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A Comparision of Several Formats of Amphotericin B as an Inhaled Antifungal Prophylaxis
A Comparision of Several Formats of Amphotericin B as an Inhaled Antifungal Prophylaxis E. SanMartı´n, P. Morales, E. Monte, and R. Vicente ABSTRACT Objective. We sought compare the economic cost, ease of preparation and administration, and tolerance of the available alternatives of amphotericin B (AmpB) as an inhaled antifungal prophylaxis for lung transplant patients. Materials and Methods. Doses administered and cost of the 3 formats: desoxycholate (desoxy; 50-mg vial); lipid complex (lipid; 100 mg/20 mL vial) and liposomal (lipos; 50-mg vial). The regimen for antifungal prophylaxis is as follows: AmpB desoxy (reconstituted and dilute): 5 mg/every 8 hours for 4 months and 5 mg/d in the following months; AmpB lipid (nonreconstituted): 25 mg/d for 7 days, 25 mg over 48 hours for days and 25 mg/wk; AmpB lipos (reconstituted): 24 mg 3 times weekly for 2 months, 24 mg/wk for 6 months and 24 mg every 2 weeks. We polled 8 nurses who prepare these drugs habitually. We also asked a random sample of treated patients regarding tolerance. Results. Number of doses, vials per year per patient, and final cost for each type were: Desoxy, 609 doses, 72 vials, €607.90; lipid, 63 doses, 15 vials, €1428.15; and lipos, 57 doses, 57 vials, €7720.10. Amp B lipid is considered to be the easiest to use, because it does not have to be reconstituted. The following cases of intolerance were recorded: AmpB desoxy 5 (45); AmpB lipid 1 (67); AmpB lipos 0 (4). Conclusions. AmpB desoxy is the most economical, but it requires greater care in handling, the highest number of doses, and has the worst tolerance. AmpB lipid has an intermediate price and is the easiest to prepare. AmpB lipos is the most expensive and it requires careful handling. NFECTIONS ARE much more frequent in lung transplant patients than in other transplant patients; most are bacterial followed by cytomegalovirus infection. However, owing to their high mortality rate, fungal infections are of great clinical importance.1 Accordingly, it is of the absolute necessity to use the right antifungal prophylaxis. At our hospital, we begin with oral fluconazole, inhaled amphotericin B (AmpB), and nystatin mouthwash.2 For many years, the only available format of amphotericin was amphotericin B desoxycholate (AmpB desoxy). Problems with supply and with some patient tolerance advised the use of other formats: The lipid complex (AmpB lipid) and the liposomal form (AmpB lipos), with differing dosage regimes. In this paper, we aimed to compare the cost, ease of preparation and administration, and tolerance of the several formats AmpB as an inhaled antifungal prophylaxis for lung transplant recipients.
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MATERIALS AND METHODS We counted the number of doses administered and the final cost of the 3 available AmpB formats: AmpB desoxy (Fungizone; 50 mg/vial); AmpB lipid complex (Abelcet; 100 mg/20 mL per vial), and AmpB lipos (Abisome; 50 mg/vial). At our hospital, the preparation and antifungal prophylaxis regime for inhaled AmpB are as follows. Amp B desoxy (reconstituted with 10 mL saline solution and diluted to 1 mg/mL with saline solution), given as 5 mg every 8 hours over the first 4 months and 5 mg/d over the following months; AmpB lipid (does not need to be reconstituted) given as 25 mg/d over the first 7 days, 25 mg every 48 hours over 14 days, and From the Servicio de Farmacia (E.S., E.M.), the Unidad de Trasplante Pulmonar (P.M.), and the Servicio de Anestesia y Reanimación (R.C.), Hospital Universitario La Fe, Valencia, Spain. Address reprint requests to Pilar Morales, Unidad de Trasplante Pulmonar, Hospital La Fe, Avda. Campanar 21, 46009, Valencia, Spain. E-mail: [email protected]
© 2009 Published by Elsevier Inc. 360 Park Avenue South, New York, NY 10010-1710
0041-1345/09/$–see front matter doi:10.1016/j.transproceed.2009.06.018
Transplantation Proceedings, 41, 2225–2226 (2009)
2225
2226 25 mg/wk the rest of the time; and AmpB lipos (reconstituted with 12 mL saline solution), given as 24 mg 3 times weekly for the first 2 months, 24 mg/wk for 2 more months, and then 24 mg every 2 weeks. The stability of each reconstituted format when kept refrigerated is as follows: AmpB desoxy, 7 days; AmpB lipid, 1 month; AmpB lipos, 1 day. The inhalation procedure is the same for the 3 drugs. Eight nurses who normally prepare and administer these drugs and a random sample of 49 out of a total of 116 patients treated were polled regarding the time required and ease of preparation and administration; the latter were also asked about tolerance.
RESULTS
On the basis of the prophylactic regimen and form of preparation for each AmpB format, we can establish that, in the first year of prophylactic treatment, the number of doses to be prepared and administered and the numbers of vials used are as follows: AmpB desoxy, 609 doses, 72 vials; AmpB lipid, 63 doses, 15 vials; and AmpB lipos, 57 doses, 57 vials. The final cost for the first year, including diluents, was: AmpB desoxy, €607.90; AmpB lipid, €1428.10; and AmpB lipos, €7720.10. The 49 patients and 8 nurses polled considered the AmpB lipid format the easiest and safest; it does not require reconstitution or dilution. The following cases of intolerance were recorded (total number of patients): AmpB desoxy, 5 (45); AmpB lipid, 1 (67); AmpB lipos, 0 (4). DISCUSSION
Under the protocol applied at our center, inhaled antifungal prophylaxis for lung transplant patients is established with AmpB desoxy and has been in use for years.2,3 However, over the past 2 years, supply problems and poor tolerance of some patients to this medicine have advised the use of the lipid formats, each of which require specific dosage regimens; their retention in the lungs is far higher. Thus, for AmpB lipos, we have applied the regimen normally used for other transplant groups,4 whereas for AmpB lipid because there was no experience published in any Spanish transplant group,5 an initial dose of 50 mg with the frequency specified above was selected. The 50-mg dose was
SANMARTIN, MORALES, MONTE ET AL
later replaced by a 25-mg dose, which is practically the only one currently available and the one used in this comparative study. Because the number of cases in which AmpB desoxy was replaced by AmpB lipos and, particularly, by AmpB lipid, advantages were observed in this format over the others. Accordingly, its use was increased and it is now the first choice treatment for most patients. The main reasons that this formulation is preferred over the others are its ease of preparation and administration (it requires no reconstitution or dilution). This has made it the favorite of nurses and of patients once they change to an out patient regimen. Tolerance levels are very high for AmpB lipos (100%) and AmpB lipid (98.5%); AmpB lipos has only been used in very few cases. The rates for AmpB desoxy are notably lower (88.9%). In short, AmpB desoxy is the least expensive by some margin, although it requires greater care in handling, a higher number of doses, and more nursing time. It also involves a higher probability of error and is the least well tolerated. AmpB lipos is the most expensive option and also requires careful handling. AmpB lipid has an intermediate cost, it is easy to prepare and administer, and is well tolerated.
REFERENCES 1. Solé A, Morant P, Salavert M, et al: Valencia Lung Transplant Group. Aspergillus fumigatus in lung transplant recipients: risk factors and outcome. Clin Microbiol Infect 11:359, 2005 2. Calvo V, Borro JM, Morales P, et al: Antifungal prophylaxis during the early postoperative period of lung transplantation. Valencia Lung Trasplant Group. Chest 115:1301, 1999 3. Monforte V, Román A, Gavaldá J, et al: Nebulized amphotericin B prophylaxis for Aspergillus infection in lung transplantation: study of risk factors. J Heart Lung Transplant 20:1274, 2001 4. Monforte V, Ussetti P, López R, et al: Nebulized liposomal amphotericin B prophylaxis for Aspergillus infection in lung transplantation: pharmacokinetics and safety. J Heart Lung Transplant 28:170, 2009 5. Corcoran TE, Venkataramanan R, Mihelc KM, et al: Aerosol deposition of lipid complex amphotericin-B (Abelcet) in lung transplant recipients. Am J Transplant 6:2765, 2006
I
MATERIALS AND METHODS We counted the number of doses administered and the final cost of the 3 available AmpB formats: AmpB desoxy (Fungizone; 50 mg/vial); AmpB lipid complex (Abelcet; 100 mg/20 mL per vial), and AmpB lipos (Abisome; 50 mg/vial). At our hospital, the preparation and antifungal prophylaxis regime for inhaled AmpB are as follows. Amp B desoxy (reconstituted with 10 mL saline solution and diluted to 1 mg/mL with saline solution), given as 5 mg every 8 hours over the first 4 months and 5 mg/d over the following months; AmpB lipid (does not need to be reconstituted) given as 25 mg/d over the first 7 days, 25 mg every 48 hours over 14 days, and From the Servicio de Farmacia (E.S., E.M.), the Unidad de Trasplante Pulmonar (P.M.), and the Servicio de Anestesia y Reanimación (R.C.), Hospital Universitario La Fe, Valencia, Spain. Address reprint requests to Pilar Morales, Unidad de Trasplante Pulmonar, Hospital La Fe, Avda. Campanar 21, 46009, Valencia, Spain. E-mail: [email protected]
© 2009 Published by Elsevier Inc. 360 Park Avenue South, New York, NY 10010-1710
0041-1345/09/$–see front matter doi:10.1016/j.transproceed.2009.06.018
Transplantation Proceedings, 41, 2225–2226 (2009)
2225
2226 25 mg/wk the rest of the time; and AmpB lipos (reconstituted with 12 mL saline solution), given as 24 mg 3 times weekly for the first 2 months, 24 mg/wk for 2 more months, and then 24 mg every 2 weeks. The stability of each reconstituted format when kept refrigerated is as follows: AmpB desoxy, 7 days; AmpB lipid, 1 month; AmpB lipos, 1 day. The inhalation procedure is the same for the 3 drugs. Eight nurses who normally prepare and administer these drugs and a random sample of 49 out of a total of 116 patients treated were polled regarding the time required and ease of preparation and administration; the latter were also asked about tolerance.
RESULTS
On the basis of the prophylactic regimen and form of preparation for each AmpB format, we can establish that, in the first year of prophylactic treatment, the number of doses to be prepared and administered and the numbers of vials used are as follows: AmpB desoxy, 609 doses, 72 vials; AmpB lipid, 63 doses, 15 vials; and AmpB lipos, 57 doses, 57 vials. The final cost for the first year, including diluents, was: AmpB desoxy, €607.90; AmpB lipid, €1428.10; and AmpB lipos, €7720.10. The 49 patients and 8 nurses polled considered the AmpB lipid format the easiest and safest; it does not require reconstitution or dilution. The following cases of intolerance were recorded (total number of patients): AmpB desoxy, 5 (45); AmpB lipid, 1 (67); AmpB lipos, 0 (4). DISCUSSION
Under the protocol applied at our center, inhaled antifungal prophylaxis for lung transplant patients is established with AmpB desoxy and has been in use for years.2,3 However, over the past 2 years, supply problems and poor tolerance of some patients to this medicine have advised the use of the lipid formats, each of which require specific dosage regimens; their retention in the lungs is far higher. Thus, for AmpB lipos, we have applied the regimen normally used for other transplant groups,4 whereas for AmpB lipid because there was no experience published in any Spanish transplant group,5 an initial dose of 50 mg with the frequency specified above was selected. The 50-mg dose was
SANMARTIN, MORALES, MONTE ET AL
later replaced by a 25-mg dose, which is practically the only one currently available and the one used in this comparative study. Because the number of cases in which AmpB desoxy was replaced by AmpB lipos and, particularly, by AmpB lipid, advantages were observed in this format over the others. Accordingly, its use was increased and it is now the first choice treatment for most patients. The main reasons that this formulation is preferred over the others are its ease of preparation and administration (it requires no reconstitution or dilution). This has made it the favorite of nurses and of patients once they change to an out patient regimen. Tolerance levels are very high for AmpB lipos (100%) and AmpB lipid (98.5%); AmpB lipos has only been used in very few cases. The rates for AmpB desoxy are notably lower (88.9%). In short, AmpB desoxy is the least expensive by some margin, although it requires greater care in handling, a higher number of doses, and more nursing time. It also involves a higher probability of error and is the least well tolerated. AmpB lipos is the most expensive option and also requires careful handling. AmpB lipid has an intermediate cost, it is easy to prepare and administer, and is well tolerated.
REFERENCES 1. Solé A, Morant P, Salavert M, et al: Valencia Lung Transplant Group. Aspergillus fumigatus in lung transplant recipients: risk factors and outcome. Clin Microbiol Infect 11:359, 2005 2. Calvo V, Borro JM, Morales P, et al: Antifungal prophylaxis during the early postoperative period of lung transplantation. Valencia Lung Trasplant Group. Chest 115:1301, 1999 3. Monforte V, Román A, Gavaldá J, et al: Nebulized amphotericin B prophylaxis for Aspergillus infection in lung transplantation: study of risk factors. J Heart Lung Transplant 20:1274, 2001 4. Monforte V, Ussetti P, López R, et al: Nebulized liposomal amphotericin B prophylaxis for Aspergillus infection in lung transplantation: pharmacokinetics and safety. J Heart Lung Transplant 28:170, 2009 5. Corcoran TE, Venkataramanan R, Mihelc KM, et al: Aerosol deposition of lipid complex amphotericin-B (Abelcet) in lung transplant recipients. Am J Transplant 6:2765, 2006