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Investigation of the Reporting System of Schedule-4 Psychotropic Substances in Thailand: A Case Study of Pinazepam นิพนธ์ต้นฉบ ับ Original Article กนกวรรณ โสภากิติบูรณ์1* และ เยาวลักษณ์ อ ่าร าไพ2 Kanokwan Sopakitiboon1* and Yaowalak Amrumpai2 1 กลุ่มก ากับดูแลหลังออกสูต่ ลาด กองควบคุมวัตถุเสพติด ส านักงานคณะกรรมการอาหารและยา 1 Post-marketing Control Unit, Narcotics Control Division, Thai Food and Drug จังหวัดนนทบุรี 1000 Administration, Nonthaburi Province, Thailand, 11000 2 ภาควชิ าเภสชั กรรมชมุ ชน คณะเภสชั ศาสตร ์ มหาวทิ ยาลยั ศลิ ปากร นครปฐม 73000 2 Department of Community Pharmacy, Faculty of Pharmacy, Silpakorn University, Nakhon Pathom, Thailand, 73000 * ติดต่อผู้นิพนธ์: [email protected] * Corresponding author: [email protected] วารสารไทยเภสชั ศาสตรแ์ ละวทิ ยาการสุขภาพ 2560;12(3):138-146. Thai Pharmaceutical and Health Science Journal 2017;12(3):138-146. บทค ัดย่อ Abstract วัตถุประสงค์: การรั่วไหลของวตั ถุออกฤทธใิ์ นประเภท 4 ออกนอกระบบควบคุม Objectives: The leakage of schedule-4 psychotropic substances from the การกระจายยาเป็นปญั หาที่ส าคัญมากแต่ยังไม่มีการวิเคราะห์อย่างชัดเจน formal distribution channel is a crucial problem but still unexplored. This การศึกษานี้จึงมุ่งตรวจสอบระบบรายงานและการสอบทานข้อมูลการซื้อ-ขายวัตถุ study aimed to investigate the reporting system of the substances using ออกฤทธฯิ์ โดยใช้พินาซีแพมเป็นกรณีศึกษา วิธีการศึกษา: เป็นการศึกษาแบบ pinazepam as a study drug. Method: In this cross-sectional study, we ภาคตัดขวางที่ใช้การตรวจสอบรายงานแบบเอกสารและแบบออนไลน์ของพินาซี investigated the reports both in paper-based and online formats submitted แพมซึ่งส่งมาที่ส านักงานคณะกรรมการอาหารและยาตั้งแต่ปี 2557 – 2558 to the FDA during 2014 – 2015. These reports were obtained from รายงานเหล่านี้ได้รับจากผู้ผลิต ผู้น าเข้า ผู้แทนจาหน่าย สถานพยาบาลและร้านยา manufacturers, importers, distributors, healthcare facilities and drugstores. ต่างๆ ข้อมูลปริมาณการซื้อ-ขายในแต่ละระดับของการกระจายยาจะได้รับ Data of purchase and sale volume at each step of distribution were วิเคราะห์เปรียบเทียบและรายงานใดยใช้สถิติเชิงพรรณนาคือความถี่และร้อยละ compared and reported as descriptive statistics, i.e. frequencies and ผลการศึกษา: ในปี 2557 ประเทศไทยมีการน าเข้าวัตถุดิบพินาซีแพม 40 percentages. Results: In 2014, 40 kg of pinazepam was imported to กิโลกรัม โดยขออนุญาตผลิตเพื่อใช้ในประเทศ 15 กิโลกรัมและผลิตเพื่อส่งออก Thailand, i.e. 15 kg being permitted to manufacture finished product for 25 กิโลกรัม ในการผลิตพินาซีแพมสาเร็จรูปเพื่อใช้ในประเทศ 7 รุ่นการผลิต ผลิต domestic use and 25 kg for exportation. Seven batches of the finished ได้จริง 2,639,500 แคปซูล (ร้อยละที่ผลิตได้ 94.27) หลังจากนั้นผู้ผลิตและผู้แทน products for domestic use were produced with a capacity of 2,639,500 จาหน่ายขายพินาซีแพมไปทั้งสิ้น 1,990,000 แคปซูลให้กับสถานพยาบาลและร้าน capsules (or 94.27% actual yield). After the sale of 1,990,000 capsules to ขายยา 168 แห่ง คงเหลือในคลังสินค้า 649,500 แคปซูล (ณ วันที่ 31 กรกฎาคม 168 healthcare facilities and drugstores combined, 649,500 capsules were 2558) มีเพียงสถานพยาบาลและร้านขายยา 64 แห่ง (ร้อยละ 38.10) ส่งรายงาน left in the inventory of the manufacturers and distributors (as of July 31, แบบเอกสารมายังสานักงานคณะกรรมการอาหารและยา (อย.) จึงทาให้ไม่สามารถ 2015). As only 64 healthcare facilities and drugstores (38.10%) submitted ตรวจสอบการกระจายยาไปยังผู้บริโภคได้ สรุป: ยังไม่พบการรั่วไหลออกนอก the reports to the FDA, the distribution to the consumers could not be ระบบควบคุมการกระจายยาพินาซีแพมตั้งแต่การน าเข้าวัตถุดิบ ผลิต ส่งออกและ examined. Conclusion: There was no leakage of pinazepam in the ขายไปยังสถานพยาบาลและร้านขายยาสามารถ แต่ยังไม่สามารถยืนยันการ distribution from the manufacturers to the healthcare facilities and กระจายยาจากสถานพยาบาลไปยังผู้บริโภคได้ ควรมีการเพิ่มพนักงานเจ้าหน้าที่ drugstores. However, the distribution to the consumers could not be verified. เพื่อตรวจสอบระบบรายงานและการปรับปรุงระบบรายงานออนไลน์ให้รองรับการ It is recommended that more officers should be allocated to the data รายงานให้สมบูรณ์มากยิ่งขึ้น verification task and a more comprehensive online reporting system should be in place. คาส าคัญ : ระบบรายงาน, วตั ถุออกฤทธใิ์นประเภท 4, พินาซีแพม Keywords: reporting system, schedule-4 psychotropic substances, pinazepam Introduction The abuse of psychotropic substances causes not only pinezepam, have been widely known as effective anxiolytic physical and mental, but societal problems as well. Such agents. This dilemma has led many countries to issue laws societal negative impacts included the epidemic of and regulations to control the use of these psychotropic psychotropic substance abuse and criminals affecting safety drugs under the Convention on Psychotropic Substances of other people’s life and asset. These problems have called (1971) of the United Nations Office on Drugs and Crime.1 In for a tight control on the psychotropic substances. Despite Thailand, the control of psychotropic drugs with abuse their abuse potentials, many psychotropic substances are potential has been under the provision of the medically useful. Benzodiazepines, such as diazepam and Psychotropic Substances Act, B.E. 2518 (A.D. 1975). ไทยเภสชั ศาสตรแ์ ละวทิ ยาการสขุ ภาพ ปี 12 ฉบับ 3, กค. – กย. 2560 138 Thai Pharm Health Sci J Vol. 12 No. 3, Jul. – Sep. 2017 The abuse of psychotropic drugs has been found in exceeds the amount allowed. Despite a strict control on various countries. In the US, the death of benzodiazepine psychotropic substances with an existing reporting system, overdose had been rising continuously from 1,500 cases in the problems of illicit distribution and access of psychotropic 2001 to 7,500 cases in 2014, a five-fold increase.2 In the substances are still prevalent and have been continuously UK, 342 cases of benzodiazepine-related death in 2013 was increasing. With such ongoing problems, this present study higher than that in 2012 by 20%.3 In Thailand, the abuse has aimed to investigate the performance of the reporting system been found in various groups of substances including opioids and the data verification process of schedule-4 psychotropic (eg. buprenorphine), sedatives and hypnotics (eg. substances under the provision of Thai FDA using pinazepam), and stimulants (eg. phentermine).4 There has pinazepam as a case study drug. The information learned been an increasing trend of cases of illegal drug use from could be useful in improving the control system to alleviate 2002 to 2011. The most found cases of illicit use were the illicit distribution and access, and subsequently the transquilizer related which increased from 346 cases in 2002 abuse of these schedule-4 psychotropic substances. to 719 cases in 2011. With such a high demand, these substances have been illicitly sold widely and the sales were Methods arrested the most. Thai Food and Drug Administration has established a In this cross-sectional study, reports of pinazepam by reporting system for each single step of the distribution of manufacturers, importers and distributors were investigated. psychotropic substances, especially those in schedule-4, Reports both in paper-based and electronic forms from 2014 from importation, manufacturing, selling, and exportation. A to 2015 were examined. Pinezepam was chosen as the good reporting system should allow for 1) immediate study drug since it was one of the widely used psychotropic documentation of purchase and sale data and 2) easy substance. Since it is a benzodiazepine, pinazepam has a correction and verification of the data. Verification process central nervous system suppression action. It provides should be able to compare data from all steps from anxiolytic, sedative, anti-epileptic and muscle relaxing importation, manufacturing, exportation and distribution to effects. In addition, pinazepam also causes amnesia or loss healthcare facilities and drugstores. In other words, volume of memory. All of these effects of pinazepam suggest a of imported substances should completely agree with the relatively high potential for abuse. In addition, the number of expected volume of the finished product. For example, for manufacturers and distributors had been known to be one gram of the psychotropic substance raw material limited, hence a high feasibility to complete the study in a imported, the manufacturer should be able to produce 100 reasonable period of time. tablets of the finished product of 10 mg tablets, and report to Definitions the FDA accordingly. Subsequently, for the sale of 100 tablets of the finished product from the manufacturer or a In this study, licensees of psychotropic substances and distributor to a healthcare facility, such purchase volume of finished products included importers, manufacturers, 100 tablets should be reported by the healthcare facility to distributors, exporters, healthcare facilities and drugstores. the FDA. In addition, the accumulated volume of Healthcare facilities included public and private hospitals, sale/dispensing of the finished product at the healthcare clinics, dental clinics, and veterinary hospital and clinics. The facility should also be reported to the FDA. Numbers from all importers could be those that imported raw materials and/or of these distribution steps should agree with each other. Any finished products of psychotropic substances. The importers discrepancy about the number of psychotropic substances could sell raw materials to manufacturers and the finished and their finished products could potentially indicate a product to distributors or directly to healthcare facilities and leakage or illicit distribution. drugstores.
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  • Appendix 1 Cross-Reference of Research, Generic and Trade Names of Benzodiazepines

    Appendix 1 Cross-Reference of Research, Generic and Trade Names of Benzodiazepines

    Appendix 1 Cross-Reference of Research, Generic and Trade Names of Benzodiazepines Table 1. Benzodiazepine research designations with corresponding generic names Research Designation Generic Name lactam demoxepam methyloxazepam temazepam A 101 nordazepam AB 35616 clorazepate AB 39083 clorazepate AH 3232 clorazepate CB 4261 tetrazepam CB 4306 clorazepate CB 4311 clorazepate CGS 8216 (antagonist) CI683 ripazepam CS 370 cloxazolam CS 430 haloxazolam D40TA estazolam EGYT 341 tofisopam ER 115 temazepam HR 158 loprazolam HR376 clobazam HR 4723 clobazam HR930 fosazepam K3917 temazepam 287 THE BENZODIAZEPINES Research Designation Generic Name LA 111 diazepam LM 2717 clobazam ORF 8063 triflubazam Ro 4-5360 nitrazepam Ro 5-0690 chlordiazepoxide Ro 5-0883 desmethy1chlordiazepoxide Ro 5-2092 demoxepam Ro 5-2180 desmethyldiazepam Ro 5-2807 diazepam Ro 5-2925 desmethylmedazepam Ro 5-3059 nitrazepam Ro 5-3350 bromazepam Ro 5-3438 fludiazepam Ro 5-4023 clonazepam Ro 5-4200 flunitrazepam Ro 5-4556 medazepam Ro 5-5345 temazepam Ro 5-6789 oxazepam Ro 5-6901 flurazepam Ro 15-1788 (antagonist) Ro 21-3981 midazolam RU 31158 loprazolam S 1530 nimetazepam SAH 1123 isoquinazepam SAH 47603 temazepam SB 5833 camazepam SCH 12041 halazepam SCH 16134 quazepam U 28774 ketazolam U 31889 alprazolam U 33030 triazolam W4020 prazepam We 352 triflubazam 288 RESEARCH, GENERIC AND TRADE NAMES Research Designation Generic Name We 941 brotizolam Wy 2917 temazepam Wy 3467 diazepam Wy 3498 oxazepam Wy 3917 temazepam Wy 4036 lorazepam Wy 4082 lormetazepam Wy 4426 oxazepam Y 6047
  • Table III. Defined Daily Doses for Statistical Purposes (S-DDD) for Psychotropic Substances

    Table III. Defined Daily Doses for Statistical Purposes (S-DDD) for Psychotropic Substances

    Table III. Defined daily doses for statistical purposes (S-DDD) for psychotropic substances The term “defined daily doses for statistical purposes (S-DDD)”, indicated defined daily doses for statistical purposes should be ­which has replaced the term “defined daily doses (DDD)”, is used considered approximate and subject to modifications if more by INCB as a technical unit of measurement for the purpose of ­precise information becomes­ available. The basis for the grouping statistical analysis and is not a recommended prescription dose. Its of the substances was, as far as possible, the anatomical definition is not free of a certain degree of arbitrariness. Certain ­therapeutic chemical (ATC) classification system used in the Nordic psychotropic substances may be used in certain countries for differ- Statistics on Medicines and recommended by the World Health ent treatments or in accordance with different medical practices, Organization (WHO) for drug utilization studies. In ­addition, the and therefore a different daily dose could be more appropriate. The grouping reflects the Schedules of the 1971 Convention. ­ ­ ­ ­ ­ ­ 25 Table III.1. Defined daily doses for statistical purposes (S-DDD) for psychotropic substances, by schedule Tableau III.1. Doses quotidiennes déterminées à des fins statistiques (S-DDD) pour les substances psychotropes, par tableau Cuadro III.1. Dosis diarias definidas con fines estadísticos (S-DDD) para las sustancias sicotrópicas, por lista S-DDD S-DDD (mg) (mg) Substances listed in Schedule II Amfepramone — Amfépramone — Anfepramona ......... 75.00 Substances inscrites au Tableau II Aminorex ......................................... — Sustancias incluidas en la Lista II Barbital .......................................... 500.00 Benzfetamine — Benzfétamine — Benzfetamina ......... 75.00 Amfetamine — Amfétamine — Anfetamina ............. 15.00 Bromazepam — Bromazépam .......................
  • Drug/Substance Trade Name(S)

    Drug/Substance Trade Name(S)

    A B C D E F G H I J K 1 Drug/Substance Trade Name(s) Drug Class Existing Penalty Class Special Notation T1:Doping/Endangerment Level T2: Mismanagement Level Comments Methylenedioxypyrovalerone is a stimulant of the cathinone class which acts as a 3,4-methylenedioxypyprovaleroneMDPV, “bath salts” norepinephrine-dopamine reuptake inhibitor. It was first developed in the 1960s by a team at 1 A Yes A A 2 Boehringer Ingelheim. No 3 Alfentanil Alfenta Narcotic used to control pain and keep patients asleep during surgery. 1 A Yes A No A Aminoxafen, Aminorex is a weight loss stimulant drug. It was withdrawn from the market after it was found Aminorex Aminoxaphen, Apiquel, to cause pulmonary hypertension. 1 A Yes A A 4 McN-742, Menocil No Amphetamine is a potent central nervous system stimulant that is used in the treatment of Amphetamine Speed, Upper 1 A Yes A A 5 attention deficit hyperactivity disorder, narcolepsy, and obesity. No Anileridine is a synthetic analgesic drug and is a member of the piperidine class of analgesic Anileridine Leritine 1 A Yes A A 6 agents developed by Merck & Co. in the 1950s. No Dopamine promoter used to treat loss of muscle movement control caused by Parkinson's Apomorphine Apokyn, Ixense 1 A Yes A A 7 disease. No Recreational drug with euphoriant and stimulant properties. The effects produced by BZP are comparable to those produced by amphetamine. It is often claimed that BZP was originally Benzylpiperazine BZP 1 A Yes A A synthesized as a potential antihelminthic (anti-parasitic) agent for use in farm animals.