FDA

FDA is reemphasizing the importance of monitoring cardiac function in patients treated with mitozantrone, sold as Novantrone and also as a generic. Mitozantrone is used to treat certain patients with prostate cancer, leukemia and multiple sclerosis (MS).

Congestive heart failure can occur while a patient is being treated with mitoxantrone, or even months or years after therapy is stopped. The risk of cardiotoxicity increases as the cumulative dose increases.

In 2005, the product labeling was updated to recommend that MS patients have their left ventricular ejection fraction (LVEF) checked before each dose of mitozantrone, in addition to having a baseline measurement before starting treatment. Since that time, a postmarketing safety study has shown that quantitative LVEF monitoring was not being performed in a majority of MS patients treated with the drug.

FDA is alerting healthcare professionals about labeling changes for ultrasound micro-bubble contrast agents, which are sold as Definity (Perflutren Lipid Microsphere) Injectable Suspension and Optison (Perflutren Protein-Type A Microspheres for Injection). These products are used during echocardiography to enhance a cardiac image.

The revised labeling continues to highlight the risk of serious cardiopulmonary reactions, either while the contrast agent is being administered or within 30 minutes afterwards, especially in patients with pulmonary hypertension or unstable cardiopulmonary conditions.

FDA is alerting healthcare professionals that the x-rays emitted during CT exams may cause some electronic medical devices to malfunction. These malfunctions are different from those related to MRI scanning, which are caused by strong electrical and magnetic fields.

Most patients with electronic medical devices do not experience problems with CT scans, but FDA has received a small number of reports in which the scans may have caused unintended shocks from neurostimulators, malfunctions of insulin pumps, and transient changes in pacemaker output. Theoretically, defibrillators, cochlear implants and retinal implants could also be affected.

Here is what FDA recommends to help reduce any possible risk:

• Before beginning a CT scan, use scout views to check whether the patient has an electronic medical device and where it is. If the device is in or very near the area to be scanned, there are several steps to take.

FDA is alerting healthcare professionals that the x-rays emitted during CT exams may cause some electronic medical devices to malfunction. These malfunctions are different from those related to MRI scanning, which are caused by strong electrical and magnetic fields.

Most patients with electronic medical devices do not experience problems with CT scans, but FDA has received a small number of reports in which the scans may have caused unintended shocks from neurostimulators, malfunctions of insulin pumps, and transient changes in pacemaker output. Theoretically, defibrillators, cochlear implants and retinal implants could also be affected.

Here is what FDA recommends to help reduce any possible risk:

• Before beginning a CT scan, use scout views to check whether the patient has an electronic medical device and where it is. If the device is in or very near the area to be scanned, there are several steps to take.

Warning on Tendon Injuries with Fluoroquinolone Antibiotics

FDA has asked that a boxed warning be added to the prescribing information for fluoroquinolone antibiotics. The warning will remind healthcare professionals that patients taking these drugs may experience an increased risk of tendinitis and tendon rupture. Fluoroquinolones include Cipro (ciprofloxacin), Factive (gemifloxacin), Levaquin (levofloxacin), Avelox (moxifloxacin), Noroxin (norfloxacin), Floxin (ofloxacin) and Proquin (ciprofloxacin hydrochloride).

FDA is concerned that large numbers of tendon problems were continuing to be reported, despite a warning that already appears in the labeling for these drugs. The boxed warning is being added to draw the practitioner's attention to this information. This can also affect the benefit-risk decisions that are made when these drugs are prescribed.

FDA is alerting healthcare professionals that severe bone, joint, or muscle pain can occur in patients taking bisphosphonate drugs such as Fosamax (alendronate sodium), Actonel (risedronate sodium), Reclast (zoledronic acid) and Boniva (ibandronate sodium). These drugs are used to treat osteoporosis and certain other diseases.

This severe, sometimes incapacitating musculoskeletal pain has occurred within days, months, or even years after starting bisphosphonates. In the most serious cases, the pain was so severe that patients could not continue their normal activities. Some patients have complete relief of symptoms after they stop taking the drug, while others have reported slow or incomplete resolution.

Note that these events are different from the acute phase response some patients experience after the first treatment with IV bisphosphonates, and occasionally after the first dose of oral bisphosphonates.

The Institute for Safe Medication Practices (ISMP) recently described an increase in reports about mixups between insulin U-100 and insulin U-500. These errors could result in dangerous hyperglycemia or hypoglycemia. Mistakes have occurred when prescribers accidentally selected U-500 regular insulin from computer screens instead of U-100.

A boxed warning alerting healthcare professionals to an increased risk of cancer death has been added to the labeling for Regranex (becaplermin), a topical medication used to treat certain diabetic foot and leg ulcers.

Based on a review of an earlier epidemiologic study, FDA has concluded that patients who use three or more tubes of Regranex experience a five-fold increase in the risk of cancer death compared to patients who do not use the drug. The duration of the study was not long enough to establish whether there is also an increased risk of new cancers.

In March 2008, FDA announced that it had received the epidemiologic study, described what the overall study findings were, and promised to analyze the study and communicate its findings to the healthcare community. The new boxed warning in the labeling is the result of that analysis.

FDA is advising healthcare professionals about an increased risk of fetal harm when women become pregnant while being treated with the immunosuppressant drugs Cellcept (mycophenolate mofetil) or Myfortic (mycophenolic acid).

Myfortic is approved to prevent kidney transplant rejection. CellCept is approved to prevent heart, liver and kidney transplant rejection. These drugs are also sometimes used to treat immune-mediated conditions such as lupus and erythema multiforme, which are not approved indications.

Taking CellCept and Myfortic during pregnancy increases the risk of spontaneous abortion during the first trimester, and can cause serious congenital malformations, especially external ear and facial abnormalities, including cleft lip and palate. Anomalies of the distal limbs, heart, esophagus, and kidney have also been reported.

FDA has informed healthcare professionals that it is investigating a possible association between drugs that block tumor necrosis factor (TNF) and the development of lymphoma and other cancers in children and young adults.

This is part of FDA's commitment to inform healthcare professionals and the public about its ongoing drug safety reviews. Because this information is preliminary and there is scientific uncertainty, FDA is not taking regulatory action at this point, nor advising healthcare professionals to stop using the drugs.

The TNF blockers in question, Remicade (infliximab), Enbrel (etanercept), Humira (adalimumab) and Cimzia (certolizumab pegol), are used to treat juvenile idiopathic arthritis, Crohn's disease, and other inflammatory conditions. The labeling for these drugs already warns about a possible risk of cancer.