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This is duplicated text of a letter from Novo Nordisk Canada Inc.
Contact the company for a copy of any references, attachments or enclosures. |
| IMPORTANT SAFETY INFORMATION ON THE
CONCOMITANT USE OF GLUCONORM® (REPAGLINIDE) AND GEMFIBROZIL |
July 17, 2003
Dear Health Care Professional:
Re: Important Safety Information on the concomitant use of GlucoNorm®
(repaglinide) and gemfibrozil.
The purpose of this letter is to provide important information regarding
a contraindication for the concomitant use of GlucoNorm®
(repaglinide) and gemfibrozil.
- The concomitant use of GlucoNorm®
(repaglinide) and gemfibrozil is contraindicated.
- The blood glucose-lowering effects of GlucoNorm®
(repaglinide) may be markedly enhanced and prolonged when administered
together with gemfibrozil.
- Patients using GlucoNorm® (repaglinide) and
gemfibrozil at the same time may be at risk of severe and prolonged
hypoglycemia
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A study was recently published in Diabetologia [2003;46(3)347-351] by
Niemi et al. The study, that was designed to address the pharmacokinetic
interaction between GlucoNorm®(repaglinide) , a short-acting
insulin secretagogue marketed by Novo Nordisk and gemfibrozil, a lipid-lowering
agent for treatment of dyslipidaemia, was sponsored independently from
the manufacturers involved. When administered concomitantly with gemfibrozil,
GlucoNorm® (repaglinide) was found to have a markedly enhanced
and prolonged glucose-lowering effect in healthy volunteers. By extrapolation,
patients using GlucoNorm® (repaglinide) and gemfibrozil
at the same time may be at risk of severe and prolonged hypoglycemia,
therefore the concomitant use of Gluconorm® (repaglinide)
and gemfibrozil is now contraindicated.
Niemi et al. reported significantly altered pharmacokinetic properties
of repaglinide following co-administration with gemfibrozil in healthy
volunteers. The area under the curve (AUC) was increased 8.1-fold (range
5.5- to 15-fold; p < 0.001) and the elimination half life (t½)
was prolonged from 1.3 hours to 3.7 hours (p < 0.001). These changes
are thought to be due to the inhibition of CYP2C8 by gemfibrozil as evidenced
by decreases in blood glucose levels that were proportional to the dose
of gemfibrozil.
In the Novo Nordisk international safety database we have identified
five serious reports of hypoglycemia during treatment with repaglinide
where the patient concomitantly received gemfibrozil. All five reports
were spontaneous (3 reports from the United States and 2 from France),
and were received between April 1999 and February 2003. No spontaneous
reports were received from Canadian sources regarding combined use of
GlucoNorm® (repaglinide) and gemfibrozil.
In light of this information, patients receiving GlucoNorm®
(repaglinide) and gemfibrozil may be at risk of severe or prolonged
hypoglycemia (low blood sugar). Therefore, patients currently receiving
GlucoNorm® (repaglinide) with gemfibrozil should be reassessed
by their physician and alternative combination treatment considered under
close monitoring of diabetic status.
Patients being treated with GlucoNorm® (repaglinide) should
note receive gemfibrozil and patients already taking gemfibrozil should
discontinue this drug before being prescribed repaglinide.
Due to the significance of these results from the referenced article,
Novo Nordisk will add this new safety information to the Canadian Product
Monograph. Health care professionals are advised to review the Product
Monograph when prescribing GlucoNorm® (repaglinide) in
the future.
It should be noted that reporting rates determined on the basis of spontaneously
reported post-marketing adverse events are generally presumed to underestimate
the risk associated with a drug treatment.
The identification, characterization, and management of drug-related
adverse events are dependent on the active participations of healthcare
professionals in adverse drug reaction reporting programmes. Healthcare
professionals are asked to report any suspected adverse reactions in patients
receiving GlucoNorm® (repaglinide) directly to Novo Nordisk
Canada Inc. at the following address:
Novo Nordisk Canada Inc.
c/o Medical and Scientific Affairs Department
2700 Matheson Blvd. East
3rd Floor, West Tower
Mississauga, ON L4W 4V9
Tel: (905) 629-4222
Toll: 1-800-465-4334
Your professional commitment in this regard has an important role in
protecting the well-being of your patients by contributing to early signal
detection and informed drug use.
Sincerely,
Novo Nordisk Canada Inc.
original signed by
Alan Davis, Ph.D., MBA
Director,
Medical and Scientific Affairs
GlucoNorm® and Novo Nordisk®
are trademarks of Novo Nordisk A/S, used under licence by Novo Nordisk
Canada Inc.
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Any suspected adverse incident can also be reported to:
Canadian Adverse Drug Reaction Monitoring Program (CADRMP)
Marketed Health Products Directorate
HEALTH CANADA
Address Locator: 0201C2
OTTAWA, Ontario, K1A 1B9
Tel: (613) 957-0337 or Fax: (613) 957-0335
Toll free for consumers and health professionals:
Tel: 866 234-2345, Fax: 866 678-6789
cadrmp@hc-sc.gc.ca
The AR Reporting Form and the AR
Guidelines can be found on the TPD web site or in The Canadian
Compendium of Pharmaceuticals and Specialties.
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