Changes to contraindication for statins in pregnancy

This column reviews details on recent recalls, alerts, and approvals.

Recalls and alerts

A class I recall of Jelco Hypodermic Needle-Pro Fixed Needle Insulin Syringes by Smiths Medical because the syringes may have graduated markings that are printed incorrectly on the syringe barrel. Specifically, the odd-numbered graduation markings on the syringe barrel may be skewed about 20 degrees upward, potentially leading to an overdose or underdose of insulin. The recall includes 1,431,000 syringes distributed from Oct. 31, 2020, to Jan. 10, 2021. There have been nine complaints reported for this issue. No injuries or deaths have been reported.

A class I recall of the Angiographic Guidewire Component by Medtronic Vascular because the devices were not sterilized before being shipped directly to hospitals. There have been two complaints and no reported injuries or deaths related to this issue; however, underreporting is possible, as physicians may not have been aware that the devices were not sterile. The recall includes 54,997 devices distributed from Nov. 23, 2007, to March 29, 2021.

A class I recall of the GENOSYL DS nitric oxide delivery system by Vero Biotech due to a software issue that leads to errors in the delivery of nitric oxide. The issue typically caused delivery of lower-than-expected dose of nitric oxide. There have been 11 complaints, three injuries, and no deaths related to this issue. The recall includes 467 devices distributed from March 15 to April 5.

A class I recall of 13 lots of LeadCare II, LeadCare Plus, and LeadCare Ultra blood lead test kits by Magellan Diagnostics due to a significant risk of falsely low results. Recalled products were distributed from Oct. 27, 2020, to June 15, 2021.

A class I recall of medical convenience kits by Avid Medical because they include the BD/Carefusion Chloraprep 3.0-mL applicator, which was recalled due to fungal contamination. The recall includes 1,570 kits distributed from May 9, 2019, to March 19, 2021. No related complaints, injuries, or deaths have been reported.

A class I recall of surgical procedure packs by DeRoyal Industries because the packs contain 1% lidocaine that has been mislabeled as 0.5% bupivacaine. This recall is related to a Hospira recall for the same mislabeling issue. The recall includes 138 packs distributed from April 19 to May 11. No related complaints, injuries, or deaths have been reported.

A class I recall of the Alaris Infusion Pump Module Model 8100 Bezel, purchased and/or installed by Infusion Pump Repair, due to possible cracked or separated bezel repair posts. The recall includes 15 devices distributed from Jan. 15 to March 14. No related complaints, injuries, or deaths have been reported.

A recall notification by Philips to mitigate potential health risks related to a component in certain sleep and respiratory care devices. The notification applies to specific bi-level positive airway pressure, continuous positive airway pressure, and mechanical ventilator devices , the majority of which are in the first-generation DreamStation product line. Despite a low complaint rate (0.03% in 2020), the company determined based on testing that the polyester-based polyurethane sound-abatement foam component in these devices may degrade into particles that may enter the device's air pathway and be ingested or inhaled and may off-gas certain chemicals. The foam degradation may be exacerbated by use of unapproved cleaning methods, such as ozone, as well as high-heat and high-humidity environments. The company will replace the current foam in all affected devices.

A recall of 12 lots of varenicline (Chantix) by Pfizer due to the presence of N-nitroso-varenicline above the manufacturer's established acceptable daily intake level. There have been no reports of related adverse events. Recalled products were distributed nationwide to wholesalers and distributors from June 2019 to June 2021.

A recall of two lots of metformin hydrochloride extended-release tablets USP (750 mg) by Viona Pharmaceuticals Inc. due to levels of N-nitrosodimethylamine impurities above acceptable daily limits. The product was manufactured in November 2019 by Cadila Healthcare Limited in India for U.S. distribution by Viona Pharmaceuticals Inc. Affected products were distributed nationwide to distributors. No related adverse events have been reported.

An alert that a clinical trial evaluating melphalan flufenamide (Pepaxto) with low-dose dexamethasone to treat patients with multiple myeloma showed an increased risk of death. The FDA approved the drug in February; however, the OCEAN trial, which compared the drug combination to pomalidomide with low-dose dexamethasone in certain patients with relapsed or refractory multiple myeloma, showed it was associated with decreased overall survival. The manufacturer was required to conduct the trial as a postapproval requirement under the FDA's accelerated approval program. Clinicians should review patients' progress on melphalan flufenamide and discuss the risks of continued administration with each patient in the context of other treatments, the FDA said. The agency continues to evaluate the trial results and may hold a public meeting to discuss the safety findings and the continued marketing of the drug.

A recall of one lot of topotecan injection (1 mg/mL) by Teva Pharmaceuticals due to the presence of particulate matter. The recall was based on a complaint received from a pharmacy after a single glass particle was observed inside one vial. Further examination revealed two other particulates in the sample, a gray silicone particle and one translucent, colorless cotton fiber. There have been no further complaints or reports of illness or injury.

A recall of seven lots of unexpired, sterile compounded drug products by Innoveix Pharmaceuticals Inc. due to a lack of sterility assurance. The affected products are injectable sermorelin/ipamorelin (3 mg) and injectable AOD-9604 (3 mg). They were distributed nationwide to customers and medical facilities.

A recall of all lots of five types of Neutrogena and Aveeno aerosol sunscreen products by Johnson & Johnson Consumer Inc. because testing identified low levels of benzene, a human carcinogen. Recalled products include the following aerosol sunscreens: Neutrogena Beach Defense, Neutrogena Cool Dry Sport, Neutrogena Invisible Daily Defense, Neutrogena Ultra Sheer, and Aveeno Protect + Refresh. They were distributed nationwide through a variety of retail channels.


Requested revisions to the prescribing information about use of statins in pregnancy, including removal of the contraindication against using the drug class in all pregnant patients. Because the benefits of statins may include prevention of serious or potentially fatal events in a small group of very high-risk pregnant patients, contraindicating these drugs in all pregnant patients is not appropriate, the FDA said. While clinicians should discontinue statin therapy in most pregnant patients, they may consider the ongoing therapeutic needs of the individual, particularly patients at very high risk for cardiovascular events during pregnancy, including those with homozygous familial hypercholesterolemia and those who've had a heart attack or stroke, the FDA said. Clinicians should also advise pregnant patients who require a statin that breastfeeding is not recommended because the medicine may pass into breast milk, the agency said.

A letter to clinicians about potential biocompatibility concerns associated with stainless steel- and titanium-based Precice orthopedic devices manufactured by NuVasive Specialized Orthopedics. The FDA recommended that clinicians stop implanting any new stainless steel-based devices and be aware that as of February, the manufacturer voluntarily removed them from the U.S. market due to adverse events related to increased pain and bone changes. With regard to the titanium-based devices, clinicians should be aware that the manufacturer has initiated a voluntary recall and that the devices are not being sold in the U.S. market due to a voluntary manufacturer ship hold placed in April, the FDA said.

A supplement to a 2015 safety communication on reprocessed flexible bronchoscopes. The supplement reminds health care facilities to follow manufacturer instructions for device reprocessing and maintenance, includes updated information on medical device adverse event reports, and provides a new recommendation for clinicians to consider using a single-use bronchoscope in situations where there is increased risk of spreading infection. Another new recommendation advised referring to recent recommendations from the American Association for Bronchology and Interventional Pulmonology when treating patients with COVID-19.

COVID-19 updates

A revised emergency use authorization (EUA) for casirivimab and imdevimab (REGEN-COV) as a treatment for COVID-19. The FDA added an authorization of the drug combination for emergency use as postexposure prophylaxis for COVID-19 in adults and children ages 12 years and older weighing at least 40 kg who are at high risk for progression to severe COVID-19, including hospitalization or death. It should only be used as postexposure prophylaxis for patients who are not fully vaccinated or who are not expected to mount an adequate immune response to complete SARS-CoV-2 vaccination and have been exposed to an individual infected with SARS-CoV-2 or who are at high risk of exposure due to infection in other individuals in the same institutional setting (e.g., nursing homes, prisons). The drug combination also remains authorized for the treatment of mild to moderate COVID-19 in adults and children ages 12 years and older weighing at least 40 kg with positive results of direct SARS-CoV-2 viral testing who are at high risk for progression to severe COVID-19. The authorized dose for both treatment and as postexposure prophylaxis is 600 mg of casirivimab and 600 mg of imdevimab, administered together. For treatment, IV infusion is strongly recommended, and subcutaneous injection is authorized as an alternative if IV infusion is not feasible and would lead to treatment delay; for postexposure prophylaxis, either IV infusion or subcutaneous injection is appropriate. The most common side effects include injection site reactions, such as erythema, pruritus, and ecchymosis.

A warning about the Johnson & Johnson (Janssen) COVID-19 Vaccine regarding an observed risk of Guillain-Barré syndrome following vaccination. The FDA revised the fact sheet for vaccination providers to include a warning that adverse events suggest an increased risk of Guillain-Barré syndrome. There have been 100 preliminary reports of Guillain-Barré syndrome following vaccination with the Janssen vaccine after about 12.5 million doses administered. Of these cases, 95 were serious and required hospitalization, and one patient died. The fact sheet for recipients and caregivers was also revised to note that vaccine recipients should seek medical attention right away if they develop any of the following symptoms: weakness or tingling sensations, especially in the legs or arms, that worsens and spreads to other parts of the body; difficulty walking; difficulty with facial movements, including speaking, chewing, or swallowing; double vision or inability to move the eyes; and difficulty with bladder control or bowel function. As the FDA continues to monitor reports, it maintains that the known and potential benefits of the vaccine clearly outweigh the known and potential risks.

A warning about the Moderna and Pfizer-BioNTech COVID-19 vaccines regarding the risks of myocarditis and pericarditis following vaccination. For each vaccine, the FDA revised the fact sheet for vaccination providers to include a warning about myocarditis and pericarditis. The warning notes that reports of adverse events suggest increased risks of myocarditis and pericarditis, particularly following the second dose, with onset of symptoms within a few days after vaccination. Available data from short-term follow-up suggest that most individuals have had resolution of symptoms. In addition, the revised fact sheet for recipients and caregivers now notes that vaccine recipients should seek medical attention right away if they have chest pain, shortness of breath, or feelings of a fast-beating, fluttering, or pounding heart after vaccination. The FDA and CDC continue to monitor the reports and will assess longer-term outcomes.

A class I recall of the Lyra SARS-CoV-2 Assay (M120) by Quidel due to a significant risk of false-negative results for patients with relatively high amounts of SARS-CoV-2 virus. The manufacturer has received five complaints about this issue. No injuries or deaths have been reported. The recall includes 18,385 tests distributed from March 17, 2020, to May 27, 2021.

A warning to stop using the Innova SARS-CoV-2 Antigen Rapid Qualitative Test for diagnostic use. The FDA expressed concerns that the performance of the test has not been adequately established. The test labeling distributed with certain configurations of the test includes performance claims that did not accurately reflect the performance estimates observed during clinical studies of the tests, the agency noted. In addition, the test has not been authorized, cleared, or approved by the FDA for commercial distribution or use in the U.S.

A revised EUA allowing baricitinib (Olumiant) to be administered alone for the treatment of COVID-19 in hospitalized adults and children ages 2 years and older requiring supplemental oxygen, noninvasive or invasive mechanical ventilation, or extracorporeal membrane oxygenation. Under the revised EUA, the drug is no longer required to be administered with remdesivir; however, it is not FDA-approved as a treatment for COVID-19.

Authorized extension of the shelf life for the refrigerated Johnson & Johnson (Janssen) COVID-19 vaccine. The authorization allows the product to be stored at 2° to 8° C for six months. The FDA granted the extension from four and a half months to six months following a thorough review of data submitted by the company. It applies to all refrigerated vials of the vaccine that have been held in accordance with the manufacturer's storage conditions.

An EUA for BD Vacutainer Plus Citrate Plasma Tubes. The sodium citrate blood specimen collection tubes are used to collect, transport, and store blood samples for coagulation testing. The device authorized under the EUA is for use in coagulation testing, performed by authorized laboratories, to aid in the identification and treatment of coagulopathy in patients, including those with known or suspected COVID-19.

An EUA for the VITROS Immuno-diagnostic Products Anti-SARS-CoV-2 IgG Quantitative Test. The quantitative serology test measures IgG antibodies to the virus from an individual's blood sample to help identify people with an adaptive immune response to SARS-CoV-2, indicating recent or previous infection.

A letter to health care personnel and facilities stating that the FDA no longer authorizes use of non-National Institute for Occupational Safety and Health (NIOSH)-approved or decontaminated disposable respirators. The FDA has revoked the EUAs for non-NIOSH-approved disposable respirators and the EUAs for decontamination and bioburden reduction systems. As a result, these devices are no longer authorized for use by clinicians in health care settings.

A drug safety communication for hand sanitizers. The FDA warned that symptoms such as headache, nausea, and dizziness can occur after applying alcohol-based hand sanitizers to the skin and inhaling the vapors that linger. The FDA reviewed case reports and cases from calls to U.S. poison control centers of such adverse events after the start of the COVID-19 pandemic. While the majority of cases resulted in minor effects, some resulted in treatment by a clinician. Consumers should use hand sanitizer in a well-ventilated area, the FDA said. In addition, one lot of Limar Hand Sanitizer by Ardil Comercial and all lots of Prairie Wolf Distillery hand sanitizer by Prairie Wolf Spirits were recalled because they resemble water bottles, posing a risk of ingestion.

Abbreviated new drug applications for certain drugs that have seen increased demand during the COVID-19 public health emergency. These medications include albuterol sulfate inhalation aerosol (90 µg [base]/actuation).


Nonprescription use of azelastine hydrochloride nasal spray, 0.15% (Astepro) to treat seasonal and perennial allergic rhinitis in patients ages 6 years and older. The approval is a first-in-class switch from prescription to nonprescription status for a nasal antihistamine and is considered a partial switch because the 0.1% strength, which includes a perennial allergy indication for children ages 6 months to 6 years and a seasonal allergy indication for children ages 2 to 6 years, will remain a prescription drug. The drug can cause drowsiness and carries a warning that users should avoid alcohol and use caution when driving a motor vehicle or operating machinery.

Sotorasib (Lumakras) to treat adults with non-small-cell lung cancer whose tumors have a KRAS G12C mutation and who have received at least one prior systemic therapy. The FDA also approved the QIAGEN therascreen KRAS RGQ PCR kit and the Guardant360 CDx as companion diagnostics for the drug, which is the first approved targeted therapy for tumors with any KRAS mutation. KRAS G12C mutations represent about 13% of mutations in non-small-cell lung cancers. Efficacy of the drug was assessed in a study of 124 patients with disease progression after receiving an immune checkpoint inhibitor and/or platinum-based chemotherapy. The objective response rate was 36%, and 58% of those patients had a duration of response of six months or longer. The most common side effects were diarrhea, musculoskeletal pain, nausea, fatigue, liver damage, and cough. Clinicians should monitor a patient's liver function tests prior to starting and when taking the drug. If liver damage occurs, the drug should be withheld, the dose should be reduced, or the drug should be permanently discontinued. In addition, the drug should be withheld if patients develop symptoms of interstitial lung disease and permanently discontinued if interstitial lung disease is confirmed. The drug received accelerated approval, and further study is required to verify and describe its anticipated clinical benefits, the FDA said.

StrataGraft for the treatment of adults with thermal burns containing intact dermal elements for which surgical intervention is clinically indicated. Produced from keratinocytes and dermal fibroblasts grown together to make a bi-layered construct, the orphan drug is for topical application, placed onto the burn by a clinician. The human keratinocytes were grown with mouse cells during the initial stages of product development; however, mouse cells are no longer used in the final manufacturing process. Effectiveness and safety were assessed in two randomized studies involving a total of 101 adult patients. In both studies, two deep partial-thickness burn wounds of comparable area and depth on each patient were identified and randomized to receive either a single topical application of the treatment or autograft. Effectiveness of the treatment was demonstrated by the percentage of treatment sites that achieved a complete wound closure, as well as the significantly decreased need for autografts at the treatment sites. Common side effects were pruritis, blisters, hypertrophic scar, and impaired healing at the treatment site. The overall safety profile regarding wound-related events, including erythema, swelling, local warmth, and wound site infections, was similar to that of autografting.

Asparaginase erwinia chrysanthemi (recombinant)-rywn (Rylaze) as a component of a chemotherapy regimen to treat certain patients with acute lymphoblastic leukemia and lymphoblastic lymphoma. The drug is indicated in adult and pediatric patients who are allergic to the Escherichia coli-derived asparaginase products used most commonly for treatment. The only other FDA-approved drug for such patients has been in global shortage for years. Efficacy of the orphan drug was evaluated in a study of 102 patients and found that the recommended dosage would provide the target level of asparaginase activity in 94% of patients. The most common side effects include hypersensitivity reactions, pancreatic toxicity, blood clots, hemorrhage, and liver toxicity.

First generic drug approvals

Tofacitinib tablets (10 mg) for the treatment of adults with moderately to severely active rheumatoid arthritis, active psoriatic arthritis, moderately to severely active ulcerative colitis, and active polyarticular course juvenile idiopathic arthritis. (Brand name: Xeljanz)

Arformoterol tartrate inhalation solution (15 µg/2 mL in unit-dose vials) for long-term, twice-daily administration in the maintenance treatment of bronchoconstriction in patients with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and emphysema. (Brand name: Brovana)

Formoterol fumarate inhalation solution (20 µg/2 mL in single-dose vials) for the maintenance treatment of bronchoconstriction in patients with COPD, including chronic bronchitis and emphysema. (Brand name: Perforomist)

Calcitonin salmon injection USP (400 USP units per 2 mL [200 USP units per mL] in multi-dose vials) for the treatment of symptomatic Paget's disease, hypercalcemia, and postmenopausal osteoporosis. (Brand name: Miacalcin)

Lopinavir and ritonavir tablets USP (100 mg/25 mg and 200 mg/50 mg) for the treatment of HIV-1 infection in adults and pediatric patients ages 14 days and older. (Brand name: Kaletra)

Etravirine tablets (25 mg, 100 mg, and 200 mg) for the treatment of HIV-1 infection in treatment-experienced patients ages 6 years and older. (Brand name: Intelence)

Eslicarbazepine acetate tablets (200 mg, 400 mg, 600 mg, and 800 mg) for the adjunctive treatment of partial-onset seizures. (Brand name: Aptiom)

Enzalutamide capsules (40 mg) for the treatment of patients with castration-resistant prostate cancer. (Brand name: Xtandi)

Lenalidomide capsules (5 mg, 10 mg, 15 mg, and 25 mg) for the treatment of multiple myeloma, transfusion-dependent anemia, mantle-cell lymphoma, previously treated follicular lymphoma, and previously treated marginal zone lymphoma. (Brand name: Revlimid)

Carfilzomib for injection (10 mg, 30 mg, and 60 mg in single-dose vials) for the treatment of adult patients with relapsed or refractory multiple myeloma who have received one to three lines of therapy in combination with dexamethasone. (Brand name: Kyprolis)

Sodium acetate injection USP (100 mEq/50 mL [2 mEq/mL] and 200 mEq/100 mL [2 mEq/mL] in pharmacy bulk package vials) as a source of sodium for addition to large-volume IV fluids to prevent or correct hyponatremia in patients with restricted or no oral intake. (Brand name: None provided)

Zinc chloride injection USP (10 mg/10 mL [1 mg/mL] in single-dose vials) for use as a supplement to IV solutions given for total parenteral nutrition. (Brand name: None provided)

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