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Vol. 133, No. 20 — May 15, 1999
Order Amending Schedules I and IV to the Controlled Drugs and Substances Act (1075)
Statutory Authority
Controlled Drugs and Substances Act
Sponsoring Department
Department of Health
REGULATORY IMPACT ANALYSIS STATEMENT
Description
The Therapeutic Products Programme of Health Canada proposes to add four drugs to the following schedules:
Schedules I and IV of the Controlled Drugs and Substances Act;
Schedule to the Narcotic Control Regulations; and
Schedule F to the Food and Drug Regulations.
This Regulatory Impact Analysis Statement provides the background information for each of the above-mentioned regulatory amendments.
The four drugs are:
1. Remifentanil hydrochloride — an ultra short-acting agent indicated for use as an opioid analgesic adjunct for the induction and maintenance of general anaesthesia.
Remifentanil hydrochloride is recommended for addition to item 16 of Schedule I to the Controlled Drugs and Substances Act (CDSA).
Remifentanil hydrochloride is a fentanyl, a class of narcotics which has high potential for abuse and therefore warrants inclusion in Schedule I to the Act.
The proposal also includes a recommendation to add remi-fentanil hydrochloride to the Schedule to the Narcotic Control Regulations. Inclusion in these Regulations will allow for controlled distribution within the legitimate pharmaceutical, medical and scientific community, thereby limiting its abuse potential.
2. Nalmefene hydrochloride — an opioid antagonist indicated for use as a treatment for complete or partial reversal of opioid drug effects and in the treatment of opioid overdose.
Nalmefene hydrochloride is recommended for exemption from Schedule I to the CDSA.
Nalmefene hydrochloride is considered to be an opioid derivative. Opioids are listed in Schedule I to the CDSA and are subject to the provisions of this Act unless specifically exempted. Nalmefene hydrochloride is not subject to abuse and therefore is recommended for exemption from the regulatory controls currently imposed on opioids listed on Schedule I to the CDSA.
Nalmefene hydrochloride is also recommended for exemption from the Schedule to the Narcotic Control Regulations. Exemption from this schedule will ensure that this drug is not subject to the Narcotic Control Regulations.
Nalmefene hydrochloride is further recommended for addition to Part I of Schedule F to the Food and Drugs Regulations. This will provide for its regulatory control under these Regulations.
3. Olanzapine — a benzodiazepine indicated for use in the acute and maintenance treatment of schizophrenia and related psychotic disorders.
Olanzapine is recommended for exemption from Schedule IV to the CDSA.
Olanzapine belongs to a class of drugs known as benzodiazepines. Benzodiazepines are listed on Schedule IV to the CDSA. This would normally limit their distribution as defined by regulation. However, benzodiazepines are currently exempted from the application of the CDSA but are listed on Schedule F to the Food and Drug Regulations. The Therapeutic Products Programme is proposing Regulations Respecting Benzodiazepines and Other Targeted Substances and the removal of their exemption from the application of the CDSA. It is proposed that most benzodiazepines, except for olanzapine, will be subject to the regulatory controls imposed by the Regulations Respecting Benzodiazepines and Other Targeted Substances.
Olanzapine is further recommended for addition to Part I of Schedule F to the Food and Drugs Regulations. This will provide for its regulatory control under these Regulations.
4. Naltrexone — an opioid antagonist indicated for use in the treatment of addictions to opiate drugs.
Naltrexone is recommended for exemption from the Schedule to the Narcotic Control Regulations.
Naltrexone was added to Schedule F to the Food and Drug Regulations on May 7, 1996, and was exempted from Schedule I to the CDSA on May 14, 1997. This recommendation to exempt naltrexone from the Regulations will provide consistency with the scheduling recommendations made in May 1996 and 1997, as the Narcotic Control Regulations are under the authority of the CDSA.
The following paragraphs are included to provide information with respect to the controls imposed when drugs are placed on these schedules.
The Controlled Drugs and Substances Act specifies restrictions and offences that apply to drugs that are subject to abuse and illicit activity. Six of the eight schedules to the CDSA list drugs and substances which are subject to the various offences and punishments described in Part I of the Act. Schedule I imposes the most severe restrictions and associated penalties while Schedules V and VI impose the least. If a drug belongs to a class listed in one of these schedules and does not warrant the associated degree of regulatory control, it must be exempted from that class.
In order to allow for possession, distribution and sale of a drug restricted by its listing in the CDSA, that drug must be listed in one of the schedules to the regulations under the authority of the CDSA. The regulations are enabling in nature. For example, the Narcotic Control Regulations allow for the possession and distribution of a drug listed in its schedule under defined conditions.
Listing a drug on Schedule F to the Food and Drug Regulations means that a prescription is required for its sale.
The degree of regulatory control for a drug listed on Schedule F is less than that which is imposed through the CDSA and the Narcotic Control Regulations. Part I of Schedule F lists those drugs which require a prescription for their sale when intended for either human or animal use. Part II of Schedule F lists drugs that are required to be sold on prescription only when intended for use in humans and which do not require a prescription when intended for veterinary use. Exemption from a particular class listed in the CDSA will allow for the lesser degree of regulatory control provided by Schedule F. This regulatory action is recommended both for olanzapine and nalmefene hydrochloride.
The degree of regulatory control recommended for these four drugs by the Drug Schedule Status Subcommittee (DSSC) of the Therapeutic Products Programme will provide Canadians with optimal drug enforcement controls to help ensure their health, safety and well-being.
The recommended degree of regulatory control is based on the risk factors associated with each specific drug and each drug's potential for abuse. Canada has obligations, as a signatory to three International Conventions of the United Nations, to effectively deal with drug control problems. In addition to meeting the requirements of the Food and Drugs Act, drugs that possess potential for abuse must also meet the requirements of the Controlled Drugs and Substances Act and its Regulations.
Alternatives
No other alternatives have been considered. Any alternatives to the recommended degree of regulatory control would need to be established through additional scientific information, clinical and enforcement experience.
Benefits and Costs
The degree of regulatory control afforded a drug has an impact on the costs associated with the enforcement. However, if the degree of regulatory control on a drug is inadequate, costs to the health care system and indirect societal cost could increase due to ill-effects caused by improper use and abuse.
This recommendation is based on a scientific evaluation and an estimation of potential risk. The Programme has not conducted a cost benefit analysis as additional costs related to the scheduling of these three drug is believed to be minimal.
This amendment will impact on the following sectors:
Public sector
— Prescription access to olanzapine, nalmefene hydrochloride and remifentanil hydrochloride will benefit Canadians by decreasing the opportunities for improper use and by ensuring professional guidance and care.
— Additional security measures for remifentanil hydrochloride are provided with its placement on Schedule I to the Narcotic Control Regulations.
— However, this will require Canadians to seek medical care in order to gain access to these drugs.
Pharmaceutical Industry Sector
— The classification of olanzapine and nalmefene hydrochloride as prescription products will limit their sale subject to professional intervention thereby reducing misuse and decreasing liability to the manufacturer. In the case of remifentanil hydrochloride, this amendment will also necessitate compliance with additional regulatory requirements, including a dealer's licence. These additional requirements may involve minor cost increases for industry.
Healthcare Sector
— The provinces may incur costs to cover medical services for patients desiring access to the three drugs recommended for addition. Professional intervention may reduce the need for health care services resulting from improper use. In addition, there will be added costs for the record keeping and related security requirements for remifentanil hydrochloride. The overall additional costs for health care services should be minimal.
Health Insurance Plan
— The scheduling of remifentanil hydrochloride, olanzapine and nalmefene hydrochloride may result in their coverage by both provincial and private health care plans.
Consultation
A notice of intent requesting comments on the proposed policy to schedule these three drugs was published in the Canada Gazette, Part I, on October 3, 1998. This public consultation provided a 60-day comment period.
Direct mailing of this notice was also provided to the Provincial Ministries of Health, medical and pharmacy licensing bodies, industry associations and the RCMP. Additionally, notice of this regulatory initiative was posted on the Therapeutic Products Programme's Web site. Information respecting scheduling initiatives can be found under "Drugs, Schedule Amendments":
http://www.hc-sc.gc.ca/hpb-dgps/therapeut
No comments were received as a result of these consultations.
A further 30-day comment period will be provided upon prepublication in the Canada Gazette, Part I.
Compliance and Enforcement
Parliament has provided the Government, through the enactment of the CDSA, with the necessary tools needed to combat illegal possession, trafficking, production, importing and exporting of controlled drugs and substances. This amendment does not alter existing compliance mechanisms under the provisions of the CDSA.
This amendment also does not alter existing compliance mechanisms under the provisions of the Food and Drugs Act and the Food and Drug Regulations enforced by the Therapeutic Products Programme Inspectors.
Contact
Joan Korol, Policy Division, Bureau of Policy and Coordination, Therapeutic Products Programme, Tower B, 2nd Floor, 1600 Scott Street, Address Locator 3102C5, Ottawa, Ontario K1A 1B6, (613) 957-1483 (Telephone), (613) 941-6458 (Facsimile), joan_ korol@hc-sc.gc.ca (Internet).
PROPOSED REGULATORY TEXT
Notice is hereby given that the Governor in Council, pursuant to section 60 of the Controlled Drugs and Substances Act (see footnote a), proposes to make the annexed Order Amending Schedules I and IV to the Controlled Drugs and Substances Act (1075).
Interested persons may make representations with respect to the proposed Order within 30 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 addressed to Joan Korol, Therapeutic Products Programme, Department of Health, Tower B, 2nd Floor, 1600 Scott Street, Address Locator 3102C5, Ottawa, Ontario K1A 1B6, (613) 941-6458 (Facsimile), joan_korol@hc-sc.gc.ca (Electronic mail).
The representations should stipulate those parts of the representations that should not be disclosed pursuant to the Access to Information Act and, in particular, pursuant to sections 19 and 20 of that Act, the reason why those parts should not be disclosed and the period during which they should remain undisclosed. The representations should also stipulate those parts of the representations for which there is consent to disclosure pursuant to the Access to Information Act.
May 6, 1999
MARC O'SULLIVAN
Assistant Clerk of the Privy Council
ORDER AMENDING SCHEDULES I AND IV TO THE CONTROLLED DRUGS AND SUBSTANCES ACT (1075)
AMENDMENTS
1. Subitems 1(34) and (34.1) (see footnote 1) of Schedule I to the Controlled Drugs and Substances Act (see footnote 2) are replaced by the following:
(34) Nalmefene (17-(cyclopropylmethyl)-4,5α-epoxy-6-methylenemorphinan-3,14-diol)
(34.1) Naloxone (4,5α-epoxy-3,14-dihydroxy-17-(2- propenyl)morphinan-6-one)
(34.2) Naltrexone (17-(cyclopropylmethyl)-4,5α-epoxy-3,14-dihydroxymorphinan-6-one)
2. Item 16 of Schedule I to the Act is amended by adding the following after subitem (11):
(11.1) Remifentanil (dimethyl 4-carboxy-4-(N-phenylpropionamido)-1-piperidinepropionate)
3. Item 18 of Schedule IV to the Act is amended by adding the following after subitem (33):
(34) Olanzapine (2-methyl-4-(4-methyl-1-piperazinyl)-10H-thieno[2,3-b][1,5]benzodiazepine) and its salts
COMING INTO FORCE
4. This Order comes into force on the day on which it is registered.
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Regulations Amending the Narcotic Control Regulations (1075)
Statutory Authority
Controlled Drugs and Substances Act
Sponsoring Department
Department of Health
REGULATORY IMPACT ANALYSIS STATEMENT
For the Regulatory Impact Analysis Statement, see the Order Amending Schedules I and IV to the Controlled Drugs and Substances Act (1075).
PROPOSED REGULATORY TEXT
Notice is hereby given that the Governor in Council, pursuant to subsection 55(1) of the Controlled Drugs and Substances Act (see footnote b), proposes to make the annexed Regulations Amending the Narcotic Control Regulations (1075).
Interested persons may make representations with respect to the proposed Regulations within 30 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 addressed to Joan Korol, Therapeutic Products Programme, Department of Health, Tower B, 2nd Floor, 1600 Scott Street, Address Locator 3102C5, Ottawa, Ontario K1A 1B6, (613) 941-6458 (Facsimile), joan_korol@hc-sc.gc.ca (Electronic mail).
The representations should stipulate those parts of the representations that should not be disclosed pursuant to the Access to Information Act and, in particular, pursuant to sections 19 and 20 of that Act, the reason why those parts should not be disclosed and the period during which they should remain undisclosed. The representations should also stipulate those parts of the representations for which there is consent to disclosure pursuant to the Access to Information Act.
May 6, 1999
MARC O'SULLIVAN
Assistant Clerk of the Privy Council
REGULATIONS AMENDING THE NARCOTIC CONTROL REGULATIONS (1075)
AMENDMENTS
1. Subitem 1(34) of the Schedule to the Narcotic Control Regulations (see footnote 3) is replaced by the following:
(34) Nalmefene (17-(cyclopropylmethyl)-4,5α-epoxy-6-methylenemorphinan-3,14-diol)
(34.1) Naloxone (4,5α-epoxy-3,14-dihydroxy-17-(2-propenyl) morphinan-6-one)
(34.2) Naltrexone (17-(cyclopropylmethyl)-4,5α-epoxy-3,14-dihydroxy-morphinan-6-one)
2. Item 15 of the Schedule to the Regulations is amended by adding the following after subitem (11):
(11.1) Remifentanil (dimethyl 4-carboxy-4-(N-phenylpropionamido)-1-piperidinepropionate)
COMING INTO FORCE
3. These Regulations come into force on the day on which they are registered.
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Regulations Amending the Food and Drug Regulations (1075 — Additions to Schedule F)
Statutory Authority
Food and Drugs Act
Sponsoring Department
Department of Health
REGULATORY IMPACT ANALYSIS STATEMENT
For the Regulatory Impact Analysis Statement, see the Order Amending Schedules I and IV to the Controlled Drugs and Substances Act (1075).
PROPOSED REGULATORY TEXT
Notice is hereby given that the Governor in Council, pursuant to subsection 30(1) (see footnote c) of the Food and Drugs Act, proposes to make the annexed Regulations Amending the Food and Drug Regulations (1075 — Additions to Schedule F).
Interested persons may make representations with respect to the proposed Regulations within 30 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 addressed to Joan Korol, Therapeutic Products Programme, Department of Health, Tower B, 2nd Floor, 1600 Scott Street, Address Locator 3102C5, Ottawa, Ontario K1A 1B6, (613) 941-6458 (Facsimile), joan_korol@hc-sc.gc.ca (Electronic mail).
The representations should stipulate those parts of the representations that should not be disclosed pursuant to the Access to Information Act and, in particular, pursuant to sections 19 and 20 of that Act, the reason why those parts should not be disclosed and the period during which they should remain undisclosed. The representations should also stipulate those parts of the representations for which there is consent to disclosure pursuant to the Access to Information Act.
May 6, 1999
MARC O'SULLIVAN
Assistant Clerk of the Privy Council
REGULATIONS AMENDING THE FOOD AND DRUG REGULATIONS (1075 — ADDITIONS TO SCHEDULE F)
AMENDMENT
1. Part I of Schedule F to the Food and Drug Regulations (see footnote 4) is amended by adding the following in alphabetical order:
Nalmefene and its salts
Nalméfène et ses sels
Olanzapine and its salts
Olanzapine et ses sels
COMING INTO FORCE
2. These Regulations come into force on the day on which they are registered.
[20-1-o]
Regulations Amending the Food and Drug Regulations (1051 — Schedule F)
Statutory Authority
Food and Drugs Act
Sponsoring Department
Department of Health
REGULATORY IMPACT ANALYSIS STATEMENT
Description
This amendment proposes to add 23 new drug substances to Schedule F to the Food and Drug Regulations. At the same time, amendments are proposed to current Schedule F listings to correct spelling errors and the omission of the drug cyclophosphamide in the French version of Schedule F to the Regulations.
Schedule F is a list of drug substances, the sale of which is controlled under sections C.01.041 to C.01.046 of the Food and Drug Regulations. Part I of Schedule F lists substances intended for human and veterinary use which require a prescription to be sold in Canada. Part II of Schedule F lists drugs which may be sold without a prescription when the drug is intended for veterinary use and is so labelled, but does require a prescription when sold for human use. The review and introduction of new drugs onto the Canadian market necessitate periodic revisions to the schedule.
Health Canada, under the Therapeutic Products Programme's Drug Schedule Status Committee, reviews the status of chemical entities proposed for marketing. A decision regarding the necessity for prescription or other status versus non-prescription status was made for each of the drugs listed on this schedule on the basis of established and publicly available criteria. These criteria include, but are not limited to, concerns related to toxicity, pharmacologic properties, and therapeutic applications.
This recommended degree of regulatory control coincides with the risk factors associated with each specific drug. The evaluation of the available information on these drugs has determined that the advice of a medical practitioner is necessary to provide the consumer with adequate risk/benefit information before taking the medication. Any alternatives to the degree of regulatory control would need to be established through additional scientific information and further clinical experience.
The drug substances to be added to Schedule F are as follows:
Amfebutamone and its salts
Amfebutamone, also known as bupropion, is an antidepressant that is indicated for the symptomatic relief of depressive illness. The safe and effective use of amfebutamone requires that an accurate diagnosis of depression be made by the physician, who must also decide on the most appropriate form of treatment. The physician must also evaluate the contraindications, warnings and precautions associated with amfebutamone use for individual patients, must provide individualized dosage and other instructions, and maintain close medical supervision and patient follow-up throughout treatment.
Anagrelide and its salts
Anagrelide is a platelet-reducing agent that is indicated in the management of patients with thrombocytosis at risk of thrombotic complications. The use of this drug requires close medical supervision to ensure that platelet counts do not drop to levels that place patients at risk for bleeding, with individualized instructions for the patient.
Brimonidine and its salts
Brimonidine tartrate ophthalmic solution is indicated for the control of intraocular pressure in patients with chronic open-angle glaucoma and to control the post-operative intraocular pressure spikes in patients undergoing laser ocular surgery. Patients using this drug should be monitored closely by specialists in ophthalmology to ensure that the drug has produced the desired effect and that undesired side effects from the use of the drug do not occur.
Carbetocin and its salts
Carbetocin is a long-acting analogue of the pituitary hormone oxytocin that is used to stimulate contractions of the postpartum uterus to prevent uterine atony and postpartum hemorrhage. Carbetocin is to be administered intravenously as part of a major surgical procedure for the prevention of potentially serious complications of obstetrical delivery.
Cerivastatin and its salts
Cerivastatin is one of a new class of lipid-lowering compounds that reduce the production of cholesterol in the body. The drug is indicated for use with diet to reduce elevated total cholesterol and low density lipoprotein cholesterol (LDL) levels in patients with primary hypercholesterolemia. The safe and effective use of cerivastatin requires an accurate diagnosis of hypercholesterolemia be made by the physician who then must decide on the appropriate forms of treatment. The physician must also evaluate the contraindications, warnings and precautions associated with cerivastatin use in individual patients, must provide individualized dosage and other instructions, and maintain close medical supervision and patient follow-up throughout treatment.
Emedastine and its salts
Emedastine difumarate is a benzimidazole derivative developed for the treatment of allergic conjunctivitis. This drug has a therapeutic effect based on new pharmacologic principles, currently not demonstrated by other available treatments, and therefore requires medical supervision to monitor the effectiveness of this therapy.
Fosfomycin and its salts
Fosfomycin tromethamine is an antibacterial indicated for single dose oral therapy in women with uncomplicated urinary tract infections. The initiation of therapy is dependent upon diagnosis of a urinary tract infection by a physician. The product needs to be taken under medical supervision, as the inappropriate use of antibacterials may lead to suboptimal therapy, aggravation of infection or bacterial resistance.
Irbesartan and its salts
Irbesartan is an angiotensin II AT1 receptor blocker used in the treatment of essential hypertension. Initiation of this drug therapy requires close medical supervision, as the patients must receive individualized instructions on their dosage regiment. The monitoring of the effectiveness of this therapy to prevent serious adverse events known to occur with this drug is also essential.
Montelukast and its salts
Montelukast is a new leukotriene receptor antagonist indicated for the prophylaxis and chronic treatment of asthma, including prevention of day and nighttime symptoms in adult and pediatric patients six years of age and older. This drug should be used under a physician's care to ensure appropriate treatment of the disease. Patient monitoring is required to ensure the safe and effective use of the drug which can include individualized instructions for the dosage regimen to be followed.
Nadroparin and its salts
Nadroparin is a low molecular weight heparin that is used for the pre-operative prophylaxis of thromboembolic disorders (particularly deep vein thrombosis and pulmonary embolism). This therapy can only be used following a positive diagnosis of a potential occurrence of a deep vein thrombosis or pulmonary embolism by a physician. Careful patient monitoring for the safety and effectiveness of the drug is essential.
Naratriptan and its salts
Naratriptan hydrochloride is an indole derivative that is used in the acute treatment of migraine headache attacks with or without aura. This drug should only be used where a clear diagnosis of migraine has been established by a physician. The safe and effective use of naratriptan requires that patients receive individualized instructions and assessments by a medical practitioner.
Nelfinavir and its salts
Nelfinavir mesylate is an inhibitor of the human immunodeficiency virus (HIV) protease that is used for the treatment of HIV infection in combination with reverse transcriptase inhibitor nucleoside analogues. The management of HIV infection with antiretroviral drugs, such as nelfinavir mesylate, necessitates physician supervision and routine laboratory monitoring, as there is a narrow margin of safety between the therapeutic and toxic doses for the combination regimen when used with concomitant Aids therapies.
Pramipexole and its salts
Pramipexole is a new non-ergot dopamine agonist indicated for the symptomatic treatment of Parkinson's disease. The safe use of pramipexole requires that an accurate diagnosis of Parkinson's disease be made by the physician, who then must decide on the most appropriate form of treatment. The physician must also evaluate the contraindications, warnings and precautions associated with pramipexole use for individual patients, must provide individualized dosage and other instructions, and maintain close medical supervision and patient follow-up throughout treatment.
Quetiapine and its salts
Quetiapine is a new antipsychotic agent that is indicated for the acute treatment of schizophrenia. The safe and effective use of quetiapine requires that an accurate diagnosis of schizophrenia be made by the physician, who then must decide on the appropriate forms of treatment. Quetiapine has been associated with adverse events related to the central nervous system, and cardiovascular system including somnolence, dizziness, and hypotension. Such adverse events require assessment and monitoring by the physician, who must determine whether dosage adjustments, changes in concomitant medications, or discontinuation of quetiapine is indicated.
Raloxifene and its salts
Raloxifene hydrochloride is a selective estrogen receptor modulator that is indicated for the prevention of osteoporosis in postmenopausal women. The use of this drug requires close medical supervision with individualized instructions to the patient in order to ensure that the prescribed therapeutic dose is safe and effective.
Rivastigmine and its salts
Rivastigmine tartrate is an anticholinesterase indicated for the symptomatic treatment of patients with mild to moderate Alzheimer's disease. This drug needs to be prescribed by clinicians familiar with Alzheimer's disease to ensure proper diagnosis of patients. Close medical supervision with individualized instructions to the patient is required in order to ensure that the prescribed therapeutic dose is safe and effective.
Tamsulosin and its salts
Tamsulosin is the first of a new class of drugs indicated for the treatment of the signs and symptoms of benign prostatic hyperplasia. The safe and effective use of tamsulosin requires individualized patient instructions by a physician and monitoring of adverse events that may occur with this therapy.
Tizanidine and its salts
Tizanidine is an imidazoline derivative, which acts as an agonist at alpha2 adrenergic receptor sites. This drug is used for the management of increased muscle tone associated with spasticity. The safe and effective use of tizanidine requires that patients receive individualized instructions and assessments by a medical practitioner.
Tolcapone
Tolcapone is used for the treatment of Parkinson's disease. The safe and effective use of tolcapone will require prior diagnosis of Parkinson's disease. Medical judgment as to when it might be desirable to add tolcapone to the treatment regimen of parkinsonian patients, and careful follow-up to ascertain effectiveness and safety is also required.
Tolterodine and its salts
Tolterodine is a competitive muscarinic receptor antagonist used in the management of symptoms of overactive bladders, characterized by urgency, frequency and urge incontinence. The safe and effective use of tolterodine requires that patients receive individualized instructions and assessments by a medical practitioner.
Toremifene and its salts
Toremifene is used for the treatment of hormone-dependent metastatic breast cancer in postmenopausal women. The safe and effective use of toremifene requires that patients receive individualized instructions and assessments by a medical practitioner.
Valsartan and its salts and derivatives
Valsartan is an angiotensin II AT1 receptor blocker used in the treatment of mild to moderate essential hypertension. Initiation of this drug therapy requires close medical supervision, as the patient must receive individualized instructions on their dosage regimen. The monitoring of the effectiveness of this therapy to prevent serious adverse events known to occur with this drug is also essential.
Zafirlukast and its salts
Zafirlukast is a leukotriene receptor antagonist used for the prophylaxis and chronic treatment of asthma in adults and children 12 years of age and older. This drug should be used under a physician's care to ensure appropriate treatment of the disease. Patient monitoring is required to ensure the safe and effective use of the drug which can include individualized instructions for the dosage regimen to be followed.
Spelling corrections are as follows:
The reference to
Follicle stimulating hormone
Folliculo-stimulante
(hormone humaine)
is replaced by:
Follicle stimulating hormone
Folliculo-stimulante
(hormone).
The reference to
Glycosaminoglycan (polysulfaté de)
Polysulfated glycosaminoglycan
in Part I of Schedule F to the French version of the Regulations is replaced by:
Glycosaminoglycan polysulfaté
Polysulfated glycosaminoglycan.
Finally, an amendment is made to correct the omission of the drug cyclophosphamide in the French version of Schedule F to the Regulations.
Alternatives
This recommended degree of regulatory control coincides with the risk factors associated with each specific drug. The review of the information filed by the sponsor of these drugs has determined that prescription status is required at this time, as the advice of a medical practitioner is necessary in order to ensure that the consumer receives adequate risk/benefit information before taking the medication.
Any alternatives to the degree of regulatory control would need to be established through additional scientific information and further clinical experience.
Benefits and Costs
The amendment, when promulgated, will impact on the following sectors:
Public
Prescription access to the previously mentioned drugs will benefit Canadians by decreasing the opportunities for improper use, and by ensuring professional guidance and care.
The pharmaceutical industry
The classification of these drugs as prescription products will limit their sale subject to professional intervention thereby reducing misuse and decreasing liability to the manufacturer.
Health Insurance Plans
These drugs, when assigned prescription status, may be covered by both provincial and private health care plans.
Provincial Health Care Services
The provinces may incur costs to cover physicians fees for services. However, the guidance and care provided by the physicians will reduce the need for health care services that may result from improper use of the drugs. The overall additional costs for health care services should therefore be minimal.
Consultation
The manufacturers affected by this amendment were informed of the intent to recommend these drugs for inclusion on Schedule F, Part I, at the time of market approval. A notice of intent to amend and add these drugs to Schedule F of the Food and Drug Regulations was published in the Canada Gazette, Part I, on July 25, 1998, with a 60-day comment period. Direct notice of this regulatory proposal was provided to the Provincial Ministries of Health, medical and pharmacy licensing bodies, and industry associations. As well, early notice of this initiative was provided through the Therapeutic Products Programme's Web site under "Drugs, Schedule Amendments, Early Consultation, Schedule 1051, at: http://www.hc-sc.gc.ca/hpb-dgps/therapeut.
Four comments were received from external stakeholders. One of the stakeholders questioned whether an approval to market based on safety and efficacy (notice of compliance) had been issued to one specific drug. A notice of compliance has not been issued for this drug yet. Therefore, this drug will not be added to Schedule F at this time. Another stakeholder indicated that one of the drugs had been voluntarily withdrawn from all markets. This drug will not be added to Schedule F. Two interested parties indicated that the indication for use for two of the drugs was inaccurate as written. The indication for use for these two drugs has been corrected.
A further 30-day comment period will be provided upon prepublication in the Canada Gazette, Part I.
Compliance and Enforcement
This amendment does not alter existing compliance mechanisms under the provisions of the Food and Drugs Act and the Food and Drug Regulations enforced by the Therapeutic Products Programme inspectors.
Contact
Julie Gervais, Policy Division, Bureau of Policy and Coordination, Therapeutic Products Programme, Tower B, 1600 Scott Street, Address Locator: 3102C5, Ottawa, Ontario K1A 1B6, (613) 952-3601 (Telephone), (613) 941-6458 (Facsimile), julie_gervais@ hc-sc.gc.ca (Electronic mail).
PROPOSED REGULATORY TEXT
Notice is hereby given that the Governor in Council, pursuant to subsection 30(1) (see footnote d) of the Food and Drugs Act, proposes to make the annexed Regulations Amending the Food and Drug Regulations (1051 — Schedule F).
Interested persons may make representations with respect to the proposed Regulations within 30 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 addressed to Julie Gervais, Therapeutic Products Programme, Department of Health, Tower B, 2nd Floor, 1600 Scott Street, Address Locator No. 3102C5, Ottawa, Ontario K1A 1B6, (613) 941-6458 (Facsimile), Julie_Gervais@hc-sc.gc.ca (Electronic mail).
The representations should stipulate those parts of the representations that should not be disclosed pursuant to the Access to Information Act and, in particular, pursuant to sections 19 and 20 of that Act, the reasons why those parts should not be disclosed and the period during which they should remain undisclosed. The representations should also stipulate the parts of the representations for which there is consent to disclosure pursuant to the Access to Information Act.
May 6, 1999
MARC O'SULLIVAN
Assistant Clerk of the Privy Council
REGULATIONS AMENDING THE FOOD AND DRUG REGULATIONS (1051 — SCHEDULE F)
AMENDMENTS
1. The reference to
Follicle stimulating hormone
Folliculo-stimulante (hormone humaine) (see footnote 5)
in Part I of Schedule F to the Food and Drug Regulations (see footnote 6) is replaced by the following:
Follicle stimulating hormone
Folliculo-stimulante (hormone)
2. The reference to
Glycosaminoglycan (polysulfaté de)
Polysulfated glycosaminoglycan (see
footnote 7)
in Part I of Schedule F to the French version of the Regulations is replaced by the following:
Glycosaminoglycan polysulfaté
Polysulfated glycosaminoglycan
3. Part I of Schedule F to the Regulations is amended by adding the following in alphabetical order:
Amfebutamone and its salts
Amfébutamone et ses sels
Anagrelide and its salts
Anagrélide et ses sels
Brimonidine and its salts
Brimonidine et ses sels
Carbetocin and its salts
Carbétocine et ses sels
Cerivastatin and its salts
Cérivastatine et ses sels
Emedastine and its salts
Émédastine et ses sels
Fosfomycin and its salts
Fosfomycine et ses sels
Irbesartan and its salts
Irbésartan et ses sels
Montelukast and its salts
Montélukast et ses sels
Nadroparin and its salts
Nadroparine et ses sels
Naratriptan and its salts
Naratriptan et ses sels
Nelfinavir and its salts
Nelfinavir et ses sels
Pramipexole and its salts
Pramipexole et ses sels
Quetiapine and its salts
Quétiapine et ses sels
Raloxifene and its salts
Raloxifène et ses sels
Rivastigmine and its salts
Rivastigmine et ses sels
Tamsulosin and its salts
Tamsulosine et ses sels
Tizanidine and its salts
Tizanidine et ses sels
Tolcapone
Tolcapone
Tolterodine and its salts
Toltérodine et ses sels
Toremifene and its salts
Torémifène et ses sels
Valsartan and its salts and derivatives
Valsartan et ses sels et dérivés
Zafirlukast and its salts
Zafirlukast et ses sels
4. Part I of Schedule F to the French version of the Regulations is amended by adding the following in alphabetical order:
Cyclophosphamide
Cyclophosphamide
COMING INTO FORCE
5. These Regulations come into force on the day on which they are registered.
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Regulations Amending the Food and Drug Regulations (1146 — Schedule F)
Statutory Authority
Food and Drugs Act
Sponsoring Department
Department of Health
REGULATORY IMPACT ANALYSIS STATEMENT
Description
Schedule F is a list of drug substances, the sale of which is controlled under sections C.01.041 to C.01.046 of the Food and Drug Regulations. Part I of Schedule F lists substances intended for human and veterinary use which require a prescription to be sold in Canada. The review and introduction of new drugs onto the Canadian market necessitates periodic revisions to the schedule. This amendment would update Schedule F to require prescription status for six new drug substances being added to Part I. In addition, amendments are proposed to correct the spelling of dimethyl sulfoxide in the French version of Part I of Schedule F to the Regulations (see footnote 8).
The Therapeutic Products Programme's Drug Schedule Status Committee reviews the status of chemical entities proposed for marketing. A decision regarding the necessity for prescription or other status versus non-prescription status was made for each of the drug substances listed on this schedule on the basis of established and publicly available criteria. These criteria include, but are not limited to, concerns related to toxicity, pharmacologic properties, and therapeutic applications.
This recommended degree of regulatory control coincides with the risk factors associated with each specific drug. The review of the information filed by the sponsor of these drugs has determined that prescription status is required at this time. Advice from a medical practitioner is necessary to ensure that consumers receive adequate risk/benefit information before taking the medication. Any alternatives to the degree of regulatory control would need to be established through additional scientific information and clinical experience.
The following drug substances are being added to Schedule F:
— Betaine and its salts — an anti-homocysteine agent indicated for the treatment of homocystinuria.
— Candesartan and its salts and derivatives — an angiotensin II AT1 receptor blocker indicated for the treatment of hypertension.
— Capecitabine and its salts and derivatives — an antineoplastic agent indicated for the treatment of metastatic carcinoma of the breast that has progressed or recurred following therapy with anthracyclines and/or taxanes.
— Clopidogrel and its salts — a platelet aggregation inhibitor indicated for the secondary prevention of vascular ischemic events in patients with a history of symptomatic atherosclerotic disease.
— Delavirdine and its salts — an inhibitor of Human Immunodeficiency Virus 1 reverse transcriptor indicated for use in combination with the reverse transcriptase inhibitor nucleoside analogues for the treatment of human immunodeficiency virus (HIV)-1 infection when antiretroviral therapy is warranted.
— Grepafloxacin and its salts and derivatives — an oral fluoroquinolone antibiotic indicated for the treatment of infections caused by susceptible bacteria.
Alternatives
Any alternatives to the degree of regulatory control recommended in this regulatory initiative would need to be established through additional scientific information and clinical experience.
No other alternatives were considered.
Benefits and Costs
The amendment would impact on the following sectors:
The Public
Prescription access to the previously mentioned drugs would benefit Canadians by decreasing the opportunities for improper use, and by ensuring professional guidance and care.
The Pharmaceutical Industry
The classification of these drugs as prescription products would limit their sale subject to professional intervention thereby reducing misuse and decreasing liability to the manufacturer.
Health Insurance Plans
These drugs, when assigned prescription status, may be covered by both provincial and private health care plans.
Provincial Health Care Services
The provinces may incur costs to cover physicians fees for services. However, the guidance and care provided by the physicians would reduce the need for health care services that may result from improper use of the drugs. The overall additional costs for health care services should therefore be minimal.
Consultation
The manufacturers affected by this proposed amendment were informed of the intent to recommend these drugs for inclusion on Schedule F, Part I, at the time of market approval. A notice of intent to solicit comments on this proposal was published in the Canada Gazette, Part I, on November 28, 1998, with a 45-day comment period. Direct notice of this regulatory proposal was provided to the Provincial Ministries of Health, medical and pharmacy licensing bodies, and industry associations. As well, this initiative was posted on the Therapeutic Products Programme Web site under: http://www.hc-sc.gc.ca/hpb-dgps/therapeut/ zfiles/english/schedule/earlycon/sch-1146.html.
A total of two comments from external stakeholders were received. No objections were received to the proposal to add these drugs to Schedule F.
A further 30-day comment period will be provided upon prepublication in the Canada Gazette, Part I.
Compliance and Enforcement
This amendment would not alter existing compliance mechanisms under the provisions of the Food and Drugs Act and Regulations enforced by the Therapeutic Products Programme inspectors.
Contact
Karolyn Lui, Policy Division, Bureau of Policy and Coordination, Therapeutic Products Programme, Tower B, 2nd Floor, 1600 Scott Street, Holland Cross, Address Locator 3102C5, Ottawa, Ontario K1A 1B6, (613) 941-3693 (Telephone), (613) 941-6458 (Facsimile), karolyn_lui@hc-sc.gc.ca (Electronic mail).
PROPOSED REGULATORY TEXT
Notice is hereby given that the Governor in Council, pursuant to section 30 (see footnote e) of the Food and Drugs Act, proposes to make the annexed Regulations Amending the Food and Drug Regulations (1146 — Schedule F).
Interested persons may make representations with respect to the proposed Regulations within 30 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 addressed to Karolyn Lui, Therapeutic Products Programme, Department of Health, Tower B, 2nd Floor, 1600 Scott Street, Holland Cross, Address Locator 3102C5, Ottawa, Ontario K1A 1B6.
The representations should stipulate those parts of the representations that should not be disclosed pursuant to the Access to Information Act and, in particular, pursuant to sections 19 and 20 of that Act, the reason why those parts should not be disclosed and the period during which they should remain undisclosed. The representations should also stipulate those parts of the representations for which there is consent to disclosure pursuant to the Access to Information Act.
May 6, 1999
MARC O'SULLIVAN
Assistant Clerk of the Privy Council
REGULATIONS AMENDING THE FOOD AND DRUG REGULATIONS (1146 — SCHEDULE F)
AMENDMENTS
1. The reference to
Diméthylsulfoxide
Dimethylsulfoxide (see footnote
9)
in Part I of Schedule F to the French version of the Food and Drugs Regulations (see footnote 10) is replaced by the following:
Diméthylsulfoxyde
Dimethyl sulfoxide
2. Part I of Schedule F to the Regulations is amended by adding the following in alphabetical order:
Betaine and its salts when sold or recommended for the treatment of homocystinuria
Bétaïne et ses sels s'ils sont vendus ou recommandés
pour le traitement de l'homocystinurie
Candesartan and its salts and derivatives
Candésartan et ses sels et dérivés
Capecitabine and its salts and derivatives
Capécitabine et ses sels et dérivés
Clopidogrel and its salts
Clopidogrel et ses sels
Delavirdine and its salts
Délavirdine et ses sels
Grepafloxacin and its salts and derivatives
Grépafloxacine et ses sels et dérivés
COMING INTO FORCE
3. These Regulations come into force on the day on which they are registered.
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S.C., 1996, c. 19
SOR/97-230
S.C., 1996, c. 19
S.C., 1996, c. 19
C.R.C., c. 1041
S.C., 1994, c. 47, s. 117
C.R.C., c. 870
S.C., 1994, c. 47, s. 117
SOR/98-291
C.R.C., c. 870
SOR/95-546
SOR/98-291
S.C., 1994, c. 47, s. 117
SOR/98-291
C.R.C., c. 870
NOTICE:
The format of the electronic version of this issue of the Canada Gazette was modified in order to be compatible with extensible hypertext markup language (XHTML 1.0 Strict).
