Boxed warning removed from asthma drugs

Recalls, warnings, and alerts

A recall of one lot of clopidogrel tablets USP (75 mg) by International Laboratories due to mislabeling. The product is labeled as containing clopidogrel tablets USP (75 mg) but may contain simvastatin tablets USP (10 mg).

A warning to Becton Dickinson (BD) & Company citing several violations of federal law. During an inspection of BD's New Jersey facility, the FDA found that the company marketed significantly modified versions of certain BD Vacutainer blood collection tubs without required agency clearance or approval, as well as failed to submit medical device reports within the required timeframe. The inspection was part of an ongoing investigation into the root cause of inaccurate blood lead test results associated with Magellan's LeadCare test systems.

An alert that BD is no longer using problematic rubber stopper material associated with loss of drug potency in its general use syringes. The company has returned to using a rubber stopper it had previously used in the syringes.

An alert that anaphylaxis, anaphylactic shock, and other serious hypersensitivity reactions have been reported with the use of rolapitant (Varubi) injectable emulsion. Most of the reactions occurred within the first few minutes of infusion, and some required hospitalization. Clinicians should consult with patients to detect any hypersensitivity to the drug's components, including soybean oil, and avoid use in patients with potential hypersensitivity.

A recall of all sterile drug products by PharMEDium Services due to a lack of sterility assurance. PharMEDium initially recalled 55 lots but has expanded the recall to all unexpired lots compounded at the company's Memphis facility.

Miscellaneous

A removal of the boxed warning about asthma-related death from the drug labels of medications containing both long-acting beta-agonists (LABAs) and inhaled corticosteroids (ICS). The FDA reviewed four safety trials of more than 41,000 patients, which showed that using LABAs in combination with ICS to treat patients with asthma did not lead to more serious asthma-related side effects (e.g., hospitalization, intubation, or death) compared to using ICS alone. The trials also assessed efficacy and found that using LABA/ICS combination therapy reduced asthma exacerbations compared to using ICS alone.

An updated product label for the cancer drug nilotinib (Tasigna) that includes information about how to discontinue the drug in certain patients. Under the updated recommendations, certain patients with early-phase chronic myeloid leukemia who have taken the drug for three years or more and have responded to treatment may be eligible to discontinue the drug. Any treatment discontinuation must be followed by regular monitoring for disease recurrence.

Approvals

Marketing of the Dermapace System, the first shock-wave device intended to treat diabetic foot ulcers. The device is intended to be used with standard diabetic ulcer care in patients ages 22 years and older presenting with ulcers lasting for more than 30 days. The system uses pulses of energy to mechanically stimulate chronic, full-thickness diabetic foot ulcers with wound areas measuring no more than 16 cm², or about the size of a soda-can top. Treatable wounds may extend through the epidermis, dermis, tendon, or capsule, but without bone exposure. In two randomized, double-blind studies of a total of 336 patients receiving usual wound care (including wet-to-dry dressings or debridement as needed) plus either the shock-wave therapy or sham therapy, patients who had between one and seven treatments with the system had an increase in wound healing at 24 weeks, with a 44% wound-closure rate compared to a 30% rate with sham treatment during the same time period. The most common side effects were pain during application of the device, local bruising and numbness, migraines, nausea, fainting, wound infection, cellulitis, osteomyelitis, and fever.

Angiotensin II (Giapreza) injection for intravenous infusion to increase blood pressure in adults with septic or other distributive shock. A trial of 321 patients with shock and critically low blood pressure found that the treatment increased blood pressure when added to conventional approaches to increase blood pressure. Significantly more patients responded to the injection compared to those treated with placebo. The drug can cause dangerous blood clots with such consequences as deep venous thrombosis, so clinicians should use prophylactic treatment for clots.

The GammaPod, a noninvasive stereotactic radiotherapy system to treat breast cancer. The system delivers a radiation dose to specific areas of the breast in conjunction with breast-conserving treatment. It has not been shown to be as effective as whole breast radiation therapy and is not intended as a replacement. In a clinical study of 17 patients, the system delivered the prescribed dose to breast tumors with minimal radiation-induced side effects, such as skin redness and erythema.

Expanded approval of olaparib tablets (Lynparza) to treat patients with certain types of metastatic breast cancer whose tumors have a specific inherited genetic mutation. The drug is the first to be approved to treat certain patients with metastatic breast cancer who have a BRCA mutation. Patients are selected for treatment with the drug based on an FDA-approved genetic test, the BRACAnalysis CDx. In a randomized trial of 302 patients, median progression-free survival for patients taking the drug was seven months, compared to 4.2 months for patients receiving chemotherapy only. Common side effects include anemia, neutropenia, nausea, fatigue, and vomiting, and severe side effects include acute myeloid leukemia and pneumonitis.

First-time generic approvals

Ibuprofen and pseudoephedrine hydrochloride capsules (200 mg/30 mg [over-the-counter]) to temporarily relieve symptoms associated with the common cold and flu. (Brand name: Advil Cold and Sinus Liqui-Gels)

Doxylamine succinate and pyridoxine hydrochloride delayed-release tablets (10 mg/10 mg) to treat nausea and vomiting of pregnancy in women who do not respond to conservative management. (Brand name: Diclegis)

Butalbital and acetaminophen capsules (50 mg/300 mg) to relieve the symptom complex of tension or muscle contraction headache. (Brand name: Phrenilin Forte)

Estradiol vaginal cream USP (0.01%) to treat moderate to severe symptoms of vulvar and vaginal atrophy due to menopause. (Brand name: Estrace)

Triamcinolone acetonide injectable suspension USP (40 mg/mL vials, 200 mg/5 mL [40 mg/mL] multidose vials, and 400 mg/10 mL [40 mg/mL] multidose vials) for use as an injectable corticosteroid therapy. (Brand name: Kenalog)

Efavirenz capsules USP (50 mg, 100 mg, and 200 mg) to treat HIV-1 infection. (Brand name: Sustiva)

Note: The FDA states that drugs are not always commercially available immediately after approval.