Search Medical Journals & Research Articles

January - March 2023 | Potential Signals of Serious Risks/New Safety I

January - March 2023 | Potential Signals of Serious Risks/New Safety Information Identified by the FDA Adverse Event Reporting System (FAERS) The drug product(s) included in any of the potential signals of serious risks/new safety information listed below may also include the generic version of the drug product(s), if there are generic versions approved for use by the FDA at the time of this publication. | Product Name: Trade (Active Ingredient) or Product Class | Potential Signal of a Serious Risk / New Safety Information | Additional Information (as of March 13, 2026) | |---|---|---| | Biktarvy (bictegravir, emtricitabine, and tenofovir alafenamide) | Weight increased | Updated The “Adverse Reactions” section of the labeling was updated in February 2024 to include weight increased. | Braftovi (encorafenib) Tafinlar (dabrafenib) | Photosensitivity reaction | Updated The “Adverse Reactions” section of the labeling was updated between February 2024 and September 2024 to include photosensitivity. Example: Tafinlar labeling | Brukinsa (zanubrutinib) Calquence (acalabrutinib) Imbruvica (ibrutinib) Jaypirca (pirtobrutinib) | Drug-induced liver injury | Updated The “Warnings and Precautions”, “Adverse Reactions”, “Patient Counseling Information”, and “Patient Information” sections of the labeling were updated between May 2024 and June 2024 to include information about drug-induced liver injury. Example: Imbruvica labeling | Entyvio (vedolizumab) Tysabri (natalizumab) | Interstitial lung disease | Updated The “Adverse Reactions” section of the labeling for Entyvio was updated in April 2024 to include interstitial lung disease. FDA determined that no action was necessary for Tysabri at the time based on available information. | Delsam Pharma’s Artificial Eye Ointment EzriCare Artificial Tears | Product contamination microbial | | Droxia (hydroxyurea) Siklos (hydroxyurea) Updated Hydrea (hydroxyurea)* | Drug-device interaction | Updated The “Warnings and Precautions”, “Drug Interactions”, “Medication Guide”, and “Patient Counseling Information” sections of the labeling were updated in November 2023 to include information about drug-device interaction. Example: Siklos labeling * An administrative error resulted in the omission of Hydrea from the list of product names and was added after the initial quarterly report was posted. | Iclusig (ponatinib) Scemblix (asciminib) | Panniculitis | Updated The “Adverse Reactions” section of the labeling was updated in March 2024 to include panniculitis. FDA determined that no action was necessary for Scemblix at the time based on available information. | | Kineret (anakinra) | Amyloidosis | Updated The “Warnings and Precautions” and “Adverse Reactions” sections of the labeling were updated in October 2025 to include information about amyloidosis. | Local anesthetics - Carbocaine (mepivacaine hydrochloride) - Prilocaine hydrochloride 4% with epinephrine 1:200,000 injection - 4% Citanest Plain Dental (prilocaine hydrochloride injection) - Clorotekal (chloroprocaine hydrochloride) - Emla Cream (lidocaine 2.5% and prilocaine 2.5%) - Exparel (bupivacaine liposome injectable suspension) - Goprelto (cocaine hydrochloride) - Kovanaze (oxymetazoline hydrochloride and tetracaine hydrochloride) - Lidoderm (lidocaine patch 5%) - Marcaine Hydrochloride (bupivacaine hydrochloride) - Naropin (ropivacaine hydrochloride) - Nesacain (chloroprocaine hydrochloride injection) - Numbrino (cocaine hydrochloride) - Orabloc (articaine hydrochloride and epinephrine) - Oraqix (lidocaine and prilocaine periodontal gel) - Pliaglis (lidocaine and tetracaine) - Posimir (bupivacaine solution) - Sensorcaine (bupivacaine hydrochloride) - Sensorcaine with epinephrine (bupivacaine hydrochloride and epinephrine) - Septocaine (articaine hydrochloride and epinephrine injection) - Synera (lidocaine and tetracaine) - Xaracoll (bupivacaine hydrochloride) - Xylocaine Dental (lidocaine hydrochloride injection) - Xylocaine (lidocaine hydrochloride and epinephrine injection) - Zingo (lidocaine hydrochloride monohydrate) - Zynrelef (bupivacaine and meloxicam) - Ztlido (lidocaine topical system) | Hepatic enzymes and function abnormalities | FDA is evaluating the need for regulatory action. | | Mavenclad (cladribine) | Infections and infestations | Updated The “Warnings and Precautions”, “Adverse Reactions”, “Patient Counseling Information”, and “Medication Guide” sections of the labeling were updated in February 2024 to include information about infections. | Mekinist (trametinib) Mektovi (binimetinib) | Photosensitivity reaction | Updated The “Adverse Reactions” section of the labeling was updated between February 2024 and September 2024 to include information about photosensitivity. Example: Mektovi labeling | Diskets (methadone hydrochloride) Methadone Hydrochloride Methadose (methadone hydrochloride) | Accidental exposure to product by child | FDA is evaluating the need for regulatory action. | Nexletol (bempedoic acid) Updated Nexlizet (bempedoic acid and ezetimibe) * | Hypersensitivity | Updated The “Adverse Reactions” section of the labeling was updated in September 2023 to include information about hypersensitivity. Example: Nexletol labeling *An administrative error resulted in the omission of Nexlizet from the list of product names and was added after the initial quarterly report was posted. | | Norepinephrine Bitartrate in Dextrose Injection | Product label confusion contributing to medication error | Updated The container and overwrap labels were revised in November 2023 to mitigate the potential for medication errors. | Opioids - Actiq (fentanyl citrate) - Alfentanil Hydrochloride Injection - Apadaz (benzhydrocodone and acetaminophen) - Belbuca (buprenorphine buccal film) - Buprenex (buprenorphine hydrochloride) - Butalbital, Acetaminophen, Caffeine, and Codeine Phosphate Capsules - Butrans (buprenorphine) - Cassipa (buprenorphine and naloxone) - Codeine Sulfate Oral Solution - Codeine Sulfate Tablets - Demerol (meperidine hydrochloride) - Dilaudid (hydromorphone hydrochloride) - Dsuvia (sufentanil) - Duramorph (morphine sulfate) - Fentanyl Citrate Injection - Fentora (fentanyl buccal tablet) - Fiorinal with Codeine (butalbital, aspirin, caffeine and codeine phosphate) - Hydromorphone Hydrochloride Injection - Hysingla ER (hydrocodone bitartrate) - Kadian (morphine sulfate) - Infumorph (morphine sulfate) - Mepergan (meperidine hydrochloride and promethazine hydrochloride) - Morphine Sulfate Injection - Morphine Sulfate Oral Solution - Morphine Sulfate Tablets - MS Contin (morphine sulfate extended release) - Nubain (nalbuphine hydrochloride) - Nucynta (tapentadol) - Nucynta ER (tapentadol) - Olinvyk (oliceridine) - Opana ER (oxymorphone hydrochloride) - Oxaydo (oxycodone hydrochloride) - Oxycodone Hydrochloride Capsules - Oxycodone Hydrochloride Oral Solution - Oxycontin (oxycodone hydrochloride) - Percodan (oxycodone and aspirin) - Probuphine (buprenorphine) - Roxicodone (oxycodone hydrochloride) - Roxybond (oxycodone hydrochloride) - Sublocade (buprenorphine extended release) - Suboxone (buprenorphine and naloxone) - Sufentanil Citrate Injection - Synalgos-DC (aspirin, caffeine, and dihydrocodeine bitartrate) - Ultiva (remifentanil hydrochloride) - Xtampza ER (oxycodone) - Zubsolv (buprenorphine and naloxone sublingual tablets) Updated - Flowtuss (hydrocodone and guaifenesin)* - Hycodan (hydrocodone bitartrate and homatropine methylbromide)* - Hycofenix (hydrocodone, pseudoephedrine, and guaifenesin)* - Obredon (hydrocodone bitartrate and guaifenesin)* - Promethazine HCl and Codeine Phosphate* - Promethazine HCl, Phenylephrine HCl, and Codeine Phosphate* - Tuxarin ER (chlorpheniramine maleate and codeine phosphate)* - Tuzistra XR (chlorpheniramine and codeine)* - Xtrelus (hydrocodone bitrate and guaifenesin)* | Hypoglycemia | Updated The “Adverse Reactions” and “Overdosage” sections of the labeling were updated in December 2023 to include information about hypoglycemia. Example: Oxycontin labeling Additional information is not provided for Fiorinal with Codeine and Kadian because approval of the marketing applications for these products was withdrawn by FDA, at the applicant’s request, prior to the labeling updates referenced above. * FDA updated this signal for Hypoglycemia to include the products Flowtuss, Hycodan, Hycofenix, Obredon, Promethazine HCl and Codeine Phosphate, Promethazine HCl Phenylephrine HCl and Codeine Phosphate, Tuxarin ER, Tuzistra XR, and Xtrelus after the initial quarterly report was posted. | | Recothrom (thrombin topical recombinant) | Thrombosis due to inadvertent IV administration | Updated The "Warnings and Precautions" section of the labeling was updated in January 2024 to include information about the risk of thrombosis due to inadvertent IV administration. A warning that Recothrom is for topical use only was added to the syringes packaged with Recothrom in July 2024 to mitigate the risk of inadvertent IV administration. | | Tepezza (teprotumumab-trbw) | Hearing impairment | Updated The “Warnings and Precautions”, “Adverse Reactions”, and “Patient Counseling Information” sections of the labeling were updated in July 2023 to include information about hearing impairment. | | Turalio (pexidartinib) | Diarrhea | Updated FDA determined that no action was necessary at the time based on available information. | | Turalio (pexidartinib) | Photosensitivity reaction | Updated The “Adverse Reactions”, “Patient Counseling Information”, and “Medication Guide” sections of the labeling were updated in November 2023 to include information about photosensitivity reaction. |

July - September 2023 | Potential Signals of Serious Risks/New Safety

July - September 2023 | Potential Signals of Serious Risks/New Safety Information Identified by the FDA Adverse Event Reporting System (FAERS) The drug product(s) included in any of the potential signals of serious risks/new safety information listed below may also include the generic version of the drug product(s), if there are generic versions approved for use by the FDA at the time of this publication. | Product Name: Trade (Active Ingredient) or Product Class | Potential Signal of a Serious Risk / New Safety Information | Additional Information (as of March 13, 2026) | |---|---|---| | Allergenic Extract – Peanut (Arachis hypogaea) - For Diagnostic Use Only, manufactured by ALK-Abelló, Inc. | Certain product lots were associated with increased reports of false negative skin test results, with some cases of anaphylaxis from subsequent peanut exposure. | The Package Insert - Allergenic Extracts was revised in February 2023 to include a Warning for Anaphylaxis Following False Negative Food Allergen Skin Test Results. | Amoxil (amoxicillin) Augmentin (amoxicillin and clavulanate potassium) Augmentin ES-600 (amoxicillin and clavulanate potassium) Augmentin XR (amoxicillin and clavulanate potassium) Moxatag (amoxicillin extended-release tablets) Omeclamox-Pak (omeprazole delayed-release capsules; clarithromycin tablets; amoxicillin capsules) Talicia (omeprazole magnesium, amoxicillin and rifabutin delayed-release capsules) Voquezna Dual Pak (vonoprazan tablets; amoxicillin capsules) Voquezna Triple Pak (vonoprazan tablets; amoxicillin capsules; clarithromycin tablets) | Drug-Induced Enterocolitis Syndrome | The “Warnings and Precautions” and “Adverse Reactions” sections of the labeling were updated in May 2024 to include information about drug-induced enterocolitis syndrome (DIES). Example: Amoxil labeling | Bactrim (sulfamethoxazole and trimethoprim) Bactrim DS (sulfamethoxazole and trimethoprim) Septra (sulfamethoxazole and trimethoprim) Septra DS (sulfamethoxazole and trimethoprim) Sulfatrim (sulfamethoxazole and trimethoprim) Sulfamethoxazole and Trimethoprim | Hemophagocytic lymphohistiocytosis | The “Warnings and Precautions” and “Adverse Reactions” sections of the labeling were updated in February 2025 to include information about hemophagocytic lymphohistiocytosis (HLH). Example: Sulfatrim labeling | BCMA- or CD19-directed genetically modified autologous T-cell immunotherapies - Abecma (idecabtagene vicleucel) - Breyanzi (lisocabtagene maraleucel) - Carvykti (ciltacabtagene autoleucel) - Kymriah (tisagenlecleucel) - Tecartus (brexucabtagene autoleucel) - Yescarta (axicabtagene ciloleucel) | Post-treatment T-cell malignancy | FDA issued a Safety Communication on April 18, 2024: FDA Requires Boxed Warning for T cell Malignancies Following Treatment with BCMA-Directed or CD19-Directed Autologous Chimeric Antigen Receptor (CAR) T cell Immunotherapies. The Boxed Warning was updated and related changes were made to other sections of the labels (Warnings and Precautions, Postmarketing Experience, Patient Counseling Information and Medication Guide) to include the serious risk of T cell malignancies following treatment with BCMA-directed or CD19-directed autologous chimeric antigen receptor (CAR) T cell immunotherapies as class safety labeling changes: | Cabometyx (cabozantinib) Cometriq (cabozantinib) | Rhabdomyolysis | FDA determined that no action was necessary at the time based on available information. | Elepsia XR (levetiracetam) Keppra (levetiracetam) Keppra XR (levetiracetam) Levetiracetam in Sodium Chloride Spritam (levetiracetam) | Drug reaction with eosinophilia and systemic symptoms | An FDA Drug Safety Communication was issued on November 28, 2023. The FDA is requiring applicants of these medicines to add new warnings about drug reaction with eosinophilia and systemic symptoms to the prescribing information and the Medication Guide for patients and caregivers. | Gemcitabine Infugem (gemcitabine in sodium chloride injection) | Drug reaction with eosinophilia and systemic symptoms | The “Dosage and Administration”, “Warnings and Precautions”, “Adverse Reactions”, and “Patient Counseling Information” sections of the labeling were updated between May 2024 and September 2024 to include information about Severe Cutaneous Adverse Reactions (SCARs). Example: Gemcitabine labeling | Gilenya (fingolimod) Mayzent (siponimod) Ponvory (ponesimod) Tascenso ODT (fingolimod) Zeposia (ozanimod) | Progressive multifocal leukoencephalopathy | The “Warnings and Precautions” section of the labeling was updated in June 2024 to include information about progressive multifocal leukoencephalopathy (PML). Example: Tascenso ODT labeling FDA required a postmarketing requirement (PMR) study in December 2024 for sphingosine 1-phosphate (S1P) receptor modulators to assess risk factors for the development of PML among patients with multiple sclerosis exposed to S1P receptor modulators. Potential risk factors to be assessed include age, duration of exposure to the therapy, prior immunosuppressant use, lymphopenia, and anti-JCV antibody status. | Glucagon-like peptide-1 (GLP-1) receptor agonists - Adlyxin (lixisenatide) - Byetta (exenatide) - Bydureon (exenatide) - Bydureon BCise (exenatide) - Mounjaro (tirzepatide) - Ozempic (semaglutide) - Rybelsus (semaglutide) - Saxenda (liraglutide) - Soliqua 100/33 (insulin glargine and lixisenatide) - Trulicity (dulaglutide) - Victoza (liraglutide) - Wegovy (semaglutide) - Xultophy 100/3.6 (insulin degludec and liraglutide) - Zepbound (tirzepatide)* | Alopecia | The “Adverse Reactions” section of the labeling for Adlyxin, Saxenda, Soliqua 100/33, Trulicity, Victoza, Mounjaro, Ozempic, Rybelsus, and Xultophy 100/3.6 was updated between December 2024 and May 2025 to include alopecia. Example: Xultophy 100/3.6 labeling FDA has determined that the last approved labeling is adequate for Byetta, Bydureon, Bydureon BCise, Wegovy, and Zepbound and that no further regulatory action is needed at the time. *An administrative error resulted in the omission of Zepbound from the list of product names and was added after the initial quarterly report was posted. | Glucagon-like peptide-1 (GLP-1) receptor agonists - Adlyxin (lixisenatide) - Byetta (exenatide) - Bydureon (exenatide) - Bydureon BCise(exenatide) - Mounjaro (tirzepatide) - Ozempic (semaglutide) - Rybelsus (semaglutide) - Saxenda (liraglutide) - Soliqua 100/33 (insulin glargine and lixisenatide) - Trulicity (dulaglutide) - Victoza (liraglutide) - Wegovy (semaglutide) - Xultophy 100/3.6 (insulin degludec and liraglutide) - Zepbound (tirzepatide) | Aspiration | The “Warnings and Precautions”, “Adverse Reactions”, and “Patient Counseling Information” sections of the labeling were updated between October 2024 and November 2024 to include information about aspiration during general anesthesia or deep sedation. Example: Adlyxin labeling FDA required a postmarketing requirement (PMR) trial in November 2024 to measure the effects of temporary withholding of GLP-1 receptor agonists and fasting duration on retained gastric contents to evaluate delayed gastric emptying associated with GLP-1 receptor agonist use and inform potential recommendations to mitigate the serious risk of pulmonary aspiration. | Glucagon-like peptide-1 (GLP-1) receptor agonists - Adlyxin (lixisenatide) - Byetta (exenatide) - Bydureon (exenatide) - Bydureon BCise (exenatide) - Mounjaro (tirzepatide) - Ozempic (semaglutide) - Rybelsus (semaglutide) - Saxenda (liraglutide) - Soliqua 100/33 (insulin glargine and lixisenatide) - Trulicity (dulaglutide) - Victoza (liraglutide) - Wegovy (semaglutide) - Xultophy 100/3.6 (insulin degludec and liraglutide) - Zepbound (tirzepatide) | Suicidal ideation | FDA is evaluating the need for regulatory action. | Kyprolis (carfilzomib) Ninlaro (ixazomib) | Anaphylactic reaction | The “Adverse Reactions” and “Patient Information” sections of the labeling for Ninlaro were updated in July 2024 to include information about angioedema. FDA determined that no action was necessary at the time for Kyprolis based on available information. | Lupkynis (voclosporin) | Nausea and vomiting symptoms | The “Adverse Reactions” section of the labeling was updated in October 2025 to include nausea and vomiting. | | Ocrevus (ocrelizumab) | Drug-induced liver injury | | Onfi (clobazam) Sympazan (clobazam) | Drug reaction with eosinophilia and systemic symptoms | An FDA Drug Safety Communication was issued on November 28, 2023. The FDA is requiring applicants of these medicines to add new warnings about drug reaction with eosinophilia and systemic symptoms to the prescribing information and the Medication Guide for patients and caregivers. | Phyrago (dasatinib) Sprycel (dasatinib) | Chylothorax | The “Adverse Reactions” section of the labeling was updated in July 2024 to include chylothorax. Example: Phyrago labeling | Sodium-glucose cotransporter-2 (SGLT2) inhibitors - Brenzavvy (bexagliflozin) - Farxiga (dapagliflozin) - Glyxambi (empagliflozin and linagliptin) - Inpefa (sotagliflozin) - Invokana (canagliflozin) - Invokamet (canagliflozin and metformin hydrochloride tablets) - Invokamet XR (canagliflozin and metformin hydrochloride tablets) - Jardiance (empagliflozin) - Qtern (saxagliptin and dapagliflozin) - Segluromet (ertugliflozin and metformin) - Steglatro (ertugliflozin) - Steglujan (ertugliflozin and sitagliptin) - Synjardy (empagliflozin and metformin) - Synjardy XR (empagliflozin and metformin) - Trijardy XR (empagliflozin, linagliptin, and metformin hydrochloride extended-release tablets) - Xigduo XR (dapagliflozin and metformin hydrochloride extended-release) | Diabetic ketoacidosis | The “Warnings and Precautions” section of the SGLT2 inhibitors product labeling was updated in September 2023 to include prolonged diabetic ketoacidosis and glucosuria. Example: Farxiga labeling | | Stivarga (regorafenib) | Thrombotic microangiopathy | FDA determined that no action was necessary at the time based on available information. | | Syfovre (pegcetacoplan injection) | Retinal vasculitis | The “Warnings and Precautions”, “Postmarketing Experience”, and “Patient Counseling Information” sections of the labeling were updated in November 2023 to include retinal vasculitis and/or retinal vascular occlusion. | Topical corticosteroids | Skin reaction | FDA is evaluating the need for regulatory action. |

FDA advises patients not to use Herbal Doctor Remedies’ medicines

FDA advises patients not to use Herbal Doctor Remedies’ medicines [4/1/2020] FDA reminds patients not to use any drugs manufactured by Herbal Doctor Remedies, Monterey Park, California, because these drugs were not manufactured under good manufacturing practices. During FDA’s March 2020 follow-up inspection, FDA investigators observed continued insanitary conditions and numerous serious violations of current good manufacturing practices (CGMP) at Herbal Doctor Remedies’ facility. On March 23, FDA recommended Herbal Doctor Remedies recall all unexpired drugs, and the company agreed. FDA encourages health care professionals and patients to report adverse events or quality problems experienced with the use of any medication to FDA’s MedWatch Adverse Event Reporting program: - Complete and submit the report online; or - Download and complete the form, then submit it via fax at 1-800-FDA-0178. [7/23/2019] FDA advises patients not to use any drugs manufactured by Herbal Doctor Remedies, Monterey Park, California, because these drugs were made under poor conditions. Herbal Doctor Remedies manufacturers a variety of unapproved new drugs, including Brain Forte, New Life, Lump Shrinker, Asma-F, Herpes-P, Anemia Off, Bone Fixer and Tumor Shrinker offered on several websites. FDA recommends patients stop using these drugs and dispose of them. During FDA’s recent inspection of the Herbal Doctor Remedies’ facility, investigators observed insanitary conditions and numerous serious violations of current good manufacturing practices (CGMP). Herbal Doctor Remedies cannot assure the quality or safety of its products due to the poor conditions and manufacturing practices at the facility. On July 11, 2019, FDA recommended that Herbal Doctor Remedies recall all unexpired drugs. Herbal Doctor Remedies initially agreed to recall; however, the company has not taken action to remove these potentially dangerous drugs from the market. To date, FDA is not aware of any reports of adverse events associated with medicines manufactured by Herbal Doctor Remedies. Patients who use Herbal Doctor Remedies’ medicines and have concerns should contact their health care professional. FDA issued a warning letter to Herbal Doctor Remedies in 2017 for marketing unapproved and misbranded drugs. Using drugs with unsubstantiated claims may prevent patients from seeking FDA-approved treatments that have been demonstrated to be safe and effective. FDA encourages health care professionals and patients to report adverse events or quality problems experienced with the use of any medication to FDA’s MedWatch Adverse Event Reporting program:

FDA alerts consumers not to use Kratom NC’s products

FDA alerts consumers not to use Kratom NC’s products [6/25/2019] FDA is warning consumers not to use products marketed by Kratom NC, of Wilmington, North Carolina, due to microbial contamination. FDA laboratory analysis of Kratom NC’s raw materials and finished products identified various microorganisms, including Klebsiella pneumoniae, Enterobacter spp. and Escherichia sp. These organisms may cause serious illnesses in vulnerable patient populations. FDA contacted Kratom NC on June 14 to recommend the company recall all of its products currently on the market. However, the company has not taken any action to recall these potentially dangerous products. The agency recently issued a warning letter to Kratom NC for illegally selling unapproved, misbranded kratom-containing drug products with unproven claims about their ability to treat or cure opioid addiction and withdrawal symptoms. The agency continues to urge consumers not to consume kratom and to seek appropriate medical care from their health care provider. To date, FDA is not aware of any reports of illness associated with the use of Kratom NC products. The agency asks health care professionals and patients to report unexpected side effects or quality problems associated with these products to FDA’s MedWatch Adverse Event Reporting program: - Complete and submit the report online at www.fda.gov/medwatch/report.htm; or - Download and complete the form, then submit it via fax at 1-800-FDA-0178. For more information

CDER alert Infusion Options

FDA alerts patients and healthcare professionals to Infusion Options’ voluntary recall due to quality issues [6/21/2019] The U.S. Food and Drug Administration is alerting healthcare professionals and patients of a voluntary recall of all unexpired compounded drugs intended to be sterile produced by Infusion Options, Inc. of Brooklyn, N.Y., due to lack of sterility assurance and other significant quality issues. These drugs may pose a safety risk to patients. Administration of a non-sterile drug intended to be sterile may result in serious and potentially life-threatening infections or death. Health care professionals should immediately check their medical supplies, quarantine any drugs prepared by Infusion Options, and not administer or provide them to patients. FDA urges health care professionals, who obtained products from Infusion Options, to make alternative arrangements to obtain medications from sources that adhere to proper quality standards. Patients who have received any drug produced by Infusion Options and have concerns should contact their health care professional. FDA investigators most recently inspected Infusion Options’ Brooklyn facilities in May and June of 2019 and observed conditions that could cause Infusion Options’ drugs to become contaminated or otherwise pose risks to patients. On June 14, Infusion Options agreed to voluntarily recall all unexpired drug products intended to be sterile, cease sterile operations until the company takes adequate corrective actions and voluntarily destroy all drugs and drug components with FDA officials present, following FDA’s recommendations. To date, FDA is not aware of any reports of illness associated with the use of Infusion Options’ drugs. The agency asks health care professionals and patients to report unexpected side effects or quality problems associated with Infusion Options’ drugs to FDA’s MedWatch Adverse Event Reporting program: - Complete and submit the report online at www.fda.gov/medwatch/report.htm; or - Download and complete the form, then submit it via fax at 1-800-FDA-0178.

FDA alerts patients of McDaniel Life-Line’s voluntary recall of Indian

FDA alerts patients of McDaniel Life-Line’s voluntary recall of Indian Herb Update [3/29/19] FDA is alerting health care professionals and patients of McDaniel Life-Line’s voluntarily recall of all lots of Life-Line Water. This product is being recalled because FDA analysis found the product to be contaminated with Pseudomonas aeruginosa. [2/12/19] FDA is alerting patients of a voluntary recall of all lots of unapproved Indian Herb made and distributed by McDaniel Life-Line, Felt, Oklahoma, because it was manufactured under poor conditions. The agency has concerns this product’s ingredients may burn through the skin, causing serious patient injury. FDA recommends patients who have Indian Herb stop using it immediately and discard it. Using the product could result in a disfiguring chemical amputation, which could require plastic surgery. FDA also recommends patients not use McDaniel’s Life-Line Water, due to the potential for hazardous microbial contamination. To date, McDaniel Life-Line has received one report of an injury related to its Indian Herb product. McDaniel distributed this product to individuals in the United States, Italy, Canada, Australia and Poland through the company’s website, www.lifelinewater.com. Patients who have questions regarding this recall can contact McDaniel Life-Line by phone 806-647-1471 or by email, lifeline@amaonline.com, Monday through Friday, from 8 a.m. to 5 p.m. Central Time. Patients should contact their physician or health care professional if they have experienced any problems that may be related to using these products. Patients and health care professionals should report any adverse reactions related to the use of McDaniel Life-Line products to FDA’s MedWatch program: - Complete and submit the report online at www.fda.gov/medwatch/report.htm - Download and complete the appropriate form, then submit it via fax at 1-800-FDA-0178.

FDA warns compounders not to use glutathione

FDA warns compounders not to use glutathione from Letco Medical to compound sterile drugs Agency is aware of adverse events related to compounded glutathione injection [2/1/2019] FDA is warning compounders not to use glutathione-L-reduced powder distributed by Letco Medical, Decatur, Alabama, to compound sterile injectable drugs for patients. Based on reported adverse events, the agency has concerns with use of the Letco distributed glutathione to compound injectable drugs due to potential endotoxins. Letco supplied this glutathione powder to about 100 compounders in 30 states. FDA urges compounders that use glutathione to make sterile injectable drugs to ensure the glutathione powder is appropriate for compounding sterile drugs, including checking with their supplier. FDA is aware of seven patients who experienced various adverse events ranging from nausea and vomiting to difficulty breathing, which required one patient to be hospitalized immediately after receiving glutathione 200mg/mL intravenous injection. FDA believes high levels of endotoxin may have contributed to these adverse events. Following these reports, FDA has received varying third-party test results on the levels of endotoxin that may be present in Letco’s glutathione powder. FDA testing is underway. Letco repackaged the glutathione into five sizes – 25gm, 50gm, 100gm, 500gm and 1kg – and distributed 13 lots with an expiration date of 6/17/2020: - 1808030041 - 1808030042 - 1808030043 - 1808030044 - 1808030045 - 1808290090 - 1808290091 - 1808290092 - 1808290093 - 1810150048 - 1810150049 - 1810150050 - 1810150051 Health care professionals should check with their compounders regarding the source of the glutathione used to make sterile drugs for their patients. Patients who have concerns should talk to their health care professionals. FDA is investigating this incident and will provide additional information as it becomes available. Patients and health care professionals should report any adverse reactions related to the use of compounded glutathione to FDA’s MedWatch program: - Complete and submit the report online at www.fda.gov/medwatch/report.htm - Download and complete the appropriate form, then submit it via fax at 1-800-FDA-0178.

HelloCig Electronic Technology

FDA alerts consumers not to use two e-liquids sold by HelloCig Electronic Technology [12/11/2018] The U.S. Food and Drug Administration is alerting consumers, particularly males, not to purchase or use two e-liquids sold by HelloCig Electronic Technology Co. Ltd. that contain undeclared prescription drugs tadalafil and/or sildenafil. FDA laboratory analysis confirmed “E-Cialis HelloCig E-Liquid” contains the undeclared drugs sildenafil and tadalafil, and “E-Rimonabant HelloCig E-Liquid” contains the undeclared drug sildenafil. These undeclared ingredients may interact with nitrates found in some prescription drugs such as nitroglycerin and may lower blood pressure to dangerous levels. People with diabetes, high blood pressure, high cholesterol, or heart disease often take nitrates. Sildenafil and tadalafil are the active pharmaceutical ingredients in FDA-approved prescription drugs used to treat erectile dysfunction. These FDA-approved prescription drugs are not approved for inclusion in e-liquid products sold over the counter and are therefore being sold illegally. FDA recently warned HelloCig of these issues and contacted the company several times to recommend they recall these products due to the risks to consumers. However, HelloCig has not responded to the agency’s recommendation. Therefore, FDA urges consumers to stop using these products and to contact their health care professional with any concerns associated with their use. To date, FDA is not aware of any adverse events associated with the use of HelloCig’s products. FDA encourages health care professionals and consumers to report adverse reactions experienced with the use of these products to the FDA’s MedWatch Adverse Event Reporting program by: - Completing and submitting the report online at www.fda.gov/medwatch/report.htm; or - Downloading and completing the form, then submit it via fax at 1-800-FDA-0178.

Donot to use products intended to be sterile from Promise Pharmacy

FDA alerts health care professionals and patients not to use drug products intended to be sterile from Promise Pharmacy Compounded drugs were produced under poor sterile production practices in an inadequately designed processing room [12/7/2018] The U.S. Food and Drug Administration is alerting health care professionals and patients not to use drug products intended to be sterile that were produced in an inadequately designed processing room and distributed by Promise Pharmacy, Palm Harbor, Florida, due to lack of sterility assurance. Administration of a non-sterile drug product intended to be sterile may result in serious and potentially life-threatening infections or death. During FDA’s recent inspection of Promise Pharmacy’s facility, investigators observed insanitary conditions, including poor sterile production practices and inadequate design of one of its processing rooms, which raised concerns about the company’s ability to assure the sterility of its drug products from that processing room. Examples of products compounded in this room include bremelanotide, sermorelin, BPC-157, arginine HCL, leucine/isoleucine/valine, dexapanthenol and/or ascorbic acid. There may be additional drug products that were compounded in that processing room. Health care professionals should contact Promise Pharmacy for any questions concerning whether drug products obtained from the pharmacy were produced in the inadequately designed processing room and immediately check their medical supplies, quarantine any purportedly sterile drug products of concern, and not administer them to patients. Health care professionals should also make alternative arrangements to replace any medications produced in the inadequately designed processing room from reliable sources that adhere to proper quality standards. Patients who have received drug products intended to be sterile compounded by Promise Pharmacy and have concerns should consult their health care professional. On November 13, 2018, FDA recommended that Promise Pharmacy recall all unexpired drug products intended to be sterile and cease sterile operations until the company makes adequate corrections at its facility. On November 14 and November 19, 2018, Promise Pharmacy informed FDA that it would voluntarily cease sterile operations in the inadequately designed processing room; however, the company refused to recall drug products it compounded in that room. During FDA’s recent inspection, on October 22, 2018, Promise Pharmacy did conduct a limited voluntary recall of prednisolone and gatifloxacin ophthalmic solutions due to small particulate floating in the solutions. FDA is not aware of any recent adverse events associated with the use of products from Promise Pharmacy. FDA encourages health care professionals and patients to report adverse reactions or quality problems experienced with the use of these products to the MedWatch Adverse Event Reporting program by: - Completing and submit the report online at www.fda.gov/medwatch/report.htm; or - Downloading and completing the form, then submit it via fax at 1-800-FDA-0178.

Some EpiPen auto-injectors may not readily slide out of carrier tube

FDA alerts patients and health care professionals that some EpiPen auto-injectors may not readily slide out of carrier tube [11/2/2018] FDA is alerting patients, caregivers and health care professionals that the labels attached to some EpiPen 0.3mg and EpiPen Jr 0.15mg auto-injectors, and the authorized generic versions, may block access to the auto-injector and prevent the ability to easily access the product. In a letter to health care professionals from Pfizer, the manufacturer of the Mylan EpiPen, the label sticker on the auto-injector unit may have been improperly applied, causing resistance when removing it from the carrier tube. The carrier tube is the immediate package in which the auto-injector is contained. In some cases, the patient or caregiver may not be able to quickly remove the epinephrine auto-injector from the carrier tube. The auto-injector device and the epinephrine it delivers are not affected by this issue and can be used as prescribed. It is vital for lifesaving products to work as designed in an emergency situation, and patients and caregivers should inspect their epinephrine auto-injector prior to needing it to ensure they can quickly access the product. The letter also describes how to inspect potentially affected products and explains that patients should contact Mylan Customer Relations at 800-796-9526 if an auto-injector does not slide out easily from the carrier tube OR the label is not fully adhered to the auto-injector. Pharmacists should inspect the products before dispensing them to patients to ensure quick access to the auto-injector and should not dispense any product which does not easily slide out of its carrier tube. FDA is not aware of any adverse event reports associated with improperly applied EpiPen or EpiPen Jr auto-injectors, or their authorized generics label. As stated on the product label, consumers should always seek emergency medical help right away after using their epinephrine auto-injector. FDA asks health care professionals and consumers to report any adverse reactions or quality problems to the FDA’s MedWatch program: - Complete and submit the report online at www.fda.gov/medwatch/report.htm. - Download and complete the form, then submit it via fax at 1-800-FDA-0178.

Sprayology’s recall of homeopathic water-based medicines

FDA alerts consumers of Sprayology’s voluntary nationwide recall of homeopathic water-based medicines due to microbial contamination [10/11/2018] The Food and Drug Administration is alerting consumers about a voluntary recall of all lots with expiration dates from October 2018 to July 2022 of Sprayology’s water-based homeopathic product line for human use. These products are labeled as a homeopathic and are being recalled due to microbial contamination at the King Bio Inc. manufacturing facility in Asheville, North Carolina. Administration or use of drug products with microbial contamination could potentially result in increased infections that may require medical intervention. Previously, FDA alerted consumers to four other voluntary recalls related to King Bio’s recall: Health care professionals and patients should report any adverse events associated with Sprayology's products to the FDA’s MedWatch Adverse Event Reporting program: - Silver Star Brand’s voluntary recall of homeopathic drug products - HelloLife’s voluntary recall of drug products labeled as homeopathic; - Beaumont Bio Med’s voluntary recall of all water- and alcohol-based products; and - BioLyte Laboratories voluntary recall of NeoRelief Health care professionals and patients should report any adverse events associated with Sprayology's products to the FDA’s MedWatch Adverse Event Reporting program: - Complete and submit the report online at www.fda.gov/medwatch/report.htm; or - Download and complete the form, then submit it via fax at 1-800-FDA-0178.

Silver Star Brand’s voluntary recall of homeopathic drug products

FDA alerts consumers and pet owners of Silver Star Brand’s voluntary recall of homeopathic drug products [10/4/2018] The Food and Drug Administration is alerting consumers and pet owners about a voluntary recall of certain lots of eight products – six products for humans, including four Native Remedies and two Healthful Naturals, and two PetAlive products for pets – distributed by Silver Star Brands Inc. (Oshkosh, Wisconsin). These products are labeled as a homeopathic and are being recalled due to microbial contamination at the King Bio Inc. manufacturing facility in Asheville, North Carolina. Administration or use of drug products with microbial contamination could potentially result in increased infections that may require medical intervention. Previously, FDA alerted consumers to three other voluntary recalls related to King Bio’s recall: - HelloLife’s voluntary recall of drug products labeled as homeopathic; - Beaumont Bio Med’s voluntary recall of all water- and alcohol-based products; and - BioLyte Laboratories voluntary recall of NeoRelief Health care professionals and patients should report any adverse events associated with Silver Star’s drug products to the FDA’s MedWatch Adverse Event Reporting program: - Complete and submit the report online at www.fda.gov/medwatch/report.htm; or - Download and complete the form, then submit it via fax at 1-800-FDA-0178. Pet owners and veterinarians are encouraged to report animal adverse drug events by following the directions for How to Report Animal Drug Side Effects and Product Problems.

Therapeutic equivalence rating for certain Prograf generics

FDA is changing the therapeutic equivalence rating for Accord Healthcare Inc.’s generics of Prograf (tacrolimus) oral capsules [9/18/2023] Based on new data, the U.S. Food and Drug Administration is changing the therapeutic equivalence rating for tacrolimus oral capsule products manufactured by Accord Healthcare Inc. under abbreviated new drug application 091195. These drugs are indicated for the prevention of organ rejection in adult patients receiving kidney, liver, or heart transplants, and in pediatric patients receiving liver transplants. FDA is concerned that the peak blood concentration of tacrolimus for Accord Healthcare Inc.’s generic tacrolimus oral capsules may be increased compared to the brand-name drug, Prograf (tacrolimus), creating a risk of toxicity. However, according to the new data, there were no significant differences in the trough blood levels, indicating no increased risk for organ rejection. In 2011, FDA determined that tacrolimus products qualified as narrow therapeutic index drugs, and in 2012, updated recommendations for the design of bioequivalence studies to support therapeutic equivalence for tacrolimus generics. This change led to concerns from the transplant community regarding the substitutability of FDA-approved generic tacrolimus oral capsules that were approved prior to 2012, for both their therapeutic equivalence to the brand-name drug, Prograf (tacrolimus) and other approved generics. FDA funded a number of studies to investigate these concerns. Multiple post-approval studies signaled a potential issue with the bioequivalence of Accord Healthcare Inc.’s tacrolimus oral capsules and this led FDA to fund an additional study by BioPharma Services USA. FDA reviewed the results of the bioequivalence study by BioPharma along with other evidence. These studies indicate that Accord Healthcare Inc.’s tacrolimus oral capsules may deliver drug to the body at a higher maximum concentration compared to Prograf’s tacrolimus oral capsules. The increased peak concentration may result in patients having too much tacrolimus in their body compared to Prograf, which may result in signs or symptoms of tacrolimus toxicity (see Figures 1–3). Figure 1. Based on the tacrolimus whole blood levels after a single dose oral administration of Accord (test) and Prograf (reference) tacrolimus oral capsules, a simulation was conducted to demonstrate the impact of switching a subject stabilized on Accord (as determined by the achievement of steady state with multiple subsequent doses of Accord every 12 hours) to Prograf. Figure 2. From Figure 1, the minimum tacrolimus whole blood levels (or Cmin or the trough concentration) after each dose of Accord (test) and Prograf (reference) tacrolimus oral capsules (i.e., the concentration at 12 hours when the subsequent dose is given). Horizontal lines represent the steady state Cmin value for each treatment. Figure 3. From Figure 1, the overall area-under-the-curve associated with each dose of Accord (test) and Prograf (reference) tacrolimus oral capsules (or AUCtau where tau is 12 hours). Horizontal lines represent the steady state AUCtau value for each treatment. Potential harms to patients from higher concentrations of tacrolimus include kidney damage (nephrotoxicity); high blood pressure (hypertension); nerve damage (neurotoxicity), such as seizures, tremors, or headache; and elevated potassium levels (hyperkalemia). However, FDA is not aware of post-marketing issues regarding safety or efficacy for Accord Healthcare Inc.’s tacrolimus oral capsules. As a result of its review of this new information, FDA has changed the therapeutic equivalence rating for Accord Healthcare Inc.’s tacrolimus oral capsules from AB to BX. A BX rating means that the data are insufficient to show that Accord Healthcare Inc.’s tacrolimus oral capsules provide the same therapeutic effect as Prograf (tacrolimus) oral capsules. This means that Accord Healthcare Inc.’s tacrolimus oral capsules are still FDA-approved and can be prescribed, but are no longer recommended as automatically substitutable at the pharmacy (or by a pharmacist) for Prograf (tacrolimus) oral capsules. Prograf (tacrolimus) oral capsules and generic tacrolimus oral capsules manufactured by companies other than Accord Healthcare Inc. are not affected by this issue. Other tacrolimus dosage forms are also not affected by this issue, including tacrolimus extended-release oral capsules, tacrolimus granules for oral suspension, tacrolimus injection products for intravenous use, and tacrolimus topical ointments. Patients can determine the manufacturer of their tacrolimus oral capsules by contacting their pharmacy. Patients currently taking Accord Healthcare Inc.’s tacrolimus oral capsules should not make changes to their treatment, except in consultation with their health care professional. Patients should also inform their health care professional if they have experienced any problems that may be related to taking Accord Healthcare Inc.’s tacrolimus oral capsules. FDA encourages health care professionals and consumers to report adverse events or quality problems with these or any medications to FDA’s MedWatch Adverse Event Reporting program: - Complete and submit the report online; or - Download and complete the form, then submit it via fax at 1-800-FDA-0178.

Consumers should not to purchase or use certain MSM eye drops

FDA warns consumers not to purchase or use certain methylsulfonylmethane (MSM) eye drops due to contamination Update [8/30/2023] Dr. Berne’s Whole Health Products voluntarily recalled Dr. Berne’s MSM Drops 5% and 15% Solution Eye Drops due to bacterial and fungal contamination on August 26, 2023. [8/22/2023] FDA is warning consumers not to purchase and to immediately stop using Dr. Berne’s MSM Drops 5% Solution and LightEyez MSM Eye Drops – Eye Repair due to bacterial contamination, fungal contamination, or both. Dr. Berne’s products are distributed by Dr. Berne’s Whole Health Products; LightEyez’ products are distributed by LightEyez Limited. FDA recommends consumers properly discard these products as FDA describes. Using contaminated eye drops could result in minor to serious vision-threatening infection which could possibly progress to a life-threatening infection. FDA is not aware of any adverse event reports associated with use of either products at this time. Patients who have signs or symptoms of an eye infection should talk to their health care professional or otherwise seek medical care immediately. The Dr. Berne’s and LightEyez eye drop products also contain methylsulfonylmethane (MSM) as an active ingredient. These products are unapproved drugs and illegally marketed in the U.S. There are no legally marketed ophthalmic drugs that contain MSM as an active ingredient. FDA conducted sampling and testing based on these products’ intended use in the eyes, and due to the industry’s recent manufacturing issues with eye drops. FDA’s testing showed the products were contaminated with microbes and were not sterile. Under the Federal Food, Drug and Cosmetic Act, eye drops must be sterile to be safe for use. The table below includes examples of specific microbes isolated from FDA testing. Dr. Berne verbally agreed on August 21, 2023, to voluntary recall the Dr. Berne’s MSM Drops 5% Solution. FDA emailed LightEyez Limited on August 21, 2023 seeking to discuss FDA’s concerns with LightEyez products distributed in the U.S. and further steps to protect consumers from using the contaminated eye drops. To date, LightEyez has not responded to FDA or taken action to protect consumers. Examples of microbial contaminants found in products: | Product | Bacterial contamination | Fungal contamination | |---|---|---| | Dr. Berne’s MSM Drops 5% Solution | Bacillus, spp. | Exophiala, sp. | | LightEyez MSM Eye Drops – Eye Repair | Pseudomonas, spp.; | N/A | FDA encourages health care professionals and consumers to report adverse events or quality problems with any medicine to FDA’s MedWatch Adverse Event Reporting program:

G-Supress DX Pediatric Cough Drops may have incorrect drug in packagin

G-Supress DX Pediatric Cough Drops may have incorrect drug in packaging [5/22/2023] FDA is alerting consumers and pharmacies to not use or sell a specific lot of over-the-counter G-Supress DX Pediatric Drops Cough Suppressant Expectorant Nasal Decongestant Cherry Flavor, manufactured by Novis PR LLC, because it contains the incorrect product and may cause patient harm. Novis received multiple complaints from pharmacies that found the wrong product – Finafta Anesthetic/Analgesic Liquid – inside the carton packaging of the G-Supress product. Novis does not manufacture Finafta Anesthetic/Analgesic Liquid, used to temporarily relieve mouth irritations and inflammation. Finafta Anesthetic/Analgesic Liquid comes in 0.5-fl. oz. (15-mL) bottles. Finafta Anesthetic/Analgesic Liquid contains 60% ethyl alcohol and 5% benzocaine. Infants and young children are at higher risk of developing alcohol toxicity, profound hypoglycemia (low blood sugar), coma, hypothermia (low body temperature), or death from ingesting even relatively small amounts of ethanol. Benzocaine can cause methemoglobinemia, a potentially life-threatening condition where too little oxygen is delivered to your cells. Novis issued a voluntary recall (also in Spanish) of Lot D20911 Exp 10/25 of G-Supress DX Pediatric Drops Cough Suppressant Expectorant Nasal Decongestant Cherry Flavor. Consumers, distributors, and retailers should stop using this lot and return it to place of purchase. The product was only distributed in Puerto Rico. To date, Novis has not received any reports of adverse events or injuries related to product use. Novis is notifying its distributors and customers by email and telephone calls and arranging return of the recalled lot. Consumers with questions regarding this recall can contact Novis PR LLC at 787-767-2072 Monday through Friday from 8:00 am – 4:00 pm EDT. Consumers should contact their physician or health care professional if they have experienced any problems that may be related to taking or using this drug. FDA encourages health care professionals and consumers to report adverse events or quality problems with these or any medications to FDA’s MedWatch Adverse Event Reporting program: