Schedule II Naloxone Reference Manual for Ontario Community Pharmacies This document lives at https://eDispensary.ca/naloxone February 2017 Contents 1 Dispensary Naloxone Program 1.1 Standard Naloxone Form ...................... 2 Patient Aids 2.1 POINT 5 Steps to Save a Life .................... 2.2 University of Waterloo Naloxone Infographic ........... 3 Ontario Naloxone Program for Pharmacies Reference 3.1 Notice from the Executive Officer: Ontario Naloxone Program for Pharmacies (ONPP) ....................... 3.2 ONPP FAQ .............................. 3.3 ONPP Quarterly Reporting Form .................. 3.4 ONPP Reminder ........................... 4 Ontario College of Pharmacists Naloxone Guidance 4.1 Guidance for pharmacy professionals when dispensing or selling naloxone as a Schedule II drug. ................... 4.2 Pharmacy Connection Winter 2017 (excerpt) ........... 5 Selected Naloxone Product Monographs 5.1 Sandoz Naloxone Hydrochloride Injection 0.4mg/mL ....... 5.2 Adapt Naloxone Hydrochloride Nasal Spray ............ 5.2.1 Patient Information .....................
Transcript
Schedule II Naloxone Reference Manual
for Ontario Community Pharmacies
This document lives at https://eDispensary.ca/naloxone
Dispensary Naloxone Program A model program to manage dispensing of naloxone in Ontario community pharmacies
ELIGIBILITY Naloxone is a Schedule II drug when indicated for use in an emergency opioid overdose
situation outside of a hospital setting
Pharmacists can dispense naloxone kits without a prescription to use to treat opioid overdose.
To receive a publicly funded naloxone kit,
patients must be one of the following:
“a person who is currently using
opioids or is a past opioid user who is
at risk of returning to opioid use,” or
“a family member, friend or other
person in a position to assist a person
at risk of overdose from opioids”
CONTENTS The Narcan nasal spray formulation of naloxone can be dispensed as a Schedule II drug.
However, every publicly-funded naloxone kit must contain injectable naloxone. Injectable
naloxone kits must include the following items:
Two 1mL ampoules or vials of naloxone hydrochloride 0.4mg/mL injection, and
Two safety engineered syringes with one inch 25G needles attached, and
Two safe ampoule opening devices, if ampoules are given, and
One pair of non-latex gloves, and
One naloxone identifier card
BILLING To ensure consistent recordkeeping, every naloxone kit should be recorded in the pharmacy
software, whether it is publicly-funded or not. Always create a separate prescription for the
dispensing of the exact drug under its DIN and for the professional services provided.
PIN DESCRIPTION COST FEE TOTAL COST 93877251 Initial training and
provision of 1 kit $35 $35 $70
93877252 Replacement of 1 kit $35 $10 $45
Follow the same procedures as you use for billing MedsChecks and other professional services:
the pharmacist should be entered as the prescriber and the PS & ML intervention codes used as
necessary for non-ODB eligible patients.
A PERSON WHO DOES NOT MEET THESE
CRITERIA IS STILL ELIGIBLE TO PURCHASE
A NALOXONE KIT TO TREAT OPIOID
OVERDOSE. THESE CRITERIA ARE STRICTLY
FOR BILLING A NALOXONE KIT TO ODB
PROCESSING To ensure consistency, use a special
recordkeeping workflow for dispensing naloxone.
When recording a naloxone prescription in the
pharmacy software for billing purposes, imagine a
generic “prescription”.
The patient should always be the person to whom
the kit is supplied, not the opioid user upon whom
they expect to use the kit.
The prescriber should always be the dispensing
pharmacist. That is, the pharmacist who actually
provides the kit, training and counselling to the
person receiving the kit.
Dispense under the actual DIN of the naloxone product and bill your training separately under
the relevant pseudo-DIN. There must be a label with the actual drug and DIN to go on the vials
containing the naloxone. You don’t want to confuse end-users in an emergency.
The first fill at your pharmacy should always include pharmacist training, even if the patient self-
declares that they have already been trained in use of a naloxone kit. Training should be
recorded under the 93877251 PIN (Initial Training) for
every patient who has not been trained in use of a
naloxone kit, even for non-publicly funded kits.
Subsequent fills (for example, to replace a used or
expired kit) should record training under 93877252.
The sig should be a concise summary of the
instructions for emergency use of naloxone. The label
will be on the vial containing the ampoules of
naloxone and could be referred to in an emergency.
For example:
FOR OPIOID OVERDOSE: CALL 911, THEN INJECT
ONE AMPOULE (1ML) INTO UPPER ARM OR LEG
MUSCLE, THEN PROVIDE CPR. REPEAT IN 3-5
MINUTES IF NO IMPROVEMENT.
Create an internal sig code/shortcut in your pharmacy
software, such as *NALOXONE
Only one publicly funded naloxone kit can be provided to a person at a time (two vials/ampoules
of naloxone). If a kit has been used or expired, another one can be billed under the 93877252
pseudo-DIN. The quantity of cash naloxone kits is at the discretion of the dispensing pharmacist.
Do not add refills to the prescription or set it to “unlimited refills”. Use new “prescriptions” every
time.
Model Prescription for processing Naloxone as a Schedule II drug in
Ontario
Patient The person to whom the
kit is being supplied
Prescriber The pharmacist
dispensing the kit and training the user
Drug The exact DIN of the naloxone dispensed
Sig Store custom sig
shortcut set by DM
Quantity 2 vials or ampoules per
kit
Refills None
2 RXs: 1 WITH THE DIN, 1 WITH THE PIN
ALWAYS CREATE ONE NEW RX FOR
DISPENSING AND ONE NEW RX FOR
TRAINING
THE 93877251 PIN DENOTES THAT THE
PHARMACIST PROVIDED INITIAL TRAINING
IN THE USE OF THE KIT.
THE 93877252 PIN DENOTES THAT THIS IS
A REPLACEMENT KIT OR THE PATIENT
DECLINES TRAINING
Recordkeeping The pharmacy team should have a common standard
when dispensing naloxone. Having a single standard
policy and documentation template file on hand keeps
everyone on the same page and gives staff a clear
workflow. It promotes consistent, and well-
documented evidence-based patient care.
Record training and dispensing under separate
prescriptions. We always want to keep an exact
record of what drug was dispensed and an exact
record of the professional services provided.
Dispensing under the naloxone DIN and recording
services under the ONPP pseudo-DIN means that we
can take advantage of automatic inventory
management and drug interaction analysis.
There is more to document when providing training
for emergency use of injectable naloxone than can
reasonably be made to fit on a single prescription
hardcopy.
Reporting The Designated Manager must make a quarterly
report to the Ministry of Health and Long-Term Care
regarding publicly-funded naloxone kits that you have
dispensed. In order to complete these reports, you
track essential statistics about how the kits that you dispensed are used and the rationale for
their use. The form should be emailed or faxed in quarterly. Using a standard form that captures
the information that you need for these reports makes your quarterly reporting a breeze.
Consider filing them separately to ensure they’re easily accessible for producing your quarterly
reports, quality assurance, and for audit purposes.
Training Materials The POINT “5 Steps to Save a Life” are a good patient aid for illicit drug users, covering overdose
prevention and response. The University of Waterloo’s naloxone infographic is a good patient aid
for chronic pain patients. The pharmacist should record which aids were actually provided. Avoid
giving more than a couple of pages of patient aids: the kit will be opened in an emergency and
it’s important that there be very straightforward and clear instructions.
Model Prescription for Documenting Naloxone Training
Patient The person to whom the
kit is being supplied
Prescriber The pharmacist
dispensing the kit and training the user
Drug
93877251
The person is receiving
a kit and first-time training
93877252
The person has already
been trained and
kit is a replacement
Sig
THIS PERSON HAS BEEN TRAINED IN
OPIOID OVERDOSE RESPONSE AND
PREVENTION
Quantity ODB 1 at a time
cash Pharmacist’s
discretion Refills None
Record of Dispensing Naloxone as a Schedule II Drug
Name or Rx# Affix a label or tag here
Rationale for Dispensing (circle one)
person is currently using opioids or is a past opioid user who is at risk of returning to
opioid use
person is prescribed chronic long-term opioid
therapy
person is a family member, friend or other person in a position to assist a person at risk
of overdose from opioids
Billing (circle one) ONPP/ODB OR CASH
Rationale for Professional Services (circle one)
93877251
OR
93877252
This person is receiving a naloxone kit and first-time training by a pharmacist
This person is receiving a replacement naloxone kit and has already received first-
time training Pharmacist Verification of Kit Contents
Two 1mL ampoules or vials of naloxone hydrochloride
0.4mg/mL injection
Naloxone is packed in cotton inside two easy-open vials with
naloxone label, including the store custom sig
Two safe ampoule opening devices, if
ampoules are given
Completed naloxone identifier card with
training label on back
Two safety engineered syringes with one inch 25G
needles attached
One pair of non-latex gloves
Patient Aids (circle which ones)
Expiry Date
POINT 5 Steps month / year
UW Naloxone Infographic
Ph. Initials
Pharmacist Verification of Allergies (circle one)
Does the person the naloxone is intended for have any known allergies to naloxone, or concomitant ingredients in specific formulations of
naloxone (methylparaben or propylparaben)?
YES DO NOT DISPENSE
NO
Ph. Initials Pharmacist’s Professional Notes
Common Counselling Points (tick which ones)
Prevention of opioid overdose Signs of and response
to opioid overdose Administration of
naloxone and aftercare Notifying pharmacy when kit
is used
Pharmacist Signature and License Number
Prevent Overdose In Toronto 5 STEPS TO SAVE A LIFE
1 SHAKE & SHOUTat shoulders their name
2 911 CALL 911if unresponsive
3 INJECT NALOXONE1 ampoule (1mL) intoarm or leg muscle
4 CHEST COMPRESSIONSor full CPR and/or rescue breathing as trained
5 ?2nd dose
IS IT WORKING?If no improvement in 3-5 minutes repeat steps 3&4
STAY! Stick around until EMS arrives in case they still need help
PH1601SS625
SIGNS of OPIOID OVERDOSE+ RECOVERY POSITION
SIGNS OF OPIOID OVERDOSE &RECOVERY POSITION
OVERDOSE
PREVENTION
• Avoid mixing drugs or using with alcohol. Try to use one at a time and use drugs before alcohol.
• Know your tolerance, if you haven’t used for a while,(3 days or more) your body can’t handle the same amount as before. Start as if you have never used before.
• Do a tester and ask around with a new supply or dealer. Taste it, smoke it, use a little and see what others are saying.
• Use with a friend but avoid injecting at the same time in case one of you needs help.
• Have a plan, talk about overdose before it happens and with people you trust.
SIGNS OF
OPIOID
OVERDOSE
• Can’t wake the person up• Breathing is very slow, erratic or has stopped• Deep snoring or gurgling sounds• Fingernails or lips are blue or purple• Body is very limp• Pupils are very small
RECOVERY POSITION
Put person in recovery position if:• Unconscious and
breathing• You have to leave
the person unattended
Head should be tilted back slightly to open airway Place their hand
under their head for support
Bend knee forward to prevent body from rolling onto stomach
The Works 277 Victoria St. Toronto, Ontario 416-392-0520
Prevent Overdose In Toronto
5 Stay Calm
Don’t put them in a bathtub/shower Don’t inject stimulants (ie. meth) Wait for help to arrive Don’t stand them up
4 Check The Person’s Breathing
Breathing Not Breathing
Push hard and fast in center of chest to the beat of Stayin’ Alive
- Hand supports head - Knee stops body from rolling onto stomach
Put person in Give compressionsrecovery position until help arrives
3 Give Naloxone
Break drug Pull into Inject intoampoule needle slowly large muscle
2 Call 911
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Soft/no breath Pinpoint Blue lips, nails, Cold, Limp Doesn’t respondor snoring pupils or skin clammy skin body to shouting
!!
Signs of an Overdose
Naloxone is an antidote for opioids which can include:
Ontario Public Drug Programs Division, Ministry of Health and Long-Term Care
Notice from the Executive Officer: Ontario Naloxone Program for Pharmacies (ONPP) Updated August 17, 2016
On June 24, 2016, the National Association of Pharmacy Regulatory Authorities (NAPRA) finalized the scheduling change for naloxone hydrochloride injection (“naloxone”). Naloxone, when indicated for emergency use for opioid overdose outside hospital settings, is now classified as a Schedule II drug in the NAPRA’s National Drug Schedule (NDS).
As a result, effective June 24, 2016, naloxone no longer requires a prescription to be sold in Ontario pharmacies if indicated for emergency use for opioid overdose outside hospital settings.
Effective June 24, 2016, all pharmacies may receive reimbursement for providing naloxone emergency kits by submitting claims through the Health Network System (HNS).
If you have any questions, please contact the ministry by email at [email protected] or the Ontario Drug Benefit (ODB) Help Desk at 1-800-668-6641.
Background
On June 3, 2016, the Ministry of Health and Long-Term Care’s (ministry) new Ontario Naloxone Program for Pharmacies (ONPP) made publicly-funded naloxone available in pharmacies that dispense opioid agonist maintenance therapy (methadone/Suboxone) under a prescription order from the Chief Medical Officer of Health (CMOH) for Ontario. The CMOH’s prescription order required this prior to NAPRA’s decision has expired, effective June 24, 2016.
In addition, completion of the “2016 Naloxone Training Module” respecting the preparation and administration of emergency naloxone kits is no longer required. Completion of a signed Attestation for Participation in the Ontario Naloxone Pharmacy Program (ONPP) is also no longer required.
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Pharmacy Compliance
This notice and the accompanying Frequently Asked Questions (FAQs) constitute a ministry policy that pharmacy operators must comply with when submitting claims through the HNS for providing naloxone kits. Compliance with the ministry policy is required under section 3.2 of the HNS Subscription Agreement for Pharmacy Operators.
Eligibility
As of June 24, 2016, all pharmacies are eligible to provide naloxone emergency kits at no cost to eligible persons, if certain terms and conditions are met. Criteria for an “eligible person” includes:
• a person who is either currently using opioids or is a past opioid user who is atrisk of returning to opioid use, or
• a family member, friend or other person in a position to assist a person at risk ofoverdose from opioids.
Procedures for Providing and Billing
Pharmacists must be trained prior to providing naloxone kits. The Ontario Pharmacists Association (OPA) has developed an online education module available on their website. There may be other resources available to pharmacists. The OCP has developed a guidance document for the providing or selling of naloxone available on their website.
The trained pharmacist who provides the publicly funded naloxone emergency kit must be identified in the pharmacist field on the claim submitted for payment through the HNS using the proper PIN that was provided.
For eligible persons, who are first time users and do not have training with the naloxone kit, the Initial Naloxone Emergency Kit (which includes a professional training component) will be provided by the pharmacist. For eligible persons, who do have training with the naloxone kit, the Replacement Naloxone Emergency Kit (excludes the professional training) can be provided by the pharmacist.
Pharmacists must ensure that the eligible person’s name, date of birth, and Ontario health card number are entered accurately as part of the HNS claims submission.
Pharmacists, where possible, must ensure that the quarterly report-back form (available at: www.health.gov.on.ca/en/pro/programs/drugs/opdp_eo/eo_communiq.aspx) relating to outcomes for individuals who were provided a naloxone emergency kit, be completed
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and returned to the ministry by 30 days after end of each quarter in a fiscal year. The first report back will be due on October 30, 2016. Please refer to the FAQs for details on the reporting schedule.
Pharmacies will procure naloxone and the required supplies to assemble the naloxone kit through usual suppliers (i.e., pharmacy-assembled naloxone kits). The emergency kit shall be assembled by a pharmacist, or a person under the supervision of a pharmacist and contain the follow:
• Two 1 ml ampoules or vials of naloxone hydrochloride 0.4 mg/ml injection;
• Two safety engineered syringes with 25 g one inch needles attached;
• Two safe ampoules opening devices (also known as “breakers”, “snappers”, or “openers”) as applicable;
• One pair of non-latex gloves;
• One rescue breathing barrier; and
• One naloxone identifier card.
The ministry is aware that some of supplies (e.g., ampoule openers/snappers/breakers, rescue breathing barriers) listed can be ordered from Canadian based suppliers such as Pharmasystem, Canadian Safety Supplies, and Kohl and Frisch. The Ontario Pharmacists Association has also compiled a list of the required kit components as well as some suppliers for these items, in the event that pharmacists are unable to procure some or all of the elements through their usual suppliers. This list can be found at www.opatoday.com/professional/naloxone_kit_tools. Types of containers that have been reportedly used to contain all the components include sunglasses cases, eyeglass cases, pencil cases, or a variation of a compact, portable container resembling a case or box. Pharmacies are encouraged to seek out these and/or other local suppliers for obtaining components required for pharmacy-assembled naloxone kits.
Pharmacy Eligibility
All pharmacies that comply with the requirements of this ministry policy are able to provide emergency naloxone kits, and bill the cost of those kits to the ministry through the HNS.
Prior to providing naloxone kits to eligible persons, pharmacies must ensure that their pharmacists are trained to provide the necessary training to eligible persons who are to receive the naloxone kits.
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Pharmacy Record Requirements
Standard record keeping requirements under current standards of practice apply. Pharmacies must keep a record when the naloxone kit (see table below) is provided to the eligible person.
For billing purposes, pharmacy records must be maintained in a readily available format for the purpose of a ministry audit of billing for a minimum of 2 years.
Pharmacists shall keep records consistent with their obligations under the Pharmacy Act, 1991, the Drug and Pharmacies Regulation Act and any instructions provided by the Ontario College of Pharmacists or the ministry. These records must include, at a minimum:
• Full instructions for use of drug; and
• The drug’s material risks, including material side-effects, contradictions orprecautions were discussed with the eligible person to ensure that they provideappropriate training to individuals receiving naloxone emergency kits.
Pharmacy billing procedure
Naloxone emergency kits will be reimbursed by the Ontario Government, effective June 24, 2016, in accordance with this ministry policy. The PINs listed in Table 1 below are to be used whenever an emergency naloxone kit is supplied to an eligible person, regardless of the person’s eligibility under the Ontario Drug Benefit (ODB) Program.
Table 1: PINs to support reimbursement of Naloxone emergency kits
PIN Description Total Amount Reimbursed
93877251
Initial Naloxone Emergency Kit (reimbursed amount includes naloxone kit at $35, plus professional fee at $10, plus professional training at $25)
$70.00
93877252 Replacement Naloxone Emergency Kit $45.00 (reimbursed amount includes naloxone kit at $35 plus professional fee at $10)
Claims must be submitted using the ministry-assigned PIN associated with the naloxone
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emergency kit and service provided. Do not use the Drug Identification Number (DIN) of the naloxone that is contained in the naloxone kit.
For ODB-eligible recipients:
The claim submission follows the normal process for submitting claims on the HNS with the following additional information:
• Intervention code ‘PS’: (Professional Care Services)
• Product Identification Number (PIN): see table above for list of PINs
• Valid Pharmacist ID
• Professional Fee: see table above for “Maximum Reimbursed Amount” for eachkit
For Non-ODB eligible recipients:
When submitting a claim for an eligible person who does not have ODB coverage, pharmacists must submit the following information:
• Person’s Gender: ‘F’ = female; ‘M’ = male
• Person’s Date of Birth: Valid YYYYMMDD
• Person’s Ontario Health Card number
• Intervention codes:o PS: Professional Care Serviceso ML: Established eligibility coverage (i.e., 1 day of the Plan ‘S’ coverage)
• Carrier ID: ‘S’
• Product Identification Number (PIN): see table above for list of PINs
• Valid Pharmacist ID
• Professional Fee: see table above for “Maximum Reimbursed Amount” for eachkit
Restrictions:
A maximum of one (1) naloxone kit may be provided to an eligible person at one time.
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Ontario Public Drug Programs Division
Ontario Naloxone Program for Pharmacies (ONPP) Frequently Asked Questions for Pharmacy Dispensers: Providing Publicly Funded Naloxone Kits and Claims Submission Using the Health Network System Updated August 17, 2016
1. When are dispensers able to provide publicly funded naloxone emergencykits for Ontarians?
All pharmacies that have a billing account under the Ontario Public Drugs Program (OPDP) are eligible to provide naloxone emergency kits free-of-charge, effective June 24, 2016, subject to their compliance with the Ministry of Health and Long-Term Care’s (ministry) policy.
2. What are the publicly available kits that dispensers can bill Health NetworkSystem (HNS) for reimbursement?
Table 1: PINs to support reimbursement of Naloxone emergency kits
PINs PIN Description Total Amount Reimbursed
93877251 Initial naloxone emergency kit (reimbursed amount includes naloxone kit at $35, plus professional fee at $10, plus professional training at $25)
$70.00
93877252 Replacement naloxone emergency kit (reimbursed $45.00 amount includes naloxone emergency kit at $35 plus professional fee at $10)
The “Initial Naloxone Emergency Kit” PIN would be entered when a pharmacist provides a naloxone emergency kit for the first time to a person, and provides the required training. The “Replacement naloxone emergency kit” PIN would be entered when an individual who has already received an initial naloxone emergency kit and the required
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training, is being provided a subsequent naloxone emergency kit.
3. What are the contents of the Naloxone Emergency Kits?
Pharmacies will purchase naloxone and the required supplies to assemble the naloxone kit through usual suppliers (i.e., pharmacy-assembled naloxone kits). The emergency kit must be assembled by a pharmacist or a person under the supervision of a pharmacist, and contain the following:
a. Two 1 mL ampoules or vials of naloxone hydrochloride 0.4 mg/ml injection;b. Two safety engineered syringes with 25 g one inch needles attached;c. Two safe ampoules opening devices (also known as “breakers”, “snappers”, or
“openers”) as applicable;d. One pair of non-latex gloves;e. One rescue breathing barrier; andf. One naloxone identifier card.
The ministry is aware that some of supplies (e.g., ampoule openers/snappers/breakers, rescue breathing barriers) listed can be ordered from Canadian based suppliers such as Pharmasystem, Canadian Safety Supplies, and Kohl and Frisch. The Ontario Pharmacists Association has also compiled a list of the required kit components as well as some suppliers for these items, in the event that pharmacists are unable to procure some or all of the elements through their usual suppliers. This list can be found at www.opatoday.com/professional/naloxone_kit_tools. Types of containers that have been reportedly used to contain all the components include sunglasses cases, eyeglass cases, pencil cases, or a variation of a compact, portable container resembling a case or box. Pharmacies are encouraged to seek out these and/or other local suppliers for obtaining components required for pharmacy-assembled naloxone kits.
4. Are dispensers authorized to provide non-publicly funded naloxone kits?
Yes, naloxone may be provided to people who do not meet the eligibility criteria for the Ontario Naloxone Program for Pharmacies (ONPP).
Eligibility
5. Are all Ontarians eligible to receive publicly funded naloxone kits?
Eligible people include a person who is either:
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• Currently using opioids;
• Is a past opioid user who is at risk of returning to opioid use; or
• A family member, friend or other person in a position to assist a person at risk of overdose from opioids.
The individual must also indicate their understanding that the person for whom the naloxone is intended has no known contraindications to the use of naloxone.
Pharmacy Eligibility
6. What do I have to do before providing naloxone emergency kits and billing the ministry through the HNS for the kits?
Only pharmacies that comply with the requirements of the ministry policy set out in the Executive Officer’s Notice, dated August 17, 2016, will be able to provide naloxone emergency kits, and bill the cost of those kits to the ministry through the HNS.
The ministry strongly encourages that pharmacists complete appropriate training prior to providing naloxone emergency kits. The ministry is aware of naloxone online webinar training (recorded) and additional resources available on the Ontario Pharmacists Association website. There may be other resources available to pharmacists.
Please refer to your professional college and/or association for guidance and/or resources for training required for providing naloxone kits.
Ministry Payment
7. How is payment made by the ministry?
The payment is paid through the ministry’s Health Network System (HNS) to the eligible pharmacy that has a billing account with OPDP.
8. Can I submit manual (paper) claims for naloxone emergency kits?
No. All claims for naloxone emergency kits must be submitted electronically through the HNS.
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Pharmacy Participation
9. What training are pharmacists required to complete prior to providing naloxone emergency kits?
The ministry strongly encourages pharmacists complete appropriate training prior to providing the naloxone emergency kits. Please refer to your professional college and/or association for guidance and/or resources for training required for the providing of naloxone kits.
Documentation and Record Keeping
10. What is the pharmacist required to document when providing a naloxone kit to eligible Ontarians?
Standard record keeping requirements under current standards of practice apply. Pharmacists must keep a record when the naloxone kit is provided to an eligible person (see question 5).
Pharmacists must keep records consistent with their obligations under the Pharmacy Act, 1991, the Drug and Pharmacies Regulation Act and any instructions provided by the Ontario College of Pharmacists or the ministry. These records must include, at a minimum:
• The name, address and phone number of the eligible person.
• Full instructions for use of drug.
• The drug’s material risks, including side-effects, contradictions or precautions were discussed with the Eligible Person.
Please refer to your professional college and/or association for guidance relating to documentation within scope of practice.
11. How long should the record be kept for billing purposes?
For billing purposes, pharmacy documentation must be maintained in a readily available format for the purpose of ministry audit for a minimum of 2 years.
12. Are pharmacists required to track outcomes of the individuals who were provided a naloxone kit?
Pharmacists, where possible, must ensure that a quarterly report (available at: http://www.health.gov.on.ca/en/pro/programs/drugs/opdp_eo/eo_communiq.aspx),
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relating to outcomes for individuals who were provided a naloxone emergency kit, be completed and returned to the ministry. The reporting schedule is as follows:
Table 2: Quarterly Reporting Requirements for Providing Naloxone
Quarter Report due date
Q1 (April – June) June 30
Q2 (July – September) October 30
Q3 (October – December) January 30
Q4 (January – March) April 30
Claim for Payment through the HNS
13. When does the pharmacist submit the claim for the payment?
Pharmacists should submit the claim for payment through the HNS after providing of the naloxone emergency kits to the eligible person the same day the naloxone kit was provided.
14. How are claims for naloxone emergency kits submitted through the HNS?
Claims must be submitted for a publicly funded naloxone emergency kit using the appropriate PIN of the kit (i.e., Initial Naloxone Emergency Kit, Replacement Naloxone Emergency Kit).
Pharmacists must ensure that the individual’s name, date of birth, and Ontario health card number are entered accurately as part of the HNS claims submission. Failure to do so may impact the ability to submit future claims for these individuals.
15. What is the procedure to submit the claim to the HNS for a publicly funded naloxone kit for an ODB eligible recipient?
The claim submission follows the normal process for submitting claims on the HNS with the following additional information:
• Intervention code ‘PS’: (Professional Care Services)
• Product Identification Number (PIN): see table above for a list of PINs
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• Valid Pharmacist ID
• Professional Fee: see table above for the “Maximum Reimbursed Amount” for each naloxone emergency kit
16. What is the procedure to submit the claim to the HNS for a publicly funded naloxone kit for an eligible person who does not have ODB coverage?
When submitting a claim for a person who does not have ODB coverage, pharmacists must submit the following information:
• Person’s Gender: ‘F’ = female; ‘M’ = male
• Person’s Date of Birth: Valid YYYYMMDD
• Person’s Ontario Health Card number
• Intervention codes: o PS: Professional Care Services o ML: Established eligibility coverage (i.e., 1 day of the Plan ‘S’ coverage)
• Carrier ID: ‘S’
• Product Identification Number (PIN): see table above for a list of PINs
• Valid Pharmacist ID
• Professional Fee: see table above for the “Maximum Reimbursed Amount” for each kit
17. I have questions about providing naloxone kits?
Please refer to your professional college and/or association regarding questions about guidance and/or resources for naloxone kits, including contents preparation and providing of the naloxone kit.
If pharmacies have any questions or concerns related to this policy or billing issues, please contact the Ontario Drug Benefit (ODB) Help Desk 1-800-668-6641.
18. Do I need to submit these PINs to the Narcotics Monitoring System (NMS)?
No. Naloxone emergency kits are not included on the Monitored Drugs List, therefore submission to the NMS is not required.
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Restrictions
19. What are the restrictions for naloxone kits?
A maximum of one (1) naloxone kit may be provided to an eligible person at one time.
Additional Questions
20. Can I process a claim via the HNS for a publicly-funded naloxone kit if the eligible person does not want to provide their Ontario health care number (OHIP) number to the pharmacy?
No. An eligible person must submit their OHIP number for a claim to be processed through HNS for a publicly-funded naloxone kit at the pharmacy.
21. I am having trouble putting the claim through. Who should I contact?
If pharmacies have any questions or concerns related to this policy or billing issues, please contact the Ontario Drug Benefit (ODB) Help Desk 1-800-668-6641.
7
Ontario Public Drug Programs, Ministry of Health and Long-Term Care
Ontario Naloxone Program for Pharmacies (ONPP) Quarterly Reporting Form
Pharmacy Name:
Date:
Contact:
Email:
Telephone:
Key Outcomes for the Quarter*
Outcome Number Number of Initial Naloxone Emergency kits dispensed to persons
a) Number of persons at-risk of opioid overdose trained to administer naloxone
b) Number of family and/or friends of persons trained to administer naloxone
Number of persons who administered naloxone that they received from a pharmacy, including how many doses were given per overdose
Number of persons who reported receiving an injection of naloxone that was acquired from a pharmacy, including how many doses were received per person
Number of times that 911 was called when naloxone was administered or received
Number of Replacement Naloxone Emergency kits dispensed
Feedback Please provide any information you feel is important to report regarding successes or challenges in regards to your naloxone distribution program:
Your reporting form may be submitted electronically (preferred) to: [email protected]
Should you not be able to submit electronically, you may submit via fax to: 416-325-6647.
* Due 30 days after the end of each quarter in a fiscal year. The first report back will be due on October 30, 2016. Please refer to the FAQs for details on the reporting schedule.
1
Ontario Public Drug Programs Division, Ministry of Health and Long-Term Care
Notice from the Executive Officer: Reminder – the Ontario Naloxone Program for Pharmacies August 17, 2016
This notice is a reminder that since June 24, 2016:
• Naloxone hydrochloride for injection is now Schedule II and no longer requires aprescription to be dispensed in pharmacies if indicated for emergency use for opioidoverdose outside hospital settings.
• All pharmacies will be reimbursed for providing naloxone emergency kits to eligible Ontarioresidents and in accordance with the Ontario Naloxone Program for Pharmacies (ONPP)through the Health Network System (HNS).
For further information on naloxone and the ONPP, please refer to the EO Notice and FAQs on naloxone posted on the ministry’s website:
If you have any questions or concerns, please call the ODB Help Desk at 1-800-668-6641.
Naloxone Nasal Spray
The nasal spray formulation of naloxone hydrochloride (NARCAN Nasal Spray, ADAPT Pharma) is now permitted for sale in Canada, without a prescription. For more information, please refer to Health Canada’s website:
Further updates on the availability and ONPP reimbursement of the nasal spray format of naloxone will follow shortly.
Pharmacist Training and Naloxone Guidance
As is required when delivering any service, it is the pharmacist’s professional responsibility to ensure that he or she has undergone the appropriate training and has the required skills and resources to ensure that the service is provided in a safe and effective manner. The Ontario Pharmacists Association (OPA) has been working very closely with the ministry on the ONPP
and has developed an online education program which can be accessed, free of charge, through the OPA website at www.opatoday.com/224122.
Pharmacies should continue to refer to the requirements outlined in the Ontario College of Pharmacists Guidance – Dispensing or Selling Naloxone with regards to providing naloxone.
Procurement of Naloxone kits
In advance of the June 2016 roll-out of the ONPP, the ministry arranged for a small, one-time-only auto-shipment of preassembled naloxone kits (i.e., “one-time bridge”) to be made to select methadone and/or Suboxone-dispensing pharmacies across the province. The ministry recognizes that access to pre-assembled kits and/or some of the individual components may be difficult at this time as they are not yet available to all pharmaceutical distributors. We have been working closely with OPA to identify the various suppliers of kits or their components. Please check the OPA website at www.opatoday.com/professional/naloxone_kit_tools for additional resources related to kit/component procurement.
Thank you for your support and contribution to the reduction of opioid overdose deaths in Ontario.
2
DISPENSING OR SELLING NALOXONE
Guidance for pharmacy professionals when dispensing or
selling naloxone as a Schedule II drug.
UPDATED ON: December 23, 2016
Dispensing or Selling Naloxone December 23, 2016 — Page 2
Purpose The intent of this document is to provide guidance for pharmacists and pharmacy technicians regarding their respective responsibilities when dispensing or selling naloxone as a Schedule II drug.
Introduction In response to the influx of opioid related overdoses across Canada, naloxone has been made available for emergency use for opioid overdose outside hospital settings. Accidental overdoses can occur in both individuals who use opioids as prescribed by their physician, and those using opioids for non-medical reasons. The goal of providing naloxone in community pharmacies is to increase public access to this life-saving medication. Naloxone is a non-addictive opioid antagonist that temporarily reverses the effects of opiates including, respiratory depression, sedation and hypotension. Naloxone is a safe and effective therapy: with proper administration naloxone is a drug that can save lives in opioid overdose situations when a person appropriately identifies the overdose and takes the required action. In the absence of an opioid, naloxone exhibits no
effects and the only contraindication to the use of naloxone is in patients known to be hypersensitive to it. Naloxone does not increase the likelihood of risk-taking behaviours, and cannot be abused.
Naloxone Availability in Community Pharmacies As of June 24, 2016 naloxone, when indicated for emergency use for opioid overdose outside hospital settings, is available as a Schedule II drug. Any patient or patient’s agent (agent) are now permitted to obtain Schedule II naloxone directly from any community pharmacist without a prescription. Pharmacists are authorized to dispense naloxone kits obtained through the Ministry of Health and Long-Term Care Ontario Naloxone Program for Pharmacies or privately procured naloxone and kit
Update as of December 23, 2016
As of December 22, 2016 naloxone hydrochloride nasal spray, when indicated for emergency use for opioid overdose outside hospital setting, is available as a Schedule II drug..
The College notes that pharmacists are authorized to dispense any formulation of naloxone available for sale and distribution in Canada.
When dispensing any formulation of naloxone, pharmacists are expected to practice in accordance with all of the requirements outlined in the College’s Guidance for pharmacy professionals when dispensing or selling naloxone.
Dispensing or Selling Naloxone December 23, 2016 — Page 3
supplies. The Ministry of Health and Long-Term Care will provide funding for naloxone for patients according to criteria defined by the Ministry. Pharmacists should always dispense two ampoules or vials (or units of any formulation) of naloxone to the patient or agent to ensure that a second dose of naloxone is available for administration if needed. When dispensing naloxone the pharmacist is strongly encouraged to also ensure that the patient or agent receives the following supplies to aid in the administration of naloxone, including:
• Two Safety syringes with 25G one inch needles attached if dispensing injectable formulation – they reduce the risk of needle stick injury, can be disposed of in the trash, prevent re-use as there is no way to push the needle back out, and are unlikely to be used for any other purpose (unlike insulin syringes);
• One rescue breathing barrier – a plastic barrier that is used when administering cardiopulmonary resuscitation (CPR);
• Two safe ampoule opening devices – small plastic snappers which prevent people from cutting their hands on broken glass when snapping an ampoule; these are not needed if vials or any other formulation are being provided; and
• One pair of non-latex gloves and alcohol swabs — optional supplies to reduce the risk of infection given that an injection can be provided through clothing.
• One naloxone identifier card – a card that can be filled out with the name of the person who has been trained in responding to opioid overdoses, the date the naloxone supplies were issued, and the expiry date of the naloxone.
Responsibilities of the Pharmacist when Dispensing Naloxone The pharmacists’ responsibilities include ensuring the following requirements are met when dispensing naloxone: Standards of Practice Schedule II drugs, when dispensed or sold in a pharmacy, must be stored and provided to patients from the dispensary where patient self-selection is restricted. Each transaction must occur under the direct supervision of a pharmacist and pharmacists are expected to counsel each patient or agent
Dispensing or Selling Naloxone December 23, 2016 — Page 4
when dispensing naloxone in order to enable the patient to receive the intended benefit of the drug therapy. Pharmacists and pharmacy technicians are expected to practice in accordance with the NAPRA Supplemental Standards of Practice for Schedule II and III Drugs, which set out the minimum acceptable standards of practice, including standards regarding the distribution or sale of Schedule II drugs. Patient Assessment When dispensing naloxone the pharmacist must determine the following:
• If the person who naloxone is intended for has any known allergies to naloxone, or concomitant ingredients in specific formulations of naloxone (methylparaben or propylparaben). Allergies are very rare and the benefits of naloxone are likely to outweigh the risks of an allergic reaction.
• Where the intended person has a known allergy to naloxone or concomitant ingredients the pharmacist should encourage the person to seek medical attention from a physician.
• Naloxone should not be dispensed where the intended person has a known allergy to naloxone unless the pharmacist confirms with a physician that the emergency kit should be dispensed.
Pharmacist Training It is the professional responsibility of a pharmacist to ensure that he or she has sufficient knowledge, skills and abilities to competently deliver any pharmacy service. As is required when delivering any new service, a pharmacist must ensure he or she has undergone the appropriate training and has the required resources to ensure that the service is provided in a safe and effective manner. There are a number of training programs and resources available to pharmacists (see links on College website). Providing Patient and/or Agent Education It is critical that the pharmacist is properly trained on the essential information required to effectively educate the patient or agent and prepare him or her for dealing with an opioid overdose, prior to providing naloxone. Patients and/or agents must be educated on more than just naloxone
Dispensing or Selling Naloxone December 23, 2016 — Page 5
therapy and how to administer it. Pharmacists should ensure patients and/or agents purchasing naloxone are also educated on such topics as:
• Harm reduction strategies when using opioids; • How to identify an opioid overdose; • Importance of immediately calling 9-1-1; • Importance of cardiopulmonary resuscitation (CPR) and how and when to give breaths; • When and how to administer naloxone; • Aftercare and the importance of staying with the person until emergency first responders
arrive; • Withdrawal symptoms occur following naloxone administration and reversal of the effects of
the opioid overdose. Doses of naloxone administered via one or two vials or ampoules will, in most cases, only produce mild withdrawal symptoms and the benefits outweigh the risks associated with withdrawal;
• Naloxone may have variable efficacy in reversing the clinical effects of an overdose due to preparations containing buprenorphine;
• Naloxone is not effective against respiratory depression due to non-opioid drugs; • Risk of secondary overdose if opioids used when patient regains consciousness; and • Any other information the pharmacist deems relevant.
Pharmacists must also provide educational information and the steps for dealing with an opioid overdose in writing to the patient and/or agent. Written resources are not a replacement for pharmacist interaction with the patient or agent, and are to be used as a supplemental resource only. Documentation Requirements The record keeping requirements for naloxone are the same as for any other Schedule II product as outlined in the College’s Documentation Guidelines and the NAPRA Supplemental Standards of Practice for Schedule II and III Drugs. There are no additional documentation requirements. Pharmacists may be required to report additional information in accordance with requirements set out by the Ontario Naloxone Program for Pharmacies.
Naloxone Hydrochloride Injection SDZ Preservative Free 0.4 mg/mL THERAPEUTIC CLASSIFICATION Opioid Antagonist CLINICAL PHARMACOLOGY Naloxone hydrochloride prevents or reverses the effects of opioids, including respiratory depression, sedation, and hypotension. Also, it can reverse the psychosomimetic and dysphoric effects of agonist-antagonists such as pentazocine. Naloxone hydrochloride is an essentially pure opioid antagonist, i.e. it does not possess the agonistic or morphine-like properties characteristic of other opioid antagonists; naloxone does not produce respiratory depression, psychosomimetic effects or pupillary constriction. In the absence of opioids or agonistic effects of other opioid antagonists it exhibits essentially no pharmacologic activity. Naloxone has not been shown to produce tolerance or to cause physical or psychological dependence. In the presence of physical dependence on opioids naloxone will produce withdrawal symptoms. While the mechanism of action of naloxone is not fully understood, the preponderance of evidence suggests that naloxone antagonizes the opioid effects by competing for the same receptor sites. Following parenteral administration naloxone is rapidly distributed in the body. It is metabolized in the liver, primarily by glucuronide conjugation, and excreted in urine. INDICATIONS AND CLINICAL USE Naloxone is indicated for the complete or partial reversal of opioid depression, including respiratory depression induced by opioids, including natural and synthetic opioids, propoxyphene, methadone and the agonist-antagonist analgesics nalbuphine, pentazocine and butorphanol. Naloxone is also indicated for the diagnosis of suspected acute opioid overdosage. Naloxone is not effective in counteracting depression due to barbiturates, tranquilizers or other non-opioid anesthetics or sedatives. It has been safely administered to patients who received both opioid and non-opioid drugs.
CONTRAINDICATION Naloxone is contraindicated in patients known to be hypersensitive to it. WARNINGS Naloxone should be administered cautiously to persons, including newborns of dependent mothers, who are known or suspected to be physically dependent on opioids. In such cases an abrupt and complete reversal of opioid effects may precipitate an acute abstinence syndrome. The severity of such a syndrome will depend on the degree of physical dependence and the dose of antagonist administered. In the presence of serious respiratory depression in a physically dependent individual, the antagonist, when indicated, should be administered with extreme care, under close monitoring, by using appropriate titration with smaller doses than usual. The patient who has satisfactorily responded to naloxone should be kept under continued surveillance and repeated doses of naloxone should be administered as necessary since the duration of action of some opioids may exceed that of naloxone. Naloxone is not effective against respiratory depression due to non-opioid drugs (see INDICATIONS AND CLINICAL USE). It has been safely administered to patients who received both opioid and non-opioid drugs. Reversal of buprenorphine-induced respiratory depression may be incomplete. If an incomplete response occurs, respiration should be mechanically assisted. Use in Pregnancy Reproduction studies performed in mice and rats at doses up to 1,000 times the human dose revealed no evidence of impaired fertility or harm to the fetus due to naloxone. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, naloxone should be used during pregnancy only if clearly needed. Nursing Mothers It is not known whether naloxone is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when naloxone is administered to a nursing woman. PRECAUTIONS In addition to naloxone other resuscitative measures such as maintenance of a free airway, artificial ventilation, cardiac massage, and vasopressor agents should be available and employed when necessary to counteract acute opioid poisoning.
Several instances of hypotension, hypertension, ventricular tachycardia and fibrillation, and pulmonary edema have been reported. These have occurred in postoperative patients in whom pre-existing cardiovascular disorders or other drugs may have contributed to the adverse cardiovascular effects. Although a direct cause-and-effect relationship has not been established, naloxone should be used with caution in patients with preexisting cardiac disease or patients who have received potentially cardiotoxic drugs. The clinical course should be monitored by ECG. ADVERSE REACTIONS Abrupt reversal of opioid depression may result in nausea, vomiting, sweating, tachycardia, increased blood pressure, and tremulousness. In postoperative patients, larger than necessary dosages of naloxone may result in significant reversal of analgesia and in excitement. Hypotension, hypertension, ventricular tachycardia and fibrillation, and pulmonary edema have been associated with the use of naloxone postoperatively (see PRECAUTIONS and USAGE IN ADULTS, Postoperative Opioid Depression). Seizures have been reported to occur infrequently after the administration of naloxone; however, a causal relationship has not been established. SYMPTOMS AND TREATMENT OF OVERDOSAGE There is no clinical experience with naloxone overdosage in humans. For management of a suspected drug overdose, contact your regional Poison Control Centre.
DOSAGE AND ADMINISTRATION Naloxone hydrochloride may be administered intravenously (IV), intramuscularly (IM), or subcutaneously (SC). The most rapid onset of action is achieved by intravenous administration, and it is recommended in emergency situations. Since the duration of action of some opioids may exceed that of naloxone, the patient should be kept under continued surveillance and repeated doses of naloxone should be administered, as necessary. Intravenous Infusion Infusion may be useful in cases of overdose with long-acting drugs such as methadone and propoxyphene. The infusion rate for adults is approximately 100 mL/hour
(0.4 mg/hour). Infusion rate and concentration should be individually adjusted to obtain the desired antagonist effect without fluid overload or production of withdrawal. Dilution for Intravenous Use Naloxone may be diluted for intravenous infusion in Sodium Chloride Injection 0.9% or Dextrose Injection 5%. The addition of 2 mg of Naloxone Hydrochloride Injection in 500 mL of diluent provides a concentration of 4 mcg (0.004 mg)/mL. Mixtures should be used within 24 hours. After 24 hours, the remaining unused solution must be discarded. The rate of administration should be titrated in accordance with the patient’s response. Parenteral drug products should be inspected visually for particulate matter and discolouration prior to administration whenever solution and container permit. Naloxone should not be mixed with preparations containing bisulphite, metabisulphite, long-chain or high-molecular-weight anions, or any solution having an alkaline pH. No drug or chemical agent should be added to naloxone unless its effect on the chemical and physical stability of the solution has first been established. USAGE IN ADULTS Opioid Overdosage – Known or Suspected An initial dose of 0.4 mg to 2 mg of naloxone may be administered intravenously. If the desired degree of counteraction and improvement in respiratory functions is not obtained, it may be repeated at two- to three-minute intervals. If no response is observed after 10 mg of naloxone has been administered, the diagnosis of opioid-induced or partial opioid-induced toxicity should be questioned. Intramuscular or subcutaneous administration may be necessary if the intravenous route is not available. Postoperative Opioid Depression For the partial reversal of opioid depression following the use of opioids during surgery, smaller doses of naloxone are usually sufficient. The dose of naloxone should be titrated according to the patient’s response. Naloxone should be injected in increments of 0.1 to 0.2 mg intravenously at two- to three-minute intervals to the desired degree of reversal – i.e. adequate ventilation and alertness without significant pain or discomfort. Larger than necessary dosage of naloxone may result in significant reversal of analgesia and increase in blood pressure. Similarly, too rapid reversal may induce nausea, vomiting, sweating, or circulatory stress. Repeat doses of naloxone may be required within one- to two-hour intervals depending upon the amount, type (i.e. short- or long-acting) and time interval since last administration of opioid. Supplemental intramuscular doses have been shown to produce a longer-lasting effect. USAGE IN CHILDREN Opioid Overdosage – Known or Suspected The usual initial dose in children is 0.01 mg/kg body weight given IV. If this dose does
not result in the desired degree of clinical improvement, a subsequent dose of 0.1 mg/kg body weight may be administered. If an IV route of administration is not available, naloxone may be administered IM or SC in divided doses. If necessary, naloxone can be diluted with sterile water for injection. Postoperative Opioid Depression Follow the recommendations and cautions under Adult Postoperative Opioid Depression. For the initial reversal of respiratory depression naloxone should be injected in increments of 0.005 mg to 0.01 mg intravenously at two- to three-minute intervals to the desired degree of reversal. USAGE IN NEONATES Opioid-Induced Depression The usual dose is 10 mcg (0.01 mg)/kg body weight administered IV, IM or SC routes. This dose may be repeated in accordance with adult administration guidelines.
Summary of Dosages Adults Opioid Overdose
0.4 to 2 mg IV repeated if necessary at 2- to 3-minute intervals. Postoperative Opioid Depression 0.1 to 0.2 mg IV repeated if necessary at 2- to 3-minute intervals. IV, IM or SC.
Children Opioid Overdose 0.01 mg/kg IV. If desired degree of improvement is not obtained, 0.1 mg/kg IV may be administered. Naloxone may be diluted with sterile water for injection. Postoperative Opioid Depression 0.005 to 0.01 mg IV repeated if necessary at 2- to 3-minute intervals.
Neonates Opioid-Induced Depression 0.01 mg/kg IV, IM or SC repeated if necessary at 2- to 3-minute intervals. Naloxone may be diluted with sterile water for injection.
PHARMACEUTICAL INFORMATION DRUG SUBSTANCE Common Name: Naloxone hydrochloride dihydrate Chemical Name: 17-Allyl-6-deoxy-7,8-dihydro-14-hydroxy-6-oxo-17-normorphine
hydrochloride dihydrate Structural Formula:
OHO O H
HO
NHCH2
, HCl , 2 H2O
Molecular Formula: C19H21NO4, HCl, 2H2O Molecular Weight: 399.9g/mol Description: Naloxone hydrochloride, an opioid antagonist, is a synthetic
congener of oxymorphone. In structure it differs from oxymorphone in that the methyl group on the nitrogen atom is replaced by an allyl group.
Naloxone hydrochloride occurs as a white to slightly off-white
powder, and is soluble in water, in dilute acids, and in strong alkali; slightly soluble in alcohol; practically insoluble in ether and in chloroform. It melts at about 200-205°C. The pH of aqueous solutions is acidic.
COMPOSITION Naloxone Hydrochloride Injection SDZ Preservative Free (0.4 mg/mL): Each mL of aqueous injectable solution contains: naloxone hydrochloride 400 mcg, sodium chloride 9.0 mg, hydrochloric acid to adjust pH and water for injection. STABILITY AND STORAGE RECOMMENDATIONS Naloxone Hydrochloride Injection SDZ Preservative Free should be stored between 15 and 25°C. Protect from light. AVAILABILITY OF DOSAGE FORMS Naloxone Hydrochloride Injection SDZ Preservative Free is available in 0.4 mg/mL, 1 mL ampoules, boxes of 10. Single use. Discard unused portion. PHARMACOLOGY Single subcutaneous doses of naloxone as high as 24 mg/70 kg (0.343 mg/kg) and multiple doses of 90 mg daily, for two weeks, administered to normal volunteers produced no behavioural or physiological changes, yet its antagonistic activity to subsequent morphine challenge persisted. Naloxone hydrochloride at doses of 0.7 to 10 mg administered intravenously to heroin addicts abolished the effects of 10 to 20 mg of heroin whether administered before or after the heroin. The effects of the heroin began to recur three hours after naloxone administration, indicating naloxone has a shorter duration of action than heroin. Naloxone was able to reverse the respiratory depression induced by various anesthetics: morphine, fentanyl, cyclazocine, pentazocine, meperidine, alphaprodine, oxymorphone, nalorphine and levallorphan in patients, whether administered IV, IM or SC at 0.4 to 2 mg/mL. Naloxone caused no respiratory depression, psychotomimetic effects, clinically significant circulatory effects, nor analgesia when administered alone. Subjects did not develop tolerance to naloxone. Temporary nausea and vomiting were reported in two studies, but as other anesthetics/analgesics were being administered concurrently, these effects could not be causally related to naloxone. When naloxone is administered intravenously the onset of action is generally apparent within two minutes; the onset of action is only slightly less rapid when it is administered subcutaneously or intramuscularly. The duration of action is dependent upon the dose and route of administration. Intramuscular administration produces a more prolonged effect than
intravenous administration. The requirement for repeat doses will also be dependent upon the amount, type, and route of administration of the opioid being antagonized. Following parenteral administration naloxone is rapidly distributed in the body. It is metabolized in the liver, primarily by glucuronide conjugation, and excreted in urine. In one study the mean serum half-life in adults was 4.7 minutes for the distribution phase and 64 minutes for the elimination phase. In a neonatal study the mean plasma half-life was observed to be 3.1 ± 0.5 hours. In a nine-week study of nine males (22 to 47 years of age) who were addicted to opioids, naloxone was administered in single daily oral doses in increments of 50 mg (3 subjects), 100 mg (4 subjects) and 300 mg (2 subjects). Up to 3,000 mg of naloxone hydrochloride daily was administered (1 subject). No significant toxic symptoms occurred over nine weeks of naloxone administration. Sporadic abnormal laboratory findings including elevated white blood cell counts occurred, but are common in cases of opioid addiction. One patient receiving 1,500 mg of naloxone daily reported psychic depression, apathy and decreased appetite, which were relieved when the dosage was decreased. TOXICOLOGY Acute Toxicity The maximum nontoxic subcutaneous dose in rats was 50 mg/kg. In acute SC toxicity studies in newborn rats, the LD50 is 260 mg/kg. Naloxone was only twice as toxic in newborn as in six week old rats. At toxic doses naloxone produced excitation, hyperactivity, salivation, tremors, and tonic-clonic convulsions. Respiration was slightly stimulated in rabbits as shown by the minute-volume measurements. Subacute Toxicity Subacute SC toxicity experiments in rats and monkeys and a subacute IV toxicity experiment in dogs demonstrated very little cumulative toxicity and no organic pathological changes. Reproduction and Teratology Reproduction studies in mice and rats using naloxone hydrochloride dosages up to 1,000 times the usual human dosage have not revealed evidence of impaired fertility or harm to the fetus. Mutagenicity and Carcinogenicity Mutagenicity and carcinogenicity studies have not been conducted using naloxone.
REFERENCES 1. Jasinski DR, Martin WR, Haertzes CA. The human pharmacology and abuse
potential of N-allynoroxymorphone (Naloxone). J Pharm. Exp Ther 1967;157(2):420.
2. Smits SE, Takemori AE. Quantitative studies on the antagonism by naloxone of
some narcotic and narcotic antagonist analgesics. Br J Pharm 1970;39:627. 3. Longnecker DE, Grazis PA, Eggers GWN. Naloxone for antagonism of
morphine-induced respiratory depression. Anesth Analg 1973;52:447. 4. Foldes FF, Davidson GM, Duncalf D, Kuwabara S, Siker ES. The respiratory,
circulatory and analgesic effects of naloxone-narcotic mixtures in anæsthetized subjects. Can Anæsth Soc J 1965;12(6):608.
5. Anderson R, Dobloug I, Refstad S. Postanæsthetic use of naloxone hydrochloride
after moderate doses of fentanyl. Acta Anæsthesiol Scand 1976;20:255. 6. Tigerstedt I. Naloxone as narcotic antagonist after balanced anaesthesia. Acta
Anæsthesiol Scand 1977;21:481. 7. Jasinski DR, Martin WR, Sapira JD. Antagonism of the subjective behavioural
pupillary and respiratory depressant effects of cyclazocine by naloxone. Clin Pharm Ther 1967;9(2):215.
8. Kallos T, Smith TC. Naloxone reversal of pentazocine-induced respiratory
depression. JAMA 1968;204:932. 9. Foldes FF, Duncalf D, Kuwabara S. The respiratory, circulatory, and narcotic
antagonistic effects of nalorphine, levallorphan and naloxone in anaesthetized subjects. Can Anæsth Soc J 1969;16(2):151.
10. Fink M, Zaks A, Sharoff R, Mora A, Bruner A, Levit S, Freedman AM. Naloxone in
heroin dependence. Clin Pharm Ther 1968;9(5):568. 11. Fujimoto JM. Isolation of naloxone-3-glucuronide from human urine. Proc Soc Exp
Biol Med 1970;133:317. 12. Ngai SH, Berkowitz BA, Yang JC, Hempstead J, Spector S. Pharmacokinetics of
naloxone in rats and in man–basis for its potency and short duration of action. Anesthesiology 1976;44:398.
13. Moreland TA, Brice JEH, Walker CHM. Naloxone pharmacokinetics in the
newborn. Br J Clin Pharmac 1980;9:609. 14. Zaks A, Jones T, Fink M, Freedman AM. Naloxone treatment of opiate dependence.
JAMA 1971;215(13):2108. 15. AHFS Drug Information 90. American Pharmacist Society 1990;1111. 16. Blumberg H, Wernick T, Dayton HB, Hansen RE, Rapaport DN. Toxicologic studies
on the narcotic antagonist naloxone. Tox Appl Pharm 1966;8:335.
Naloxone Hydrochloride Nasal Spray Page 1 of 28
PRODUCT MONOGRAPH
INCLUDING PATIENT MEDICATION INFORMATION
NALOXONE HYDROCHLORIDE NASAL SPRAY
2 mg/0.1 mL and 4 mg/0.1 mL
Opioid Antagonist
Adapt Pharma Operations Limited
45 Fitzwilliam Square
Dublin 2
Ireland
Date of Preparation:
October 3, 2016
Submission Control No: 193199
Naloxone Hydrochloride Nasal Spray Page 2 of 28
Table of Contents
PART I: HEALTH PROFESSIONAL INFORMATION ..........................................................3 SUMMARY PRODUCT INFORMATION ........................................................................3 INDICATIONS AND CLINICAL USE ..............................................................................3
CONTRAINDICATIONS ...................................................................................................3 WARNINGS AND PRECAUTIONS ..................................................................................4
ADVERSE REACTIONS ....................................................................................................7 DRUG INTERACTIONS ....................................................................................................8 DOSAGE AND ADMINISTRATION ................................................................................8 ACTION AND CLINICAL PHARMACOLOGY ............................................................11 STORAGE AND STABILITY ..........................................................................................15 DOSAGE FORMS, COMPOSITION, AND PACKAGING ............................................16
PART II: SCIENTIFIC INFORMATION ................................................................................17 PHARMACEUTICAL INFORMATION ..........................................................................17 CLINICAL TRIALS ..........................................................................................................18 DETAILED PHARMACOLOGY .....................................................................................18 TOXICOLOGY .................................................................................................................18
