Novartis Oncology Products and Compounds
Zometa is currently used for the prevention of skeletal-related events
(pathological fractures, spinal compression, radiation or surgery to bone, or
tumor-induced hypercalcemia) in patients with advanced malignancies involving
bone.
RAD001 (everolimus) is an investigational oral once-daily inhibitor of
mTOR, a protein that controls tumor cell division and blood vessel growth.
Everolimus is approved under the trade-name Certican(R) for the prevention of
organ rejection in heart and kidney transplant recipients. Certican was first
approved in the EU in 2003 and is available in more than 60 countries.
Tasigna(R) (nilotinib) is a next-generation tyrosine kinase inhibitor
recently approved in the US and EU as second-line therapy for patients with
Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML).
ASA404 is an investigational small-molecule Tumor-VDA that selectively
disrupts existing tumor blood vessels.
Zometa Safety Information
ZOMETA is generally well tolerated. The most common side effects you may
experience with ZOMETA therapy are fatigue, nausea, vomiting, bone pain,
headache, fever, shortness of breath, anemia, constipation, or lack of
appetite. These side effects with ZOMETA were usually mild and transient. Your
doctor may recommend a mild pain reliever to make you more comfortable.
In some cases, ZOMETA and other bisphosphonates have been known to cause
kidney damage. Prior to each infusion, your doctor will routinely do blood
tests to monitor your kidney function. If you have kidney problems, your
doctor may decide that you need a lower dose of ZOMETA or that ZOMETA should
not be given. Patients with severe kidney problems should not receive ZOMETA.
If you are pregnant, you should not receive ZOMETA because of the
potential harm to the unborn child. While on ZOMETA therapy, you should avoid
becoming pregnant.
Osteonecrosis of the jaw (ONJ) has been reported mostly in cancer patients
receiving treatments, including intravenous bisphosphonates, chemotherapy,
and/or corticosteroids. The majority of reported cases have been associated
with dental procedures such as tooth extraction. You should maintain good oral
hygiene and should have a dental examination with appropriate preventive
dentistry prior to treatment with bisphosphonates. While on treatment, you
should avoid invasive dental procedures if possible. No data are available as
to whether discontinuation of bisphosphonate therapy reduces the risk of ONJ
in patients requiring dental procedures. A connection between the use of
bisphosphonates and ONJ has not been established. Based on your condition,
your doctor will determine the treatment plan you will receive.
In postmarketing experience, severe and occasionally incapacitating bone,
joint, and/or muscle pain has been reported infrequently in patients taking
bisphosphonates.
ZOMETA contains the same active ingredient as found in Reclast(R)
(zoledronic acid). If you are treated with ZOMETA, you should not be treated
with Reclast.
You should take an oral calcium supplement of 500 mg and a multiple
vitamin containing 400 IU of vitamin D daily.
It is important to keep up with your fluid intake while on ZOMETA therapy.
Signs and symptoms of low fluid intake include thirst, sagging skin, low urine
output, and dry mouth. Be sure to drink plenty of water or other fluids.
Please see enclosed full Prescribing Information in the ZOMETA resource
book.
Tasigna Safety Information
WARNING: QT PROLONGATION AND SUDDEN DEATHS
Tasigna prolongs the QT interval. Sudden deaths have been reported in
patients receiving nilotinib. Tasigna should not be used in patients with
hypokalemia, hypomagnesemia, or long QT syndrome. Hypokalemia or
hypomagnesemia must be corrected prior to Tasigna administration and should be
periodically monitored. Drugs known to prolong the QT interval and strong
CYP3A4 inhibitors should be avoided. Patients should avoid food 2 hours before
and 1 hour after taking dose. Use with caution in patients with hepatic
impairment. ECGs should be obtained to monitor the QTc at baseline, seven days
after initiation, and periodically thereafter, as well as following any dose
adjustments.
Warnings and precautions
Myelosuppression: Associated with Grade 3/4 neutropenia, thrombocytopenia,
and anemia. Complete blood counts should be performed every 2 weeks for the
first 2 months, then monthly thereafter as clinically indicated.
Myelosuppression with Tasigna was generally reversible and usually managed by
withholding Tasigna temporarily or dose reduction.
QT prolongation: Tasigna prolongs the QT interval. Correct hypokalemia or
hypomagnesemia prior to administration and monitor periodically. Avoid drugs
known to prolong the QT interval and strong CYP3A4 inhibitors. Use caution in
patients with hepatic impairment. Obtain ECGs at baseline, seven days after
initiation, and periodically thereafter, as well as following any dose
adjustments.
Sudden deaths: There were sudden deaths reported in the safety population
and the expanded access program. Ventricular repolarization abnormalities may
have contributed to their occurrence.
Elevated serum lipase: Caution is recommended in patients with history of
pancreatitis. Check serum lipase periodically. Liver function abnormality
Serum bilirubin and hepatic transaminases: Tasigna may result in elevations in
bilirubin, AST/ALT, and alkaline phosphatase. Check hepatic function tests
periodically.
Electrolyte abnormalities: Tasigna can cause hypophosphatemia,
hypokalemia, hyperkalemia, and hyponatremia. Correct electrolyte abnormalities
prior to initiating TASIGNA and monitor periodically during therapy.
Hepatic impairment: Metabolism of Tasigna is mainly hepatic. Tasigna has
not been investigated in patients with hepatic impairment. Caution is
recommended in these patients and QT interval should be monitored closely.
Drug interactions: Avoid concomitant use of QT prolonging drugs and strong
inhibitors or inducers of CYP3A4 should be avoided as they may affect serum
concentration of Tasigna.
Concomitant strong CYP3A4 inhibitors
The concomitant use of strong CYP3A4 inhibitors should be avoided
(including, but not limited to, ketoconazole, itraconazole, clarithromycin,
atazanavir, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir,
telithromycin, voriconazole). Should treatment with any of these agents be
required, it is recommended that therapy with Tasigna be interrupted. If
interruption of treatment with Tasigna is not possible, patients who require
treatment with a drug that prolongs QT or strongly inhibits CYP3A4 should be
closely monitored for prolongation of the QT interval, and a dose reduction to
1/2 the daily dose is recommended (400 mg once daily). If the strong inhibitor
is discontinued, a washout period should be allowed before Tasigna is adjusted
upward to the indicated dose. Close monitoring for prolongation of the QT
interval is indicated for patients who cannot avoid strong CYP3A4 inhibitors.
Grapefruit products and other foods that are known to inhibit CYP3A4 should
also be avoided.
Concomitant strong CYP3A4 inducers
The concomitant use of strong CYP3A4 inducers should be avoided
(including, but not limited to, dexamethasone, phenytoin, carbamazepine,
rifampin, rifabutin, rifapentin, phenobarbital). Patients should also refrain
from taking St John's Wort. If patients must be co-administered a strong
CYP3A4 inducer, the dose of Tasigna may need to be increased, depending on
patient tolerability. If the strong inducer is discontinued, the Tasigna dose
should be reduced to the indicated dose. Tasigna is a competitive inhibitor of
CYP3A4, CYP2C8, CYP2C9, CYP2D6, and UGT1A1. Since warfarin is metabolized by
CYP2C9 and CYP3A4, it should be avoided if possible. Tasigna inhibits human
P-glycoprotein. If Tasigna is administered with drugs that are substrates of
Pgp, increased concentrations of the substrate are likely and caution should
be exercised. Tasigna may also induce CYP2B6, CYP2C8, and CYP2C9. Therefore,
Tasigna may alter serum concentration of other drugs.
Food effects: Food increases blood levels of Tasigna. Patients should
avoid food 2 hours before and 1 hour after taking dose. Since the capsules
contain lactose, Tasigna is not recommended for patients with rare hereditary
problems of galactose intolerance, severe lactase deficiency, or of
glucose-galactose malabsorption.
Pregnancy: Fetal harm can occur when Tasigna is administered to a pregnant
woman. Women should be advised not to become pregnant when taking Tasigna.
Adverse reactions
In chronic phase patients, the most commonly reported adverse reactions
( >10%) were rash (33%), pruritus (29%), nausea (31%), fatigue (28%), headache
(31%), constipation (21%), diarrhea (22%), and vomiting (21%). The most common
( >10%) Grade 3/4 adverse reactions were thrombocytopenia (28%), neutropenia
(28%), elevated lipase (15%), and hyperglycemia (11%). In accelerated phase
patients, the most commonly reported adverse reactions ( >10%) were rash
(28%), pruritus (20%), and constipation (18%). The most common ( >10%)
Grade 3/4 adverse reactions were thrombocytopenia (37%), neutropenia (37%),
anemia (23%), and elevated lipase (17%). Other serious adverse reactions
included pneumonia, febrile neutropenia, leukopenia, intracranial hemorrhage,
and pyrexia (Grade 3/4: 2%).
Dose adjustments or modifications: Tasigna may need to be temporarily
withheld and/or dose reduced for QT prolongation, hematological toxicities
that are not related to underlying leukemia, clinically significant moderate
or severe nonhematologic toxicities, laboratory abnormalities, or concomitant
use of strong CYP3A4 inhibitors. With concomitant use of strong CYP3A4
inducers, the dose of Tasigna may need to be increased, depending on patient
tolerability.
Other patients in whom Tasigna should be used with caution: Tasigna should
not be used during pregnancy. Sexually active female patients should use
effective contraception during treatment. Women should not breast feed while
taking Tasigna. There are no data to support the use of Tasigna in pediatric
patients. Use with caution in patients with hepatic impairment.
Please see full Prescribing Information.
Disclaimer
The foregoing release contains forward-looking statements that can be
identified by terminology such as "pipeline", "to develop", "to highlight",
"to feature", "to be", "will", "potential", or similar expressions, or by
express or implied discussions regarding potential new products, potential new
indications or labelling for existing products, or regarding potential future
revenues from such products. Such forward-looking statements reflect the
current views of the Company regarding future events, and involve known and
unknown risks, uncertainties and other factors that may cause actual results
to be materially different from any future results, performance or
achievements expressed or implied by such statements. There can be no
guarantee that any new products will be approved for sale in any market, or
that any new indications or labelling will be approved for any existing
products. Nor can there be any guarantee that any such products will achieve
any particular levels of revenue in the future. In particular, management's
expectations could be affected by, among other things, unexpected clinical
trial results, including unexpected new clinical data and unexpected
additional analysis of existing clinical data; unexpected regulatory actions
or delays or government regulation generally; the company's ability to obtain
or maintain patent or other proprietary intellectual property protection;
competition in general; government, industry and general public pricing
pressures, and other risks and factors referred to in Novartis AG's current
Form 20-F on file with the US Securities and Exchange Commission. Should one
or more of these risks or uncertainties materialize, or should underlying
assumptions prove incorrect, actual results may vary materially from those
anticipated, believed, estimated or expected. Novartis is providing the
information in this press release as of this date and does not undertake any
obligation to update any forward-looking statements contained in this press
release as a result of new information, future events or otherwise.
About Novartis
Novartis Pharmaceuticals Corporation researches, develops, manufactures
and markets leading innovative prescription drugs used to treat a number of
diseases and conditions, including those in the cardiovascular, metabolic,
cancer, organ transplantation, central nervous system, dermatological,
gastrointestinal and respiratory areas. The company's mission is to improve
people's lives by pioneering novel healthcare solutions.
Located in East Hanover, New Jersey, Novartis Pharmaceuticals Corporation
is an affiliate of Novartis AG (NYSE: NVS), a world leader in offering
medicines to protect health, cure disease and improve well-being. Our goal is
to discover, develop and successfully market innovative products to treat
patients, ease suffering and enhance the quality of life. We are strengthening
our medicine-based portfolio, which is focused on strategic growth platforms
in innovation-driven pharmaceuticals, high-quality and low-cost generics,
human vaccines and leading self-medication OTC brands. Novartis is the only
company with leadership positions in these areas. In 2006, the Group's
businesses achieved net sales of USD 37.0 billion and net income of USD 7.2
billion. Approximately USD 5.4 billion was invested in R&D. Headquartered in
Basel, Switzerland, Novartis Group companies employ approximately 100,000
associates and operate in over 140 countries around the world. For more
information, please visit http://www.pharma.us.novartis.com.
