Generic pioglitazone, new HIV combination pill approved

This regulatory update covers approvals of the first generic form of pioglitazone and a combination form of emtricitabine, tonofavir and two new drugs for patients new to HIV treatment.

Recalls, warnings and label changes

An alert that Reumofan Plus and Reumofan Plus Premium, pain relief supplements, contain undeclared active pharmaceutical ingredients not listed on the label that could be harmful, including diclofenac sodium and methocarbamol. Clinicians should ask patients about use of this and other dietary supplements when patients present with unexplained symptoms suggesting NSAID toxicity, depression or the use or abrupt discontinuation of corticosteroids.


A recall of one lot of Hospira hydromorphone injection, USP, 2 mg/mL (C-II), 1 mL fill in 2.5 mL Carpuject, NDC 0409-1312-30, due to a reported complaint of one injection containing more than 1 mL.

A recall of three lots of Hospira propofol injectable emulsion, 1%, 1g/100 mL, due to visible particles embedded in the glass. There may be potential for product to come into contact with the embedded particles and the particles may become dislodged into the solution.

A recall of one lot of nimodipine capsules, 30 mg, marketed by Caraco Pharmaceutical Laboratories, Ltd. due to the presence of crystals of nimodipine within the capsule solution, identified by a customer complaint. No adverse events have been reported at this time.

A narrowing of the indication for the Stryker Wingspan stent system to only patients with severe intracranial stenosis and recurrent stroke despite continued medical management who have not had any new symptoms of stroke within seven days.

A recall of certain lots of DGPHP RFA high-power single-use grounding pads due to the potential degradation of foil, which may have resulted in reports of burns at the pad site on patients.

A safety communication about St. Jude Medical Riata implantable cardioverter defibrillator (ICD) leads, which were previously recalled. The leads have an increased risk of premature insulation failure, beginning approximately four years after implant. Lead insulation failure may cause the ICD lead to malfunction. Physicians should continue to closely monitor patients who have a Riata or Riata ST lead and reprogram the device to increase the chance to detect an abnormality.

A class I recall of the CareFusion 303, Alaris Pump Module, Model 8100, due to a potential for the pump module door keypad overlay to become loose, peel away, or separate from the door assembly, which could lead to a keypad malfunction, causing the infusion to stop.

A class I recall of the I-Flow ON-Q Pump with on-demand bolus button because it may not lock in the down position when depressed and/or the orange bolus refill indicator may stay in the lowest position, leading to continuous infusion at a rate greater than expected.

A class I recall of Baxter Healthcare Automix Automated Nutrition Compounder Systems, due to incorrect key press responses, caused by fluid entry into device keypads, and intermittent electrical failures, which could lead to improperly mixed total parenteral nutrition solutions.

A recommendation against the off-label use of sildenafil (Revatio) in children to treat pulmonary arterial hypertension. This recommendation is based on a recent trial showing that children taking a high dose had a higher risk of death than children taking a low dose and the low dose was not effective in improving exercise ability.


A new indication for ranibizumab injection (Lucentis) to treat diabetic macular edema. Clinical trials showed 34% to 45% of patients who received monthly injections of 0.3 mg gained at least three lines of vision compared with 12% to 18% of those who did not receive an injection. The most common side effects include bleeding of the conjunctiva, eye pain, floaters and increased intraocular pressure.

Linaclotide (Linzess) to treat chronic idiopathic constipation and irritable bowel syndrome with constipation in adults. It is a capsule taken once daily on an empty stomach, at least 30 minutes before the first meal of the day. In trials, it was more effective than placebo in reducing abdominal pain and increasing the number of complete spontaneous bowel movements. A boxed warning notes that the drug should not be used in patients 17 years of age and younger.

The first generic version of pioglitazone hydrochloride (Actos) to improve blood glucose control in adults with type 2 diabetes, along with diet and exercise.

A new combination pill (Stribild) to treat HIV-1 infection in adults. The pill contains emtricitabine, tenofovir disoproxil fumarate and two new drugs: elvitegravir and cobicistat. It is approved for patients not previously treated for HIV. In a clinical trial, 88% to 90% of patients on the drug had an undetectable amount of HIV in their blood at 48 weeks.

Vincristine sulfate liposome injection (Marqibo) to treat adults with Philadelphia chromosome negative acute lymphoblastic leukemia. The once-weekly injection is approved for patients whose leukemia has relapsed two or more times, or whose leukemia has progressed following two or more regimens of anti-leukemia therapy. It was approved under the FDA's accelerated approval program.

A new dosage of everolimus (Afinitor Disperz) to treat subependymal giant-cell astrocytoma in children. It is the first approved pediatric-specific dosage developed for the treatment of a pediatric tumor. It also dissolves easily in a small volume of water.

Tbo-filgrastim, a biologic drug to reduce severe neutropenia in patients receiving cancer chemotherapy. It is intended for use in adults who have non-myeloid malignancies and are taking chemotherapy drugs that cause a substantial decrease in the production of neutrophils in the bone marrow. Tbo-filgrastim stimulates increased production of neutrophils. It is administered as an injection beginning 24 hours after chemotherapy treatment.

Enzalutamide (Xtandi) to treat metastatic castration-resistant prostate cancer that has spread or recurred, even with medical or surgical therapy to minimize testosterone. In a clinical trial, median overall survival for patients receiving the drug was 18.4 months, compared with 13.6 months on placebo. Seizures occurred in approximately 1% of those taking the drug.


The FDA is currently conducting a safety review of codeine after reports of children developing serious adverse effects or dying after taking codeine after tonsillectomy and/or adenoidectomy for obstructive sleep apnea syndrome. These children (age two to five) had evidence of an inherited ability to convert codeine into life-threatening or fatal amounts of morphine in the body. All children had received doses of codeine that were within the typical dose range. The estimated number of people who are ultra-rapid metabolizers of codeine is generally 1 to 7 per 100 people, but may be as high as 28 per 100 people in some ethnic groups. The FDA is currently assessing whether there have been additional cases of inadvertent overdose or death in children taking codeine, and if these adverse events occur during treatment of other kinds of pain, such as post-operative pain following other types of surgery.