amphotericin B treatment only when patients began to exhibit excessive potassium requirements. It should be noted that the majority of patients in the current study had acute leukaemias, a population with inherent potassium deficits.5 Initiation was based upon health provider discretion, and was not limited by any pre-set serum electrolyte or supplementation values. This resulted in a large variability in the supplementation given for a specific serum potassium concentration.
Overall, mean total potassium intake was not different for the 5 days before and after amiloride initiation. However, the mean potassium intake (Figure 2) shows a trend in reduction following amiloride therapy. A similar trend was observed in potassium supplementation, with the mean supplementation requirements differing by nearly 20 mmol/day in the two study periods. Changes in the serum potassium concentrations were significant with an increase of 0.5 mmol/L after initiation of amiloride, despite no change in total potassium intake. This suggests that the increase may be a result of the activity of amiloride, and not a greater potassium intake. Because of the retrospective nature of the study, urinary potassium excretion was not available.
No changes in serum magnesium concentrations or total intake were observed with amiloride therapy in the present study. The minimal need for magnesium supplementation (mean 0.60.9 mmol/day) may have prohibited any differences from being identified. Additionally, the time frame of the current study may have preceded the period of maximal magnesium loss suggested to occur later in amphotericin B therapy.1
Most of the patients observed showed benefits from amiloride therapy, with 16/19 patients exhibiting an increase in serum potassium, a decrease in total potassium intake or a combination of the two. Adverse reactions were limited to excessive increases in potassium. This occurred in two patients who received amiloride 10 mg bd. Hyperkalaemia may be related to the higher doses of amiloride but concurrent increases in potassium intake may have been a confounding factor. Four additional patients received 10 mg bd without incident.
The current report supports the use of amiloride in patients receiving amphotericin B who require increasing amounts of potassium supplementation. Initiation of amiloride in patients with an observed need is a more conservative approach than the prophylactic regimen studied by Smith et al.3 Early utilization of amiloride may be considered in patients with underlying risk factors for hypokalaemia (i.e. leukaemia, cisplatin use, diuretics) in whom a prolonged course of amphotericin is anticipated. The addition of another medication to a patient population receiving multidrug therapy is not recommended in all instances, and should be considered on a case-by-case basis. This retrospective study suggests that amiloride may benefit patients by decreasing total potassium requirements and supplementation, as well as increasing serum potassium concentrations. Careful monitoring of serum electrolytes is still required in all patients. Controlled studies are needed to better characterize the activity of amiloride in this and other patient groups.
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Acknowledgments |
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Notes |
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References |
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2 . Denning, D. W. (1998). Invasive aspergillosis. Clinical Infectious Diseases 26, 781805.[ISI][Medline]
3 . Smith, S. R., Galloway, M. J., Reilly. J. T. & Davies, J. M. (1987). Amiloride prevents amphotericin B related hypokalemia in neutropenic patients. Journal of Clinical Pathology 41, 4947.[Abstract]
4 . Wazny, L. D. & Brophy, D. F. (2000). Amiloride for the prevention of amphotericin B-induced hypokalaemia and hypomagnesemia. Annals of Pharmacotherapy 34, 947.[Abstract]
5 . Milionis, H. J., Bourantas, C. L., Siamopoulos, K. C. & Elisaf, M. S. (1999). Acidbase and electrolyte abnormalities in patients with acute leukemia. American Journal of Hematology 62, 2017.[ISI][Medline]
Received 30 October 2000; returned 14 February 2001; revised 9 March 2001; accepted 6 April 2001