Warnings on citalopram, ondansetron; polypill approved

Details on new warnings for higher doses of citalopram hydrobromide, and more.

Recalls and warnings

A warning on the antidepressant citalopram hydrobromide (Celexa) against doses greater than 40 mg/d, due to the potential for prolongation of the QT interval and abnormal heart rhythm (including torsade de pointes). The drug label previously stated that certain patients may require a dose of 60 mg/d.

Photo by Thinkstock
Photo by Thinkstock.

A warning on antinausea drug ondansetron (Zofran) about the risk of prolongation of the QT interval, which can lead to abnormal and potentially fatal arrhythmias, including torsade de pointes. Physicians should avoid the use of ondansetron in patients with congenital long QT syndrome and electrocardiogram monitoring is recommended in patients with electrolyte abnormalities, congestive heart failure and bradyarrhythmias, or patients taking concomitant medications that prolong the QT interval.

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.

An update to the boxed warning for tumor necrosis factor-alpha (TNF-α) blockers to include the risk of infection from two bacterial pathogens, Legionella and Listeria. The FDA has identified cases of both infections in patients taking the medications.

A voluntary recall of Povidone Iodine Swabsticks, Povidone Iodine Prep Solutions, Povidone Iodine Scrub Solutions, and Povidone Iodine Prep Gel manufactured by H&P Industries, Inc. due to insufficient precautions against microbial contamination during manufacturing. No adverse events have been reported.

A warning on psychiatric drug asenapine maleate (Saphris) about the risk of type I hypersensitivity reactions (including anaphylaxis, angioedema, low blood pressure, rapid heart rate, swollen tongue, difficulty breathing, wheezing, or rash). In several cases, the reactions occurred after the first dose. Physicians should counsel patients receiving the drug about how to recognize the signs and symptoms of a serious allergic reaction.

An update to the drug label for zoledronic acid (Reclast) regarding the risk of kidney failure. Cases of acute renal failure requiring dialysis or having a fatal outcome following use of the drug have been reported. The revised label states that the medication is contraindicated in patients with creatinine clearance less than 35 mL/min or in patients with evidence of acute renal impairment and recommends that healthcare professionals screen patients prior to administering it.

A Class I recall of the SynchroMed II Infusion system due to reduced battery performance resulting from formation of a film within the pump battery, which can lead to the sudden loss of therapy and the return of underlying symptoms and/or therapy withdrawal symptoms.


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.

Crizotinib (Xalkori) to treat certain patients with locally advanced or metastatic, non-small cell lung cancers (NSCLC) who express the abnormal anaplastic lymphoma kinase (ALK) gene. The drug, a pill taken twice a day, was approved with a companion diagnostic test to determine if a patient has the abnormal ALK gene. About 1% to 7% of those with NSCLC have the ALK gene abnormality.

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.

Vemurafenib (Zelboraf) to treat patients with metastatic or unresectable melanoma. It is specifically indicated for patients whose tumors express the BRAF V600E gene mutation and was approved with a companion diagnostic test that will help determine if a patient's melanoma cells have the BRAF V600E mutation. Safety and effectiveness were established in a single international trial of 675 patients in which survival on the drug exceeded that with dacarbazine.

Brentuximab vedotin (Adcetris) to treat Hodgkin lymphoma (HL) and systemic anaplastic large cell lymphoma (ALCL). It is to be used in patients with HL whose disease has progressed after autologous stem cell transplant, or after two prior chemotherapy treatments for those who cannot receive a transplant. It may also be used in patients with ALCL whose disease has progressed after one prior chemotherapy treatment. The drug, which was approved under the accelerated approval program, is the first new treatment for HL since 1977 and the first specifically indicated to treat ALCL.

A new indication for onabotulinumtoxinA (Botox) injection to treat urinary incontinence in people with neurologic conditions, such as spinal cord injury and multiple sclerosis, who have overactivity of the bladder. The treatment consists of injections into the bladder. Two clinical studies involving 691 patients showed statistically significant decreases in the weekly frequency of incontinence episodes in the active treatment group compared with placebo.

Icatibant (Firazyr) injection for the treatment of acute attacks of hereditary angioedema (HAE) in people age 18 years and older. Median time to reported onset of symptom relief was two hours for patients treated with the drug compared with almost 20 hours with placebo. The most common side effects were injection site reactions, fever, increased liver enzymes, dizziness, and rash.

Eculizumab (Soliris) to treat patients with atypical hemolytic uremic syndrome (aHUS). Eculizumab is a targeted therapy that works by inhibiting proteins and was first approved as an orphan drug to treat paroxysmal nocturnal hemoglobinuria in March 2007. There are no other FDA-approved treatments for aHUS, and the safety and effectiveness of current standard treatments has not been studied in well-controlled trials. The drug will be available only through a restricted program requiring prescribers to enroll in a registration program.

A new indication for infliximab (Remicade) to treat moderately to severely active ulcerative colitis in children older than 6 years who have had inadequate response to conventional therapy. Its safety and efficacy was supported by a multi-center, randomized, open-label study in 60 children ages 6 to 17. The drug, a TNF blocker which is approved for treatment of other autoimmune diseases, carries a boxed warning for risk of serious infections and cancer.

LeGoo, a gel that allows surgeons to temporarily stop blood flow during surgery so that they can join blood vessels without clamps or elastic loops. A temperature sensitive gel that is liquid at room temperature and solid at higher temperatures, it has been shown to minimize blood flow into the surgical area without damaging blood vessels.

Deferiprone (Ferriprox) to treat iron overload due to blood transfusions in patients with thalassemia who had an inadequate response to prior chelation therapy. Safety and effectiveness were proven in twelve clinical studies in 236 patients. Half of the patients experienced at least a 20% decrease in ferritin levels. The most common side effects included nausea, vomiting, abdominal and joint pain, chromaturia, neutropenia, and an increase in the level of a liver enzyme that may be indicative of tissue or liver damage at unsafe amounts. The most serious side effect was the development of agranulocytosis. The therapy is being approved under the FDA's accelerated approval program.


Epinephrine inhalers (Primatene Mist) containing chlorofluorocarbons will not be sold after Dec. 31, 2011, the FDA reminded clinicians and consumers. It is the only FDA-approved inhaler for the temporary relief of occasional symptoms of mild asthma available over-the-counter without a prescription. Patients should contact a health care professional about switching to a different medicine to treat asthma, the FDA advised. Many manufacturers have changed their inhalers to replace CFCs with an environmentally-friendly propellant called hydrofluoroalkane (HFA). There is currently no HFA version of epinephrine inhalers, but there are many other safe and effective inhalers to treat asthma symptoms.