Warnings about dabigatran with mechanical valves and telaprevir combo

Details on recalls, warnings, label changes and approvals.

Recalls, warnings and label changes

A warning that dabigatran (Pradaxa) should not be used in patients with mechanical heart valves to prevent major stroke or blood clots. A trial of patients with mechanical heart valves was recently stopped because the patients taking dabigatran were more likely than those taking warfarin to experience strokes, heart attacks and blood clots that formed on the valves.

Photo by Thinkstock
Photo by Thinkstock.

An update to the warnings and precautions on varenicline (Chantix) based on an FDA safety review that found a higher occurrence of major adverse cardiovascular events in patients using the drug compared to placebo. However, the events were uncommon and the increased risk was not statistically significant, so the agency advises clinicians to weigh the risks and benefits and counsel patients to seek medical attention if they experience new or worsening symptoms of cardiovascular disease.

An update on the recall of carboplatin injection by Hospira because visible particulates have been identified as carboplatin crystals. If particulate matter from crystallization is injected into a patient, it may potentially become lodged in and obstruct blood vessels, potentially causing local infarction, thromboembolism and vasculitis.

A boxed warning about combination treatment with telaprevir (Incivek) and peginterferon alfa and ribavirin being associated with serious skin reactions, some fatal. Patients died when they continued to receive combination treatment after developing a progressive rash and systemic symptoms. According to the new warning, all three components of treatment must be immediately stopped in patients experiencing a rash with systemic symptoms or a progressive severe rash.

A new contraindication on using sodium oxybate (Xyrem) with alcohol because the combination can markedly impair consciousness and may lead to respiratory depression. The drug label already contraindicates use with insomnia drugs. Use with other central nervous system depressant drugs, such as opioid analgesics, benzodiazepines, sedating antidepressants or antipsychotics, general anesthetics, and muscle relaxants, should generally be avoided.

A recall of three lots of hydrocodone bitartrate and acetaminophen tablets, USP 10 mg/500 mg, by Qualitest Pharmaceuticals and Mylan Institutional due to the possibility that a small number of tablets from the affected lots may exceed the weight requirement and could exceed the label claim potency requirements. Unintentional administration of tablets with increased acetaminophen content could result in liver toxicity.

A class I recall of certain lots of SURGIFLO Hemostatic Matrix and Kit due to a potential for packaging breach.

A recall of one lot of Zicam extreme congestion relief nasal gel after a small amount of Burkholderia cepacia was found in a single sample of the product taken from the affected lot.

A warning that SynchroMed infusion pumps may intermittently or permanently stall and cease infusion when unapproved drugs are used with them. Currently, the approved drugs for use are morphine sulfate (Infumorph), baclofen (Lioresal, Gablofen), ziconotide acetate (Prialt), floxuridine and methotrexate. Compounded drugs, unapproved concentrations, or unapproved formulations should not be used with the pump.

A recall of Ventlab adult and pediatric manual resuscitators because they may have a valve leak that prevents the flow of air to the patient and may not be easily observable to the user because the bag still deflates when compressed. Lack of air can cause life-threatening health consequences for patients, including hypoxia, hypoventilation or death.

A recall of Bunnell Life Pulse high-frequency ventilator patient circuits due to heater wire insulation that can melt, causing sparking and smoke, close to the humidifier cartridge. This can cause serious adverse consequences, including death.

A class I recall of Praxair Inc., Grab ‘n Go Vantage portable oxygen cylinder units because fires may occur inside the cylinder unit, causing the wall of the unit to break and release oxygen. The fires are self-extinguishing and may be caused by physical impact such as dropping or knocking over the cylinder unit. If a fire occurs, users may experience burns or hypoxia.

A class I recall of Fisher and Paykel Healthcare reusable breathing circuit due to pinholes in the tubes. If these pinholes are not detected during the standard leak test before patient use, a gas leak in the breathing system could result, which may lead to a loss of pressure for the intended ventilation therapy. Usage of the defective device may result in patient death.


Teduglutide (Gattex) to treat adults with short bowel syndrome who need additional nutrition from parenteral nutrition. The once-daily injection improves intestinal absorption of fluids and nutrients. Potential risks include cancer, polyps or obstructions in the intestine, gallbladder disease, biliary tract disease and pancreatic disease. In a trial, 63% of patients taking the drug achieved at least a 20% reduction in the volume of weekly parenteral nutrition after 24 weeks of treatment versus 30% of those on placebo.

Raxibacumab, an injection to treat inhalational anthrax, and to prevent inhalational anthrax when alternative therapies are not available or appropriate. It is the first monoclonal antibody approved under the FDA's Animal Efficacy Rule, which allows findings from adequate and well-controlled animal studies to support approval when it is not feasible or ethical to conduct trials in humans.

Bedaquiline (Sirturo) as part of combination therapy to treat adults with multidrug-resistant pulmonary tuberculosis when other alternatives are not available. A boxed warning notes the risk of QT prolongation and some unexplained deaths in study patients treated with the drug. Safety and effectiveness were established in 440 patients in two phase 2 trials, in which time to sputum culture conversion was reduced compared to placebo.

Crofelemer (Fulyzaq) to relieve symptoms of diarrhea in HIV/AIDS patients taking antiretroviral therapy. Derived from the red sap of the Croton lechleri plant, it is the second botanical prescription drug approved. Safety and efficacy were established in a clinical trial of 374 patients with a history of diarrhea not caused by infection or parasite lasting one month or longer, in which 17.6% of patients on the drug experienced clinical response compared with 8% taking placebo.

An expanded use for oseltamivir (Tamiflu) to treat children younger than one year. Dosing for children younger than one year (but older than two weeks) must be calculated based on exact body weight, 3 mg per kg twice daily for five days. These smaller doses will require a different dispenser than what is currently packaged with the medication.

Pasireotide diaspartate (Signifor) injection for the treatment of patients with Cushing's disease who cannot be helped through surgery. Safety and effectiveness were evaluated in a trial of 162 patients, which resulted in decreased cortisol levels as early as one month after starting treatment. About 20% of patients achieved urine cortisol levels into the normal range, but the drug did increase in blood sugar levels and will be subject to post-marketing studies.

Lomitapide (Juxtapid) to reduce LDL cholesterol, total cholesterol, apolipoprotein B, and non-HDL cholesterol in patients with homozygous familial hypercholesterolemia. Safety and effectiveness were evaluated in a clinical trial of 29 patients in which, on average, LDL cholesterol fell by approximately one-half during the first 26 weeks among those who tolerated the drug. The drug reduces the absorption of fat-soluble nutrients, interacts with several other medications, and carries a boxed warning about risk of liver toxicity.

Ponatinib (Iclusig) to treat adults with chronic myeloid leukemia and Philadelphia chromosome-positive acute lymphoblastic leukemia, under the FDA's priority approval program. Safety and effectiveness were evaluated in a single clinical trial of 449 patients in which all participants were treated with the drug and the majority saw a reduction in the percentage of cells expressing the Philadelphia chromosome genetic mutation. It carries a boxed warning about blood clots and liver toxicity.

Flucelvax, the first seasonal influenza vaccine licensed in the United States produced using cultured animal cells, instead of fertilized chicken eggs. In a trial, the vaccine was 83.8% effective in preventing influenza compared to placebo. Reactions were typical of those seen with current influenza vaccines.

The HeartWare Ventricular Assist System, a left ventricular assist device, to support heart function and blood flow in patients with end-stage heart failure who are awaiting a heart transplant. The implantable pump with an external driver and power source is designed for use inside or outside the hospital and is small enough to be implanted in the chest rather than the abdomen. It was approved based on data from the ADVANCE trial.

The Zilver PTX stent, the first drug-eluting stent indicated to re-open the femoropopliteal artery when narrowed or blocked as a result of peripheral artery disease. The paclitaxel-coated stent was approved based on trials which found it to be at least as safe as and significantly more effective than percutaneous transluminal angioplasty and bare-metal stents.

Cabozantinib (Cometriq) to treat medullary thyroid cancer that has metastasized. The safety and effectiveness of this kinase inhibitor were established in a placebo-controlled study in which patients taking the drug had an average of 11.2 months of progression-free survival compared to four months on placebo. It carries a boxed warning about the risk of severe and fatal bleeding and perforations and fistula in the colon.

An expanded approval of abiraterone acetate (Zytiga) to treat metastatic castration-resistant prostate cancer prior to chemotherapy. The drug was initially approved in November 2011 for use in patients whose prostate cancer progressed after treatment with docetaxel. In a trial of patients who hadn't received chemotherapy, the drug increased overall and progression-free survival compared to placebo.