Recalls and warnings
A warning that combination dasabuvir, ombitasvir, paritaprevir, and ritonavir (Viekira Pak) and combination ombitasvir, paritaprevir, and ritonavir used in combination with ribavirin (Technivie) can cause serious liver injury, mostly in patients with underlying advanced liver disease. After identifying cases of hepatic decompensation and liver failure in patients with underlying liver cirrhosis who were taking these combinations, the FDA required the manufacturer to add information about serious liver injury adverse events to the drug labels. In most cases, liver injury occurred within 1 to 4 weeks of the time that treatment was started, with some events resulting in liver transplantation or death.
A recall of all 0.15-mg and 0.3-mg epinephrine injections (Auvi-Q) that expire from March to December 2016, due to potentially inaccurate dosage delivery. As of Oct. 26, 2015, the manufacturer had received 26 reports of suspected device malfunctions in both the United States and Canada. No fatal outcomes have been reported among these cases.
A strengthened warning on canagliflozin (Invokana, Invokamet) about increased risk of bone fractures and decreased bone mineral density. Clinicians should consider factors that contribute to fracture risk before they start patients on canagliflozin, which has also been linked to decreases in bone mineral density at the hip and lower spine. The FDA continues to evaluate the risk of bone fractures with other sodium glucose cotransporter-2 inhibitors, such as dapagliflozin and empagliflozin, to determine if additional label changes or studies are needed.
A recall of all lots of sterile products aseptically compounded and packaged by US Compounding, Inc., because of concerns by the FDA over lack of sterility assurance. The products were distributed nationwide to patients, clinicians, hospitals, and clinics between March 14 and Sept. 9, 2015, and should not be used.
A warning not to use drug products made and distributed by Chen Shwezin, Inc,. that were intended to be sterile. Upon inspection of the facility, FDA investigators observed poor sterile production practices. The company, operating as Park Compounding Pharmacy, has agreed to cease sterile operations but has refused to recall its products. The FDA is not aware of any adverse events resulting from use of these products.
A recall of sterile products compounded and packaged by Downing Labs, LLC, because of concerns over sterility assurance. All clinicians and patients who received the affected products, distributed from April 20 and Sept. 15, 2015, should discontinue use.
Pembrolizumab (Keytruda) for patients with metastatic non-small-cell lung cancer whose disease has progressed after other treatments. Eligible patients have tumors that express a protein called PD-L1, detected with a companion diagnostic, and the drug blocks the cellular pathway known as PD-1/PD-L1. The safety of pembrolizumab was studied in 550 patients with advanced non-small-cell lung cancer, and the most common side effects included fatigue, decreased appetite, dyspnea, and cough. Pembrolizumab also has the potential to cause severe immune-mediated side effects. In an efficacy trial of 61 patients, the drug shrank tumors in 41% of patients, and this effect lasted between 2.1 and 9.1 months.
Nivolumab (Opdivo) to treat patients with metastatic non-small-cell lung cancer whose disease progressed during or after platinum-based chemotherapy. The drug blocks the cellular pathway PD-1/PD-L1. In a study of 582 participants with metastatic non-small cell-lung cancer, those treated with nivolumab lived an average of 12.2 months, compared to an average of 9.4 months in those who were treated with docetaxel. Complete or partial shrinkage of the tumors occurred in 19% of those receiving nivolumab, with an effect lasting an average of 17 months, compared to 12% of those taking docetaxel, lasting an average of 6 months. The most common side effects are fatigue, musculoskeletal pain, decreased appetite, cough, and constipation, although the drug can also cause serious immune-mediated side effects.
Insulin degludec injection (Tresiba) and insulin degludec/insulin aspart injection (Ryzodeg 70/30) to improve glucose control in adults with diabetes. The former agent, a long-acting insulin analog for both type 1 and 2 diabetes, is subcutaneously administered once daily at any time of day. The latter agent, administered once or twice daily, is a mixture of a long-acting insulin analog (insulin degludec) and a rapid-acting human insulin analog (insulin aspart). The most common side effects are hypoglycemia, allergic reactions, injection-site reactions, lipodystrophy, itching, rash, edema, and weight gain. Both drugs are contraindicated for patients with diabetic ketoacidosis.
Irinotecan liposome injection (Onivyde) to be used in combination with fluorouracil and leucovorin to treat metastatic pancreatic cancer previously treated with gemcitabine-based chemotherapy. In a randomized trial, patients treated with the full combination lived an average of 6.1 months, compared to an average of 4.2 months for those treated with fluorouracil and leucovorin alone. Patients receiving the 3-drug combination also had a delay in the amount of time to tumor growth. The most common side effects included diarrhea, fatigue, vomiting, nausea, decreased appetite, stomatitis and fever. Lymphopenia and neutropenia, including death due to sepsis following neutropenia, have been reported.
Aripiprazole lauroxil (Aristada) for adults with schizophrenia. Aripiprazole lauroxil is administered every 4 to 6 weeks using an injection in the arm or buttocks. In a trial of 622 patients with acute schizophrenia who had been stabilized with oral aripiprazole, the drug maintained the treatment effect compared to placebo. The most common side effect is akathisia.
Patiromer for oral suspension (Veltassa) to treat hyperkalemia. Taken with water, the powdered medication works by binding potassium in the gastrointestinal tract, decreasing its absorption. The drug effectively lowered potassium levels in hyperkalemic participants with chronic kidney disease who were taking at least 1 drug that inhibited the renin-angiotensin-aldosterone system. The most common adverse reactions were constipation, hypomagnesemia, diarrhea, nausea, abdominal discomfort, and flatulence. The drug carries a boxed warning that it may decrease the absorption and effects of other oral drugs.
Trabectedin (Yondelis) to treat unresectable or metastatic-specific soft-tissue sarcomas (STS)—liposarcoma and leiomyosarcoma—previously treated with chemotherapy that contained anthracycline. Approval is based on a trial finding that patients taking trabectedin experienced a delay in tumor growth of 4.2 months, compared to the delay of 1.5 months experienced by those receiving dacarbazine. The most common side effects among participants who received trabectedin were nausea, fatigue, vomiting, diarrhea, constipation, decreased appetite, dyspnea, headache, peripheral edema, neutropenia, thrombocytopenia, anemia, elevated liver enzymes, and decreases in albumin level. The drug's label warns of risks of severe and fatal neutropenic sepsis, rhabdomyolysis, hepatotoxicity, extravasation, tissue necrosis, and cardiomyopathy.
Idarucizumab (Praxbind) for emergency situations when there is a need to reverse dabigatran (Pradaxa). The intravenous injection, the first reversal agent approved specifically for dabigatran, works by binding to the drug compound to neutralize its effect. In 3 trials of 283 healthy volunteers taking dabigatran, idarucizumab immediately reduced the amount of dabigatran in participants' blood, and this effect lasted for at least 24 hours. The most common side effect from idarucizumab was headache. In another trial of 123 patients taking dabigatran who had uncontrolled bleeding or who needed to have emergency surgery, the anticoagulant effect was fully reversed in 89% of patients within 4 hours of receiving idarucizumab. The most common side effects in this trial were hypokalemia, confusion, constipation, fever, and pneumonia.
Combination trifluridine and tipiracil (Lonsurf) for metastatic colorectal cancer that is no longer responding to chemotherapy and biological therapy. In a study of 800 patients with previously treated metastatic colorectal cancer, patients treated with the oral drug lived an average of 7.1 months, compared to an average of 5.3 months among those treated with placebo. Average time to disease progression was 2 months for treated patients, compared to 1.7 months for those receiving placebo. The most common side effects are anemia, neutropenia, thrombocytopenia, physical weakness, fatigue, nausea, decreased appetite, diarrhea, vomiting, abdominal pain, and fever. Clinicians should obtain complete blood counts before starting each treatment cycle and monitor patients throughout treatment, as myelosuppression may result.
Human coagulation factor X (Coagadex) for controlling bleeding episodes in individuals age 12 years and older with hereditary factor X deficiency. Derived from human plasma, it is the first specific coagulation factor replacement therapy approved for such patients. In a multicenter, nonrandomized study of 16 participants with mild to severe factor X deficiency, the drug controlled spontaneous, traumatic, and menorrhagic bleeding episodes. In addition, the drug controlled loss of blood during and after surgery in 5 individuals who had mild factor X deficiency. No safety concerns were identified in either study.
An expanded indication for the Optune device to treat newly diagnosed glioblastoma multiforme. Initially approved in 2010 for patients with glioblastoma multiforme that recurred or progressed after chemotherapy, the device may now be given along with temozolomide, following standard treatments including surgery, chemotherapy, and radiation therapy. In a clinical trial of 695 patients, those treated with the device and temozolomide lived on average 3 months longer than those treated with the drug alone. The most common side effect of the device is skin irritation.
Daratumumab (Darzalex) to treat multiple myeloma in patients who have received at least 3 prior treatments. Given as an infusion, daratumumab injection is a monoclonal antibody that helps certain cells in the immune system attack cancer cells. In a trial of 106 patients, 29% experienced a complete or partial reduction in their tumor burden, lasting an average of 7.4 months. Another study showed that 36% of 42 participants receiving the drug had complete or partial reduction in tumor burden. The most common side effects were infusion-related reactions, fatigue, nausea, back pain, fever, and cough. The drug may also result in lymphopenia, neutropenia, leukopenia, anemia, and thrombocytopenia.
Antihemophilic factor (recombinant), PEGylated (Adynovate) to treat hemophilia A in patients age 12 and older. This drug is modified to last longer in the blood, potentially requiring less frequent injections than unmodified antihemophilic factor when used to reduce bleeding frequency. In a clinical trial of 137 participants, the drug effectively reduced the number of bleeding episodes during routine care, and no safety concerns were identified.
Talimogene laherparepvec (Imlygic), a genetically modified live oncolytic herpesvirus therapy, for the treatment of unresectable melanoma lesions in the skin and lymph nodes. The drug is injected directly into the lesions, where it replicates inside cancer cells, causing them to rupture and die. A study of 436 participants with metastatic melanoma that could not be surgically removed showed that 16.3% of the patients who received the drug experienced a decrease in the size of their lesions that lasted a minimum of 6 months, compared to 2.1% of the patients receiving the comparator therapy. Talimogene laherparepvec has not been shown to improve overall survival or have an effect on melanoma that has spread to internal organs. The most common side effects were fatigue, chills, fever, nausea, flu-like symptoms, and pain at the injection site. Since herpesvirus infection can occur, the drug should not be given to immunocompromised or pregnant patients.
An FDA review has determined that long-term use of clopidogrel (Plavix) does not increase or decrease overall risk of death in patients who have or are at risk for heart disease. Compared to short-term (6 months or less) dual antiplatelet therapy with clopidogrel and aspirin or aspirin alone, long-term (12 months or longer) clopidogrel and aspirin did not appear to change the overall risk of death or cancer-related adverse events.
A safety review found no clear evidence of a link between entacapone (Comtan) for the treatment of Parkinson's disease and increased risk of heart attacks, stroke, or other cardiovascular events. Therefore, recommendations for using entacapone and combination entacapone, carbidopa, and levodopa (Stalevo) will remain the same. Carbidopa and levodopa have not been shown to have an increased cardiovascular risk.
A permanent injunction prohibiting the manufacture and distribution of QLaser low-level laser devices unless and until the company obtains premarket approval or FDA clearance. Although the FDA cleared 2 QLaser devices for providing temporary relief of pain associated with osteoarthritis of the hand, the agency has not cleared or approved any of the devices to treat any other medical conditions.
A safety alert on sodium polystyrene sulfonate (Kayexalate) and the possibility of drug interactions. The drug's approved labeling contains a warning not to take other oral medications within 6 hours of administration and describes the potential of the hyperkalemia drug to decrease absorption of lithium and thyroxine, but extensive drug interactive studies have not been performed. In addition, the FDA recently identified interactions with another potassium-lowering drug. The manufacturer is studying the issue, and if these studies confirm interactions with other medications, the FDA will require drug label updates.