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Important Changes to the Dose Conversion Guidelines for Fentanyl Transdermal Systems - Notice to Hospitals

Starting date:
January 2, 2009
Posting date:
January 7, 2009
Type of communication:
Notice to Hospitals
Subcategory:
Drugs
Source of recall:
Health Canada
Audience:
Healthcare Professionals
Identification number:
RA-170002023

This is duplicated text of a letter from Janssen-Ortho Inc., Cobalt Pharmaceuticals Inc., Novopharm Limited, Ranbaxy Pharmaceuticals Canada Inc. and ratiopharm inc.
Contact the company for a copy of any references, attachments or enclosures.

Notice about Health Canada advisories

Notice to Hospitals - Health Canada Endorsed Important Safety Information on Fentanyl Transdermal Systems

January 2, 2009

To: Hospital Chief of Medical Staff

Please distribute to relevant Departments of Surgery, Emergency Medicine, Pharmacy, Paediatrics, Anaesthesia, Geriatrics, Internal Medicine, Family Medicine, Nursing, Intensive Care and/or other Departments as required, and other involved professional staff and post this Notice in your institution.

Subject: Important Changes to the Dose Conversion Guidelines for Fentanyl Transdermal Systems

The manufacturers of Fentanyl Transdermal Systems (FTS), in collaboration with Health Canada wish to provide you with important information regarding changes to the Dose Conversion Guidelines (Table 1.1) and to the analgesic equivalency table: Opioid Analgesics: Parenteral/Oral/Rectal Equianalgesic Potency Conversion (Table 1.2) in the Dosage and Administration section of the Canadian Product Monographs for FTS. The Dose Conversion Guidelines are to be used to convert adult patients from their current oral or parenteral opioid therapy to the fentanyl transdermal patch. The analgesic equivalency table Opioid Analgesics: Parenteral/Oral/Rectal Equianalgesic Potency Conversion, may be used for adult patients taking opioids or doses not listed in Table 1.1, using the conversion methodology outlined for Table 1.1 with Table 1.2.

The revised Dose Conversion Guidelines and Opioid Analgesics: Parenteral/Oral/Rectal Equianalgesic Potency Conversion Table are attached for your reference and should be retained for future consultation. Changes have been highlighted for ease of reference.

Serious or life-threatening hypoventilation can result if appropriate conversions are not used.

Based on clinical experience in patients with chronic pain:

  • The conversion from IM/IV morphine to the fentanyl transdermal patch has been revised to reflect a conversion ratio of 1:2 and 1:3 of parenteral morphine to oral morphine.
  • The conversion from IV hydromorphone to the fentanyl transdermal patch has been revised to reflect a conversion ratio of 1:2 of parenteral hydromorphone to oral hydromorphone.

The use of fentanyl transdermal systems in opioid-naïve patients and in patients with acute or postoperative pain is contraindicated.

In addition, the analgesic equivalency table 1.2 has been revised to remove the data equating 10 mg parenteral morphine to 60 mg oral morphine derived from single or intermittent dosing studies. Data referring to IM//IV oxycodone and to IM meperidine have been removed from both Tables 1.1 and 1.2 as the former drug is not marketed in Canada as an Injectable, and the latter drug causes CNS toxicity if used by the parenteral route chronically.

Manufacturers of all fentanyl transdermal patches are working with Health Canada to include this safety information in the Dosage and Administration section in all Canadian Product Monographs for Fentanyl Transdermal Systems:
Duragesic® (fentanyl transdermal system)
CO Fentanyl
Novo-fentanyl
RAN-fentanyl transdermal system
ratio-FENTANYL Transdermal System

Managing marketed health product-related adverse reactions depends on health care professionals and consumers reporting them. Reporting rates determined on the basis of spontaneously reported post-marketing adverse reactions are generally presumed to underestimate the risks associated with health product treatments. Any serious or unexpected adverse reactions in patients receiving fentanyl transdermal systems should be reported to the manufacturers or Health Canada at the following addresses:

Janssen-Ortho Inc.
Drug Safety Department
19 Green Belt Drive
Toronto, Ontario M3C 1L9
Telephone: 1-800-567-3331 or Fax: 1-866-767-5865
E-mail: dsscan@joica.jnj.com

Cobalt Pharmaceuticals Inc.
6500 Kitimat Road
Mississauga, Ontario L5N 2B8
Telephone: 1-866-254-6111
Fax: 905-542-0478

Novopharm Limited
Pharmacovigilance and Drug Safety
30 Novopharm Court
Toronto, Ontario M1B 2K9
Telephone: 416-291-8888 ext. 5005
Fax: 416-335-4472
E-mail: PhV@Novopharm.com

Ranbaxy Pharmaceuticals Canada Inc.
2680 Matheson Blvd. East, Suite 200
Mississauga, Ontario L4W 0A5
Telephone: 1-866-840-1340
Fax: 905-602-4216

ratiopharm inc.
17800 Lapointe
Mirabel, Quebec J7J 1P3
Telephone: 1-800-337-2584
Fax: 1-800-313-7673
E-mail: drugsafety@ratiopharm.ca

Any suspected adverse reaction can also be reported to:
Canada Vigilance Program
Marketed Health Products Directorate
HEALTH CANADA
Address Locator: 0701C
Ottawa, Ontario, K1A 0K9
Tel: 613-957-0337 or Fax: 613-957-0335
To report an Adverse Reaction, consumers and health professionals may call toll free:
Tel: 1-866-234-2345
Fax: 1-866-678-6789
CanadaVigilance@hc-sc.gc.ca

The Adverse Reaction Reporting Form and the Adverse Reaction Guidelines can be found on the Health Canada web site or in The Canadian Compendium of Pharmaceuticals and Specialties.

For other inquiries related to this communication, please contact Health Canada at:
Marketed Health Products Directorate (MHPD)
E-mail: mhpd_dpsc@hc-sc.gc.ca
Tel: 613-954-6522
Fax: 613-952-7738

Please contact the appropriate manufacturer with any questions or concerns.

Authorized by:
Janssen-Ortho Inc.
Cobalt Pharmaceuticals Inc.
Novopharm Limited
Ranbaxy Pharmaceuticals Canada Inc.
ratiopharm inc.

References:
Johnson BL, Gross J. Chapter 8, Pharmacological Treatment of Cancer Pain in Handbook of Oncology Nursing, Jones & Bartlett Publishers, 1998. p.313-327

Ripamont, C, Pharmacology of Opioid Analgesia: Clinical Principles in Cancer Pain: Assessment and Management, edited by Bruera E and Portenoy RK. Cambridge University Press, 2003. p.124

[Text of letter ends]

Attachment

Dosage conversion guidelines for fentanyl transdermal systems

Table 1.1 Table 1.1 footnote # Table 1.1 footnote 1
From Current Opioid to DURAGESIC or other Fentanyl Transdermal Systems (FTS):
Dose Conversion Guidelines
Current Analgesic Daily Dosage (mg/d)
Oral morphine 60-134 135-179 180-224 225-269 270-314 315-359 360-404
IM/IV morphineTable 1.1 footnote 2 30-66 67-90 91-111 112-134 135-157 158-179 180-202
Oral oxycodone 30-66 67-90 91-112 113-134 135-157 158-179 180-202
Oral codeine 150-447 448-597 598-747 748-897 898-1047 1048-1197 1198-1347
Oral hydromorphone 8-16 17-22 23-28 29-33 34-39 40-45 46-51
IV hydromorphoneTable 1.1 footnote 3 4.0-8.4 8.5-11.4 11.5-14.4 14.5-16.5 16.6- 19.5 19.6-22.5 22.6-25.5
 
Recommended Fentanyl Transdermal System (FTS) Dose 25 
mcg/h
37 
mcg/h
50 
mcg/h
62 
mcg/h
75 
mcg/h
87 
mcg/h
100 
mcg/h

Alternatively, for adult patients taking opioids or doses not listed in Table 1.1, use the conversion methodology outlined above with Table 1.2.

Table 1.1 footnotes

Table 1.1 footnote #

12 mcg/h dose is not included in this table because it generally should not be used as the initiating dose, except in the case of patients for whom clinical judgment deems it appropriate to start DURAGESIC and other FTS at less than 25 mcg/h; DURAGESIC and other FTS at any dose is contraindicated in opioid-naive patients (see CONTRAINDICATIONS).

Return to table 1.1 footnote # referrer

Table 1.1 footnote 1

Table 1.1 should not be used to convert from DURAGESIC and other FTS to other therapies because this conversion to DURAGESIC and other FTS is conservative. Use of Table 1.1 for conversion to other analgesic therapies can overestimate the dose of the new agent. Overdosage of the new analgesic agent is possible (see DOSAGE AND ADMINISTRATION, Safe Use of Tables 1.1, 1.2, and 1.3).

Return to table 1.1 footnote 1 referrer

Table 1.1 footnote 2

Based on clinical experience in patients with chronic pain, the conversion ratio of 10 mg parenteral morphine is equal to approximately 20 – 30 mg oral morphine. In the table above, calculation is based on a 1:2 parenteral to oral dose ratio.  For some patients, a 1:3 parenteral to oral dose ratio (10 mg parenteral morphine = 30 mg oral morphine) may be more appropriate.

The respective IM/IV morphine equivalents for the various fentanyl transdermal doses with a 1:3 ratio are:

 
IM/IV morphine (mg/d) at 
1:3 parenteral to oral dose ratio
20-44 45-60 61-75 76-90 91-104 105 -119 120-134
Recommended FTS Dose 25
mcg/h
37
mcg/h
50
mcg/h
62
mcg/h
75
mcg/h
87
mcg/h
100
mcg/h

Return to table 1.1 footnote 2 referrer

Table 1.1 footnote 3

The conversion ratio of parenteral hydromorphone to oral hydromorphone of 1:2 is based on clinical experience in patients with chronic pain. Reference: Parenteral Drug Therapy Manual, Vancouver General Hospital, Pharmaceutical Sciences Clinical Services.

Return to table 1 footnote 3 referrer

Opioid analgesics: parenteral/oral/rectal equianalgesic potency conversion

Table 1.2 Opioid Analgesics: Parenteral/Oral/Rectal Equianalgesic Potency Conversion Table 1.2 footnote 1
Drug Equivalent Dose (mg)Table 1.2 footnote 2
(compared to morphine 10 mg IM)
Duration of Action
(hours)
Parenteral Oral
Strong Opioid Agonists:
Morphine (repeated dosing) 10 20-30 Table 1.2 footnote 3

 

3-4
Hydromorphone 1.5 7.5 2-4
Anileridine 25 75 2-3
Levorphanol 2 4 4-8
Oxymorphone 1 10 (rectal) 3-4
MethadoneTable 1.2 footnote 4 --- --- ---
Weak Opioid Agonists:
Codeine 130 200 3-4
Oxycodone --- 30 2-4
Propoxyphene 50 100 2-4

References:

Tableau 1.2 Footnotes

Tableau 1.2 footnote 1

Foley K.M. Cancer, Principles and Practice of Oncology, 4th Ed., V.T. Devita, Jr., S. Hellman, S.A. Rosenberg (Ed.), J.B. Lippincott Co., Philadelphia: 1993. p. 2417-2448.

Foley K. M. The Treatment of Cancer Pain, New Engl. J. Med. 313(2): 84-95, 1985.

Aronoff G.M Evans, W.O., Evaluation and Treatment of Chronic Pain, 2nd Ed., G.M. Aronoff (Ed.), Williams and Wilkins, Baltimore, p. 359-368, 1992.

Cherny N.I,Portenoy, R.K., Textbook of Pain, 3rd Ed., P.D. Wall and R. Melzack (Eds.), Churchill Livingstone, London, p. 1437-1467, 1994.

Return to table 1.2 footnote 1

Table 1.2 footnote 2

Most of these data were derived from single-dose, acute pain studies and should be considered an approximation for selection of doses when treating chronic pain.

Return to table 1.2 footnote 2

Table 1.2 footnote 3

The conversion ratio of 10 mg parenteral morphine = 20 – 30 mg oral morphine is based on clinical experience in patients with chronic pain.

References:

Skaer TL. Practice Guidelines for Transdermal Opioids in Malignant Pain. Drugs: 64 (23) 2629 – 2638, 2004.

Berdine HJ, Nesbit SA.  Equianalgesic Dosing of Opioids. Journal of Pain & Palliative Care Pharmacotherapy: 20 (4) 79 – 84, 2006.

Return to table 1.2 footnote 3

Table 1.2 footnote 4

Extremely variable equianalgesic dose.  Patients should undergo personalized titration starting at an equivalent to 1/10 of the morphine dose.

Return to table 1.2 footnote 4