[ETHICAL PERSPECTIVES AND DILEMMAS IN PRESCRIBING AND DISPENSING MEDICINAL PRODUCTS IN ISRAEL].

INTRODUCTION: Drug therapy is a central pillar in the provision of medical care. A significant number of doctor-patient encounters conclude with a prescription for a drug. These are subsequently followed by a pharmacist-patient interaction that ends with the dispensing of prescription drugs and/or a recommendation for an over-the-counter drug and other products. In Israel, the fields of medicine and pharmacy are highly regulated with extensive legislation.

Drug shortages in Israel, revisited: a bitter pill to swallow.

BACKGROUND: In 2017, we published an article addressing drug shortages (DS) in Israel, exploring regulatory perspectives, challenges, and potential solutions. Since then, DS remain a significant concern for patients, healthcare providers, and policymakers globally. In this updated article, we revisit the topic, providing new insights, data, and analysis on the current DS landscape in Israel, efforts to mitigate them, and propose strategies to combat this escalating issue. METHODS: We conducted a comprehensive search of the Israeli Ministry of Health (MOH) DS database, spanning from 2014 to the present. We extracted DS numbers and their reasons. Further searches on the Israeli MOH website, pharmaceutical division archives, and the internet yielded official MOH publications and correspondence regarding regulatory responses to DS from 2017 onwards. Additionally, two specific cases of DS were examined to analyze their handling. Recent activities and publications from the Israeli MOH aimed at reducing DS were also reviewed. RESULTS: Between 2014 and 2022, DS surged 2.66-fold. Total DS were 3228; 672 due to commercial reasons, and 2556 to operational reasons (20.5% and 79.5% respectively). The average duration of intermittent DS increased 1.56-fold, from 85 to 133 days. Manufacturers informed the MOH 22 days prior to actual shortage on average. Analyzing 2022's DS (640) by ATC groups, prominent categories included nervous system drugs (18%), drugs acting on the alimentary tract and metabolism (14%), and dermatologicals (11%). Operational DS in 2022 (n = 564) were primarily due to stock delivery delays (38%), stock over-utilization (12%), and raw material shortages (9%). Sixteen official MOH publications on DS were identified from 2017 onwards. Moreover, two high-impact DS case studies were examined. CONCLUSION: Despite routine monitoring by the Israeli MOH and updating the DS policy throughout this period, DS persist, intensifying annually and posing serious health risks. This trend mirrors international patterns, affecting countries globally. In Israel's uniquely structured healthcare system, with its swift stakeholder cooperation and implementation capabilities, more effective DS management is conceivable. We propose ten universally applicable rules to address DS challenges.

Process of drug registration in Israel: the correlation between the number of discussions within the Ministry of Health and postapproval variations by EMA and/or FDA.

OBJECTIVES: US FDA and EMA allow facilitated regulatory pathways to expedite access to new treatments. Limited supportive data may result in major postapproval variations. In Israel, partly relying on Food and Drug Administration (FDA) and European Medicines Agency (EMA), clinical data are reviewed independently by the Advisory Committee of Drug Registration (ACDR). In this study, the correlation between the number of discussions at the ACDR and major postapproval variations is examined. DESIGN: This is an observational retrospective comparative cohort study. SETTING: Applications with FDA and/or EMA approval at time of assessment in Israel were included. The timeframe was chosen to allow a minimum of 3 years of postmarketing approval experience for potential major label variations. Data regarding the number of discussions at ACDR were extracted from protocols. Data on postapproval major variations were extracted from the FDA and EMA websites. RESULTS: Between 2014 and 2016, 226 (176 drugs) applications, met the study criteria. 198 (87.6%) and 28 (12.4%) were approved following single and multiple discussions, respectively. A major postapproval variation was recorded in 129 (65.2%) compared with 23 (82.1%) applications approved following single and multiple discussions, respectively (p=0.002). Increased risk for major variation was found for medicines approved following multiple discussions (HR=1.98, 95% CI: 1.26 to 3.09) with a median time of 1.2 years, applications approved based on phase II trials (HR=2.58, 95% CI: 1.72 to 3.87), surrogate endpoints (HR=1.99, 95% CI: 1.44 to 2.74) and oncologic indications (HR=2.48, 95% CI: 1.78 to 3.45). CONCLUSIONS: Multiple ACDR discussions associated with limited supportive data are predictive for major postapproval variations. Moreover, our findings demonstrate that approval by the FDA and/or EMA does not pave the way to automatic approval in Israel. In a substantial per cent of the cases, submission of the same clinical data resulted in different safety and efficacy considerations, requiring additional supporting data in some cases or even rejection of the application in others.

Antimicrobial resistance in food-producing animals: towards implementing a one health based national action plan in Israel.

BACKGROUND: Development of antimicrobial resistance poses a major threat to human and animal health worldwide. Antimicrobials are frequently used in animal husbandry, making food-producing animals a widespread and important source of antimicrobial resistance. Indeed, recent evidence demonstrates that antimicrobial resistance in food-producing animals poses a threat to the health of humans, animals and the environment. To address this threat, national action plans have been implemented based on a 'One Health' approach, which integrates actions across human and animal health sectors to combat antimicrobial resistance. Although under development, Israel has yet to publish a national action plan against antimicrobial resistance, despite alarming findings of resistant bacteria in food-producing animals in the country. Here we review several national action plans against antimicrobial resistance around the world in order to suggest approaches to develop a national action plan in Israel. MAIN BODY: We investigated worldwide national action plans against antimicrobial resistance based on a 'One Health' approach. We also conducted interviews with representatives of relevant Israeli ministries to understand antimicrobial resistance policy and regulatory frameworks in Israel. Finally, we present recommendations for Israel towards implementing a 'One Health' national action plan against antimicrobial resistance. Many countries have developed such plans, however, only a few are currently funded. Furthermore, many countries, especially in Europe, have taken action to reduce the use of antimicrobials and the spread of antimicrobial resistance in food-producing animals by banning the use of antimicrobials to promote growth, reporting data on the use and sales of antimicrobials in food-producing animals, operating centralized antimicrobial resistance surveillance systems and preventing the use of antimicrobials important to human medicine to treat food-producing animals. CONCLUSIONS: Without a comprehensive and funded national action plan, the risks of antimicrobial resistance to the public health in Israel will escalate. Thus, several actions should be considered: (1) Reporting data on the use of antimicrobials in humans and animals. (2) Operating a centralized surveillance system for antimicrobial resistance in humans, animals and the environment. (3) Improving awareness regarding antimicrobial resistance in the general public and in health practitioners from both human and animal sectors. (4) Composing a list of critically important antimicrobials to human medicine that's use should be avoided in food-producing animals. (5) Enforcing best practices of antimicrobial use at the farm-level. (6) Reducing incidence of infection through farm biosecurity. (7) Supporting research and development of new antimicrobial treatments, vaccines and diagnostic tools.

Clinical pharmacy in Israel versus the US, can we "compare apples to apples"?-commentary.

Clinical pharmacy is an umbrella of pharmaceutical services that is practiced by clinical pharmacists. Clinical pharmacists improve the quality of drug therapy, minimize the risk for drug related problems, reduce the risk of morbidity and mortality associated with polypharmacy and decrease the overall healthcare expenditure. Consequently, clinical pharmacy is focused on both the needs of the individual patient, as well as of the healthcare system. Clinical pharmacy is now well-established and practiced worldwide and in the last two decades has been implemented successfully in Israel. This commentary maintains that the comparison of clinical pharmacy practice in Israel and in the United States, published by AJ Rose et al., has several limitations that need to be considered when devising a road map that will fit the Israeli health care system and its environment. Emphasis should be placed on the implementation of automation and robotics, promulgating regulations to allow for integration of pharmacy technicians, and allocating funds for such services.

Clinical and other specialty services offered by pharmacists in the community: the international arena and Israel.

The community pharmacy setting is a venue that is readily accessible to the public. In addition, it is staffed by a pharmacist, who is a healthcare provider, trained and capable of delivering comprehensive pharmaceutical care. As such, community pharmacists have a colossal opportunity to serve as key contributors to patients' health by ensuring appropriate use of medications, preventing medication misadventures, identifying drug-therapy needs, as well as by being involved in disease management, screening, and prevention programs. This unique position gives the pharmacist the privilege and duty to serve patients in roles other than solely that of the stereotypical drug dispenser.Worldwide, as well as in Israel, pharmacists already offer a variety of pharmaceutical services and tend to patients' and the healthcare system's needs. This article provides examples of professional, clinical or other specialty services offered by community pharmacists around the world and in Israel and describes these interventions as well as the evidence for their efficacy. Examples of such activities which were recently introduced to the Israeli pharmacy landscape due to legislative changes which expanded the pharmacist's scope of practice include emergency supply of medications, pharmacists prescribing, and influenza vaccination. Despite the progress already made, further expansion of these opportunities is warranted but challenging. Independent prescribing, as practiced in the United Kingdom or collaborative drug therapy management programs, as practiced in the United States, expansion of vaccination programs, or wide-spread recognition and reimbursement for medication therapy management (MTM) programs are unrealized opportunities. Obstacles such as time constraints, lack of financial incentives, inadequate facilities and technology, and lack of professional buy-in, and suggested means for overcoming these challenges are also discussed.

Changes in consumption of opioid analgesics in Israel 2009 to 2016: An update focusing on oxycodone and fentanyl formulations.

PURPOSE: The purpose of the study is to assess opioid (morphine, methadone, oxycodone, pethidine, and fentanyl) consumption in Israel during 2009 to 2016 and identify recent trends. METHODS: Data for all treatment settings, private and public, for the years 2009 to 2016, were extracted from the Israel Ministry of Health's Pharmaceutical Administration database. The data were used to calculate defined daily doses (DDD) per 1000 inhabitants per day, of the various drugs. RESULTS: Consumption of the 5 opioids increased by 68%, from 3.40 DDD/1000 inhabitants/day in 2009 to 5.72 DDD/1000 inhabitants/day in 2016. This trend resulted mostly from increases in oxycodone consumption from 0.50 DDD/1000 inhabitants/day to 2.03 DDD/1000 inhabitants/day (namely, 4-fold) and in fentanyl consumption, from 1.09 DDD/1000 inhabitants/day to 2.33 DDD/1000 inhabitants/day (about 2-fold). The use of the 3 remaining opioids decreased substantially as follows: pethidine from 0.03 DDD/1000/day in 2009 to 0.007 DDD/1000 inhabitants/day in 2016 (-67%), methadone from 1.61 DDD/1000 inhabitants/day to 1.20 DDD/1000 inhabitants/day (-25%), and morphine from 0.17 DDD/1000 inhabitants/day to 0.15 DDD/1000 inhabitants/day (-12%). An increasing trend was also observed in the use of oxycodone/naloxone (Targin) and oxycodone/acetaminophen (Percocet) combinations, while a decrease was observed in the use of pure oxycodone formulations. CONCLUSIONS: The increase in opioid consumption persisted throughout the years 2009 to 2016. This has been associated with substantial changes in the patterns of prescribing opioids, characterized by increases in oxycodone and fentanyl prescriptions and decreases in morphine, methadone, and pethidine prescriptions. A national program aiming to ensure safe use of opioids in the treatment of chronic pain is warranted.

Strategies for patient empowerment through the promotion of medicines in Israel: regulatory framework for the pharmaceutical industry.

The correct and rational use of medications can have a positive direct impact on disease outcomes, as well on the utilization of the health system resources. Unfortunately, 50% of the patients do not take their medications as prescribed, largely due to lack of patients' understanding of their medical condition, as well as the lack of reliable medicine information.There are multiple strategies implemented in many countries to tackle this challenge including: disease awareness campaigns (DAC) to raise the public awareness to specific diseases, direct-to-consumer advertisement (DTCA) to raise the public awareness to prescription medicines, specific treatments and over-the-counter (OTC) products to improve the accessibility of patients to specific medicines.Prior to 2013, the Israeli policy prohibited prescribing medication advertising and prevented the flow of information from pharmaceutical companies to the patient. In the last five years, the Pharmaceutical division in the Israeli Ministry of Health, as part of the "empowering the patient" agenda, has taken new innovative approaches to raise public awareness to diseases, medications and appropriate usage, as well as promotion of information to improve patient adherence to the prescribed medication.This paper elaborates on the aforementioned strategies implemented in developed countries, and specifically focuses on newly implemented strategies and regulations in Israel regarding pre- and post-prescription information, to improve patient appropriate utilization and adherence to medication.

Trends in utilization of benzodiazepine and Z-drugs in Israel.

BACKGROUND: Studies on benzodiazepine (BZDs) as well as Zopiclone and Zolpidem (Z-drugs) utilization are important for estimating the prevalence of medical conditions, providing the basis for pharmacovigilance, and identifying temporal trends of consumption. Such studies that involve the Israeli population have not been conducted yet. PURPOSE: Identify trends over time in utilization of BZDs and Z-drugs in a nationwide population in Israel. METHODS: Data on BZD and Z-drugs utilization (for all indications) for the period 2005 to 2013 were obtained from pharmaceutical companies that distribute BZDs in Israel. Prevalence of BZD utilization was reported as defined daily doses (DDD)/1000 inhabitants/day. RESULTS: The utilization of BZDs and Z-drugs aimed to treat sleeping disorders increased over the period of the study from 10.22 to 22.49 DDD/1000 inhabitants/day. The greatest increases in utilization of drugs established in Israel were observed for brotizolam (83%), zopiclone (59%), and zolpidem (94%). Decreases in use were recorded for lorazepam (14%), diazepam (16%), and oxazepam (27%). Use of hypnotic BZDs appeared to be relatively high, compared with the use of non-BZD hypnotics ("Z-drugs") such as zolpidem or zopiclone. Nationwide stressful conditions did not appear to be reflected in the annual BZD sales. CONCLUSIONS: Conventional BZDs and Z-drugs remained the treatment of choice for sleeping disorders in Israel during the study period. These results are, in certain cases, in contrast to current practice recommendations and guidelines and point at a need in better dissemination of these guidelines among prescribers in Israel.

Genetic risk factors for antiepileptic drug-induced hypersensitivity reactions in Israeli populations.

The human leukocyte antigen (HLA) alleles B*15:02 and A*31:01 have been identified as predictive markers of adverse cutaneous effects of carbamazepine and phenytoin in Asian and North European populations, respectively. Our aim was to estimate the distribution of these alleles in Jewish and Arab populations in Israel. The HLA-B*15:02 and HLA-A*31:01 carrier rate was estimated based on data from the Hadassah Bone Marrow Registry. Data on Stevens-Johnson syndrome (SJS)- and toxic epidermal necrolysis (TEN)-related hospitalizations were obtained from the Israeli Ministry of Health (MOH) registries and from four Israeli medical centers. Of 83,705 Jewish and Arab-Muslim donors, 81 individuals of known origin carried the HLA-B*15:02. Among them, 66 were Jews of India-Cochin descent. Of the Cochin Jewish donors, 12.7% were B*15:02 carriers. HLA-A*31:01 carrier incidence among Arab and Jewish Israeli populations (3.5% and 2.2%, respectively) was within the range reported in other countries. We did not identify SJS- or TEN-related hospitalizations of Jews of Indian descent. Yet, this population should be considered at greater risk for antiepileptic drug-induced SJS and TEN. Until further data on actual risk are available, such patients should be typed for HLA-B before treatment with carbamazepine or phenytoin.

Utilization of antiepileptic drugs in Israel.

PURPOSE: The aim of the study was to identify trends in utilization of antiepileptic drugs (AEDs) over time in a nation-wide population in Israel. METHODS: Data on AED utilization (for all indications) for the period 2010-2014 were obtained from pharmaceutical companies that distribute AEDs in Israel. Prevalence of AED utilization was reported as defined daily doses (DDD)/1000 inhabitants/day. RESULTS: The utilization of most AEDs included in our analysis remained stable over the study period. The greatest increases in utilization of drugs established in Israel were observed for lamotrigine (33%), oxcarbazepine (31%), and primidone (18%). Decreases in use were recorded for carbamazepine (18%) and phenobarbital (15%). Use of older AEDs appeared to be relatively high, compared with the use of newer AEDs. CONCLUSIONS: During the study period of 2010-2014, conventional AEDs remained a main treatment choice in Israel, in certain cases in contrast to current recommendations and guidelines, for reasons yet to be revealed in further research.

Trends in the use of antipsychotics in the Israeli inpatient population, 2004-2013.

BACKGROUND: Although serious mental illneses are treated with both typical and atypical antipsychotic grugs, trends in their use in psychiatric inpatient population in Israel are unrecognized. The aim of this study was to detect trends in the use of typical and atypical antipsychotic drugs in the Israeli inpatient psychiatric population throughout the last decade. METHODS: Data regarding allocation of typical and atypical antipsychotics, over the period 2004 to 2013, were extracted from the electronic records of SAREL, Israel's largest private supplier of drugs to healthcare and medical facilities. The data were converted to defined daily doses (DDD) per 1000 inpatients per day. RESULTS: Usage of the ten atypical antipsychotic agents allocated through Israel's national health care system increased by 73 %, from 128.09 DDD/1000 inpatients/day in 2004 to 221.69 DDD/1000 inpatients/day in 2013. This rise from 2004 to 2013 was largely due to a 1.6-fold increase in the administration of olanzapine (48.31 to 79.57 DDD/1000 inpatients/day), a 4.4-fold increase of quetiapine (9.74 to 43.04 DDD/1000 inpatients/day) and 3.7-fold increase of amisulpride (5.54 to 20.38 DDD/1000 inpatients/day). At the same period, the total utilization of 12 main typical antipsychotics decreased by 15.5 %, from 148.67 DDD/1000 inpatients/day in 2004 to 125.57 DDD/1000 inpatients/day in 2013. Over the entire period, total DDDs of both classes of antipsychotics (typical and atypical) increased by 38 %. CONCLUSIONS: Similar to trends in the treatment of psychiatric outpatients in other countries, there was a substantial increase in the administration of atypical antipsychotic drugs to the Israeli psychiatric inpatient population across the study period. A decrease in the use of typical antipsychotics (substitution), polypharmacy, administration for more indications (supplementation) and the use of larger doses of antipsychotics may account, in part, for this increase. The findings have implications for mental health policy in the context of the Mental Health Care System Reform. Systematic studies on appropriate dosing of antipsychotics and augmentation strategies are warranted.

Trends in attention deficit hyperactivity disorder drugs consumption, Israel, 2005-2012.

PURPOSE: The aim of this study was to describe trends in attention deficit hyperactivity disorder (ADHD) drugs consumption in Israel (Ritalin, Concerta, Daytrana, Vyvanse, Focalin, and Adderall) over the 8 years, 2005-2012, and to explore explanations for changes in amounts and patterns of the utilization. METHODS: Data for the period from 2005 to 2012 were extracted from the database maintained by the Israel Ministry of Health's Pharmaceutical Administration. The data were converted into a defined daily dose (DDD) per 1000 inhabitants per day. RESULTS: Consumption of all ADHD drugs covered by Israel's national health care system doubled over the study period, from 4.02 DDD/1000 inhabitants/day in 2005 to 9.92 DDD/1000 inhabitants/day in 2012. This rise was largely due to a fivefold increase in Concerta consumption (from 0.46 DDD/1000 inhabitants/day in 2005 to 2.28 DDD/1000 inhabitants/day in 2012) and a threefold increase in Ritalin consumption (from 1.43 DDD/1000 inhabitants/day in 2005 to 4.84 DDD/1000 inhabitants/day in 2012). Adderall (amphetamine mixed salts) consumption rose by 30% for the same period. A substantial trend was noted for increased utilization of high-dose formulations together with proportional decline in low-dose consumption. In the same period, cost of the medications has been reduced an average by 20-25%. CONCLUSIONS: There has been a drastic rise in ADHD drugs consumption in Israel over 2005-2012. This has been associated with substantial reduction in cost and changes in the pattern of prescribing that characterized by increased prescription of high-dose long-acting preparations of ADHD drugs and decreased prescription of their low-dose, short-acting formulations.

Differences in the consumption rates and regulatory barriers to the accessibility of strong opioid analgesics in Israel and St. Petersburg.

OBJECTIVE: To compare trends in opioid consumption in Israel and St. Petersburg/Russia (morphine, oxycodone, pethidine, fentanyl, methadone, buprenorphine, trimeperidine, and papaveretum) over the period 2000-2008, and to describe the regulatory barriers to their accessibility as an exploratory variable for between-country differences. METHODS: Data were drawn from the databases maintained by the Israel Ministry of Health's Pharmaceutical Administration and the St. Petersburg Central Pharmaceutical Reserve. The data were converted into a defined daily dose (DDD)/1,000 inhabitants/day. Regulation was evaluated according to the WHO guidelines for the assessment of national opioid regulation. RESULTS: The opioid consumption rates in Israel were substantially higher than those in St. Petersburg. The excess in DDD/1,000 inhabitants/day was for fentanyl +0.287 in 2000 and +1.206 in 2008, for morphine +0.245 in 2000 and +0.122 in 2008, and for pethidine/trimeperidine +0.035 in 2000 and +0.007 in 2008. Oxycodone consumption increased in Israel from 0.31 DDD/1,000 inhabitants/day in 2000 to 0.46 DDD/1,000 inhabitants/day in 2008, whereas this analgesic is not available in St. Petersburg. Methadone and buprenorphine consumption rose in Israel, whereas these drugs are not available in Russia. Conversely, omnopon consumption decreased in St. Petersburg from 0.0206 DDD/1,000 inhabitants/day in 2000 to 0.00304 DDD/1,000 inhabitants/day in 2008, whereas the compound is not available in Israel. St. Petersburg differs from Israel with less opioid formulary availability and greater regulatory restrictions. CONCLUSION: The results suggest that strong opioid analgesics consumption rates in St. Petersburg yield those in Israel, and that the between-countries differences in opioid formularies availability and legal and regulatory barriers to opioids accessibility are responsible for the consumption discrepancies.

[The over the counter drugs reform in Israel--two years later].

INTRODUCTION: In the last two decades there has been a world wide increase in the number of drugs that are being switched from the prescription-only category to non-prescription categories. In Israel, until recently, non-prescription medicines were only permitted to be sold by a pharmacist in pharmacies. In May 2005, following amendments to the law, several non-prescription medicines which were previously sold under a pharmacist's supervision, were reclassified as general-sales-list (GSL) medicines and permitted to be displayed and sold directly off the shelves in pharmacies and in other places such as grocery stores and petrol stations. OBJECTIVE: To study the change in the patterns of consumption of non-prescription drugs in Israel two years after the reform began. METHODS: A representative sample of the population of Israel was chosen and interviews were conducted at two time points: before the reform commenced and two years after the beginning of the reform. Statistical processing was performed in order to examine the changes in patterns of consumption of non-prescription drugs in Israel between these two time points. RESULTS: In both surveys it was found that: approximately 70% of the Israeli public buys non-prescription medicines; 70% of the people interviewed said that they had been aware of the reform, but of these, about 75% continued buying nonprescription drugs from the pharmacist while 21% bought medicines off the shelves at the pharmacy and 4% purchased medications at grocery stores. The most common reasons for buying medicines off the shelves without a pharmacist were earlier knowLedge about the medication, convenience and availabiLity when the pharmacies were closed. An insignificant difference was observed for the purchase of non-prescription drugs from the different types of pharmacies: the health maintenance organizations (HMO) pharmacies continue to be the leading pharmacies from which the public purchased their non-prescription medicines, white there was a slight increase in the purchases from pharmacy chains. In the two surveys, the purchaser's personal experience was the biggest factor influencing the decision to buy a certain drug, followed by the doctor's and the pharmacist's recommendation. Only 15% thought that non-prescription medicines are not safe. IN CONCLUSION: Two years after the reform began no breakthrough was observed in the pattern of purchase of non-prescription medicines. Despite exposure to the reform, most Israelis continue to buy these medicines from the pharmacists. Therefore, it appears that more time will be needed for this reform to actually start making an impact and changing the habits of Israeli consumers when purchasing non-prescription drugs.

[Over the counter drugs--a new era in Israel].

The reformation in the marketing of non-prescription medicinal products has been launched. As of May 10th 2005, the pharmacist regulations 2004 (marketing of over-the-counter (OTC) drugs outside of pharmacies, as well as not by a pharmacist) will be in effect. This change aLlows the marketing of medicines outside of pharmacies, as has been the custom in the U.S.A., England and some of the European Union countries for many years. This reformation is incorporated in a policy that encourages self-medication by the use of non-prescription drugs. The self-medication policy originates from the point of view of the consumers who wish to be responsible for their own health and save precious time wasted on doctor visits; and the government's assumption that self-medication of OTC medicines by citizens wiLL decrease expenses for the HMOs in both doctor's billings as well as medication costs. In order to regulate the marketing terms of these medicinal products, regulations and complimentary guidelines were written and published. These documents encompass the following issues: the list of OTC medicines, marketing reguLations, packaging regulations, Licensed marketing Locations, storage regulations as well as display regulations, advertising regulations, monitoring and control. The medicinal products in this category only included medicines containing "safe" active ingredients with restrictions regarding the strength/concentration and packaging size; this category does not include medicines requiring special storage conditions (such as refrigeration or freezing), medicines containing an active ingredient that is addictive, medicines containing an active ingredient with danger of poisoning if misused, and medicines containing an active ingredient that has the potential to harm. The implementation of the regulations and guidelines will improve the consumer's ability to diagnose and treat oneself when sick with minor ailments, without consulting a doctor.

Trends in opioid analgesics consumption, Israel, 2000-2008.

OBJECTIVE: To describe trends in opioid consumption in Israel (morphine, methadone, oxycodone, pethidine, fentanyl, buprenorphine, codeine, and dextropropoxyphene) over the 9 years, 2000-2008, and to explore explanations for changes in consumption, in amounts and the pattern. METHODS: Data for the 2000-2008 period (all treatment settings, private and public) were drawn from the database maintained by the Israel Ministry of Health's Pharmaceutical Administration. The data were converted into a defined daily dose (DDD)/1,000 inhabitants/day. RESULTS: Consumption of the five strong opioids (requiring a special prescription form) increased by 47%, from 2.46 DDD/1,000 inhabitants per day in 2000 to 3.61 DDD/1,000 inhabitants per day in 2008. This rise was mainly the result of a 4-fold increase in fentanyl consumption from 0.32 DDD/1,000 inhabitants per day in 2000 to 1.28 DDD/1,000 inhabitants per day in 2008. Oxycodone and methadone consumption levels increased moderately, and buprenorphine and dextropropoxyphene consumption rose drastically, whereas morphine, pethidine, and codeine use significantly fell. CONCLUSION: There has been a modest increase in opioid consumption in the years 2000-2008. This has been associated with substantial changes in the pattern of differential opioid prescribing characterized by increased prescription of oxycodone, fentanyl, buprenorphine, and dextropropoxyphene, and decreases in morphine, pethidine, and codeine.

[Synthetic cannabinoids--the new "legal high" drugs].

Recently, a new Law, named the "derivative law" (first addition, schedule drug change--2010), was accepted in the Israeli parliament. It will mean that dangerous substances that are closely related structurally to a drug that is listed in the dangerous drugs ordinance will automatically enter the dangerous drugs ordinance. The dangerous drugs that were sold in kiosks were related to 4 major groups: Amphetamines, methamphetamines, cathinone and methcathinone. Over 90% of the substances known as "legal highs" or "hagigat" belong to these groups. Before the law was accepted, merchandisers and clandestine Laboratories took advantage of a state in which every small molecular change in a controlled substance of amphetamines, methamphetamines, cathinone and methcathinone required a long legal process in order to include the new substance in the controlled substance law. During this process, we believe that public health was endangered. The chemists and merchandisers found a new solution to "legally" bypass the "derivative law", by marketing a new group of substances named "synthetic cannabinoids". The synthetic cannabinoids do not resemble the chemical structure of tetrahydrocannabinol (THC] which appears in marijuana or hashish, but affects the body in the same manner and according to the literature, are five times more potent. The synthetic cannabinoids are sold in Israel under different nicknames such as: "Mabsuton", "Mr. Nice Guy", "Spice", "Sabbaba" and "Lemon Grass". The substance can be used in different ways such as smoking, inhaling or swallowing. The use of synthetic cannabinoids causes side effects that include: euphoria, dizziness, headache, thirst, paranoia, insomnia, fatigue and disturbed vision. Cases of hospital admission in Israel due to the use of these substances have been reported. The symptoms included psychiatric disturbances. In an urgent meeting of the multi-ministry committee on psychotropic substances held in December 2010 in the Israel Anti-Drug Authority, it was decided to recommend to the Minister of Health to insert an inclusive group of "synthetic cannabinoids" into the control drug list in Israel. On April 5, 2011, after receiving the approval of the health and welfare committee in the Israeli parliament, the dangerous drugs ordinance (new version)--5732-1973 was amended with the addition of an inclusive group of "synthetic cannabinoids". These include: JWH-018, JWH-133, JWH-073, CP 47, 497, CP 55, 940, HU-331, HU-210, HU-211, HU-250.