New cholesterol drug class; FDA investigates gadolinium

Details on the latest recalls, warnings, and approvals.

Recalls and warnings

A warning on Hospira's Symbiq Infusion System about cybersecurity vulnerabilities. The FDA strongly encourages health care facilities to discontinue use of these pumps and transition to alternative infusion systems, as the systems could be accessed remotely through a hospital's network, possibly allowing an unauthorized user to control the devices and change the dosage the pumps deliver. No unauthorized access in a health care setting has been reported.

A warning about confusion between vortioxetine (Brintellix) and ticagrelor (Brilinta) resulting in the wrong medication being prescribed or dispensed, due to the similarity of their brand names. Clinicians can reduce the risk of name confusion by including the generic name of the medication, in addition to the brand name, and the indication for use when prescribing these medications, the FDA said.

Photo by Thinkstock
Photo by Thinkstock

A recall of 6 lots of fluorouracil injection (Adrucil), 5 g/100 mL (50 mg/mL), by Teva Parenteral Medicines because of the potential presence of particulate matter, identified as aggregate of silicone rubber pieces from a filler diaphragm and fluorouracil crystals.

A recall of 3 lots of prolotherapy with phenol injection (5-mL and 100-mL vials) by Hartley Medical because of concerns regarding sterility.

A recall of 2 lots of 0.9% sodium chloride injection intravenous solution by Baxter due to reports of particulate matter, determined to be an insect.

A recall of another lot of 0.9% sodium chloride injection intravenous solution by Baxter because of the potential for leaking containers, particulate matter, and missing port protectors, which could result in contamination of the solution.

A warning that implantable left ventricular assist devices for bridge-to-transplant or destination therapy can cause serious adverse events, including an increased rate of pump thrombosis with Thoratec's HeartMate II and a high rate of stroke with the HeartWare HVAD since approval of the devices. There are also bleeding complications related to both systems, although the benefits of these devices continue to outweigh the risks, the FDA said.

A recall of 2,239 lots of Beacon Tip angiographic catheters by Cook Medical due to 26 complaints of catheter tip-splitting and/or separation, with 14 resulting in adverse events. Catheter separation can cause the tip to enter the patient's bloodstream, which can cause serious injury. Tip separation may require medical intervention to retrieve a separated segment or may occlude blood flow to end organs.

A warning and label change that fingolimod (Gilenya) has resulted in cases of progressive multifocal leukoencephalopathy, with 1 definite case and 1 probable case in patients with multiple sclerosis. These are the first cases reported in patients who had not been previously treated with an immunosuppressant drug.

A recall of compounded drugs by Moses Lake Professional because of lack of sterility assurance upon recent inspection.


Alirocumab (Praluent) injection to treat heterozygous familial hypercholesterolemia or clinical atherosclerotic cardiovascular disease in addition to diet and maximally tolerated statin therapy. It is the first in a new class, PCSK9 inhibitors. In trials of 2,476 participants, those taking the drug had an average reduction in LDL cholesterol ranging from 36% to 59% compared to placebo. The most common side effects include itching, swelling, pain, or bruising where injection is given, nasopharyngitis, and flu. Allergic reactions, such as hypersensitivity vasculitis and hypersensitivity reactions requiring hospitalization, have been reported.

Daclatasvir (Daklinza) for use with sofosbuvir to treat hepatitis C virus (HCV) genotype 3 infections. This is the first drug that has demonstrated safety and efficacy to treat genotype 3 without the need for co-administration of interferon or ribavirin. In a trial, 98% of treatment-naive participants with no cirrhosis and 58% of those with cirrhosis achieved sustained virologic response taking daclatasvir, 60 mg, plus sofosbuvir, 400 mg, once daily. Among treatment-experienced patients, 92% of those with no cirrhosis and 69% of those with cirrhosis were successfully treated. The most common side effects were fatigue and headache. The drug carries a warning that serious symptomatic bradycardia sometimes requiring pacemaker intervention has been reported when amiodarone is co-administered with sofosbuvir in combination with another HCV direct-acting antiviral, including daclatasvir.

Combined ombitasvir, paritaprevir, and ritonavir (Technivie) for use in combination with ribavirin for the treatment of HCV genotype 4 infections in patients without scarring and cirrhosis. This is the first approved drug for genotype 4 HCV infections without the need for co-administration of interferon. In a trial, 100% of those who received the combination with ribavirin achieved a sustained virologic response, as did 91% of those who received it without ribavirin. The most common side effects with ribavirin were fatigue, asthenia, nausea, insomnia, pruritus, and other skin reactions. The drug carries a warning about elevations of liver enzymes to greater than 5 times the upper limit of normal, which occurred in approximately 1% of trial participants, more frequently in females taking contraceptives containing ethinyl estradiol. Such contraceptives must be discontinued prior to starting the drug.

The ReShape Integrated Dual Balloon System to treat obesity without invasive surgery. The device is indicated for patients with a body mass index of 30 to 40 kg/m2 and 1 or more obesity-related conditions in whom previous attempts at weight loss through diet and exercise alone have failed. It is inserted into the stomach through an endoscopic procedure and, once in place, is inflated with a sterile solution. The balloon is meant to be temporary and should be removed 6 months after insertion. Approval was based on a placebo-controlled study finding that 187 patients randomly selected to receive the device lost 14.3 pounds on average by 6 months, compared to 7.2 pounds in controls. Six months after removal, treated patients had kept off an average of 9.9 pounds. Potential side effects include headache, muscle pain, and nausea from the sedation and procedure; in rare cases, severe allergic reaction, heart attack, esophageal tear, infection, and breathing difficulties can occur. Once the device is placed in the stomach, patients may experience vomiting, nausea, abdominal pain, gastric ulcers, and feelings of indigestion.

Flibanserin (Addyi) to treat acquired, generalized hypoactive sexual desire disorder in premenopausal women. This 100-mg, once-nightly medication has a potentially serious interaction with alcohol; therefore, treatment will only be available through certified health care professionals and pharmacies, and alcohol use is contraindicated. In 3 randomized, double-blind, placebo-controlled trials, the drug increased the number of satisfying sexual events by 0.5 to 1 additional event per month, increased sexual desire score by 0.3 to 0.4, and decreased the distress score related to sexual desire by 0.3 to 0.4. The most common adverse reactions are dizziness, somnolence, nausea, fatigue, insomnia, and dry mouth. The drug can cause hypotension and syncope, and these risks are increased and more severe when patients drink alcohol or take it with moderate or strong CYP3A4 inhibitors.

Sonidegib (Odomzo) to treat locally advanced basal cell carcinoma that has recurred following surgery or radiation therapy, or in patients who are not candidates for surgery or radiation therapy. The once-daily pill inhibits the Hedgehog pathway. In a trial of 66 patients, 58% of those who received a 200-mg daily dose had their tumors shrink or disappear, and about half of the responding patients' tumor shrinkage lasted 6 months or longer. The most common side effects were muscle spasms, alopecia, dysgeusia, fatigue, nausea, musculoskeletal pain, diarrhea, decreased weight, decreased appetite, myalgia, abdominal pain, headache, pain, vomiting, and pruritus. The drug also has the potential to cause serious musculoskeletal-related side effects, including increased serum creatine kinase levels (with rare reports of rhabdomyolysis), muscle spasms, and myalgia. The drug carries a boxed warning that it may cause death or severe birth defects in a developing fetus.

The Bio-Rad BioPlex 2200 HIV Ag-Ab assay to aid in diagnosis of HIV-1 and HIV-2. It is the first FDA-approved diagnostic that differentiates between HIV-1 antibodies, HIV-2 antibodies, and HIV-1 p24 antigen in human serum or plasma specimens. Reporting of distinct results also helps differentiate between acute and established HIV infection. It may be used in adults, children aged 2 years and older, and pregnant women, as well as potential organ donors.

Gefitinib (Iressa) for first-line treatment of metastatic non-small-cell lung cancer in which tumors harbor specific types of epidermal growth factor receptor gene mutations. A companion test to identify appropriate patients was also approved. A clinical trial of 106 patients resulted in tumors shrinking in about 50% of patients after treatment, and this effect lasted an average of 6 months. The most common side effects are diarrhea and skin reactions. More serious potential side effects include interstitial lung disease, liver damage, gastrointestinal perforation, severe diarrhea, and ocular disorders.

The Osseoanchored Prosthesis for the Rehabilitation of Amputees device, the first prosthesis marketed in the U.S. for adults who have amputations above the knee and cannot use a conventional socket prosthesis. The device uses fixtures and screws implanted into the patient's remaining thigh bone to connect an external prosthetic limb. A 2-year, 51-subject clinical trial found that participants reported improved mobility, comfort, function, and quality of life compared to their own prior status. Infection was the most common adverse event.


The FDA is investigating the risk of brain deposits following repeated use of gadolinium-based contrast agents (GBCA) for MRI. Studies have reported that deposits of these agents remain in the brains of some patients, even those with normal kidney function, who undergo 4 or more contrast MRI scans, long after the last administration. It is unknown whether these deposits are harmful or can lead to adverse health effects. The FDA recommends that clinicians consider limiting GBCA use to clinical circumstances in which the additional information provided by the contrast is necessary and reassess the necessity of repetitive GBCA MRIs. This issue does not apply to other types of scanning agents used for other imaging procedures, such as those that are iodine-based or radioisotopes, the agency noted.

The FDA recently released a detailed list of supplemental duodenoscope reprocessing measures that emerged from an agency-led expert panel meeting earlier this year. Hospitals and health care facilities that utilize duodenoscopes can, in addition to following manufacturer reprocessing instructions, take 1 or more of the following steps to further reduce the risk of infection and increase the safety of these medical devices: microbiological culturing, ethylene oxide sterilization, use of a liquid chemical sterilant processing system, and repeat high-level disinfection.