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Vol. 138, No. 21 — May 22, 2004 Regulations Amending the Food and Drug Regulations (1272 — Levonorgestrel)Statutory Authority Food and Drugs Act Sponsoring Department Department of Health REGULATORY IMPACT Description Part II of Schedule F to the Food and Drug Regulations lists substances intended for human use that require a prescription to be sold in Canada. Presently all dosage strengths of levonorgestrel are included in Schedule F, Part II, in the group listing for sex hormones. The proposed amendment would remove from Schedule F, levonorgestrel, when sold in a concentration of 0.75 mg per oral dosage unit. This is the dosage strength of levonorgestrel recommended for use as an emergency contraceptive (EC). The term "emergency contraceptive" has been used internationally for many years to describe contraceptive methods that can be used by women within a few days after unprotected intercourse or contraceptive failure to prevent an unwanted pregnancy. Some forms of EC have been available for almost 30 years. Timely access to levonorgestrel is important for it to be effective as an EC. It can prevent pregnancy if the first dose is taken within 72 hours following unprotected intercourse or a contraceptive failure, and the second dose is taken 12 hours after the first dose. Efficacy is greatest when treatment commences within the first 24-hour period. Currently, because a prescription is required from a physician, levonorgestrel is not always available within the recommended time period, especially during weekends and holidays. Levonorgestrel 0.75 mg is the only type of EC that has been approved for use in Canada. It acts as an EC by preventing the release of an egg from the ovary, preventing fertilization of the egg or preventing the fertilized egg from attaching to the wall of the uterus. Levonorgestrel 0.75 mg has been available to Canadian women as a prescription drug for EC use since February 2000. Its listing on Schedule F did not require a regulatory amendment, as it was automatically included in the Part II group listing for sex hormones. The federal Food and Drug Regulations define a practitioner as a person authorized by the law of a province of Canada to treat patients with any drug listed or described in Schedule F to the Regulations. The provincial laws regarding practitioners and authority to prescribe drugs vary from province to province. For example, British Columbia, Saskatchewan and Quebec have enacted legislative changes allowing pharmacists in those provinces to prescribe levonorgestrel 0.75 mg as an EC. Other provinces and territories have not done so. Therefore levonorgestrel for EC use is not equally available to women across the country. The decision by Health Canada to recommend the removal of levonorgestrel 0.75 mg from Schedule F was made following a review of the clinical evidence and safety data provided in a Supplement to a New Drug Submission. The review included an assessment of levonorgestrel against a set of factors for prescription status such as the potential for side effects or adverse reactions, the abuse potential of the drug, whether the medical condition can be easily self-diagnosed, whether dosage instructions are straightforward or complex and whether the medicinal ingredient is so new that not all of its potential effects are known. The specific factors are available on the Therapeutic Products Directorate (TPD) Web site at http://www.hc-sc.gc.ca/hpfb-dgpsa/tpd-dpt/ listschf_e.html. Levonorgestrel as a component of oral contraceptive products has been widely used as a prescription drug in women for several decades. There is therefore a large amount of post-market data available regarding the long-term effects of daily use of levonorgestrel by women. There is also a long history of safe and effective use of levonorgestrel as an EC. The first clinical trials using levonorgestrel as an EC were conducted in the 1970s. Post-marketing surveillance by pharmacovigilance agencies indicates no safety problems. There have been no adverse drug reaction reports in Canada for levonorgestrel as an EC during the three years that it has been available as a prescription drug. The World Health Organization (WHO) supports the use of ECs and their ready availability. Levonorgestrel for emergency contraception is available without a doctor's prescription in 28 countries, including the United Kingdom, France, Denmark and Norway. The WHO has concluded that emergency contraceptives are appropriate for general use and do not have a clinical effect on pre-existing conditions such as heart or liver disease. It has also concluded that it is unlikely that there will be an increased risk of heart attack and stroke with the short duration use of levonorgestrel for emergency contraception. Levonorgestrel, when used occasionally as an EC, does not increase either the absolute risk of ectopic (tubal) pregnancy or the chance that a pregnancy following its use will be ectopic. There is no increased risk of birth defects in women who have inadvertently continued taking levonorgestrel when pregnant. Experience in other countries shows that easier access to ECs does not lead to excessive use. Excessive use or use of levonorgestrel 0.75 mg as a form of regular contraception is unlikely to occur. There are several reasons why levonorgestrel 0.75 mg is not a logical choice for ongoing contraception: — any method of ongoing contraception is more effective than repeated use of an EC; — long-term overuse can cause prolonged menstrual bleeding; — the possible side-effects of nausea and vomiting associated with the use of levonorgestrel would deter from its routine use. The place of sale for a drug once it is removed from Schedule F is determined by provincial and territorial pharmacy regulatory authorities. However, the National Drug Scheduling Advisory Committee (NDSAC) of the National Association of Pharmacy Regulatory Authorities (NAPRA) makes recommendations to the provincial and territorial pharmacy regulatory authorities on the appropriate conditions and place of sale of a drug in Canada. NDSAC evaluates a drug and then recommends its placement on an appropriate schedule. NDSAC Schedule II drugs require professional intervention from the pharmacist at the point of sale and must be retained within an area of the pharmacy where there is no public access and no opportunity for patient self-selection. NDSAC has recommended that provinces and territories adopt Schedule II status for levonorgestrel as an EC. Given their expertise and accessibility when access to other health professionals is limited, pharmacists are well-positioned to play a major role in increasing women's access to emergency contraception and in providing counselling about contraceptive options. Wider availability and use of levonorgestrel for EC could significantly reduce the number of unwanted pregnancies. The Canadian Pharmacists Association (CPhA) has developed guidelines and extensive training for pharmacists who would be dispensing levonorgestrel 0.75 mg to ensure that women are appropriately screened and counselled before receiving it. Alternatives Status quo The alternative option would be to leave levonorgestrel 0.75 mg on Schedule F. As measured against the factors for listing drugs on Schedule F, it has been determined that maintaining levonorgestrel 0.75 mg on Schedule F is not appropriate. The benefits of more timely access to levonorgestrel as an EC would outweigh any theoretical risks. It has been determined that any potential risks could be managed by appropriate labelling and additional information provided when the product is requested. Benefits and costs The proposed amendment would impact on the following sectors: 1. Public The availability of levonorgestrel 0.75 mg as a nonprescription product would provide women with more convenient access to emergency contraception. Women may be required to pay directly for the product as nonprescription products are not usually covered by drug insurance plans. However, coverage is decided on a case-by-case basis by each drug plan. Strong support for continued coverage of levonorgestrel 0.75 mg has been expressed. There may be an additional cost to women for a pharmacist's counselling fee. The current cost for a physician visit is covered by provincial and territorial health plans. Coverage for the pharmacist's counselling fee under provincial and territorial health plans is not under federal jurisdiction and would be negotiated at the provincial/territorial level. 2. Provincial Health Care Systems Most public drug benefit plans do not cover the cost of nonprescription drugs. However, there is strong interest in having the cost of levonorgestrel covered under these plans. The provincial health care system presently pays the cost of a physician visit for women requiring a prescription for levonorgestrel. There would be negligible impact on the system if a similar fee were paid to pharmacists. 3. Private Drug Benefit Plans These plans do not usually cover the cost of nonprescription drugs. Coverage is determined on a case-by-case basis by each company. Consultation A letter dated June 16, 2003, outlining this regulatory proposal was sent
by electronic mail to provincial and territorial Deputy Ministers of Health,
provincial and territorial drug program Managers, deans of pharmacy, registrars
of provincial medical and pharmacy associations, industry and regulatory
associations, professional health and consumer associations, the Canadian
Food Inspection Agency, Industry Canada, the Standards Council of Canada
and other interested parties with a 30-day comment period. The letter
was also posted on the TPD Web site at Responses were received from 64 stakeholders. Two respondents requested information or more time to respond and did not otherwise comment on the proposal. Support the proposal Thirty-four respondents (27 associations or organizations and seven individuals) expressed support for the proposal. Sixteen respondents indicated that they support the proposal because timely access to EC is the key to its effectiveness. Two respondents suggested the amendment would result in reduced costs to the health care system with the removal of the requirement for a physician visit. Five respondents indicated support for provincial and territorial Schedule II status because of the safety measures provided through patient counselling by a pharmacist. These respondents also raised the following issues, summarized with TPD's responses. 1. An implementation strategy regarding counselling and follow-up must be in place. Appropriate and effective patient safety measures are required. Proper patient screening is crucial. Response: The CPhA has developed training programs and a package of information for pharmacists that includes pharmacist guidelines for provision of levonorgestrel 0.75 mg as a Schedule II product, pharmacist counselling notes, screening form, workflow chart, action plan checklist for preparing the pharmacy and its staff and a handout sheet for women on how to use emergency contraceptive pills. 2. Guidelines developed for pharmacists should be available to physicians and health care providers. Response: These documents are available on the CphA's Web site at http://www.pharmacists.ca/content/about_cpha/whats_happening/ 3. Cost is an important consideration. EC should be an insured benefit. Response: Cost coverage for nonprescription drugs is determined on a case-by-case basis by private and publicly funded drug benefit plans. Any representation regarding cost coverage should be made directly to drug plan managers. 4. Patient and pharmacists information packages should state that recurrent use is inappropriate for contraceptive purposes. Response: The product labelling will include a section that addresses recurrent use. The information sheet prepared by CPhA for pharmacists to provide to women seeking EC will also address this issue. 5. The impact on the changing nature of relationships between pharmacists and family doctors should be evaluated. Response: This is an important issue but such an evaluation is beyond the scope of this proposed amendment. 6. There is a need to ensure the privacy and confidentiality of patient information. Patient consent should be required before sharing information between professionals. Response: Professional practice issues fall under provincial jurisdiction. It should be noted, however, that the CPhA guidelines for pharmacists for the provision of levonorgestrel 0.75 mg address the issue of confidentiality. 7. Four stakeholders supported the removal of levonorgestrel 0.75 mg from Schedule F but strongly oppose the NDSAC recommendation for Schedule II status. They felt that it will compromise a woman's privacy, increase cost and will create a barrier to access in small and remote communities. Response: The place of sale for drugs not listed on Schedule F is determined by provincial pharmacy licensing bodies and co-ordinated through the National Association of Pharmacy Regulatory Authorities (NAPRA). Comments regarding the recommendation for Schedule II status should be addressed to NAPRA's National Drug Scheduling Advisory Committee (NDSAC). 8. One stakeholder provided a detailed list of information that should be included in the labelling and advertisements for levonorgestrel. Many of the items listed will be included on the label or package insert. However, the list also included the following recommendations: — that advertising, label and use information be available in a variety of languages, not just English and French; — that detailed instructions be available on a Web site in a variety of languages and pictures and other communication methods be available for women with limited literacy skills; — that label information include the telephone numbers for provincial health information lines and/or Planned Parenthood organizations. Response: The Food and Drug Regulations define the information that is required on the labelling of drug products in the English and French languages. The manufacturer may decide to include non-required information on the label or package insert. Additional information such as community resources, Web sites or third-party telephone numbers may also be made available by parties other than the manufacturer through means other than the product label. 9. One respondent requested that the Patented Medicines Prices Review Board (PMPRB) monitor costs of prescription versus nonprescription availability of levonorgestrel. Response: The PMPRB regulates the prices charged by manufacturers for patented medicines sold in Canada (whether prescribed or not) to ensure that they are not excessive. The PMPRB should be contacted concerning information regarding the patent status of levonorgestrel 0.75 mg products. 10. One respondent requested that the process for the regulatory amendment be expedited. Response: Health Canada must follow the process for regulatory amendments as set out in the Government of Canada Regulatory Policy. 11. Two respondents expressed the view that registered nurses also be allowed to dispense levonorgestrel. Response: The extent and conditions under which nurses and other professionals may dispense medications is governed by provincial and territorial legislation. Requests for amendments to allow nurses to dispense levonorgestrel should be addressed to provincial and territorial regulatory authorities. Object to the proposal Twenty-eight respondents (four organizations or associations and 24 individuals) objected to the proposal and expressed the concerns summarized below. 12. Twenty-two stakeholders objected either to levonorgestrel 0.75 mg being available in Canada at all or to the proposal to move levonorgestrel to nonprescription status. These stakeholders believe levonorgestrel causes an abortion because one of the several ways in which it may prevent a pregnancy is to prevent implantation of a fertilized egg. Some of those stakeholders also objected to the use of the term "emergency contraceptive" for the same reason and requested that the term not be used on the labelling. Response: The drug being proposed for nonprescription status is identical to the drug currently available to Canadian women as a prescription drug. The ways in which levonorgestrel 0.75 mg may work as an EC are the same whether it is on prescription or not and are described on the product labelling. The information is also included in the CPhA information sheet to be provided by pharmacists. Canadian women will continue to have the information needed to make a personal, informed choice. The term emergency contraceptive (EC) has been used internationally for many years to refer to all methods of contraception that are used after intercourse and before implantation. It is the term used by the World Health Organization for levonorgestrel at this dosage strength. 13. Eighteen stakeholders were concerned about side effects and long-term health risks (including deep-vein thrombosis), the risk of ectopic pregnancy, and potential health risks associated with repeat use of levonorgestrel 0.75 mg. Response: Health risks — The hormones used in an EC are used for a short period of time and the contraindications associated with regular use of oral contraceptives do not apply to ECs. Studies sponsored by the manufacturer in the 1970s and 1980s and by the World Health Organization in the late 1980s and early 1990s, covering approximately 3 700 women, demonstrated that even regular postcoital use is associated with no serious or lasting adverse events other than reversible menstrual irregularities. No substantial increased risk for developing deep-vein thrombosis has been found with use of an EC. Ectopic pregnancies — Up to 10 percent of pregnancies in women who routinely use progestin-only contraceptives are ectopic. The background incidence for ectopic pregnancies is approximately 2 percent of reported pregnancies. However, levonorgestrel, when used occasionally as an EC, does not increase either the absolute risk of ectopic pregnancy or the chance that a pregnancy following the use of the levonorgestrel-containing EC pill will be ectopic. A history of ectopic pregnancy need not be considered a contraindication to use of emergency contraception. The levonorgestrel label advises women to contact their doctor if their menstrual period does not occur within 21 days after using levonorgestrel. Further, the label instructs women to call their doctor immediately if they experience cramping or severe pain in their stomach or belly prior to their next normal period, since that can be a warning sign of tubal (ectopic) pregnancy. Repeated use — Studies have shown that repeated use results in no serious or lasting adverse events other than menstrual irregularities. The most common side effects, nausea and vomiting, make regular use of EC undesirable for most women. Information that EC is not for repeated use is included in both the product labelling and the pharmacists' counselling material. 14. One stakeholder objected to EC use based on the reported lack of a reduction in abortion rates in Scotland following the introduction of ECs in that country. Response: Abortions have declined in some countries where ECs are available (e.g. the United States), but not in others (e.g. Scotland). Many factors contribute to a change in abortion rates, including access to ECs outside of health clinic or physician hours, access to abortion, access to sexual and reproductive health services, education, use of regular contraception, and cost of the EC. 15. One stakeholder asked that Health Canada look into a report that EC availability has not resulted in a reduction in teen pregnancies in another country, perhaps Great Britain. Response: There was no report attached to the response and no further information was provided. A search for such a report was unsuccessful. Rather, the search found a study released in 2002, in which teenage birthrates in the United States were found to have dropped more than 20 percent since 1990. The study also found that although the teen pregnancy rate in the United States declined, it has done so less steeply than in other developed countries (including England and Wales), due to lower contraceptive use among American teenagers. 16. Three stakeholders expressed concern that minors may be requesting the EC. Response: Forms of birth control such as condoms and spermicides are widely available to minors without parental notification or consent. Provincial laws guide health care professionals in providing medications for minors in the absence of consent from their parents or legal guardians. 17. Emergency contraceptives do not provide protection against sexually transmitted infections (STI). Six stakeholders were concerned about an increase in STIs, and four were concerned about irresponsible sexual activity. Response: None of the regular birth control methods, with the exception of condoms, prevent STIs. The labelling for levonorgestrel will clearly state that it does not provide any protection against contracting STIs. However, counselling associated with the provision of ECs has been identified as an opportunity to address STI prevention. 18. Three stakeholders commented that pharmacists do not have access to the patient's full medical history and cannot foresee adverse reactions, nor can a health care provider determine that an adverse reaction is a result of taking an EC. Response: In situations where the patient obtains an EC from a physician who is not her regular physician (e.g. at a clinic), the patient's medical history is likewise unavailable. That being said, the only contraindications for the use of levonorgestrel 0.75 mg are existing confirmed pregnancy or allergy to one of the product constituents. The package insert directs women to consult their physician before taking levonorgestrel if they have or have had undiagnosed vaginal bleeding, known or suspected breast cancer or liver disease or tumour. The CPhA screening form includes sections to list all current medications, medical conditions and allergies. Part of counselling includes telling the patient that it may be useful to inform her physician or health care professional of the EC use. 19. Three stakeholders were concerned that pharmacists will not provide adequate counselling. Response: The CPhA has developed an education program to aid pharmacists in their assessments, counselling and follow-up of patients, and in their ability to refer patients to other health-care providers if necessary. 20. Whether there would be adequate privacy when requesting and discussing the use of an EC was questioned by one stakeholder. Response: Part of the CPhA education program for pharmacists addresses the issue of privacy and includes instructions to pharmacists that counselling be done in a private or semi-private location, by a registered pharmacist only. 21. Some pharmacists have moral objections to emergency contraception. Four stakeholders wanted to know if pharmacists have the right to refuse to dispense ECs and their liability for adverse events when they do dispense. Response: Most provinces and territories have adopted a policy that allows pharmacists to have the right to refuse to dispense medication for moral reasons but they would be expected, as a standard of care, to refer the woman to another pharmacist, a physician, or health facility where the medication could be readily obtained. Questions regarding liability issues related to the dispensing of any drugs should be directed to provincial pharmacy regulatory bodies. 22. The lack of follow-up visits and ability to track repeated use of ECs was an area of concern for one stakeholder. Response: Occasional use of levonorgestrel for emergency contraception is safe for virtually all women. Follow-up of patients is generally not required unless — there is a delay in the return of menstrual period, or — additional counselling could provide information on the options for ongoing contraception and the correct use of the chosen method(s) of contraception. Delay of menses and regular contraception are addressed in product labelling. A woman may authorize the release of information regarding her use of EC to her primary health care professional. 23. One stakeholder asked that pharmacist counselling include reference to a local pro-life organization. Response: Counselling information for use by pharmacists has been prepared by CPhA. Comments concerning the content of this information should be directed to CPhA and/or provincial pharmacy associations. Compliance and enforcement This amendment would not alter existing compliance mechanisms under the provisions of the Food and Drugs Act and its Regulations, enforced by the Health Products and Food Branch (HPFB) Inspectorate. Additional enforcement is provided through responses to complaints from the medical profession and competitors. Inspection mechanisms at both the federal and provincial levels would be maintained. Ms. Karen Ash, Policy Bureau, Therapeutic Products Directorate, Holland Cross, Tower B, 2nd Floor, 1600 Scott Street, Address Locator 3102C5, Ottawa, Ontario K1A 1B6, (613) 957-6455 (telephone), (613) 941-6458 (facsimile), karen_ash@hc-sc.gc.ca (electronic mail). Notice is hereby given that the Governor in Council, pursuant to subsection 30(1) (see footnote a) of the Food and Drugs Act, proposes to make the annexed Regulations Amending the Food and Drug Regulations (1272 — Levonorgestrel). Interested persons may make representations with respect to the proposed Regulations within 75 days after the date of publication of this notice. All such representations must cite the Canada Gazette, Part I, and the date of publication of this notice and be sent to Karen Ash, Policy Division, Bureau of Policy, Therapeutic Products Directorate, Department of Health, Address Locator 3102C5, 1600 Scott Street, Holland Cross, Tower B, 2nd Floor, Ottawa, Ontario K1A 0K9 (tel.: (613) 957-6455; fax: (613) 941-6458; e-mail: karen_ash@hc-sc.gc.ca). Persons making representations should identify any of those representations the disclosure of which should be refused under the Access to Information Act, in particular under sections 19 and 20 of that Act, and should indicate the reasons why and the period during which the representations should not be disclosed. They should also identify any representations for which there is consent to disclosure for the purposes of that Act. Ottawa, May 11, 2004
EILEEN BOYD
REGULATIONS AMENDING THE AMENDMENT 1. The drug description "Sex hormones" in Part II of Schedule F to the Food and Drug Regulations (see footnote 1) is amended by adding to its list of exceptions the following, in alphabetical order: Levonorgestrel, when sold in concentrations of 0.75 mg per oral dosage unit
COMING INTO FORCE 2. These Regulations come into force on the day on which they are registered. [21-1-o] S.C. 1999, c. 33, s. 347 C.R.C., c. 870 |
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