Polypill gets approval, fenofibric acid gets label change

Recalls, warnings, approvals and other regulatory news.

Recalls and warnings

A market withdrawal of drotrecogin alfa (Xigris) after it failed to show a survival benefit for patients with severe sepsis and septic shock in a large recent study. The drug should not be started in new patients and should be stopped in patients currently being treated.


A label change on fenofibric acid (Trilipix) to warn that it may not lower a patient's risk of having a heart attack or stroke, based on data from the ACCORD trial. Physicians should consider and counsel patients about the benefits and risks when deciding whether to prescribe the drug.

A nationwide recall of multiple lots of oral contraceptives from Qualitest Pharmaceuticals because of a packaging error, where select blisters were rotated 180 degrees within the card, reversing the weekly tablet orientation and making the lot number and expiry date no longer visible. As a result, the daily regimen for these oral contraceptives may be incorrect and could leave women without adequate contraception.

A warning that dasatinib (Sprycel) may increase the risk of pulmonary arterial hypertension (PAH). Clinicians should evaluate patients for signs and symptoms of underlying cardiopulmonary disease prior to starting the drug and also during treatment, as some reported cases developed as late as a year into treatment. If PAH is confirmed, the drug should be permanently discontinued.

A class I recall of some of Carefusion's EnVe ventilators, manufactured between December 2010 and May 2011, due to a potential for delay in resuming ventilation after reconnection, automatic reset and disconnection upon transport.

A class I recall of Mizuho OSI Modular Table Systems, used for patient positioning during surgery procedures, because incorrect removal of the T-pins that support the bottom base, instead of the T-pins that support the top, may result in unexpected movement or tilting of the table and patients falling to the floor.

A recall of Fenwal's 4C2223 blood component infusion set due to a labeling issue in which the package label incorrectly lists 80 microns when the actual filter size is a standard 170-260 micron in size.


A fixed-dose combination pill of sitagliptin and simvastatin (Juvisync). The first product to combine a type 2 diabetes drug and a statin, it is currently available in dosage strengths for sitagliptin/simvastatin of 100 mg/10 mg, 100 mg/20 mg and 100 mg/40 mg and the manufacturer plans to develop 50 mg/10 mg, 50 mg/20 mg and 50 mg/40 mg doses. Prescribing information for the drug informs doctors of the potential for statins to increase blood sugar levels in patients with type 2 diabetes.

A new indication for tadalafil (Cialis) to treat the signs and symptoms of benign prostatic hyperplasia (BPH) and for the treatment of BPH and erectile dysfunction (ED), when the conditions occur simultaneously. It was approved in 2003 for the treatment of ED. In two clinical trials, men with BPH who took 5 mg of tadalafil once daily experienced a statistically significant improvement in their symptoms compared to men treated with placebo.

The Kimberly-Clark pediatric/child face mask, designed to be worn by children in hospitals and health care facilities to help reduce the spread of airborne respiratory tract bacteria, viruses, and other pathogens. The mask is designed to fit children ages 5 to 12 years. Children do not breathe as forcefully as adults, particularly children with respiratory infections, so the face mask is less resistant to airflow than an adult mask.

An ipratropium bromide and albuterol sulfate inhalation spray (Combivent Respimat) for patients with chronic obstructive pulmonary disease who are on a regular aerosol bronchodilator but continue to have evidence of bronchospasm and require a second bronchodilator. It is an alternative to Combivent inhalation aerosol, which will not be available in the future because it contains chlorofluorocarbons.

A new indication for rivaroxaban (Xarelto) to reduce the risk of stroke in patients who have non-valvular atrial fibrillation. The drug's safety and efficacy were evaluated in a clinical trial with more than 14,000 patients, in which it showed similar ability to warfarin in preventing stroke. Bleeding was the most common adverse event. The risk of major bleeding associated with rivaroxaban was similar to that with warfarin; however, rivaroxaban caused less bleeding into the brain and more bleeding into the stomach and intestines. The drug carries a boxed warning to make clear that patients should not discontinue it before talking with their health care professional. On July 1, 2011, the FDA approved rivaroxaban to reduce the risk of blood clots, deep vein thrombosis, and pulmonary embolism following knee or hip replacement surgery.

The first generic versions of olanzapine tablets (Zyprexa and Zyprexa Zydus [orally disintegrating tablets]) to treat schizophrenia and bipolar disorder. The drug carries a boxed warning alerting that this type of drug can raise the risk of death in elderly people with psychosis or dementia and it must be dispensed with a medication guide that describes the risks and adverse reactions, which include hyperglycemia, increased cholesterol and triglycerides and weight gain.

Clobazam tablets (Onfi) for use as an adjunctive treatment for seizures associated with Lennox-Gastaut syndrome in adults and children two years of age and older. The drug was granted orphan drug designation by the FDA based on effectiveness in two multicenter controlled studies in which it improved seizure control.

A new indication for cetuximab (Erbitux) for use with chemotherapy to treat patients with metastatic head and neck cancer. The safety and effectiveness for this indication is based on the results of a multi-center clinical study conducted outside the U.S., which used a non-U.S. approved version of cetuximab. Patients received either the combination of cetuximab with chemotherapy or chemotherapy only, and those receiving cetuximab lived, on average, 10.1 months compared with 7.4 months. The drug is already FDA-approved for certain types of colon cancer, and has been approved since 2006 for treatment of non-metastatic head and neck cancer in combination with radiation therapy (first-line) or as a single agent (following standard treatment).


The FDA has not yet reached a conclusion, but remains concerned, about the potential increased risk of blood clots with the use of drospirenone-containing birth control pills. Preliminary results of an FDA-funded study suggest an approximately 1.5-fold increase in the risk of blood clots with drospirenone-containing birth control pills compared to other hormonal contraceptives. Given the conflicting nature of the existing research findings on this issue, the FDA has scheduled a joint meeting of the Reproductive Health Drugs Advisory Committee and the Drug Safety and Risk Management Advisory Committee. Prescribing clinicians should consider the risks and benefits of drospirenone-containing combination oral contraceptives on an individual patient basis and counsel patients about the current information regarding the risk of VTE. The FDA also noted that studies assessing the risk of blood clots have evaluated only the combination of 3 mg of drospirenone with 0.03 mg of ethinyl estradiol. It is not known whether these study results apply to other drospirenone-containing products with a lower dose of estrogen.

Varenicline (Chantix) does not appear to be associated with an increase in neuropsychiatric hospitalizations but an increased risk of other neuropsychiatric events cannot be ruled out, a recent FDA review concluded. The FDA is continuing to evaluate the issue but in the meantime the agency has concluded that the drug's benefits outweigh the risks and the current label warnings are appropriate.

Additional information has been provided by the FDA about the risks of prescribing either methylene blue or linezolid to patients taking serotonergic psychiatric medications. The agency had previously warned about reports of serotonin syndrome associated with these drug combinations. The new report notes that most incidents with methylene blue occurred in the context of parathyroid surgery, which involved the intravenous administration of the drug as a visualizing agent in doses ranging from 1 mg/kg to 8 mg/kg. It is not known whether there is a risk of serotonin syndrome in patients taking serotonergic psychiatric medications who are given methylene blue by other routes (e.g., orally or by local tissue injection) or at lower intravenous doses. Most problems with linezolid occurred in patients taking a selective serotonin reuptake inhibitor (SSRI) or a serotonin norepinephrine reuptake inhibitor (SNRI). It is unclear whether linezolid administration in patients receiving other psychiatric drugs with lesser degrees of serotonergic activity poses a comparable risk, the FDA said.

Medications for attention-deficit/hyperactivity disorder (ADHD) were not associated with adverse cardiovascular events in a large, recently-completed study in children and young adults, the FDA said. The medications studied include stimulants (amphetamine products and methylphenidate), atomoxetine, and pemoline (no longer marketed).

Enhanced safety surveillance is being required on the use of tumor necrosis factor (TNF) blockers in patients under 30, the FDA said. An ongoing safety review by the FDA will analyze malignancies in this patient group. Healthcare professionals should remain vigilant for cases of malignancy in patients treated with TNF blockers and report them to the FDA MedWatch program or to the manufacturer.