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Special Article

Opioid Availability in Latin America: The Declaration of Florianopolis

Key Words
Opioid availability, Latin America, WHO, drug regulation

Utilization

Unfortunately, the findings suggest that opioid use is still limited to a minority of physicians, and that most Latin American cancer patients with pain continue to die without having received a single dose of a strong opioid agonist.

The main reasons identified for this pattern of utilization were (1) old national pharmacopeias oriented to a short-term management of acute pain have predominantly parenteral preparation of mild opioids; (2) the cost of commercially available preparations makes them unaffordable to most patients (this issue will be discussed in depth below); (3) physicians choose mild opioids that do not require special prescription pads because of the severe bureaucratic limitations imposed by current prescription regulation (this issue will also be addressed later); (4) there is severe lack of physicians and pharmacist education on cancer pain management; physicians are frequently afraid of prescribing, and pharmacies frequently do not carry the opioids, forcing patients and families to go long distances to fill an analgesic prescription; (5) existing legislation in most Latin American countries limits the access of patients to analgesics without having substantial impact on the illegal drug markets (this issue will be addressed later as well); and (6) clinicians, palliative care, pain, and cancer associations are not informed regularly by their government of their patterns of opioid use in their countries.

Recommendations on Utilization

1. The World Health Organization (WHO) Cancer Pain and Palliative Care Program for Latin America will regularly report to members from different countries on patterns of opioid utilization. This will be coordinated by David Joranson, WHO Collaborating Center for Symptom Evaluation at the University of Wisconsin Medical School in Madison.
2. The members from each country will jointly address the utilization issue with their Ministry of Health. Each report by the national members will include the report on opioid availability prepared by the Wisconsin Collaborating Center, the new guidelines for opioid availability produced by the WHO Cancer Unit, (currently available in Spanish), and a copy of the report by the International Narcotics Control Board (INCB) to each national government in 1989: "Demand for, and supply of opiates for medical and scientific needs." This report expresses the concern of the INCB with the lack of opioid availability to patients and reminds governments that, as signatories of the Single Convention on Narcotic Drugs, they are responsible for ensuring access to opioids for their patients. In addition, the Declaration of Florianopolis and letters of support from the WHO Cancer Unit should be added.
3. Drug regulators from different Latin American countries will be encouraged to contact David Joranson in order to consult on problems associated with current legislation issues that limit access to opioids. It will also be suggested that these members contact Dr. Jose Felix Olalla, the drug regulator from the Spanish Government, in order to inquire on the changes that the Spanish Government has made in the area of utilization. These issues are discussed in depth below.

Cost of Opioids

The reasons identified for the increased cost are the following: (1) In some countries, the more inexpensive forms of opioids are not available (short-acting morphine or methadone). (2) Multinational pharmaceutical companies apply for licenses to sell the more expensive drugs such as slow-release morphine, fentanyl patches, or buprenorphine. The main reason for this is the higher overhead cost of these companies and the fact that these drugs are protected by a patent. (3) Smaller, local companies are not applying for a license to sell inexpensive opioids. This is based on two factors: a) they have limited awareness of the size of the potential market; and/or they are discouraged by governments with unreasonable bureaucratic regulations for the production or distribution of opioids. (4) While simple capsules, oral solutions and even parenteral solutions of morphine can be prepared by volunteers or hospital pharmacies using morphine powder, most Latin American countries do not allow the entry of morphine powder. (5) The fear of legal consequences is deterring a large number of pharmacies from preparing the drugs in their local pharmacies and also hospital pharmacies from preparing and distributing opioids to the community. (6) Limited utilization of opioids by physicians decreases the size of the market and the interest of companies to produce these drugs.

Recommendations

1. Availability of opioid analgesics. Opioids can be made available in the following ways:
   1. Multinational companies: They have the ability to manufacture, import, and distribute opioids. Their higher overhead costs make it less interesting for them to produce cheaper drugs, but they can be very effective in introducing more-expensive and modern drugs. These companies should be encouraged to bring drugs; to assist in the educational process among physicians, nurses, and pharmacists; and to assist through their international and legal expertise in updating the legislative and regulatory practices of each country.
   2. National companies: Because of their lower overhead and better knowledge of the local scene, these companies can produce cheaper opioid preparations. These companies, however, have limited expertise in licensing and distribution of opioids. These companies should be encouraged to produce useful simple commercial preparations. Clinicians, nongovernmental organizations (cancer leagues, volunteer associations, and pain societies), and drug regulators should assist these small companies in the process of making these commercial preparations available.
   3. State-owned or semiprivate companies: These companies have as their main mandate to produce low-cost drugs. Many Latin American countries have these companies, but they have not been interested in the production of opioid analgesics. In Spain, a semiprivate company was helpful in keeping costs of opioids down when the demand was still low and commercial preparations were limited. Some of these companies (e.g., in Spain and in the state of San Paulo, Brazil) have export capabilities. These companies should be interested in the production and distribution of low-cost preparations of simple opioids.
   4. Importing of opioids: Several Latin American countries produce low-cost opioids that could easily be imported and distributed for either local companies, governments, or nongovernmental organizations such as cancer leagues. These companies do not have legal resources to maneuver in the complex bureaucracy of a country. Clinicians, nongovernmental organizations, and drug regulators should help these companies in the process of importing opioid analgesics. Companies have been identified in Argentina and Mexico and can be contacted through the local palliative care physicians.
2. Production of opioid preparation by other groups.
   1. Local pharmacists: Drug regulators and clinical groups should provide simple guidelines for the effective preparation of liquid solutions and capsules of opioids. These guidelines could be distributed through the local colleges of pharmacy to empower pharmacists to produce analgesics in the community. Local drug regulators should be educated on the importance of making these drugs available to cancer patients.
   2. Volunteer groups: Volunteer groups, under the supervision of pharmacists, have been effective in producing high-quality opioids in San Nicolas, Argentina. Volunteer groups have also been highly effective in importing and distributing commercial preparations of opioids in Santo Domingo, Dominican Republic. This model of community involvement should be encouraged using existing nongovernmental organizations such as cancer societies or pain societies. Drug regulators and pharmaceutical companies should assist these organizations in making the drugs available to patients.
   3. Local hospitals: Local hospitals, through their pharmacies, have been highly effective in the production and distribution of opioids in the city of Cordoba, Argentina. This model is highly effective because of the ability of these large pharmacies to produce high volumes and, therefore, decrease the cost of the drugs. Hospital pharmacies that could take over the production and distribution of opioids in each region should be identified. In a given country, a decrease in cost is only likely to be achieved as a result of a combination of several of these recommendations. Each individual government should outline the strategy chosen for cost reduction. WHO Cancer Pain and Palliative Care Programs will support and advise clinicians, governments and companies in this regard.
3. Monitoring of costs. The WHO Latin American Program will monitor the cost of opioids with the help of different local programs. Success in cost containment will be judged by (a) availability of simple opioid preparations; (b) increase in the access of the population to these preparations; and (c) decrease in the cost of these preparations to the level of cost currently existing in North America and Europe.

Legislation/Regulations

The following findings were made regarding legislation/regulations: The bureaucratic burden is too high on physicians and pharmacists for the adequate prescription of opioids. (a) Triplicate prescription pads are difficult to obtain and expensive, often requiring the physician to personally pick them up from a government office. (b) The maximal amount/ duration of prescriptions is too small, resulting in physicians and patients being required to falsify information in order to avoid frequent visits to the physician's office and the pharmacy. (c) Pharmacy regulations regarding storage of opioids are so restrictive that, in many Latin American cities, there are no pharmacists carrying opioid analgesics. (d) The regulatory aspects discourage pharmaceutical companies from producing or importing new opioid preparations.

The following recommendations were made: (a) Governments should be presented with a detailed list of the local legislative/regulatory obstacles to opioid availability. This list will be generated by the local physicians, ideally with input from pharmacists and pharmaceutical companies. (b) Latin American regulators should be presented with the information package describing utilization. (c) Latin American regulators will be encouraged to meet the representatives of the Spanish Minister of Health during their annual meeting. Dr. José Felix Olalla has expressed an interest in sharing the Spanish experience with legislative and regulatory changes. (d) Governments will be encouraged to seek advice from the Division of Policy Research, WHO Collaborating Center for Symptom Evaluation, University of Wisconsin. David Joranson has offered support in this area. (e) The WHO Cancer Pain and Palliative Care Program will monitor legislative and regulatory improvements. This will be reported in 2 years.

Conclusions

The recommendations require the cooperation of professionals (physicians, nurses, and pharmacists), governments (ministers of health and drug regulators), and pharmaceutical companies (multinational, national, and state owned). Volunteer organizations, political organizations, and the press should assist in increasing awareness of the seriousness of the problem and the simplicity of the solutions required.

Regular monitoring will take place in order to assess the degree of implementation of these recommendations in each country and the success of these recommendations in producing the necessary changes.