Sandoz Initiates Voluntary Recall in the US of all 50mg/2mL and 250mg/10mL Vials of Methotrexate Injection, USP due to the Presence of Glass Particulates

PRINCETON, N.J., Oct. 27 /PRNewswire/ -- Sandoz Inc. announced today it has initiated a voluntary recall in the US of all 50mg/2mL and 250mg/10mL vials of Sandoz and Parenta brand Methotrexate Injection, USP product ("methotrexate") to the consumer/user level. Consistent with its commitment to quality and patient safety, Sandoz is initiating this voluntary recall of all 24 lots of the affected product following the finding of small glass flakes by Sandoz quality control in a limited number of vials in four lots. The flakes are the result of delamination of the glass used to manufacture the vials of these two dosage presentations.

Due to particle size, there is the potential to develop adverse reactions in areas where the particles lodge.  While it is unlikely, parenteral injection of drug from the affected lots could lead to serious adverse events, resulting in disability and death.  Additionally, neurologic damage could result from intrathecal administration.  Potential adverse events after intravenous administration include local damage to blood vessels in the lung, localized swelling, and granuloma formation. Intramuscular administration could result in foreign-body inflammatory response, with local pain, swelling and possible long term granuloma formation. Intra-arterial administration could result in damage to blood vessels in the distal extremities or organs.  To date, Sandoz has not received any adverse event reports or product complaints attributable to particles from any lot of methotrexate, including the lots where flakes have been found.

Methotrexate is an antimetabolite used in the treatment of neoplastic diseases, severe psoriasis, and rheumatoid arthritis, including polyarticular juvenile rheumatoid arthritis.  The affected products are only the 50mg/2mL and 250mg/10mL presentations of methotrexate. The product lot numbers, label type and expiration dates are listed below as well as on the Sandoz US website at www.us.sandoz.com.

Sandoz has sent out recall letters to inform all distributors, wholesalers and pharmacies of the voluntary recall. The recall is being conducted with the knowledge of the United States Food and Drug Administration (FDA).

Customers and patients should immediately discontinue use of this product and patients should contact their physician or healthcare provider if they experience any problem that might be related to the use of this product.  Additionally, as noted in the product's labeling, parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration.

Adverse events related to the use of Sandoz methotrexate product should be reported to Sandoz at 1-800-525-8747 or to the FDA's MedWatch Adverse Event Reporting Program either online, by regular mail or by fax:

• Online: www.fda.gov/medwatch/report.htm
• Regular Mail: use postage-paid FDA form 3500 available at:
  www.fda.gov/MedWatch/getforms.htm.
  Mail to MedWatch, FDA, 5600 Fishers Lane, Rockville, MD 20852-9787
• Fax: 1-800-FDA-0178

Customers and patients can arrange for return and reimbursement through GENCO Pharmaceutical Services, the returns vendor for Sandoz, by calling the dedicated Methotrexate Recall Hotline of 1-888-896-4565 or by sending a message to the dedicated Methotrexate Recall Email address of [email protected].  Operators are available 24 hours, seven days per week to provide assistance.

IMPORTANT SAFETY INFORMATION (PRODUCT LABELING)

WARNINGS

Methotrexate should be used only by physicians whose knowledge and experience include the use of antimetabolite therapy. Because of the possibility of serious toxic reactions (which can be fatal), Methotrexate should be used only in life-threatening neoplastic diseases, or in patients with psoriasis or rheumatoid arthritis with severe, recalcitrant, disabling disease which is not adequately responsive to other forms of therapy.

Deaths have been reported with the use of methotrexate in the treatment of malignancy, psoriasis, and rheumatoid arthritis.

Patients should be closely monitored for bone marrow, liver, lung and kidney toxicities.

Patients should be informed by their physician of the risks involved and be under a physician's care throughout therapy.

The use of methotrexate high dose regimens recommended for osteosarcoma requires meticulous care. High dose regimens for other neoplastic diseases are investigational and a therapeutic advantage has not been established. Methotrexate formulations and diluents containing preservatives must not be used for intrathecal or high dose methotrexate therapy.

1. Methotrexate has been reported to cause fetal death and/or congenital anomalies. Therefore, it is not recommended for women of childbearing potential unless there is clear medical evidence that the benefits can be expected to outweigh the considered risks. Pregnant women with psoriasis or rheumatoid arthritis should not receive methotrexate.
2. Methotrexate elimination is reduced in patients with impaired renal function, ascites, or pleural effusions. Such patients require especially careful monitoring for toxicity, and require dose reduction or, in some cases, discontinuation of methotrexate administration.
3. Unexpectedly severe (sometimes fatal) bone marrow suppression, aplastic anemia, and gastrointestinal toxicity have been reported with concomitant administration of methotrexate (usually in high dosage) along with some nonsteroidal anti-inflammatory drugs (NSAIDs).
4. Methotrexate causes hepatotoxicity, fibrosis and cirrhosis, but generally only after prolonged use. Acutely, liver enzyme elevations are frequently seen. These are usually transient and asymptomatic, and also do not appear predictive of subsequent hepatic disease. Liver biopsy after sustained use often shows histologic changes, and fibrosis and cirrhosis have been reported; these latter lesions may not be preceded by symptoms or abnormal liver function tests in the psoriasis population. For this reason, periodic liver biopsies are usually recommended for psoriatic patients who are under long term treatment. Persistent abnormalities in liver function tests may precede appearance of fibrosis or cirrhosis in the rheumatoid arthritis population.
5. Methotrexate-induced lung disease, including acute or chronic interstitial pneumonitis, is a potentially dangerous lesion, which may occur acutely at any time during therapy and has been reported at low doses. It is not always fully reversible and fatalities have been reported. Pulmonary symptoms (especially a dry, nonproductive cough) may require interruption of treatment and careful investigation.
6. Diarrhea and ulcerative stomatitis require interruption of therapy; otherwise, hemorrhagic enteritis and death from intestinal perforation may occur.
7. Malignant lymphomas, which may regress following withdrawal of methotrexate, may occur in patients receiving low-dose methotrexate and, thus, may not require cytotoxic treatment. Discontinue methotrexate first and, if the lymphoma does not regress, appropriate treatment should be instituted.
8. Like other cytotoxic drugs, methotrexate may induce "tumor lysis syndrome" in patients with rapidly growing tumors. Appropriate supportive and pharmacologic measures may prevent or alleviate this complication.
9. Severe, occasionally fatal, skin reactions have been reported following single or multiple doses of methotrexate. Reactions have occurred within days of oral, intramuscular, intravenous, or intrathecal methotrexate administration. Recovery has been reported with discontinuation of therapy.
10. Potentially fatal opportunistic infections, especially Pneumocystis carinii pneumonia, may occur with methotrexate therapy.

Methotrexate is contraindicated in:

• Pregnant women with psoriasis or rheumatoid arthritis and should be used in the treatment of neoplastic diseases only when the potential benefit outweighs the risk to the fetus.
• Nursing mothers.
• Patients with psoriasis or rheumatoid arthritis with alcoholism, alcoholic liver disease or other chronic liver disease.
• Patients with psoriasis or rheumatoid arthritis who have overt or laboratory evidence of immunodeficiency syndromes.
• Patients with psoriasis or rheumatoid arthritis who have preexisting blood dyscrasias, such as bone marrow hypoplasia, leukopenia, thrombocytopenia, or significant anemia.
• Patients with known hypersensitivity to methotrexate.

DISCLAIMER

The foregoing release contains forward-looking statements that can be identified by terminology such as "may," "potential," "could," or similar expressions, or by express or implied discussions regarding the recall of methotrexate injection, or regarding potential future revenues from methotrexate injection. You should not place undue reliance on these statements.  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.  In particular, management's expectations could be affected by, among other things, unexpected regulatory actions or delays or government regulation generally; uncertainties regarding actual or potential legal proceedings, including, among others, product liability litigation, government investigations and intellectual property disputes; competition in general; government, industry and general public pricing pressures; unexpected patent litigation outcomes; unexpected issues in remedying the methotrexate injection manufacturing process; the impact that the foregoing factors could have on the values attributed to the Novartis Group's assets and liabilities as recorded in the Group's consolidated balance sheet, 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 Sandoz

Sandoz, a Division of the Novartis group, is a global leader in the field of generic pharmaceuticals, offering a wide array of high-quality, affordable products that are no longer protected by patents. Sandoz has a portfolio of about 1000 compounds and sells its products in more than 130 countries. Key product groups include antibiotics, treatments for central nervous system disorders, gastrointestinal medicines, cardiovascular treatments and hormone therapies. Sandoz develops, produces and markets these medicines along with pharmaceutical and biotechnological active substances and anti-infectives. In addition to strong organic growth in recent years, Sandoz has made a series of acquisitions including Lek (Slovenia), Sabex (Canada), Hexal (Germany), Eon Labs (US), EBEWE Pharma (Austria) and Oriel Therapeutics (US). In 2009, Sandoz employed around 23,000 people worldwide and posted sales of USD 7.5 billion.

SOURCE Sandoz Inc.