Recalls and warnings
A warning that serious infections have occurred in adults who received investigational fecal microbiota transplantation (FMT) containing multidrug-resistant organisms. One immunocompromised patient died and another was infected after receiving preparations that used the same donor's stool, which contained extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli. The donor stool and resulting FMT preparation were not tested for ESBL-producing gram-negative organisms prior to use. In response to the cases, the FDA proposed additional safety protections for the investigational use of FMT, including screening donors for risk factors for colonization with multidrug-resistant organisms and excluding individuals at increased risk of colonization. The FDA also recommended testing donor stool for multidrug-resistant organisms and excluding stool that tests positive.
A class I recall of certain lots of Hudson RCl Sheridan Endotracheal Tubes by Teleflex Incorporated due to potential disconnection between the connector and the endotracheal tube, which could result in insufficient oxygenation of the patient. There have been four reported deaths and additional reports of serious injuries where this disconnection may have been a factor. More than six million recalled products were distributed from October 2016 to May 2019.
A class I recall of the SoloPath Balloon Expandable TransFemoral System and Re-Collapsible Balloon Access System by Terumo Medical Corporation due to a potential for the tip to dislodge from the outer rim of the sheath. The single-use devices are designed to help insert and guide placement of catheters and other medical devices. There have been 14 reports of incidents related to device malfunction, including two injuries. The recall includes 3,474 devices distributed from July 22, 2016, to March 13, 2019.
A class I recall of the Advance Enforcer 35 Focal-Force PTA Balloon Catheter (6 mm × 4 cm) by Cook Incorporated due to multiple complaints about balloons bursting below the rated burst pressure. While there were no related reports of malfunctions, deaths, or injuries, there was a high occurrence rate. The recall includes 33 devices distributed from Oct. 29, 2018, to March 21, 2019.
An expanded recall of six lots of bulk losartan potassium USP tablets (two lots of 50-mg strength and four lots of 100-mg strength) by Teva Pharmaceuticals USA, Inc., due to the detection of an impurity. N-Nitroso-N-methyl-4-aminobutyric acid, a potential human carcinogen, was detected in one lot of the active pharmaceutical ingredient manufactured by Hetero Labs Limited, which was used in the manufacturing of the recalled products.
Recall of all unexpired sterile products by RXQ Compounding, LLC, Infusion Options, Inc., and Premier Pharmacy Labs due to lack of sterility assurance.
A warning to two companies for illegally selling kratom products with unproven claims about their ability to treat or cure opioid addiction and withdrawal symptoms. The companies, Cali Botanicals of Folsom, Calif., and Kratom NC of Wilmington, N.C., also make claims about treating pain, as well as depression, anxiety, and cancer. The FDA continues to warn consumers not to use the plant Mitragyna speciosa, commonly known as kratom, which is not legally marketed in the U.S. as a drug or dietary supplement. Available data suggest that certain substances in kratom have opioid properties that may expose users to the risks of addiction, abuse, and dependence.
A labeling change for flibanserin (Addyi), which was approved in 2015 to treat acquired, generalized hypoactive sexual desire disorder in premenopausal women. The labeling currently includes a boxed warning and contraindication stating that women must avoid alcohol when taking the drug due to concerns of severe hypotension and syncope. Based on the results of postmarketing studies, the FDA determined that the updated drug labeling should convey that patients do not need to avoid alcohol completely. Women should either discontinue drinking alcohol at least two hours before taking the drug at bedtime or skip the dose that evening. The updated label will also state that women should not consume alcohol at least until the morning after taking the drug at bedtime. The FDA will not remove the boxed warning and contraindication completely from the product labeling.
A new indication for ceftolozane and tazobactam (Zerbaxa) to treat adults with hospital-acquired or ventilator-associated bacterial pneumonia. The drug was initially approved in 2014 to treat complicated intra-abdominal infections and complicated urinary tract infections. The new indication was based on results from a multinational, double-blind study of 726 hospitalized adults, which showed similar mortality and cure rates between the medication and a comparator antibacterial drug. The most common adverse reactions in the trial were elevated liver enzyme levels, renal impairment or failure, and diarrhea. The injection drug should not be used in patients with hypersensitivity to piperacillin/tazobactam or other members of the beta-lactam class.
Romosozumab-aqqg (Evenity) to treat osteoporosis in postmenopausal women at high risk of fracture. These are women with a history of osteoporotic fracture or multiple risk factors for fracture, or those who are intolerant to other osteoporosis therapies or in whom such therapies have failed. One dose of the drug, a monoclonal antibody, consists of two injections, one immediately following the other, given once a month by a health care professional. More than 12 doses should not be used, as the drug's bone-forming effect wanes after 12 doses. In two trials of more than 11,000 women, one year of treatment with the drug (followed by one year of denosumab) lowered the risk of a new vertebral fracture by 73% compared to placebo followed by denosumab, and one year of treatment with romosozumab-aqqg (followed by one year of alendronate) reduced the risk of a new vertebral fracture by 50% compared to two years of alendronate alone. Common side effects include joint pain, headache, and injection-site reactions. A boxed warning states that the drug may increase the risk of heart attack, stroke, and cardiovascular death and should not be used in patients who have had a heart attack or stroke within the previous year.
Dolutegravir and lamivudine (Dovato) as a complete regimen for the treatment of HIV-1 infection. The drug, taken as one daily tablet, is indicated for adults with no antiretroviral treatment history and with no known or suspected substitutions associated with resistance to its individual components. It is the first FDA-approved two-drug, fixed-dose, complete regimen for HIV-infected adults who have never received treatment for HIV. In two trials of 1,433 patients, the drug regimen had a similar effect of reducing the amount of HIV in the blood compared to a regimen of dolutegravir, emtricitabine, and tenofovir. The most common adverse reactions were headache, diarrhea, nausea, insomnia, and fatigue. A boxed warning cautions that patients co-infected with hepatitis B should add additional treatment for their hepatitis B or consider a different drug regimen.
Erdafitinib (Balversa) to treat adults with locally advanced or metastatic bladder cancer with a specific type of genetic alteration. The drug is indicated for adults with fibroblast growth factor alterations 2 or 3 whose cancer has progressed during or following prior platinum-containing chemotherapy. Patients should be selected for therapy using an FDA-approved companion diagnostic device. In one trial of 87 patients, the overall response rate was 32.2%, with 2.3% of patients having a complete response and almost 30% having a partial response. The response lasted for an average of about five and a half months. Common side effects include increased phosphate level, mouth sores, feeling tired, change in kidney function, diarrhea, dry mouth, nails separating from the bed or poor formation of the nail, change in liver function, low sodium levels, decreased appetite, change in sense of taste, anemia, dry skin, dry eyes, and hair loss. The drug may cause serious eye problems, including inflamed eyes, inflamed cornea, and disorders of the retina.
Polivy (polatuzumab vedotin-piiq), in combination with the chemotherapy bendamustine and a rituximab product (BR), to treat adults with diffuse large B-cell lymphoma that has progressed or returned after at least two prior therapies. The antibody-drug conjugate binds to a specific protein found only on B cells, then releases the chemotherapy drug into those cells. In a study that randomized 80 patients to receive the drug with BR or BR alone, the complete response rate to treatment was 40% with the combination compared to 18% with BR alone. Of the 25 patients who achieved a partial or complete response to the drug plus BR, 16 (64%) had a duration of response of at least six months, and 12 (48%) had a duration of response of at least 12 months. The most common side effects include neutropenia, thrombocytopenia, anemia, peripheral neuropathy, fatigue, diarrhea, fever, decreased appetite, and pneumonia. Clinicians should monitor patients closely for infusion-related reactions, low blood counts, serious infections, tumor lysis syndrome, hepatotoxicity, and progressive multifocal leukoencephalopathy.
Galcanezumab-gnlm (Emgality) solution for self-injection to treat adults with episodic cluster headaches. The form of headache generally lasts between 15 minutes and three hours and tends to cause extreme pain, occurring in clusters for several weeks to months, often at the same time of day. In a trial of 106 patients, patients taking the drug experienced 8.7 fewer weekly cluster headache attacks than they did at baseline, compared to 5.2 fewer attacks for patients on placebo. The most common side effect was injection-site reactions, and there is also a risk of hypersensitivity reactions to the drug, which was previously approved in September 2018 for the preventive treatment of migraine in adults.
First-time generic approvals
Diclofenac sodium injection (37.5 mg/mL single-dose vials) for the management of mild to moderate pain or the management of moderate to severe pain, alone or in combination with opioid analgesics. (Brand name: Dyloject)
Micafungin for injection (50 mg/vial and 100 mg/vial single-dose vials) for the treatment of candidemia, acute disseminated candidiasis, candida peritonitis, and abscesses; also for the treatment of esophageal candidiasis and prophylaxis of Candida infections in patients undergoing hematopoietic stem-cell transplantation. (Brand name: Mycamine)
Mesalamine delayed-release capsules (400 mg) for the treatment of patients ages 5 years and older with mildly to moderately active ulcerative colitis and for maintenance of remission of ulcerative colitis in adults. (Brand name: Delzicol)
Sildenafil for oral suspension (10 mg/mL) to improve exercise ability and delay clinical worsening in adults with WHO Group I pulmonary arterial hypertension (Brand name: Revatio)
Penicillamine capsules USP (250 mg) to treat patients with Wilson's disease or cystinuria, as well as those with severe, active rheumatoid arthritis who have not responded to an adequate trial of conventional therapy. (Brand name: Cuprimine)
Sapropterin dihydrochloride tablets (100 mg) for the reduction of blood phenylalanine levels in patients with hyperphenylalaninemia due to tetrahydrobiopterin-responsive phenylketonuria. (Brand name: Kuvan)
Dapiprazole hydrochloride ophthalmic solution (0.5%) for the treatment of iatrogenically induced mydriasis produced by adrenergic (phenylephrine) or parasympatholytic (tropicamide) agents. (Brand name: None provided)
Note: The FDA states that drugs are not always commercially available immediately after approval.