Patients with liver or lung metastases may also be offered novel ablative therapies such as stereotactic radiotherapy xerostomia medications side effects cheap zofran 8 mg without a prescription, radioembolism and radiofrequency ablation symptoms vaginal yeast infection buy zofran 8 mg online, however these treatments may not be suitable for all patients and their benefts have not yet been proven treatment kidney cancer symptoms cheap zofran 4 mg mastercard. Bone modifying agents such as bisphosphonates and denosumab can help to reduce the occurrence of fractures commonly associated with the presence of bone metastases as well as pain treatment group order genuine zofran on line. Chemotherapies are usually given sequentially for metastatic disease but may be given in combination if the cancer is progressing quickly medicine 223 buy cheap zofran 8mg. Taxanes or anthracyclines may be used again if they have been given before as neoadjuvant or adjuvant therapy medications emts can administer buy zofran american express, if the patient has been considered to be disease-free for at least 1 year and the doctor considers it safe schedule 8 medications victoria effective zofran 8mg. There are also several other chemotherapy choices which your doctor may discuss with you (Cardoso et al medications 5 rights buy discount zofran 8 mg line. A platinum-containing chemotherapy such as carboplatin or cisplatin might also be used in patients with triple-negative disease who have been treated with anthracyclines previously. In pre and perimenopausal patients, ovarian function suppression or ablation (surgical removal) is recommended in combination with endocrine therapy. Megestrol acetate and estradiol (a type of oestrogen) are options for further lines of treatment. Endocrine resistance is a term used when a patient experiences a relapse (or progression of metastatic disease) while taking endocrine therapy, or within 12 months of completing endocrine therapy (Cardoso et al. Patients showing signs of endocrine resistance will usually have their treatment switched to a different endocrine therapy, or to chemotherapy. Some patients may also receive second-line treatment with trastuzumab in combination with lapatinib. Further treatment lines may include combinations of trastuzumab with other chemotherapy drugs, or a combination of lapatinib and capecitabine. Breast cancer and pregnancy There is no contraindication to becoming pregnant after having breast cancer. Endocrine therapy must be stopped before trying to get pregnant and should be resumed after delivery and breastfeeding. If you wish to get pregnant, please discuss all of the issues carefully with your doctor. Treating breast cancer that occurs during pregnancy is a very diffcult situation that should be handled by an experienced team. However, this is a delicate decision that must be taken by the woman and her partner, after being well informed of all available options. Several types of treatment are possible during pregnancy, depending on the trimester (Peccatori et al. Chemotherapy is safe during the second and third trimesters; anthracycline-based chemotherapy is usually the frst choice of treatment in pregnancy and taxanes may also be used. Young women In younger, premenopausal patients, treatment for breast cancer can reduce fertility and can cause an early or temporary menopause. Before starting treatment, your doctor will discuss all possible fertility issues with you and will give you information about any suitable fertility-preservation options available to you (Peccatori et al. It is important to understand that a lack of menstruation does not mean you are postmenopausal, therefore you will still need to take contraceptive measures. If you are frail, it may be necessary to adjust standard treatments to balance the benefts of the treatment against the risks for you. Men Almost all cases of breast cancer in men are hormone receptor-positive for both oestrogen and androgen hormone receptors. Approaches to surgery and radiotherapy are similar to those used in female breast cancer. Although mastectomy is more common than breast conserving surgery, the latter is also possible, as well as some forms of less invasive mastectomy such as nipple-sparing mastectomy (removal of breast tissue without removal of the skin, nipple or areola). For male metastatic breast cancer, endocrine therapy with tamoxifen is standard, but an aromatase inhibitor in combination with gonadotropin-releasing hormone analogues or surgical removal of the testicles to reduce androgen levels (orchiectomy), may also be considered (Cardoso et al. Clinical trials help to improve knowledge about cancer and develop new treatments, and there can be many benefts to taking part. You would be carefully monitored during and after the study, and the new treatment may offer benefts over existing therapies. If your doctor does not ask you about taking part in a clinical trial and you want to fnd out more about this option, you can ask your doctor if there is a trial for your type of cancer taking place nearby (ClinicalTrials. Supportive care Supportive care involves the management of cancer symptoms and the side effects of therapy. Palliative care Palliative care is a term used to describe care interventions in the setting of advanced disease, including the management of symptoms and support for coping with prognosis, making diffcult decisions and preparation for end-of-life care. Survivorship care Support for patients surviving cancer includes social support, education about the disease and rehabilitation. Survivor care plans can help patients to recover wellbeing in their personal, professional and social lives. End-of-life care End-of-life care for patients with incurable cancer primarily focusses on making the patient comfortable and providing adequate relief of physical and psychological symptoms, for example palliative sedation to induce unconsciousness can relieve intolerable pain, dyspnoea, delirium or convulsions (Cherny 2014). Discussions about end-of-life care can be very distressing, but support should always be available to patients and their families at this time. The most common side effects for each type of treatment are summarised below, along with some information on how they can be managed. It is important to talk to your doctor or nurse specialist about any potential side effects that are worrying you. Grade 1 side effects are considered to be mild, Grade 2 moderate, Grade 3 severe, and Grade 4 very severe. The aim is always to identify and address any side effect before it becomes severe, so you should always report any worrying symptoms to your doctor or nurse specialist as soon as possible. It is important to talk to your doctor or nurse specialist about any treatment-related side effects that are worrying you Fatigue is very common in patients undergoing cancer treatment and can result from either the cancer itself or the treatments. Your doctor or nurse specialist can provide you with strategies to limit the impact of fatigue, including getting enough sleep, eating healthily and staying active (Cancer. It affects up to 25% of patients after axillary lymph node removal, but is less common after sentinel lymph node biopsy, affecting less than 10% of patients (Cardoso et al. Following surgery, your arm and shoulder on the operated side may feel stiff and sore for several weeks. Your nurse specialist or a physiotherapist can give you some gentle exercises to help you regain the movement you had before the operation. Radiotherapy There are several common side effects of radiotherapy, including fatigue and skin irritation, aches and swelling in the treated breast. Let your doctor know of any symptoms as he/she may be able to help; for example, creams or dressings can help with skin irritation. You should also avoid exposing the treated area to sun for at least a year after treatment. As radiotherapy for breast cancer will also result in some irradiation to the heart and lungs, the risk of heart disease and lung cancer (particularly in people who smoke) may be slightly higher in patients who have undergone radiotherapy(Henson et al. Patients who receive a combination of different chemotherapy drugs are likely to experience more side effects than those who receive a single chemotherapy drug. The main areas of the body affected by chemotherapy are those where new cells are being quickly made and replaced. Reductions in your levels of neutrophils (a type of white blood cell) can lead to neutropenia, which can make you more susceptible to infections. Nausea and vomiting are common and may be distressing in patients receiving chemotherapy, but your doctor will be able to use a variety of approaches to manage and prevent these symptoms(Roila et al. Your treatment schedule may need to be adjusted if you experience severe hand-foot syndrome but in most cases, symptoms will be mild and treatable with creams and ointments and will subside once you have fnished treatment. Many extravasations cause very little damage, but you may need to be treated with an antidote and apply compresses to the area for a few days (Perez Fidalgo et al. For more severe (grade 2 and above) stomatitis, your doctor may suggest lowering the dose of treatment, or delaying therapy until thestomatitisresolves, but in most cases, symptoms will be mild and will subside once you have fnished treatment. For more severe (grade 2 and above) stomatitis, your doctor may suggest lowering the dose of treatment, or delaying therapy until the stomatitis resolves, but in most cases, symptoms will be mild and will subside once you have fnished treatment. Extravasationscan cause necrosis and you may need to have treatment for the tissue damage(Perez Fidalgo et al. Extravasations can cause necrosis and you may need to have treatment for the tissue damage (Perez Fidalgo et al. Your doctor function will be able to help you to prevent or manage these side effects. Important side effects associated with individual chemotherapy drugs used in the treatment of breast cancer. Many of the side effects from endocrine therapies can be prevented or managed effectively. Always tell your doctor or nurse as soon as possible if you notice any side effects from taking an endocrine therapy. Ovarian function suppression can cause menopausal symptoms such as hot fushes, increased sweating, vaginal dryness and a loss of interest in sex. There can also be some potentially serious side effects such as cardiac disorders, although these risks are vastly reduced by avoiding concurrent treatment with cardiotoxic chemotherapy regimens, such as anthracyclines (Florido et al. Please consult your doctor and/or local product prescribing information for further details. Many of these side effects can be prevented or managed effectively, and you should always tell your doctor or nurse as soon as possible if you notice any side effects from treatment. Troublesome dyspnoea can be treated with drugs called opioids or benzodiazepines, and in some cases steroids are used (Kloke and Cherny 2015). If you develop non-infectious infammation of the lungs (pneumonitis) of grade 2, your doctor might pause or reduce the dose of everolimus. If you suffer from grade 3 or higher non-infectious pneumonitis then everolimus will probably be stopped. Hypercholesterolaemia of grade 2 and 3 might be treated with drugs called statins and fbrates. Important side effects associated with targeted therapies in the treatment of breast cancer. Other treatments Supportive therapy with bisphosphonates can result in side effects including fu-like symptoms, renal toxicity and low calcium levels. Bisphosphonates can also occasionally lead to osteonecrosis (death of bone tissues) in the jaw. Although this is very rare, it is important that you clean your teeth regularly and carefully and report any oral problems to your doctor and dentist. Denosumab therapy can also potentially lead to osteonecrosis of the jaw, as well as low calcium levels and skin infections. It is crucial that you inform your doctor or nurse well in advance of any planned dental treatments, as bisphosphonates and denosumab therapy will have to be temporarily stopped. Follow-up appointments You will be able to discuss any concerns you have at your follow-up appointments After your treatment has fnished, your doctor will arrange follow-up appointments. Typically, these will be every 3 4 months in the frst 2 years, every 6 8 months from years 3 5 and once a year thereafter (Cardoso et al. During these appointments, your doctor will review your medical history with you, note any treatment-related side effects, and conduct a clinical examination. If you are taking aromatase inhibitors, you will have your bone density measured regularly. Based on your results, your doctor will let you know how often you need to return for further follow-up appointments. The treatment that you will be offered depends on the extent of the recurrence and the previous treatment(s) you have received.
Until common standards are fnally used interchangeably if both are absorbed into the blood achieved treatment 101 discount zofran 4mg on-line, purchasers must specify which dosage form stan stream at the same rate and to the same extent symptoms 5th disease order zofran 4 mg on-line. Human bioequivalence studies are required for a number For pharmaceutical procurement organizations mueller sports medicine buy zofran 4 mg fast delivery, pharma of medicines symptoms 10 weeks pregnant purchase 4mg zofran free shipping. Box 19-1 lists some medicines documented ceutical quality is assessed as the products compliance with to have problems in bioavailability that require studies to specifcations concerning identity treatment xeroderma pigmentosum buy discount zofran 8 mg line, purity symptoms of diabetes cheap zofran 8mg fast delivery, strength medications excessive sweating discount zofran on line, potency treatment for bronchitis purchase cheapest zofran and zofran, determine the bioequivalence of products. Uniformity of the dosage form, available for the study of bioavailability, as well as specifc bioavailability, and stability are important characteristics bioavailability protocols for a small number of medicines that are also considered in the specifcations. The identity test should confrm the existence of If purchasing is done through established and reliable sup the active ingredient(s) indicated on the label. This charac pliers, the bioavailability of most brand-name and generic teristic is generally the easiest to check. Deciding which made with ingredients added for bulk, consistency, or color pharmaceuticals have a potential bioavailability problem that should not contain potentially harmful contaminants is important, because manufacturers cannot supply clini or microorganisms. The product should not have signifcant cal studies for all products, and government procurement quantities of other products from cross-contamination. The Biopharmaceutical Classifcation System can help whose members comprise experts from the major pharma identify potential bioavailability problem products (Kasim ceutical manufacturing countries, has established guide et al. Table 19-1 lists the medicines is under warranty, which ends with the expiration date. A that have been found to have problems under tropical and products stability depends on the active ingredient, which high-temperature conditions. Improper storage and distribution can lead to physical deterioration Consequences of poor pharmaceutical quality and chemical decomposition, reduced potency, and occa sionally, formation of toxic by-products of degradation. A poor-quality medicine is one that does not meet specif Tese efects are more likely to occur under tropical condi cations. The use of poor-quality products may have unde tions of high temperature and humidity. Clinical efects that are less stable and therefore require particular atten can include prolonged illness or death or adverse reactions. However, few data are available on the On the economic side, limited fnancial resources may be stability of medicines under true feld conditions. Table 19-1 Medicines found to have stability problems under tropical or high-temperature conditions Oral solids (tablets) Oral liquids (syrups) Inhalation Injections/injectables Acetylsalicylic acid Paracetamol Ipratropium Ergometrine Amoxicilline Lidocaine Ampicillin Methylergometrine Diltiazem Succinylcholine Lopinavir/ritonavir Naloxone Penicillin V Retinol Sources: Gammon et al. With others, such as cold remedies ment, manufacturing equipment, and technical know-how and minor painkillers, a reduction of up to 50 percent in the invested in developing and manufacturing the pharmaceuti content of the active ingredient may not have serious conse cal. The medicine that ultimately reaches the patient, how quences apart from inefectiveness, although the best pro ever, is further afected by packaging and by transportation curement policy requires all products to meet specifcations. Poor-quality pharmaceuticals may induce toxic or Tese infuences, especially factors in the manufacturing adverse reactions. For example, the excipient sub exposed to adverse climatic conditions (for example, exces stances used to give tablets bulk and consistency may not sive heat and humidity), they may undergo physical or afect the color, texture, or chemical quality of a pharma chemical changes that can result in the formation of pos ceutical until the immediate container is opened in a hot, sibly toxic degradation products. Ten, depending on the ingredients, pharmaceutical degradation in tropical climates is preva the tablet may remain frm and dry or become moist and lent, tetracycline is the only common medicine in which it is crumble within a matter of days. Contamination of creams, and other factors can have an efect that may not appear syrups, and other medicines in jars and tubes is especially until the medicine reaches the point of consumption. Figure common in tropical environments, but the consequences 19-2 summarizes these infuences. When contaminants are highly toxic or when toxic substances Prevalence of poor-quality pharmaceuticals are inadvertently included in the product, the result can be catastrophic. Data summarized in Table 19-2 indicate the extent of the Poor pharmaceutical quality wastes money. Inefective pharmaceutical quality problem, as detected by pharmaceu care or the need to treat adverse drug reactions resulting tical quality testing in the public, private, and nongovern from poor product quality leads to more costly treatments. Poor pharmaceutical packaging casts doubts on prod In recent years, national and international authorities uct quality, leading to rejection by health personnel and have recognized the emergence of counterfeit medicines patients. In most industrialized countries with stores shelves, wasting limited fnancial resources. Changes in product appearance, such where many of the counterfeit medicines are produced, and as discoloration, crumbling of tablets, and hardening of oral in Africa, where poverty and loose regulatory oversight suspensions, or changes in taste and smell rightly infuence make marketing of counterfeit products easier (see Box patients perceptions of product quality. However, counterfeiting is an increasing problem in couraged from using health facilities, and worker morale all countries, including developed countries, where Internet may be afected, particularly if medicine shortages are also purchases are popular. Procedures to monitor and maintain the quality of pharmaceutical products through selective tarifs and other pharmaceuticals from the moment they are received mechanisms, no incentive exists for the development of a until the medicine is fnally consumed by the patient. The dearth of tively manage all the possible quality assurance activities internationally recognized specifcations leaves each mar for all the medicines that are procured. Among the realistic goals must be set to identify the combination of major pharmacopoeias, only the British Pharmacopoeia managerial and technical quality assurance activities that and the U. Pharmacopeia have standards for a signif will be most efective under existing conditions. The criti cant number of products, and even they have essentially cal elements in quality assurance for pharmaceutical pro no specifcations for products under patent protection in curement are listed in Figure 19-3, and Country Study 19-1 their markets. They operate in the most lucrative mar roughly summarized as follows in the table below. Generally a few privately held stores Very good Good Label examination Major petty Yes Generally a limited market segment Excellent Good Label examination in a given country Substitution No Generally a few privately held stores Good Good Testing, examination a In general, only the relabelers may have the correct product. Vital lifesaving medicines (antibiotics, cardiac medi bioavailability problems, when cations, and intravenous solutions) warrant greater atten possible tion than other important but not lifesaving medications, such as analgesics. For a few medicines, such as certain heart, asthma, and seizure medicines, studies 7. Plastic contain ers may be better than glass bottles for intravenous solu tions, oral liquids, and disinfectants. In some countries, unit-of-use packages (blister 19 / Quality assurance for pharmaceuticals 19. Standard Tese measures aim to avoid quality loss afer the containers procedures should include requiring certifcations, gather are opened or as a result of frequent handling. The increased ing information on supplier reliability and product quality, costs should be weighed against the wastage and contamina inspecting product samples, and if necessary, conducting tion that may occur with bulk containers, plus the costs of laboratory testing of pharmaceuticals with high potential for any repackaging. Box 19-3 has more this step may be the most critical in quality assurance (see information on the program. As part of a 2001 The fow charts and procedures have been compiled assessment, the Strategies for Enhancing Access to into a Level One Drug Inspectors Handbook. Only 26 percent of the medicines surveyed in non-laboratory-based testing (using thin-layer the thirty-nine duka la dawa baridi, which are private chromatography Minilab). School of Pharmacy fac drug shops, were registered, while a further 24 percent ulty at the Muhimbili University College for Health were notifed. The quality of notifed and unregistered Sciences collaborated on the development and over medicines cannot be assured, since they have not passed sight of the inspectors training. The main focus of the intervention was on product ance program established in 2002. Since then, improved examination and testing at ports of entry and surveil efciencies have resulted in a doubling of the number of lance and testing of products circulating in the market. The program also prequalifed three Fund, and with support from the World Bank, launched new quality-control laboratories to bring the total to its prequalifcation of medicines program to assess and eleven. Since then, the program has agencies, the program has become a valuable resource for added medicines and commodities related to reproductive any purchaser, including countries themselves. It also includes the list of ofers training workshops on how to meet prequalifca prequalifed medicines and their manufacturers. Publications by medicine information services and when assessing ofers and awarding supply contracts. They include mation on suppliers performance and develop and apply criteria for personnel, facilities, equipment, materials, man operational defnitions and criteria to assess the reliability ufacturing operations, labeling, packaging, quality control, of suppliers and avoid subjectivity. A manufacturer may have accept samples of the product, packaging, and labeling is impor able standards for solid dosage forms but not for sterile tant. Ofen, a detect defective products, bear in mind that the samples supplier must approve or at least expedite requests for per are provided by the supplier, which will make every efort formance reports from national pharmaceutical control to ensure that the samples meet the standards. The sam agencies, and failure to obtain such reports for the buyer ples may not, however, be representative of what is actually makes past performance suspect. Keeping a record of condition of received goods, compliance Countries that participate in the scheme agree to certify with contract terms, and timeliness of delivery is essential. For the turing take place in diferent countries before the product procurement ofce, it is an inexpensive means to help ensure reaches the fnal destination. Local manu pharmaceutical product submitted, especially when it facturers that do not have their own quality-control labo is submitted through the manufacturer or importing ratories may contract quality-control testing services from agent other manufacturers, private testing facilities, or national reference laboratories. For this reason, certifcates should be ratory testing of samples from individual batches. To facilitate registration of generic medicines, the Contract specifications evaluation and approval process should not be complicated. Moreover, in some countries, manufactur material is used to assign qualitative and quantita ers may produce exclusively for export; the exporting coun tive properties, its identity must be assured and its 19 / Quality assurance for pharmaceuticals 19. Its uses range rial is generally assessed by infrared spectral com from tracking shipping containers to individual dosage parisons and quantitative assessments performed by units. The airline industry makes extensive use of this ultraviolet-visible spectral measures, either directly technology to track and direct baggage, and the retail or in conjunction with chromatographic procedures. Because of their widespread use identity and quality of solid materials can be assessed and simplicity, bar-code detecting devices are relatively by melting point/mixed melting point measurements, inexpensive. Holograms: Hologram technology provides visual authenti To reduce thef and resale, some programs may require cation that can be very difcult to counterfeit or remove labeling and logos to indicate that the product is solely for (although instances of fake holograms have been found distribution within a particular health care program (for on counterfeit antimalarial products in Southeast Asia). However, the technology is not easily automated and Contract specifcations are discussed in detail in Chapter optimally requires an authentic label or accurate image 39. As The quality of products received should be verifed as soon the technologies mature, several will likely be used to assure as possible by physically inspecting each shipment and diferent aspects of the supply chain. The continuing adop testing selected products in the laboratory as required by tion of these authentication technologies will make product regulation. In addition, more advanced product-tracking counterfeiting more difcult and expensive, but unfortu technologies have been introduced to help ensure the integ nately will not likely eliminate it. Inspection of shipments Product identification technology Regardless of other quality assurance procedures in use, eachthe traditional approach to assuring product integ pharmaceutical shipment should be physically inspected. This means verifying adherence to contract specifcations Unfortunately, this labeling is easily duplicated. To make and order completeness as well as inspecting samples of fraud more difcult, several approaches are available that all items to spot any major problems. Overt technologies are visible receiving staf can be an economical means of ensuring to the eye, and covert technologies require devices for detec pharmaceutical quality and reducing losses from supplier tion. The Minilab uses a thin-layer chromatography method that does not require stan Tiered pharmaceutical quality assessments dard laboratory resources, so it can be used in the feld, such as at ports of entry, while providing a good level As mentioned earlier in the chapter, the safety and efcacy of quality assurance. Tat level of efcacy is called the therapeu technologies are required to support litigation con tic window (see Box 19-4). Specialized instruments: Methods such as high whether products are grossly substandard and to performance liquid chromatography coupled with Box 19-4 Therapeutic window Fortunately, the overwhelming majority of pharmaceuti cal products have a large therapeutic window, which is 50 a great advantage for manufacturers and consumers. A 45 Maximum tolerated dose wide therapeutic window allows the production of fewer dosage levels, which reduces production, supply, and 40 inventory costs and allows consumers to more easily take a dose of a medicine that is efcacious and well toler 35 ated. Products with a narrow therapeutic window require strict monitoring of the patients therapeutic response; 30 for example, patients taking the anticoagulant warfarin Therapeutic sodium must have their individual coagulation times 25 window strictly monitored to determine the ideal dose. A further 20 indicator of the critical dosing requirement for this prod uct is the large number of tablets available containing 1, 15 2, 2. Tese dosing levels contrast markedly with those of acetaminophen (paracetamol), 10 which has a wide therapeutic window. In the United Minimum therapeutic effect States, acetaminophen is ofen marketed as a 325-mg 5 dosage unit, whereas in Europe the dosage unit gener ally is 500 mg. The dosing instructions for both products 0 0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 instruct the user to take one or two units up to four times per day. Generally, these or potency, uniformity, impurities, disintegration, and dis technologies are expensive and require highly trained solution. Biological testing is more specialized and can be per formed only in established facilities with staf trained In summary, wide-therapeutic-index products may be to use microbiological and pharmacological methods. Narrow medicines and eye preparations and microbiological assays therapeutic-index products and those that fail the rapid of antibiotics and vitamins. Pharmacological tests include screening technologies should be assessed by validated the pyrogen test; toxicity tests; hormone assays, such as for technologies that are fast and efcient. Products that fail the insulin and pituitary derivatives; and tests to determine the validated technologies may require further assessments by bioavailability of selected pharmaceuticals. Testing by ity construction, testing equipment, furniture, sup exception means that analyses are done only when a supplier plies, equipment maintenance, salaries, training, and or a particular product is suspect. In some countries, a college of pharmacy or an inde Suppliers whose failure rates are unacceptable are dropped pendent laboratory may have some of the required test from future tenders. Also, many international quality-control pliers is done much less frequently, ofen only for at-risk laboratories provide pharmaceutical analyses at a relatively products. If analyses are performed by foreign Programs that require routine testing of samples for all laboratories, foreign exchange and billing problems may products prior to distribution to health facilities ofen pro be reduced by requiring the suppliers to pay the labora duce signifcant delays in product availability at the health tory directly, with the arrangement clearly described in facility level. In addition, chain-of-custody and reported to have problems should be carefully assessed; legal standing of the testing laboratory in the importing many problems with quality are detectable on visual inspec country may be at issue. For example, verifed observations of tablets that crumble before their expiry date, oral suspensions that harden, or injectable solu 19. Maintaining medicine quality requires careful attention to The tests that should be performed depend on the phar storage conditions and transport, as well as to dispensing maceutical and the reason for testing. The prescriber and the dispenser should counsel the patient on the proper use of medications, explaining what Product problem reporting system the medicine is, why the patient needs it, how to take it, and where and how to store it until treatment is completed, in Establishing a national product problem reporting system addition to possible contraindications and adverse reactions is important so that health workers can report suspected (see Chapter 30). Product problem reporting should be part of an overall Pharmaceutical product presentations: treatment pharmacovigilance system, which also includes monitoring kits, co-packaging, and fixed-dose combinations and reporting adverse drug events and medication errors. Chapter 35 covers those areas of pharmacovigilance in Medicines can be packaged according to therapeutic detail. For example, els can use to report suspected lapses in pharmaceutical or a tuberculosis treatment kit could include enough anti packaging quality. Standard procedures for product prob microbial products for a particular number of patients. Product problem reports and results should be employed at all levels, including the district hospitals, and recorded to provide information for future procurement. In addition, they report problems or questions Product recalls concerning individual medicines to the main ofce. In other countries, locally trained dispensers are responsible for Pharmaceutical products found to be defective should be much of the day-to-day work and must be trained to detect recalled quickly. The central distributors In addition to pharmacists and pharmaceutical assis inventory control system should include information on all tants, other staf members involved in quality assurance batches that have been received. Because tracking individual need training and supervision as a part of quality assurance batches to the health facility is ofen either impractical or eforts. The procurement ofce should pursue with pharmaceutical labeling and packaging materials other remedies specifed in the contract, such as withhold to determine whether contract conditions regarding ing payment or obtaining reimbursement for or replace pharmaceutical dosage, packaging, and labeling have ment of the defective products.
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Many countries and organizations already prepare reports on the environment and development which review current conditions and indicate future trends medicine z pack order cheap zofran on line. Regional and global assessments could make full use of such reports but should be broader in scope and include the results of detailed studies of future conditions for a range of assumptions about possible future human responses treatment anemia zofran 8 mg cheap, using the best available models medications causing hair loss order 8mg zofran. Such assessments should be designed to map out manageable development pathways within the environmental and socio-economic carrying capacity of each region medications ocd zofran 4mg cheap. The primary objective is to provide assessments of the current status and trends in major developmental and environmental issues at the national treatment zinc toxicity buy zofran 4mg, subregional medicine kit for babies buy zofran overnight delivery, regional and global levels on the basis of the best available scientific knowledge in order to develop alternative strategies symptoms yeast infection order zofran us, including indigenous approaches symptoms constipation purchase cheap zofran online, for the different scales of time and space required for long-term policy formulation. Coordinate existing data and statistics-gathering systems relevant to developmental and environmental issues so as to support preparation of long-term scientific assessments for example, data on resource depletion, import/export flows, energy use, health impacts and demographic trends; apply the data obt ained through the activities identified in programme area B to environment/development assessments at the global, regional and local levels; and promote the wide distribution of the assessments in a form that is responsive to public needs and can be widely understood; b. Develop a methodology to carry out national and regional audits and a five-year global audit on an integrated basis. The standardized audits should help to refine the pattern and character of development, examining in particular the capacities of global and regional life-supporting systems to meet the needs of human and non-human life forms and identifying areas and resources vulnerable to further degradation. This task would involve the integration of all relevant sciences at the national, regional, and global levels, and would be organized by governmental agencies, non-governmental organizations, universities and research institutions, assisted by international governmental and non governmental organizations and United Nations bodies, when necessary and as appropriate. The Conference secretariat has estimated the average total annual cost (1993-2000) of implementing the activities of this programme to be about $35 million, including about $18 million from the international community on grant or concessional terms. With regard to the existing data requirements under programme area A, support should be provided for national data collection and warning systems. This would involve setting up database, information and reporting systems, including data assessment and information dissemination in each region. In view of the increasing role the sciences have to play in dealing with the issues of environment and development, it is necessary to build up scientific capacity and strengthen such capacity in all countries particularly in developing countries to enable them to participate fully in the generation and application of the results of scientific research and development concerning sustainable development. Some of the most important of them are the following: education and training in science and technology; assistance to developing countries to improve infrastructures for research and development which could enable scientists to work more productively; development of incentives to encourage research and development; and greater utilization of their results in the productive sectors of the economy. Such capacity-building would also form the basis for improving public awareness and understanding of the sciences. Special emphasis must be put on the need to assist developing countries to strengthen their capacities to study their own resource bases and ecological systems and manage them better in order to meet national, regional and global challenges. Furthermore, in view of the size and complexity of global environmental problems, a need for more specialists in several disciplines has become evident world wide. The primary objective is to improve the scientific capacities of all countries in particular, those of developing countries with specific regard to: a. Education, training and facilities for local research and development and human resource development in basic scientific disciplines and in environment-related sciences, utilizing where appropriate traditional and local knowledge of sustainability; b. A substantial increase by the year 2000 in the number of scientists particularly women scientists in those developing countries where their number is at present insufficient; c. Reducing significantly the exodus of scientists from developing countries and encouraging those who have left to return; d. Improving access to relevant information for scientists and decision makers, with the aim of improving public awareness and participation in decision-making;. Involvement of scientists in national, regional and global environmental and developmental research programmes, including multidisciplinary research; f. Periodic academic update of scientists from developing countries in their respective fields of knowledge. Promote the education and training of scientists, not only in their disciplines but also in their ability to identify, manage and incorporate environmental considerations into research and development projects; ensure that a sound base in natural systems, ecology and resource management is provided; and develop specialists capable of working in interdisciplinary programmes related to environment and development, including the field of applied social sciences; b. Strengthen the scientific infrastructure in schools, universities and research institutions particularly those in developing countries by the provision of adequate scientific equipment and access to current scientific literature, for the purpose of achieving and sustaining a critical mass of highly qualified scientists in these countries; c. Develop and expand national scientific and technological databases, processing data in unified formats and systems, and allowing full and open access to the depository libraries of regional scientific and technological information networks. Promote submission of scientific and technological information and databases to global or regional data centres and network systems; d. Develop and expand regional and global scientific and technological information networks which are based on and linked to national scientific and technological databases; collect, process and disseminate information from regional and global scientific programmes; expand activities to reduce information barriers due to language differences. Increase the applications particularly in developing countries of computer based retrieval systems in order to cope with the growth of scientific literature;. Develop, strengthen and forge new partnerships among national, regional and global capacities to promote the full and open exchange of scientific and technological data and information and to facilitate technical assistance related to environmentally sound and sustainable development. This should be done through the development of mechanisms for the sharing of basic research, data and information, and the improvement and development of international networks and centres, including regional linking with national scientific databases, for research, training and monitoring. Such mechanisms should be designed so as to enhance professional cooperation among scientists in all countries and to establish strong national and regional alliances between industry and research institutions; f. Improve and develop new links between existing networks of natural and social scientists and universities at the international level in order to strengthen national capacities in the formulation of policy options in the field of environment and development; g. Compile, analyse and publish information on indigenous environmental and developmental knowledge, and assist the communities that possess such knowledge to benefit from them. The Conference secretariat has estimated the average total annual cost (1993-2000) of implementing the activities of this programme to be about $750 million, including about $470 million from the international community on grant or concessional terms. Such means include increasing and strengthening regional multidisciplinary research and training networks and centres making optimal use of existing facilities and associated sustainable development and technology support systems in developing regions. Promote and use the potential of independent initiatives and indigenous innovations and entrepreneurship. Support and coordination of scientific cooperation among all nations in the region; b. Linking with monitoring centres and carrying out assessment of environmental and developmental conditions; c. Support and coordination of national studies of pathways towards sustainable development; d. Establishment and maintenance of information, monitoring and assessment systems and databases. Enhancing national, regional and global capacities for carrying out scientific research and applying scientific and technological information to environmentally sound and sustainable development. This includes a need to increase financial resources for global and regional scientific and technological information networks, as may be appropriate, so that they will be able to function effectively and efficiently in satisfying the scientific needs of developing countries. Ensure the capacity-building of women by recruiting more women in research and research training. Education, raising of public awareness and training are linked to virtually all areas in Agenda 21, and even more closely to the ones on meeting basic needs, capacity-building, data and information, science, and the role of major groups. This chapter sets out broad proposals, while specific suggestions related to sectoral issues are contained in other chapters. Education, including formal education, public awareness and training should be recognized as a process by which human beings and societies can reach their fullest potential. Education is critical for promoting sustainable development and improving the capacity of the people to address environment and development issues. While basic education provides the underpinning for any environmental and development education, the latter needs to be incorporated as an essential part of learning. It is also critical for achieving environmental and ethical awareness, values and attitudes, skills and behaviour consistent with sustainable development and for effective public participation in decision-making. To be effective, environment and development education should deal with the dynamics of both the physical/biological and socio-economic environment and human (which may include spiritual) development, should be integrated in all disciplines, and should employ formal and non-formal methods and effective means of communication. Recognizing that countries, regional and international organizations will develop their own priorities and schedules for implementation in accordance with their needs, policies and programmes, the following objectives are proposed: o To endorse the recommendations arising from the World Conference on Education for All: Meeting Basic Learning Needs 2/ (Jomtien, Thailand, 5-9 March 1990) and to strive to ensure universal access to basic education, and to achieve primary education for at least 80 per cent of girls and 80 per cent of boys of primary school age through formal schooling or non-formal education and to reduce the adult illiteracy rate to at least half of its 1990 level. Efforts should focus on reducing the high illiteracy levels and redressing the lack of basic education among women and should bring their literacy levels into line with those of men; o To achieve environmental and development awareness in all sectors of society on a world-wide scale as soon as possible; o To strive to achieve the accessibility of environmental and development education, linked to social education, from primary school age through adulthood to all groups of people; o To promote integration of environment and development concepts, including demography, in all educational programmes, in particular the analysis of the causes of major environment and development issues in a local context, drawing on the best available scientific evidence and other appropriate sources of knowledge, and giving special emphasis to the further training of decision makers at all levels. Recognizing that countries and regional and international organizations will develop their own priorities and schedules for implementation in accordance with their needs, policies and programmes, the following activities are proposed: a. All countries are encouraged to endorse the recommendations of the Jomtien Conference and strive to ensure its Framework for Action. This would encompass the preparation of national strategies and actions for meeting basic learning needs, universalizing access and promoting equity, broadening the means and scope of education, developing a supporting policy context, mobilizing resources and strengthening international cooperation to redress existing economic, social and gender disparities which interfere with these aims. Non-governmental organizations can make an important contribution in designing and implementing educational programmes and should be recognized; b. Governments should strive to update or prepare strategies aimed at integrating environment and development as a cross cutting issue into education at all levels within the next three years. The strategies should set out policies and activities, and identify needs, cost, means and schedules for their implementation, evaluation and review. A thorough review of curricula should be undertaken to ensure a multidisciplinary approach, with environment and development issues and their socio-cultural and demographic aspects and linkages. Due respect should be given to community-defined needs and diverse knowledge systems, including science, cultural and social sensitivities; c. Countries are encouraged to set up national advisory environmental education coordinating bodies or round tables representative of various environmental, developmental, educational, gender and other interests, including non governmental organizations, to encourage partnerships, help mobilize resources, and provide a source of information and focal point for international ties. These bodies would help mobilize and facilitate different population groups and communities to assess their own needs and to develop the necessary skills to create and implement their own environment and development initiatives; d. Educational authorities, with the appropriate assistance from community groups or non-governmental organizations, are recommended to assist or set up pre-service and in-service training programmes for all teachers, administrators, and educational planners, as well as non-formal educators in all sectors, addressing the nature and methods of environmental and development education and making use of relevant experience of non-governmental organizations;. Relevant authorities should ensure that every school is assisted in designing environmental activity work plans, with the participation of students and staff. Schools should involve schoolchildren in local and regional studies on environmental health, including safe drinking water, sanitation and food and ecosystems and in relevant activities, linking these studies with services and research in national parks, wildlife reserves, ecological heritage sites etc. Educational authorities should promote proven educational methods and the development of innovative teaching methods for educational settings. They should also recognize appropriate traditional education systems in local communities; g. Within two years the United Nations system should undertake a comprehensive review of its educational programmes, encompassing training and public awareness, to reassess priorities and reallocate resources. Regional organizations and national authorities should be encouraged to elaborate similar parallel programmes and opportunities by conducting an analysis of how to mobilize different sectors of the population in order to assess and address their environmental and development education needs; h. There is a need to strengthen, within five years, information exchange by enhancing technologies and capacities necessary to promote environment and development education and public awareness. Countries should cooperate with each other and with the various social sectors and population groups to prepare educational tools that include regional environment and development issues and initiatives, using learning materials and resources suited to their own requirements; i. Countries could support university and other tertiary activities and networks for environmental and development education. Existing regional networks and activities and national university actions which promote research and common teaching approaches on sustainable development should be built upon, and new partnerships and bridges created with the business and other independent sectors, as well as with all countries for technology, know-how, and knowledge exchange; j. Countries, assisted by international organizations, non governmental organizations and other sectors, could strengthen or establish national or regional centres of excellence in interdisciplinary research and education in environmental and developmental sciences, law and the management of specific environmental problems. Such centres could be universities or existing networks in each country or region, promoting cooperative research and information sharing and dissemination. At the global level these functions should be performed by appropriate institutions; k. Countries should facilitate and promote non-formal education activities at the local, regional and national levels by cooperating with and supporting the efforts of non-formal educators and other community-based organizations. The appropriate bodies of the United Nations system in cooperation with non-governmental organizations should encourage the development of an international network for the achievement of global educational aims. At the national and local levels, public and scholastic forums should discuss environmental and development issues, and suggest sustainable alternatives to policy makers; l. These authorities and industry should encourage business, industrial and agricultural schools to include such topics in their curricula. The corporate sector could include sustainable development in their education and training programmes. Programmes at a post-graduate level should include specific courses aiming at the further training of decision makers; m. Governments and educational authorities should foster opportunities for women in non-traditional fields and eliminate gender stereotyping in curricula. This could be done by improving enrolment opportunities, including females in advanced programmes as students and instructors, reforming entrance and teacher staffing policies and providing incentives for establishing child-care facilities, as appropriate. Priority should be given to education of young females and to programmes promoting literacy among women; n. Governments should affirm the rights of indigenous peoples, by legislation if necessary, to use their experience and understanding of sustainable development to play a part in education and training; o. The United Nations could maintain a monitoring and evaluative role regarding decisions of the United Nations Conference on Environment and Development on education and awareness, through the relevant United Nations agencies. With Governments and non-governmental organizations, as appropriate, it should present and disseminate decisions in a variety of forms, and should ensure the continuous implementation and review of the educational implications of Conference decisions, in particular through relevant events and conferences. The Conference secretariat has estimated the average total annual cost (1993-2000) of implementing the activities of this programme to be about $8 billion to $9 billion, including about $3. In the light of country -specific situations, more support for education, training and public awareness activities related to environment and development could be provided, in appropriate cases, through measures such as the following: a. Giving higher priority to those sectors in budget allocations, protecting them from structural cutting requirements; b. Shifting allocations within existing education budgets in favour of primary education, with focus on environment and development; c. Promoting conditions where a larger share of the cost is borne by local communities, with rich communities assisting poorer ones; d. Obtaining additional funds from private donors concentrating on the poorest countries, and those with rates of literacy below 40 per cent;. Lifting restrictions on private schooling and increasing the flow of funds from and to non-governmental organizations, including small-scale grass-roots organizations; g. Promoting the effective use of existing facilities, for example, multiple school shifts, fuller development of open universities and other long-distance teaching; h. Facilitating low-cost or no-cost use of mass media for the purposes of education; i. There is still a considerable lack of awareness of the interrelated nature of all human activities and the environment, due to inaccurate or insufficient information. There is a need to increase public sensitivity to environment and development problems and involvement in their solutions and foster a sense of personal environmental responsibility and greater motivation and commitment towards sustainable development. The objective is to promote broad public awareness as an essential part of a global education effort to strengthen attitudes, values and actions which are compatible with sustainable development. It is important to stress the principle of devolving authority, accountability and resources to the most appropriate level with preference given to local responsibility and control over awareness-building activities. Recognizing that countries, regional and international organizations will develop their own priorities and schedules for implementat ion in accordance with their needs, policies and programmes, the following activities are proposed: a. Countries should strengthen existing advisory bodies or establish new ones for public environment and development information, and should coordinate activities with, among others, the United Nations, non-governmental organizations and important media. They should encourage public participation in discussions of environmental policies and assessments. Governments should also facilitate and support national tolocal networking of information through existing networks; b. The United Nations system should improve its outreach in the course of a review of its education and public awareness activities to promote greater involvement and coordination of all parts of the system, especially its information bodies and regional and country operations. Systematic surveys of the impact of awareness programmes should be conducted, recognizing the needs and contributions of specific community groups; c. Countries and regional organizations should be encouraged, as appropriate, to provide public environmental and development information services for raising the awareness of all groups, the private sector and particularly decision makers; d. Countries should stimulate educational establishments in all sectors, especially the tertiary sector, to contribute more to awareness building. Educational materials of all kinds and for all audiences should be based on the best available scientific information, including the natural, behavioural and social sciences, and taking into account aesthetic and ethical dimensions;. Countries and the United Nations system should promote a cooperative relationship with the media, popular theatre groups, and entertainment and advertising industries by initiat ing discussions to mobilize their experience in shaping public behaviour and consumption patterns and making wide use of their methods. Such cooperation would also increase the active public participation in the debate on the environment. Countries, in cooperation with the scientific community, should establish ways of employing modern communication technologies for effective public outreach. National and local educational authorities and relevant United Nations agencies should expand, as appropriate, the use of audio-visual methods, especially in rural areas in mobile units, by producing television and radio programmes for developing countries, involving local participation, employing interactive multimedia methods and integrating advanced methods with folk media; g. Countries should encourage non-governmental organizations to increase their involvement in environmental and development problems, through joint awareness initiatives and improved interchange with other constituencies in society; i. Countries and the United Nations system should increase their interaction with and include, as appropriate, indigenous people in the management, planning and development of their local environment, and should promote dissemination of traditional and socially learned knowledge through means based on local customs, especially in rural areas, integrating these efforts with the electronic media, whenever appropriate; j. Public awareness should be heightened regarding the impacts of violence in society. Training is one of the most important tools to develop human resources and facilitate the transition to a more sustainable world. It should have a job-specific focus, aimed at filling gaps in knowledge and skill that would help individuals find employment and be involved in environmental and development work. At the same time, training programmes should promote a greater awareness of environment and development issues as a two-way learning process. To establish or strengthen vocational training programmes that meet the needs of environment and development with ensured access to training opportunities, regardless of social status, age, gender, race or religion; b. To promote a flexible and adaptable workforce of various ages equipped to meet growing environment and development problems and changes arising from the transition to a sustainable society; c. To strengthen national capacities, particularly in scientific education and training, to enable Governments, employers and workers to meet their environmental and development objectives and to facilitate the transfer and assimilation of new environmentally sound, socially acceptable and appropriate technology and know-how; d. To ensure that environmental and human ecological considerations are integrated at all managerial levels and in all functional management areas, such as marketing, production and finance. Countries with the support of the United Nations system should identify workforce training needs and assess measures to be taken to meet those needs. A review of progress in this area could be undertaken by the United Nations system in 1995. National professional associations are encouraged to develop and review their codes of ethics and conduct to strengthen environmental connections and commitment. The training and personal development components of programmes sponsored by professional bodies should ensure incorporation of skills and information on the implementation of sustainable development at all points of policy and decision-making.
However symptoms mononucleosis purchase zofran 8 mg with visa, a truer picture such as for certain antibacterial medications resembling percocet 512 buy 4mg zofran otc, antitubercular medicine man gallery buy 4 mg zofran visa, or anti may emerge if broader measures of efectiveness are used malarial drugs for which drug resistance is high symptoms night sweats purchase discount zofran. For example symptoms definition buy 8 mg zofran fast delivery, in an area of moder guidelines for chronic diseases medicine reminder generic 8mg zofran fast delivery, such as hypertension 2d6 medications buy zofran 4 mg amex, ate resistance treatment programs zofran 8 mg otc, a more efective second-line antimalarial and for antibiotic prophylaxis for surgery. This section highlights the information that the patient lines would change irrational prescribing patterns. Tese criteria describe when to refer the guidelines to all prescribers is not enough to bring about patient to a higher level of care. To be efective, condition does not improve within four hours, refer the guidelines must be properly introduced to the prescrib patient to a hospital. For this reason, an index of the guidelines, and training courses should be organized with both drug names and health problems makes the man to introduce the guidelines and teach health workers how ual more useful. Treatment guidelines for paramedical prescrib ers are usually well received and are common in develop Use of treatment guidelines ing countries, as is also true of national treatment guidelines for general doctors. National guidelines for tertiary care are Treatment guidelines should be used for basic training of rare, but general care guidelines are ofen used in tertiary health workers, in-service training, supervision, reference, institutions. They are potentially valuable in promot each for adult and pediatric patients in the hospital setting ing the rational use of medicines, because many prescribers and a combined version for primary health care, which also recognize them as useful references. In developed to the list of essential medicines, they should also serve as countries, treatment protocols are usually drawn up for the basis for the supply of essential medicines. Despite the widespread availability Outcome measures (n = 12) (n = 12) of standard treatment guidelines in health centers, evi Medicines prescribed dence suggested that health professionals did not always per encounter 4. Average prescription Twenty-four health centers from two districts were ran costs (rupiahs) 1,123/750 1,296/1,151 domly assigned to receive the intervention (Group A) or act as controls (Group B). In ticipated in a feedback seminar where the results of the addition, afer presentation of the study results to both study were presented. The level of compliance with the groups, the control health centers experienced signif cant improvements on all outcome measures. Monitoring programs can focus specifcally on been used to modify existing treatment guidelines. Many the issue of treatment failure, and reports of high rates of malaria-endemic countries have changed their national clinical failure should prompt a thorough investigation malaria treatment policy afer antimicrobial resistance and evaluation. For example, are there problems in the monitoring indicated that chloroquine or sulfadoxine treatment guidelines themselves or in the implementa pyrimethamine was no longer efective in the country. Are quality medications For most infectious diseases, however, formal monitor available and used properly by patients If authorities should have a procedure in place for respond the evaluation fnds high rates of clinical failure despite ing to concerns by conducting studies or investigations. The information is usually presented in the form of drug Treatment guidelines have the strongest long-term impact information sheets or drug monographs. The frst edi in the national formulary list are limited to those on the tion of guidelines should be reviewed and updated afer one national list of essential medicines. However, a formulary year to rectify errors and ambiguities; afer that, revisions manual may also include some information on commonly should occur every two to three years, or as indicated by new used medicines whose use is not recommended, stating evidence to support changes (see Box 17-3). Acknowledgments should list all persons or agencies that contributed to the formulary; this back As noted in Chapter 16, the term formulary can be applied ground enhances its authority and credibility. The introduc to a simple formulary list, the formulary manual (the sub tion should briefy describe the development process and ject of this discussion), or a fully developed formulary the manuals intended use. A formulary system develops from the essential Basic information for each medication should be easy medicines or formulary list and the formulary manual. The format and wording includes drug information and other resources to support should be carefully chosen so that the information can be good pharmaceutical management and the rational use of easily understood. This information may be presented in tables or guidelines, the production of a formulary manual is one bar charts. If the manual includes information that pre step in an ongoing process, and formulary manuals should scribers or dispensers should give to patients to ensure the periodically be reviewed and updated. Each of these A section on prescribing and dispensing guidelines can can be numbered and cross-referenced in the drug sheets. For example, general A comprehensive index of all drug groups and drug points to consider before writing a prescription include the names (including brand names in italics, where appropri use of International Nonproprietary (generic) Names, the ate) should be provided at the end of the publication. A good importance of nondrug treatment and simple advice, sug index greatly enhances the usefulness of the formulary man gestions for dealing with patients demands for injections ual and the accessibility of its information. Dispensing guidelines may include such comments by including a formulary revision form, correct dispensing practices and types of information to be containing a request for supporting references. With this approach, all participants will consider tematic process for the development, printing, and distribu the formulary as partly their own creation and thus will be tion of the manual should be agreed upon, with sufcient more committed to ensuring its acceptance and widespread time, personnel, and resources allocated. The Many aspects of the formulary process have already formulary system must not tolerate infuence or pressure been described, in discussions of essential medicines lists from pharmaceutical manufacturers or suppliers concern (Chapter 16) and standard treatment guidelines (in this ing any product being considered for addition to or deletion chapter). When a sufcient number of revisions has been mulary committee could be the national drug committee received and accepted, the development process must be itself or a smaller subcommittee of it. Producing new editions committee should include a clinical pharmacist or phar regularly is important for maintaining the usefulness and macologist, a physician, and additional prominent medi credibility of the formulary. Specifc issues to In developing a formulary manual, consideration needs to be addressed regarding the nature, content, and format of be given to such issues as sequencing, presentation of the the formulary manual are summarized in the next section. One person (or a maximum of two inclusion of brand-name drugs (see Figure 17-1), and pric coeditors) should be appointed to draf the text of the for ing choices. Structuring drug infor the pharmaceutical, pharmacological, and clinical aspects of mation by therapeutic class is ofen preferred to alphabetical the information required and of the level of language appro order. This format places each medicine in its therapeutic priate for the target audience. When the first draft has been pro The therapeutic classifcation of the national list of essen duced, it should be presented to the formulary committee tial medicines (Chapter 16) should be used. Future users of the manual, guidelines for antiretroviral therapy at the beginning of the such as doctors, nurses, pharmacists, and other health care listings for the antiretroviral therapeutic class). Information on medicines not on the national list of A special national meeting involving committee members essential medicines. Should information be included on and stakeholders, including future users of the formulary medicines that are not recommended but are used in manual, should then be called to discuss any outstanding some settings or that complement medicines on the list It is important for the credibility and accept vided through a drug information circular or drug bulletin, 17 / Treatment guidelines and formulary manuals 17. Contraindications: respiratory depression, obstructive airways disease, acute asthma attack; where risk of paralytic ileus. Precautions: renal impairment (Appendix 4) and hepatic impairment (Appendix 5); dependence; pregnancy (Appendix 2) and breastfeeding (Appendix 3); overdosage: section 4. Including private not yet familiar with generic names to locate the required sector medicines that are not on the national list of essential monograph easily. However, inclusion production of a formulary manual is time-consuming and of these medicines means that many more monographs costly, and recovering some of these costs may be necessary. And including infor sector health workers and students and to charge the full mation that is not relevant to the public sector may induce price to users in the private sector. Ideally, the formulary an unwanted demand for items that are not on the national manual should be distributed without charge to everyone in list of essential medicines. A formulary manual may be pocket size for day-to-day use or a larger, desktop reference Hospital formularies for occasional use. If In many countries, especially those with highly developed the focus is on individual drugs, the formulary is probably health systems, hospitals develop their own formulary man most useful as a desktop reference. A example by using color-coded pages for each section, edge hospital formulary committee is given responsibility for indexes, and headers. A quick reference listing of commonly producing and subsequently revising the formulary list used topics can be included on the back cover. Although the drug formulary manuals may include details of recommended monographs should always appear under the generic name hospital procedures, hospital antibiotic policy, and guide of the drug, listing common brand names may be useful. If these names are included, they should appear in italics, Hospital formularies usually refect consensus on the treat both in the main text and in the index, so that they are eas ment of frst choice and thus are not always distinct from ily identifable. In addition to the information in Section 17-3, the following practical advice is useful for The most common failure in implementing treatment producing local reference manuals. The greater stakeholders involvement in It is important to defne a standard style for chapters, the development process, the more likely they are to accept, tables, and monographs before requesting outside experts use, and defend the outcome. Terefore, it is important to to write sections of a publication (treatment guidelines or involve health workers at various levels, including rural formulary manual). If standards are not set, large difer health care and training institutions, in both the develop ences in approach, level of detail, and style (for example, ment and the review process. A broad range of opinions on for headings, abbreviations, and use of bullets) can be the proposed content and format of a frst edition and subse expected. Correcting those diferences at a later stage is quent revisions should be solicited. It is a good Afer the treatment guidelines manual or formulary idea to include one or two examples and a few sample pages manual has been developed and distributed, work is still along with instructions to the writers. A typographical error in a dosage, for example, usage in the health care community will vary depending could be fatal. A common of copies required, consider whether the target audience is mistake with treatment guidelines is the selection of medi likely to increase in the time between editions. The number cations that are too sophisticated, too expensive, or not gen of copies required is commonly underestimated. However, increasing the number of copies is usually relatively cheap, acceptance can be improved by ensuring that medicine including an extra margin of at least 10 to 20 percent is rec availability matches the guidelines, by using the materials ommended. If possible, free copies should be made available to from government mail, distribution may be carried out all health workers and all types of students (nursing, phar through workshops, professional associations, or sales, or macy, paramedical, and medical) and the material should by adding the manuals to regular pharmaceutical supply be ofcially adopted in training institutions. Whatever distribution method is chosen, Printed reference materials may include manuals, posters, the introduction and distribution costs should be included and training materials. A procedure should be set up to monitor ments involved, printed references may be in the form of distribution and to handle requests for additional printed wall charts, pocket handbooks, or larger, shelf-size refer copies. Afer the materials are distributed, a careful introduction also inform this updating process (see Box 17-2). Any new campaign is needed to promote their general acceptance medicines ofering an advantage over the current selections and use. This campaign may include the ofcial launch of should be considered for addition, and medicines that are the publication by an upper-level ofcial, press reviews, no longer used or for which there is insufcient evidence of introductory workshops in key educational institutions, efcacy, safety, or quality should be recommended for dele articles in drug information circulars and drug bulletins, tion. The cost of such a campaign should be included in the As with the list of essential medicines (Chapter 16), planning. Especially for treatment guidelines, a second edition mittee reviews and evaluates the latest evidence regarding will be needed soon afer the frst. Mistakes will undoubt treatment of diseases and conditions as well as therapeu edly have occurred that need correction, and comments tic drug classes, and considers which medicines should be and proposals for change are bound to be received from added to or deleted from the formulary list. A monitoring people who may not have taken the trouble to comment and evaluation system that tracks treatment failure can on the frst draf. References and further readings National Health and Medical Research Council [Australia]. A Guide to the Development, Implementation and Evaluation of Clinical H = Key readings. Framework pdf> for Use of Antimicrobial Resistance Surveillance in the Development of New Zealand Guidelines Group. Undertaking Systematic Reviews of Research on Medical Practice: A Systematic Review of Rigorous Evaluations. Efectiveness and Efciency of Guideline Dissemination and Implementation Strategies. Agency for Terapeutics Committee Training Course, Session 10: Standard International Development by the Rational Pharmaceutical Treatment Guidelines. Antiretroviral Drugs for Treating Pregnant Women and H Joint Formulary Committee [Great Britain]. London: British Medical Association and the Royal Towards Universal Access: Recommendations for a Public Health Pharmaceutical Society of Great Britain. Accra: Ministry of Health/ Adolescents: Recommendations for a Public Health Approach. Diferent combinations of these tion, and direct procurement, which vary with respect to models may be used at diferent levels of the system or for their efect on price, delivery times, and workload of the diferent medicines. In recent years, some public-sector procurement systems (particularly in Latin America) Efective procurement is a mechanism for managing have introduced e-procurement (Internet tendering) the buyer-seller relationship to ensure transparent and and more specifcally the reverse auction approach, ethical transactions that result in the buyer receiving the although these methods have not been widely used to correct goods and the seller receiving timely payment. Funding sources (governments collaborative process is needed between the procurement and donors) ofen dictate which procurement method ofce, with requirements for trained staf and appro to use. Finally, some developing-country health systems priate management systems, and technical and policy purchase medicines and health commodities directly committees, which may make fnal decisions as to which from international procurement agents, many of which medicines to buy, in what quantities, and from which are based in Europe. In most developing countries, pharmaceutical and United Nations Development Programme have long purchases represent the single largest health expenditure functioned as pooled procurement systems serving their afer personnel costs. In recent years, a number of new global major share of health-related foreign currency exchange. Good procurement management tems; or purchasing from international procurement agents. Pharmaceutical procure way through medicines fees, or through some combina ment costs include several diferent components; some costs tion of fnancing alternatives. Unit prices Over the last twenty years, formal pooled procurement programs have become common in some industrialized What determines the tender price of a container of 1,000 countries (known in the United States as group purchasing amoxicilline tablets or ten ampoules of adrenaline Tere organizations), and the factors that make them successful are many considerations involved in pharmaceutical pricing are known. Regional approaches to multicountry pooled by manufacturers and distributors, and many factors that 18. The health centers and hospitals might order on registration, licensing for manufacturing and distribu most items monthly, with a weekly supplemental order, and tion, authority to prescribe and dispense, generic substitu so forth. In some markets, even sole-source The reorder frequency infuences the types of procure suppliers may ofer discount pricing to the public sector that ment methods and purchasing contracts that can be used is not necessarily related to purchase volume to establish or (see Section 18. However, this works both ways; indi maintain market share or to negotiate with international vidual country circumstances (typically storage conditions development entities. The ment method or contract, which then limits the options strategies and issues discussed in Section 18. For example, if only or indirectly infuence the degree of competition and the fxed-quantity tenders are allowable under local laws, imple degree of discount pricing available to the health system. If all pharmaceuticals are imported and average lead times are six Reorder frequency and the total cost of purchasing to nine months, avoiding an annual purchasing system for most items will be a challenge. Pharmaceutical acquisition prices are only one part of the The systems and formulas used to estimate needs and total cost of pharmaceutical purchasing; the other important defne order quantities vary with the purchasing model components are the costs associated with holding inventory, and with the availability of information on past consump the costs of operating the purchasing system, and the extra tion. The procedures for estimating annual procurement costs incurred when stockouts occur (shortage costs). However, other cost components may increase the total purchasing some situations may require the use of a procedure such as cost by 50 percent or more of the acquisition costs. For each morbidity-based forecasting to estimate needs for procure countrys situation, total purchasing costs can be mini ment (Chapter 20). Systems holding costs, purchasing operations costs, and shortage minimize costs by striking the right balance between the costs. In a competitive tender, a large number of suppliers with varying technical and commercial back Open tender: Open tendering is a formal procedure by grounds may submit bids, and their quoted prices will vary which quotes are invited from any suppliers repre considerably. Because no cost adjustments for performance sentative on a local or worldwide basis, subject to the are permitted to be considered during the tender assessment terms and conditions specifed in the tender invitation. The prequalifca examples of hidden costs of medicines that are controlled tion process is ofen open to any supplier that wishes to through national pharmaceutical policy. Pharmaceutical procurement methods, at any level of a prices are submitted; then the lowest posted bid wins health system, generally fall into a few basic categories: open the contract. This approach has rarely been used for tender; restricted tender; competitive negotiation, includ pharmaceutical procurement (with most experience in ing international or local shopping; and direct procurement. Latin America); however, it may gain traction as global Each of these methods can be used with any of the standard Internet capacity and use increase. Buyers may also bargain with these suppliers to achieve spe International open tenders usually attract the largest cifc price or service arrangements. This procurement number of competitive ofers and potentially the lowest method is used primarily in the private sector, because prices. International tenders for pharmaceuticals are limited public-sector procurement organizations are generally to primary manufacturers and commercial suppliers or to forbidden from negotiating or bargaining with suppliers. Some procurement ofces use a combination of methods: Direct procurement: The simplest, but usually most expen open or restricted tender for large-volume items, and com sive, method of procurement is direct purchase from petitive negotiation or direct procurement for lower-volume a single supplier, either at the quoted list price or at or emergency supplies. For In many country situations it may not be feasible or single-source medicines (generally those under patent cost-efective to satisfy demand for medicines and obtain Country study 18-1 Hidden costs in the procurement process: Examples from nine countries Understanding the many component costs related to infuenced tarifs and charges was collected from the lit procuring medicines is an important step in reducing erature and through personal communication.
