o investigate the list of cancer drugs with the highest rate of dividing dose in preparation of cancer drugs by individualized doses at Choray Hospital in year of 2015; to analyze the optimal supply of some typical cancer drugs in drug preparation.
Journal of military pharmaco-medicine n08-2018 OPTIMAL ANALYSIS OF THE SUPPLY OF SOME CANCER DRUGS PREPARATION BY DOSAGE AT CHORAY HOSPITAL Nguyen Van Tung1; Nguyen Quoc Binh2 Nguyen Truong Son2; Nguyen Thi Thu Thuy3 SUMMARY Objectives: To investigate the list of cancer drugs with the highest rate of dividing dose in preparation of cancer drugs by individualized doses at Choray Hospital in year of 2015; to analyze the optimal supply of some typical cancer drugs in drug preparation Method: Crosssectional description based on retrospective data of cancer drugs at Choray Hospital in the year of 2015 Data were processed by Microsoft Excel 2010 Results were presented in figures and tables Results: Top 10 active ingredients with the highest rate of dividing dose in 2015: Cytarabine had the highest rate (92.5%), followed by etoposide (76%), epirubicin and cisplatin (61%), doxorubicin (52%) The remaining active ingredients (oxaliplatin, carboplatin, pemetrexed, gemcitabine) had a lower percentage and ranged from 20% to 50% Oxaliplatin had preparation concentration ranged from 10 to 420 mg in different preparation rates Most of them had the preparation rate under 1%, preparation concentration of 200 mg had the highest rate (26.5%), followed by 150 mg (18.0%), 100 mg (10.9%), the remaining preparation concentrations were below 10% Doxorubicin had preparation concentration ranged from to 100 mg, most of which had the preparation rate less than 10% The concentration of 50 mg had the highest rate (18.6%), followed by 70 mg (15.8%), 60 mg (12.9%) and concentrations with very low rate were mg, 17 mg, 18 mg and 45 mg (less than 2%) Conclusion: Optimal analysis of the supply of some drugs showed that 3,842 preparations of oxaliplatin and 653 preparation of doxorubicin were inappropriate Appropriate distribution for each concentration saves 6.96 billion VND in oxaliplatin and 2.07 billion in doxorubicin * Keywords: Cancer drug preparation; Individual dosage; Dividing dose INTRODUCTION Individualized dosage preparation (IDP) has been proven to bring optimum efficacy at a lower cost than nomal preparation [1, 2] which are available in many countries around the world, particularly in the use of cancer drugs [4, 5] Since 2012, Vietnam has officially applied the IDP on patients with the pioneer hospital is Choray Hospital [3] In IDP, dividing dose is regularly made to save the cost of drug use This leads to the need of considering the supply of drugs, especially for drugs with different concentrations at different prices and in different ways of dividing Therefore, sufficient and reasonable supply of drugs in differrent concentrations needs to optimize the dividing Vietnam Military Medical University Choray Hospital University of Medicine and Pharmacy, Hochiminh City Corresponding author: Nguyen Van Tung (trangtungtruc@gmail.com) Date received: 31/07/20181 Date accepted: 24/09/2018 109 Journal of military pharmaco-medicine n08-2018 dose and cost of drug use Thus, a study to optimize the percentage of each concentration among the packaged drug supplying for IDP would be a suggestion for the rationalized drug list in the hospital So the study "Optimal analysis of the supply of some cancer drugs preparation by dosage at Choray Hospital" was conducted SUBJECTS AND METHODS Subjects Reserved data on concentrated preparation in 2015 at Choray Hospital (trade names of drugs, number of dispensaries, number of split, unit price ) Methods Study design: Cross-sectional description based on retrospective data of cancer drugs at Choray Hospital in the year of 2015 Data processing: Data were processed by Microsoft Excel 2010, results were presented in figures and tables RESULTS AND DISCUSSION Investigate the list of cancer drugs with the highest rate of dividing dose in preparation of cancer drugs by individualized doses at Choray Hospital in 2015 * The list of cancer drugs had a high rate of dividing dose: A list of high-dividing-dose cancer drug groups (alkylated, anti-tumor antibiotics, anti-metabolism and topoisomerase inhibitors) was presented in table Table 1: List of drugs from groups with high rate of dividing dose by 2015 Drug group Topoisomerase inhibitors Anti-metabolism Anti-tumor antibiotics 110 Active ingredient Concentration/ Number of dose preparation Number of dividing dose Percent (%) Usage value (VND) Irinotecan 40 mg/2 mL 100 mg/5 mL 1,533 33 2.15 6,151,160,022 Etoposid 100 mg/5 mL 1,226 936 76.35 239,702,947 5-fluorouracil 500 mg/10 mL 566 114 20.14 106,811,040 Cytarabine 500 mg/10 mL 1,000 mg 518 479 92.47 80,762,008 Fludarabine 50 mg 30 0.00 68,238,000 Gemcitabin 200 mg, g 3,670 1,074 29.26 3,404,110,965 Pemetrexed 500 mg 215 77 35.81 5,718,209,490 Idarubicin mg, 10 mg 16 0.00 159,399,999 Bleomycin 15 mg 238 1.68 154,872,000 Daunorubicin 20 mg 148 4.05 77,933,623 Doxorubicine 10 mg/5 mL 20 mg/10 mL 50 mg/25 mL 1,939 1,012 52.19 2,728,423,771 Journal of military pharmaco-medicine n08-2018 Alkylated Epirubicin 50 mg 10 mg/5 mL 50 mg/5 mL 50 mg/25 mL 809 495 61.19 933,803,020 Farmorubicin 10 mg/5 mL 50 mg 749 0.00 607,824,195 Carboplatin 150 mg/15 mL 450 mg/15 mL 3,112 1,279 41.10 2,628,760,017 Carmustine 100 mg 0.00 254,400,000 Cisplatin 10 mg/10 mL 10 mg/20 mL 50 mg/50 mL 2,657 1,617 60.86 1,191,788,787 Cyclophosph a-mide 200 mg, 500 mg 2,768 168 6.07 385,910,199 Dacarbazine 200 mg 142 21 14.79 128,875,996 Ifosfamide 1g 416 74 17.79 918,228,942 Melphalan 50 mg 14 0.00 493,999,999 Methotrexate 50 mg/2 mL 1,000 mg 193 4.15 1,470,218,924 Oxaliplatin 50 mg/10 mL 100 mg/20 mL 200 mg/40 mL 6,192 2,968 47.93 27,301,955,865 According to table 1, four groups of drugs with high rate of dividing dose consisted of 22 active ingredients Among them, the alkylated group had the highest number of active ingredients (9), followed by the anti-tumor group (6 active ingredients), anti-metabolism (5 active ingredients) and topoisomerase inhibitor (2 active ingredients) Drugs in the list had a percentage ranging from 0% to 92.5%, with the highest rate from cytarabine in the anti-metabolism antibiotics (92.5%) Some ingredients did not divided included: fludarabine, idarubicin, farmorubicin, carmustine, melphalan The highest number of dividing dose times was oxaliplatin (2968), 26 times higher than the lowest 5-fluorouracil (114) The remaining active ingredients which had high proportion in dividing dose included cisplatin, carboplatin, gemcitabine, doxorubicine, etoposid, epirubicin, cytarabine and cyclophosphamide * Top 10 active ingredients had the highest percentage of dividing dose: Survey on the top 10 active ingredients with the highest rate of dividing dose in 2015, the result indicated that: Cytarabine had the highest rate (92.5%), followed by etoposide (76%), epirubicin and cisplatin (61%), doxorubicin (52%) The remaining active ingredients (oxaliplatin, carboplatin, pemetrexed, gemcitabine) had a lower percentage and ranged from 20% to 50% 111 Journal of military pharmaco-medicine n08-2018 * Top 10 active ingredients had the highest cost of drug use: Survey on the top 10 active substances with the highest cost of drug use in 2015, the following results were obtained: Oxaliplatin had the highest cost (over 27 billion VND), followed by irinotecan (6.15 billion VND), pemetrexed (5.7 billion VND) and gemcitabine (3.4 billion VND) The remaining active ingredients ranged from 0.9 to 2.7 billion VND including ifosfamide, ebirubicin, ciplastin, methotrexate, carboplatin and doxorubicine Analyze the optimal supply of some typical cancer drugs in drug preparation In the list of drugs with high rate of dividing dose and the high cost of drug use, some drugs appeared in both categories included oxaliplatin, pemetrexed, gemcitabine, doxorubicin, carboplatin, epirubicine and cisplatin For optimal analysis of the quantity supplied in drug preparation, the study selected two typical drugs including oxaliplatin (the highest cost, average percentage and four different concentrations); doxorubicin (the fifth highest cost, average percentage and three different concentrations) - Optimal analysis of the supply of oxaliplatin: + The status of the preparation of oxaliplatin in 2015: Investigate the status of the preparation of oxaliplatin based on preparation concentration and preparation rate in each concentration in 2015, the results were presented in figure Figure 1: Status of the preparation of oxaliplatin in 2015 According to figure 1, oxaliplatin had preparation concentration ranged from 10 to 420 mg in different preparation rates Most of them had the preparation rate under 1%, preparation concentration of 200 mg had the highest rate (26.5%), followed by 150 mg (18.0%), 100 mg (10.9%), the remaining preparation concentrations were below 10% 112 Journal of military pharmaco-medicine n08-2018 + Reckon up the unreasonable preparation of oxaliplatin: More detailed investigations were conducted in each preparation of oxaliplatin, the study recorded many cases of unreasonable preparation such as the use of small doses for multiple doses (50 mg dose used to prepare a concentration of 210 mg), or use a high concentration to prepare a small dose (200 mg dose to prepare 120 mg) or use a small concentration to a large concentration already available (50 mg dose used for concentration phase 150 mg) This unreasonable preparation can be traced back to the lack of essential ingredients in the preparation process The use of unreasonable concentrations at various costs can increase the cost of drug use Sum up unreasonable preparations in 2015 and provide new preparation methods based on the reduction of unit price per preparation, results were presented in table Table 2: Status of the preparation of oxaliplatin in 2015 and optimal methods proposed in preparation Status in 2015 Prepara Number Unit price/ Concention of Dose preparation tration concent prepara (VND) ration tion Optimal methods Cost (VND) Preparat Number Unit price/ Concentr ion of Dose preparatio ation concentr prepara n (VND) ation tion Cost (VND) 50 1.4 70 1,450,890 5,803,560 100 0.70 70 955,500 3,822,000 50 1.6 80 70 2,988,768 209,213,760 100 0.80 80 70 1,092,000 76,440,000 50 100 152 3,792,597 576,474,760 100 1.00 100 152 2,373,477 360,768,519 50 2.4 120 65 2,747,988 178,619,232 100 1.20 120 65 1,650,417 107,277,130 50 2.5 125 1,701,000 6,804,000 100 1.25 125 1,855,000 7,420,000 50 2.6 130 21 6,502,862 136,560,112 100 1.30 130 21 1,774,500 37,264,500 50 2.8 140 23 3,445,758 79,252,432 100 1.40 140 23 1,960,980 45,102,540 50 150 424 5,956,771 2,525,671,020 100 1.50 150 424 2,224,863 943,341,936 50 3.2 160 3,696,000 3,696,000 100 1.60 160 2,184,000 2,184,000 50 3.4 170 15 3,264,743 48,971,152 100 1.70 170 15 2,541,191 38,117,864 50 3.5 175 186 4,574,814 850,915,380 100 1.75 175 186 2,527,583 470,130,500 50 3.6 180 140 5,444,807 762,272,928 100 1.80 180 140 2,854,112 399,575,730 50 3.8 190 37 5,916,596 218,914,048 100 1.90 190 37 3,188,500 117,974,500 50 200 513 6,461,151 3,314,570,240 200 1.00 200 513 4,200,000 2,154,600,000 50 4.2 210 85 5,454,343 463,619,184 100 2.10 210 85 3,549,063 301,670,328 50 4.4 220 23 5,235,227 120,410,224 100 2.20 220 23 3,395,700 78,101,100 50 4.6 230 4,172,813 12,518,440 100 2.30 230 4,781,700 14,345,100 50 250 4,984,000 14,952,000 100 2.50 250 3,412,500 10,237,500 113 113 Journal of military pharmaco-medicine n08-2018 100 200 1,003 4,607,908 4,621,731,660 200 1.00 200 1003 150 0.8 120 150 0.83 150 36 4,544,000 163,584,000 100 1.20 120 36 1,650,417 59,415,026 124.5 4,714,400 4,714,400 150 0.83 124.5 4,714,400 4,714,400 0.86 129 4,884,800 9,769,600 150 0.86 129.0 4,884,800 9,769,600 150 0.87 130.5 11 4,941,600 54,357,600 150 0.87 130.5 11 4,941,600 54,357,600 150 0.93 139.5 5,282,400 10,564,800 150 0.93 139.5 5,282,400 10,564,800 150 150 334 5,680,000 1,897,120,000 100 1.50 150 334 150 1.13 169.5 6,418,400 12,836,800 100 1.70 170 150 1.2 180 128 6,816,000 872,448,000 100 1.80 180 128 2,854,112 365,326,382 150 1.27 190.5 19 7,213,600 137,058,400 150 1.27 191 19 7,213,600 137,058,400 150 1.33 199.5 317 7,554,400 2,394,744,800 150 1.33 200 317 7,554,400 2,394,744,800 150 1.4 210 72 7,952,000 572,544,000 100 2.10 210 72 3,549,063 255,532,513 150 1.46 219 8,292,800 8,292,800 150 1.46 219 8,292,800 150 1.47 220.5 26 8,349,600 217,089,600 150 1.47 221 26 8,349,600 217,089,600 150 1.53 229.5 8,690,400 43,452,000 150 1.53 230 8,690,400 43,452,000 150 1.67 250.5 9,485,600 56,913,600 150 1.67 251 9,485,600 56,913,600 150 2.34 351 13,291,200 13,291,200 150 2.34 351 13,291,200 13,291,200 200 0.6 120 2,520,000 20,160,000 100 1.20 120 1,650,417 13,203,339 200 0.7 140 2,940,000 8,820,000 100 1.40 140 1,960,980 5,882,940 200 0.8 150 46 3,150,000 144,900,000 100 1.50 150 46 2,224,863 102,343,701 200 0.9 180 23 3,780,000 86,940,000 100 1.80 180 23 2,854,112 65,644,584 200 1.0 190 3,990,000 19,950,000 100 1.90 190 3,188,500 15,942,500 200 1.1 210 4,410,000 39,690,000 100 2.10 210 3,549,063 31,941,564 200 1.1 220 10 4,620,000 46,200,000 100 2.20 220 10 3,395,700 33,957,000 200 1.15 230 4,830,000 4,830,000 100 2.30 230 4,781,700 4,781,700 200 1.25 250 5,250,000 10,500,000 100 2.50 250 3,412,500 6,825,000 Total cost 21,001,741,732 4,200,000 4,212,600,000 2,224,863 743,104,261 2,541,191 Total cost 5,082,382 8,292,800 14,040,204,941 According to table 2, in 2015, oxaliplatin had 3,842 unreasonable preparations among 6,192 total preparations, concentration of 50 mg had the highest number (1,769 times), followed by the concentration of 100 mg (1,003), 150 mg (963) and the lowest was 200 mg (107) The total cost of these unreasonable preparations was about 21 billion VND, after the redistribution of the dosage and the reasonable concentration based on the reduction of unit cost/preparation, total cost was 14.04 billion Thus, oxaliplatin preparation using appropriate concentration helped to save 6.96 billion VN 114 Journal of military pharmaco-medicine n08-2018 + Optimal supply of oxaliplatin: Based on the current status of drug preparation in 2015, the study results of the optimal analysis on supplying of oxaliplatin by each concentration were presented in table Table 3: Optimal supplying number of oxaliplatin by each concentration Concentration (mg) Total preparation concentration (mg) Order quantity (bottle) Order percentage (%) 50 16,850 337 4.22 100 543,188 5,432 68.08 150 34,801,5 232 2.91 200 395,451,5 1,977 24.78 As shown in table 3, with the different total preparation concentration of each concentration in 2015, the number of orders of oxaliplatin in 2015 should be: 100 mg with 5,432 bottles (accounted for 68.08%), followed by 200 mg with 1,977 bottles (24.78%) 50 mg and 150 mg had lower order quantities with 337 bottles (4.22%) and 232 bottles (2.91%), respectively - Optimal analysis on the supply of doxorubicin: + The status of the preparation of doxorubicin in 2015: Investigate the status of doxorubicin preparation according to the preparation concentration and preparation rate in each concentration in 2015, the results were presented in figure Figure 2: Status of doxorubicin preparation in 2015 As shown in figure 2, doxorubicin had preparation concentration ranged from mg to 100 mg Most of them had the preparation rate less than 10%, the concentration of 50 mg had the highest rate (18.6%), followed by 70 mg (15.8%), 60 mg (12.9%) and concentrations with very low rate were mg, 17 mg, 18 mg and 45 mg (less than 2%) 115 Journal of military pharmaco-medicine n08-2018 + Reckon up the unreasonable preparation of doxorubicin: A more detailed investigation of each preparation time of doxorubicin has found that many of the unsuitable preparation are similar to those of oxaliplatin Sum up unreasonable preparation in 2015 and propose new preparation plans based on the reduction of unit cost per preparation, the results were presented in table Table 4: The status of doxarubicin preparation in 2015 and optimal methods in preparation proposed Status in 2015 Preparat- Number Unit price/ ion of preparation concentr prepara(VND) ation tion Concentration Dose 10 1.5 15 21 10 20 10 10 Optimal methods Prepara- Number Unit price/ tion of preparation concent- prepar(VND) ration ation Cost (VND) Concentration Dose 131,250 2,756,250 50 0.3 15 21 100,485 2,110,185 99 191,927 19,000,800 50 0.4 20 99 131,521 13,020,612 30 92 290,690 26,743,500 50 0.6 30 92 195,491 17,985,143 3.5 35 306,250 918,750 50 0.7 35 213,514 640,541 10 40 41 372,059 15,254,400 50 0.8 40 41 248,887 10,204,367 10 4.5 45 453,600 453,600 50 0.9 45 261,765 261,765 10 50 504,000 4,032,000 50 50 324,395 2,595,156 10 60 29 604,800 17,539,200 50 1.2 60 29 376,302 10,912,757 10 70 51 700,124 35,706,300 50 1.4 70 51 445,245 22,707,485 10 80 47 806,400 37,900,800 50 1.6 80 47 479,862 22,553,527 10 90 907,200 8,164,800 50 1.8 90 594,898 5,354,083 10 10 100 1,008,000 6,048,000 50 100 609,714 3,658,283 20 20 18 3,655,555 65,799,997 50 0.4 20 18 131,521 2,367,384 20 1.5 30 10 5,040,000 50,400,000 50 0.6 30 10 195,491 1,954,907 20 40 86 7,524,186 647,079,964 50 0.8 40 86 248,887 21,404,282 20 2.5 50 49 8,400,000 411,600,000 50 50 49 324,395 15,895,332 20 60 74 10,511,351 777,839,983 50 1.2 60 74 376,302 27,846,345 20 3.5 70 11,760,000 58,800,000 50 1.4 70 445,245 2,226,224 20 80 17,429,998 69,719,992 50 1.6 80 479,862 1,919,449 Total cost 2,255,758,336 Total cost Cost (VND) 185,617,826 According to table 4, in 2015 doxorubicin had 653 unreasonable preparations among 1,939 preparations, the concentration of 10 mg had the highest unreasonable number of preparations (407 times), followed by 20 mg (246) and 50 mg had no unreasonable preparation The total cost of these preparations was about 2.2 billion VND After the redistribution of the dosage and the reasonable concentration based on the reduction of unit cost per preparation, the total cost was 185.6 million VND Thus, doxorubicin preparation using appropriate concentration helped to save 2.07 billion VND 116 Journal of military pharmaco-medicine n08-2018 + Optimal supply of doxorubicin: Based on the current status of drug preparation in 2015, the study results of the optimal analysis on supplying of doxorubicin by each concentration were presented in table Table 5: Optimal supplying number of doxorubicin by each concentration Concentration (mg) Total preparation concentration (mg) Order quantity (bottle) Order percentage (%) 10 885 89 4.09 50 103,635 2,073 95.91 20 0 0.00 According to table 5, with the total preparation concentration of each concentration in 2015, the optimal quantity supply of doxorubicin in 2015 should be: 50 mg with 2,073 bottles (accounting for 95.91%), followed by 10 mg with 89 bottles (4.09%) With a unit cost/preparation of 20 mg much higher than 50 mg, the study noted that it would be more cost-effective to use a 50 mg bottle to divide the dose Therefore, don’t need to order the concentration of 20 mg CONCLUSION In 2015, the four drug classes with the highest dividing rates include alkylated; anti-tumor antibiotic, topoisomerase inhibitor and anti-metabolism group Of the 22 active ingredients from four groups of drug, the alkylated group had the highest number of active ingredients (9) Active ingredients that are both high in dividing rate and in total cost were: Oxaliplatin, pemetrexed, gemcitabine, doxorubicin, carboplatin, epirubicine, cisplatin Optimal analysis of the supply of some drugs showed that 3,842 preparations of oxaliplatin and 653 preparation of doxorubicin were inappropriate Reasonable distribution for each concentration saved 6.96 billion VND in oxaliplatin and 2.07 billion in doxorubicin Optimal suppling number in 2015 of oxaliplatin and doxorubicin were as followed: 100 mg oxaliplatin (68.08%), oxaliplatin 200 mg (24.78%), oxaliplatin 50 mg (4.22%), oxaliplatin 150 mg (2.91%); doxorubicin 50 mg (95.91%), doxorubicin 10 mg (4.09%) and doxorubicin 20 mg (0%) This will help guide the development of the drug portfolio at a more reasonable rate between pack sizes for the following year (assuming that the patient morbidity and disease patterns are constant for most of the time) REFERENCES Nguyễn Văn Tùng, Nguyễn Quốc Bình, Nguyễn Trường Sơn, Lê Vân Anh, Nguyễn Thị Thu Thủy Phân tích hiệu kinh tế dự án pha chế thuốc ung thư theo liều cá thể Bệnh viện Chợ Rẫy giai đoạn 2013 - 2015 Tạp chí Y học Việt Nam 2018, 462 (1), tr.152 Phạm Thùy Linh PTH, Nguyễn Mai Hương Tổng quan cá thể hóa sử dụng thuốc điều trị ung thư Hà Nội, Trường Đại học Dược Hà Nội 2017 Bộ Y Tế Thông tư số 22/2011/TT-BYT ban hành ngày 10/06/2011 quy định tổ chức hoạt động khoa dược bệnh viện 2011 Richard L, Schilsky O.R, Lori Minasian, Daniel Auclair, Atiqur Rahman, Richard Pazdur Optimizing dosing of oncology drugs Conference on Clinical Cancer Research 2013 Green D, E Breslow N, Beckwith J et al Comparison between single-dose and divided-dose administration of dactinomycin and doxorubicin for patients with Wilms' tumor: A report from the National Wilms' Tumor Study Group 1998, Vol 16 117 ... concentrations) - Optimal analysis of the supply of oxaliplatin: + The status of the preparation of oxaliplatin in 2015: Investigate the status of the preparation of oxaliplatin based on preparation. .. Investigate the list of cancer drugs with the highest rate of dividing dose in preparation of cancer drugs by individualized doses at Choray Hospital in 2015 * The list of cancer drugs had a high rate... would be a suggestion for the rationalized drug list in the hospital So the study "Optimal analysis of the supply of some cancer drugs preparation by dosage at Choray Hospital" was conducted SUBJECTS