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This is duplicated text of a letter from Hoffmann-La
Roche Limited.
Contact the company for a copy of any references, attachments or
enclosures. |
Health Canada Endorsed Important Safety Information
on
INVIRASE® (saquinavir mesylate) and
FORTOVASE® (saquinavir) |
February 10, 2005
| Subject: |
Drug-Induced Hepatitis with Marked Transaminase Elevations in Healthy
Volunteers Receiving Rifampin 600 mg Once Daily in Combination with
Ritonavir 100 mg / Saquinavir 1000 mg Twice Daily (Ritonavir Boosted
Saquinavir). |
Dear Health Care Professional,
Hoffmann-La Roche Limited, following discussions with Health Canada, would
like to inform you of new safety information regarding the use of rifampin
in combination with ritonavir/saquinavir (ritonavir boosted saquinavir).
Please note that the boosted dosage recommendation of saquinavir/ ritonavir
has not been formally approved by Health Canada at this time.
In a Phase I, randomized, open-label, multiple-dose clinical pharmacology
study in healthy volunteers, 11/28 (39.3%) subjects exposed to rifampin
600 mg once daily taken together with ritonavir 100 mg / saquinavir 1000
mg given twice daily (ritonavir boosted saquinavir) developed significant
hepatocellular toxicity during the 28 day study period. Among these subjects,
transaminase elevations of up to > 20X upper limit of normal values
were noted and one subject was admitted to the hospital with marked transaminase
elevations. For all study participants, dosing of study medications was
immediately terminated and the study was discontinued. Following drug discontinuation,
liver function tests in all affected subjects are returning to normal,
clinical symptoms have abated and to date, no deaths from this clinical
study have been reported.
The current prescribing information for both INVIRASE (saquinavir mesylate
capsules) and FORTOVASE (saquinavir soft gelatin capsules) contraindicate
the use of rifampin together with saquinavir. This contraindication is
based on a pharmacokinetic interaction between rifampin and saquinavir
that results in reduced saquinavir plasma levels. The clinical pharmacology
study reported above was undertaken to determine if boosting of saquinavir
with ritonavir would overcome the interaction. However, as a result of
the high incidence of hepatotoxicity in this study, Hoffmann-La Roche now
advises prescribers that:
- Rifampin should not be administered to patients also receiving
saquinavir/ritonavir (ritonavir boosted saquinavir) as part of their
combination antiretroviral therapy (ART) for HIV infection.
|
Hoffmann-La Roche is collaborating closely with Health Canada on this
issue, and appropriate changes to both the INVIRASE and FORTOVASE product
monographs will be made as soon as possible.
The identification, characterization, and management of marketed health
product-related adverse reactions are dependent on the active participation
of health care professionals in adverse reaction reporting programmes.
Health care professionals are asked to report any serious and/or unexpected
adverse events in patients receiving saquinavir (INVIRASE or FORTOVASE)
to Hoffman-La Roche Ltd. or Health Canada at the following address:
Hoffmann-La Roche Limited
Drug Information and Safety Department
2455 Meadowpine Boulevard
Mississauga, Ontario, L5N 6L7
or call toll free at: 1-888-762-4388
or Fax at: 905-542-5610
or email to: mississauga.canada_medinfo@roche.com
Any suspected adverse reaction can also be reported to:
Canadian Adverse Drug Reaction Monitoring Program (CADRMP)
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: 866 234-2345
Fax: 866 678-6789
cadrmp@hc-sc.gc.ca
For other inquiries, please refer to contact information:
Bureau of Gastroenterology, Infection and Viral Diseases (BGIVD)
E-mail: BGIVD_Enquiries@hc-sc.gc.ca
Tel: (613) 941-3207
Fax: (613) 941-1183
The AR Reporting Form and the AR
Guidelines can be found on the Health Canada web site or in The
Canadian Compendium of Pharmaceuticals and Specialties. |
Should you have any questions or require additional information regarding
the use of INVIRASE (saquinavir mesylate) or FORTOVASE (saquinavir), please
contact the Drug Information and Safety Department at Hoffmann-La Roche
Limited at 1-888-762-4388 from 8:30 a.m. to 4:30 p.m. Monday to Friday
Eastern Standard Time.
Sincerely,
original signed by
Lorenzo Biondi,
Vice President, Medical and Regulatory Affairs
|
