Novartis Pharmaceuticals Corporation
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Appendix 7:
Package Insert Revisions
re: Osteonecrosis of the Jaw
Zometa®
(zoledronic acid) Injection
and
Aredia®
(pamidronate disodium) Injection
Submitted:
Oncologic Drugs
Advisory Committee Meeting
Property of Novartis Pharmaceuticals Corporation
All rights reserved
Available for public disclosure without
redaction
Table of
contents................................................................................................................... 2
1.... Zometa package insert revisions re: osteonecrosis of
the jaw................................................... 3
1.1 Package insert dated September 2003....................................................................... 3
1.2 Package insert dated March 2004.............................................................................. 3
1.3 Package insert dated August 2004............................................................................. 3
2.... Aredia package insert revisions re: osteonecrosis of
the jaw.................................................... 4
2.1 Package insert dated October 2003........................................................................... 4
2.2 Package insert dated August 2004............................................................................. 4
The following paragraph was added under Post-Marketing Experiences in the Adverse Events section:
Cases of osteonecrosis (primarily of the jaws) have been reported
since market introduction. Osteonecrosis
of the jaws has other well documented multiple risk factors. It is not possible to determine if these
events are related to Zometa or other bisphosphonates, to concomitant drugs or
other therapies (e.g., chemotherapy, radiotherapy, corticosteroid), to patient’s
underlying disease, or to other comorbid risk factors (e.g., anemia, infection,
preexisting oral disease).
The paragraph added in September 2003 was revised in the package insert dated March 2004 to read:
Cases of osteonecrosis (primarily of the jaws) have been reported in patients treated with bisphosphonates. The majority of the reported cases are in cancer patients attendant to a dental procedure. Osteonecrosis of the jaws has multiple well documented risk factors including a diagnosis of cancer, concomitant therapies (e.g. chemotherapy, radiotherapy, corticosteroids) and co-morbid conditions (e.g. anemia, coagulopathies, infection, pre-existing oral disease). Although causality cannot be determined, it is prudent to avoid dental surgery as recovery may be prolonged.
A statement re: Osteonecrosis of the jaw was added in the Precautions section and reads as follows:
Osteonecrosis of the jaw (ONJ) has been reported in patients with
cancer receiving treatment regimens including bisphosphonates. Many of these
patients were also receiving chemotherapy and corticosteroids. The majority of
reported cases have been associated with dental procedures such as tooth
extraction. Many had signs of local
infection including osteomyelitis.
A dental examination with appropriate preventive dentistry should
be considered prior to treatment with bisphosphonates in patients with concomitant
risk factors (e.g., cancer, chemotherapy, corticosteroids, poor oral hygiene).
While on treatment, these patients should avoid invasive dental procedures if possible. For patients who develop ONJ while on bisphosphonate therapy, dental surgery may exacerbate the condition. For patients requiring dental procedures, there are no data available to suggest whether discontinuation of bisphosphonate treatment reduces the risk of ONJ. Clinical judgment of the treating physician should guide the management plan of each patient based on individual benefit/risk assessment.
The following paragraph was added under Post-Marketing Experiences in the Adverse Events section:
Cases of osteonecrosis (primarily of the jaws) have been reported
since market introduction. Osteonecrosis
of the jaws has other well documented multiple risk factors. It is not possible to determine if these
events are related to Zometa or other bisphosphonates, to concomitant drugs or
other therapies (e.g., chemotherapy, radiotherapy, corticosteroid), to
patients’s underlying disease, or to other comorbid risk factors (e.g., anemia,
infection, preexisting oral disease).
A statement re: Osteonecrosis of the jaw was added in the Precautions section and reads as follows:
Osteonecrosis of the jaw (ONJ) has been reported in patients with
cancer receiving treatment regimens including bisphosphonates. Many of these
patients were also receiving chemotherapy and corticosteroids. The majority of
reported cases have been associated with dental procedures such as tooth
extraction. Many had signs of local
infection including osteomyelitis.
A dental examination with appropriate preventive dentistry should
be considered prior to treatment with bisphosphonates in patients with
concomitant risk factors (e.g., cancer, chemotherapy, corticosteroids, poor
oral hygiene).
While on treatment, these patients should avoid invasive dental procedures if possible. For patients who develop ONJ while on bisphosphonate therapy, dental surgery may exacerbate the condition. For patients requiring dental procedures, there are no data available to suggest whether discontinuation of bisphosphonate treatment reduces the risk of ONJ. Clinical judgment of the treating physician should guide the management plan of each patient based on individual benefit/risk assessment.