New Drugs Approved by the FDA;New Dosage Forms and Indications Approved by the FDA;Agents Pending FDA Approval;New Drug Applications Filed by Manufacturer;Supplemental Applications Filed by Manufacturer;Significant Labeling Changes or “Dear Health Care Professional” Letters Related to Safety

NEW CONTRAINDICATION

Rare cases of hypersensitivity reactions, including urticaria, angioedema, and rash.

NEW WARNING AND PRECAUTION

Hypokalemia.

WARNINGS AND PRECAUTIONS Infusion reactions: Serious infusion reactions requiring medical intervention and immediate, permanent discontinuation of the drug included rapid onset of airway obstruction, hypotension, shock, loss of consciousness, myocardial infarction, and/or cardiac arrest.

Dermatology toxicity: Dermatologic toxicities occurred, including acneform rash, skin drying and fissuring, paronychial inflammation, infectious sequelae, and hypertrichosis.

WARNINGS

Administration: Injection into the buttock may not provide effective treatment of anaphylaxis; accidental injection into the digits, hands, or feet may result in loss of blood flow to the affected area; the presence of a sulfite in this product should not defer administration of the drug for treatment of serious allergic or other emergency situations, even if the patient is sensitive to sulfites; may precipitate or aggravate angina pectoris, as well as produce ventricular arrhythmias, following administration.

WARNINGS

Patients with hepatic impairment: Treatment with erlotinib should be used with extra caution in patients with total bilirubin levels greater than 3 x ULN; patients with hepatic impairment (total bilirubin levels greater than ULN or Child-Pugh class A, B, and C) should be closely monitored during therapy; dosing should be interrupted or discontinued if changes in liver function are severe, such as doubling of total bilirubin levels and/or tripling of transaminase levels in the setting of pretreatment values outside normal range.

Hepatotoxicity: Cases of hepatic failure and hepatorenal syndrome (including fatalities) have been reported. Renal failure: Cases of hepatorenal syndrome, acute renal failure (including fatalities), and renal insufficiency have been reported.

WARNINGS

Fatal medication errors: Do not use as a catheter lock flush product because of the high concentration; an error could result in fatal hemorrhages, especially in pediatric patients.

HIT and HITT: Serious antibody-mediated reaction resulting from irreversible aggregation of platelets.

Delayed onset of HIT and HITT: HIT and HITT can occur up to several weeks after the discontinuation of heparin therapy.

Use in neonates: Confirm choice of the correct strength before administration of the drug.

http://www.fda.gov/medwatch/safety/2008/Sep_PI/Heparin_PreservativeFree_PI.pdf

http://www.fda.gov/medwatch/safety/2008/Sep_PI/Heparin%20Inj_PI.pdf

WARNINGS AND PRECAUTIONS

Hepatotoxicity: When used in combination with chemotherapy, liver toxicity in the form of transaminase elevation and hyperbilirubinemia has been observed. Hemorrhage: From various sources (eg, any site, gastrointestinal, intratumoral).

Hypothyroidism: Clinical cases of hypothyroidism have been reported in patients who have undergone thyroidectomy and who are undergoing levothyroxine replacement during treatment; TSH levels should be closely monitored in these patients.

Wording changes in the warning regarding hypersensitivity reactions. Addition of the following: Other serious and sometimes fatal events, some caused by hypersensitivity and some caused by uncertain etiology, have been reported rarely in patients receiving therapy with quinolones, including Noroxin; these events may be severe and generally occur following administration of multiple doses; clinical manifestations may include 1 or more of the following:

The drug should be discontinued immediately and supportive measures should be instituted at the first appearance of a skin rash, jaundice, or any other sign of hypersensitivity.

WARNINGS AND PRECAUTIONS

PML: JC virus infection resulting in PML and death can occur in patients who have hematologic malignancies or autoimmune diseases; most cases of PML were diagnosed within 12 months of the last infusion of rituximab.