Sublimaze FDA Alerts

Drug Safety Communication: All Opioid Pain Medicines - FDA Updates Prescribing Information to Provide Additional Guidance for Safe Use

ISSUE: The FDA is requiring several updates to the prescribing information for both immediate-release (IR) and extended release/long acting (ER/LA) opioid pain medicines. This includes stating for all opioid pain that the risk of overdose increases as the dose increases.

• The updates to IR opioids state these products should not be used for an extended period unless the pain remains severe enough to require them and alternative treatments continue to be inadequate, and that many acute pain conditions treated in the outpatient setting require no more than a few days of an opioid pain medicine. This may include pain occurring with a number of surgical conditions or musculoskeletal injuries.
• The FDA is also updating the approved use for ER/LA opioid pain medicines to recommend they be reserved for severe and persistent pain that requires an extended treatment period with a daily opioid pain medicine and for which alternative treatment options are inadequate.
• The FDA is also adding a new warning about opioid-induced hyperalgesia (OIH) for both IR and ER/LA opioid pain medicines. This includes information describing the symptoms that differentiate OIH from opioid tolerance and withdrawal.
• Information in the Boxed Warning, FDA’s most prominent warning, for all IR and ER/LA opioid pain medicines will be updated and reordered to elevate the importance of warnings concerning life-threatening respiratory depression, and risks associated with using opioid pain medicines in conjunction with benzodiazepines or other medicines that depress the central nervous system (CNS).
• Other changes are also being required to several sections of the prescribing information, including to the Indications and Usage, Dosage and Administration, and Warnings and Precautions sections. The FDA is also requiring updates to the existing patient Medication Guides to help educate patients and caregivers about these risks.

BACKGROUND: Opioid pain medicines are a class of powerful pain medicines prescribed to treat pain that does not respond well to other treatments or non-opioid pain medicines. They activate an area of nerve cells in the brain and body that block pain signals. These medicines have benefits when used appropriately, but they also have serious risks, including misuse and abuse, addiction, overdose, and death. Examples of common opioid pain medicines include codeine, hydrocodone, hydromorphone, morphine, oxycodone, oxymorphone, fentanyl, buprenorphine, and tramadol.

RECOMMENDATIONS:

Patients/Parents/Caregivers

• Always take your opioid medicines exactly as prescribed. Do not take more of the medicine or take it more often than prescribed without first talking to your health care professional. Talk with them if your pain increases, you feel more sensitive to pain, or if you have new pain, especially from touch or other things that are not usually painful such as combing your hair.
• Store your opioid pain medicines securely, out of sight and reach of children, and in a location not accessible by others, including visitors to the home. Do not share these medicines with anyone else, and immediately dispose of unused or expired opioids or take them to a drug take-back site, location, or program. If provided, use the prepaid mail-back envelopes included with the prescription.
• Seek emergency medical help or call 911 immediately if you or someone you are caring for experiences symptoms of respiratory problems, which can be life-threatening. Signs and symptoms include serious slowed, shallow, or difficult breathing, severe sleepiness, or not being able to respond or wake up.
• Talk to your health care professionals about the benefits of naloxone, which can reverse an opioid overdose, and how to obtain it. Your health care professional can give you a prescription for naloxone. Additionally, in most states and the District of Columbia you can obtain naloxone from a pharmacy under a standing order that takes the place of an individual prescription. Some states also allow you to obtain naloxone without a prescription from a community-based program or pharmacy. Check with your state Health Department for more information. In March 2023, FDA approved an inhaled nasal spray version of naloxone to be sold over-the-counter without a prescription while multiple forms of naloxone remain available as prescription only.

Health Care Professionals 

• In assessing the severity of pain, discuss with the patient the impact of the pain on their ability to function and their quality of life. Assessment of pain should consider both the cause of pain and individual patient factors.
• If the patient’s pain is severe enough to require an opioid pain medicine and alternative treatment options are insufficient, prescribe the lowest effective dose of an IR opioid for the shortest duration of time to reduce the risks associated with these products.
• Reserve ER/LA opioid pain medicines only for severe and persistent pain that requires an extended treatment period with a daily opioid pain medicine and for which alternative treatment options are inadequate.
• For all patients prescribed opioid pain medicines, discuss the availability of naloxone, and consider prescribing it to those at increased risk of overdose.
• Be aware that the symptoms of OIH, a condition where opioids cause an increase in pain (called hyperalgesia) or an increased sensitivity to pain (called allodynia), are distinct from opioid tolerance and withdrawal and can be difficult to recognize.
• If a patient is suspected to be experiencing OIH, carefully consider an appropriate decrease in dose of the current opioid pain medicine or safely switching them to a different opioid product, if tolerated. Advise patients about the risk of OIH and tell them to never increase the opioid dosage without first consulting a health care professional, because this could worsen the pain and increase the risk of respiratory depression.

Health care professionals and patients are encouraged to report adverse events or side effects related to the use of these products to the FDA's MedWatch Safety Information and Adverse Event Reporting Program:

• Complete and submit the report online.

• Download form or call 1-800-332-1088 to request a reporting form, then complete and return to the address on form, or submit by fax to 1-800-FDA-0178.

[04/13/2023 - Drug Safety Communication - FDA] 
[04/13/2023 - CDER Statement - FDA] 

Source: FDA

FDA Alerts Health Care Professionals of Risks to Patients Exposed to Xylazine in Illicit Drugs

Xylazine is FDA-approved for use in animals as a sedative and pain reliever. Xylazine is not safe for use in humans and may result in serious and life-threatening side effects that appear to be similar to those commonly associated with opioid use, making it difficult to distinguish opioid overdoses from xylazine exposure. However, we do not know if side effects from xylazine exposure can be reversed by naloxone. Since we do not know if reversal agents regularly used in veterinary medicine (e.g., yohimbine hydrochloride, tolazoline hydrochloride) are safe or effective in humans, they should not be used.

Routine toxicology screens do not detect xylazine, and additional analytical techniques are required to detect xylazine when it might be involved in illicit drug overdoses, particularly when there are other signs or symptoms of xylazine exposure.

Health care professionals should continue to administer naloxone for opioid overdoses and consider xylazine exposure if patients are not responding to naloxone or when there are signs or symptoms of xylazine exposure (e.g., severe, necrotic skin ulcerations). Health care professionals should provide appropriate supportive measures to patients who do not respond to naloxone.

FDA issued a letter to stakeholders providing clinical information about the risks of severe, necrotic skin ulcerations from repeated xylazine exposure, possible withdrawal symptoms, and xylazine’s interference with successful treatment of opioid overdoses.

It is not known at this time whether the xylazine used in these scenarios is illicitly produced (unapproved) or diverted from the animal drug supply. FDA is continuing to investigate the source of xylazine in the illicit drug supply and will provide an update when new information is available.

FDA encourages health care professionals and patients to report adverse events in humans associated with possible illicit xylazine exposure 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.

Source: FDA

Opioid Pain Relievers or Medicines to Treat Opioid Use Disorder - FDA Recommends Health Care Professionals Discuss Naloxone with All Patients when Prescribing

ISSUE: FDA is requiring drug manufacturers for all opioid pain relievers and medicines to treat opioid use disorder (OUD) to add new recommendations about naloxone to the prescribing information.  This will help ensure that health care professionals discuss the availability of naloxone and assess each patient’s need for a naloxone prescription when opioid pain relievers or medicines to treat OUD are being prescribed or renewed.  The patient Medication Guides will also be updated.

BACKGROUND: Opioid pain relievers are medicines that can help manage pain when other treatments and medicines are not able to provide enough pain relief.  Certain opioids are also used to treat OUD.  Opioids have serious risks, including misuse and abuse, addiction, overdose, and death.  Naloxone can help reverse opioid overdose to prevent death.

The misuse and abuse of illicit and prescription opioids and the risks of addiction, overdose, and death are a public health crisis in the United States.  As a result, FDA is committed to encouraging health care professionals to raise awareness of the availability of naloxone when they are prescribing and dispensing opioid pain relievers or medicines to treat OUD.  FDA held discussions about naloxone availability with the Anesthetic and Analgesic Drug Products and the Drug Safety and Risk Management Advisory Committees, which recommended that all patients being prescribed opioids for use in the outpatient setting would benefit from a conversation with their health care professional about the availability of naloxone. 

RECOMMENDATION:
Patients: 

• Talk to your health care professionals about the benefits of naloxone and how to obtain it.  
• Recognize the signs and symptoms of a possible opioid overdose.  These include slowed, shallow, or difficult breathing, severe sleepiness, or not being able to respond or wake up.  If you know or think someone is overdosing, give the person naloxone if you have access to it, and always call 911 or go to an emergency room right away.  Naloxone is a temporary treatment, so repeat doses may be required.  Even if you give naloxone, you still need to get emergency medical help right away.
• If you have naloxone, make sure to tell your caregivers, household members, and other close contacts that you have it, where it is stored, and how to properly use it in the event of an overdose.  When using opioid medicines away from home, carry naloxone with you and let those you are with know you have it, where it is, and how to use it.  Read the Patient Information leaflet or other educational material and Instructions for Use that comes with your naloxone because it explains important information, including how to use the medicine.  

Health Care Professionals: 

• Discuss the availability of naloxone with all patients when prescribing or renewing an opioid analgesic or medicine to treat OUD.  
• Consider prescribing naloxone to patients prescribed medicines to treat OUD and patients prescribed opioid analgesics who are at increased risk of opioid overdose.  
• Consider prescribing naloxone when a patient has household members, including children, or other close contacts at risk for accidental ingestion or opioid overdose.
• Additionally, even if the patients are not receiving a prescription for an opioid analgesic or medicine to treat OUD, consider prescribing naloxone to them if they are at increased risk of opioid overdose. 
• Educate patients and caregivers on how to recognize respiratory depression and how to administer naloxone.  Inform them about their options for obtaining naloxone as permitted by their individual state dispensing and prescribing requirements or guidelines for naloxone. Emphasize the importance of calling 911 or getting emergency medical help right away, even if naloxone is administered. 

Patients and health care professionals are encouraged to report adverse events or side effects related to the use of these products to the FDA's MedWatch Safety Information and Adverse Event Reporting Program:

• Complete and submit the report online.
• Download form or call 1-800-332-1088 to request a reporting form, then complete and return to the address on the form, or submit by fax to 1-800-FDA-0178

[07/23/2020 - Drug Safety Communication - FDA] 

Source: FDA

Alvogen Inc. Issues Voluntary Nationwide Recall of Fentanyl Transdermal System Due to Product Mislabeling

April 19, 2019 -- Alvogen, Inc. is voluntarily recalling two lots of Fentanyl Transdermal System 12 mcg/h transdermal patches to the consumer level. A small number of cartons labeled 12 mcg/h Fentanyl Transdermal System patches contained 50 mcg/h patches. The 50 mcg/h patches that were included in cartons labeled 12 mcg/h are individually labeled as 50 mcg/h. This transdermal system is manufactured by 3M Drug Delivery Systems, St. Paul, MN.

Application of a 50 mcg/h patch instead of a prescribed 12 mcg/h patch could result in serious, life threatening, or fatal respiratory depression. Groups at potential increased risk could include first time recipients of such patches, children, and the elderly. To date, Alvogen Inc. has not received any reports of adverse events related to this issue.

The product is indicated for the management of pain in opioid tolerant patients and is packaged in primary cartons of five individually wrapped and labeled pouches. The affected Fentanyl Transdermal System lots include:

Lot 180060 of Fentanyl Transdermal System, 12 mcg/h, expiration date 05/2020.

Lot 180073 of Fentanyl Transdermal System, 12 mcg/h, expiration date 06/2020.

The mislabeled product is packaged in a 12 mcg/h primary carton. These lots of Fentanyl Transdermal System were distributed Nationwide to the pharmacy level.

See images example for lot 180073.

Alvogen Inc. is notifying its distributors and direct customers by certified letter and is arranging for return and replacement of all recalled products. Pharmacies are requested not to dispense any product subject to this recall. Patients that have product subject to this recall should immediately remove any patch currently in use and contact their health care provider. Patients with unused product should return it to point of purchase for replacement.

Questions regarding this recall should be directed to Alvogen Customer Complaints by calling 866-770-3024 or sending an e-mail to pharmacovigilance@alvogen.com from Monday to Friday from 9:00 am to 5:00 pm EST. Consumers should contact their physician or health care provider if they have experienced any problems that may be related to taking or using this drug product.

Adverse reactions or quality problems experienced with the use of this product may be reported to the FDA's MedWatch Adverse Event Reporting program either online, by regular mail or by fax.

Injectable Products by SCA Pharmaceuticals: Recall - Potential Contamination

ISSUE: SCA Pharmaceuticals LLC (“SCA Pharmaceuticals”) is voluntarily recalling various lots of injectable products to the hospital level. There is a potential for the products to contain microbial contamination.  See the recall notice for a full list of products.

BACKGROUND: Administration of a drug product, intended to be sterile, that may contain microbial contamination has the potential to result in serious adverse events which may include life-threatening infections. SCA Pharmaceuticals has not received any customer complaints or reports of adverse events related to this issue.

RECOMMENDATION: SCA Pharmaceuticals is notifying its customers via telephone, email and US mail and is arranging for return/replacement of all recalled products. Customers that have product which is being recalled, as indicated in the list above, should discontinue use immediately and return the product to SCA Pharmaceuticals.

Consumers with questions regarding this recall can contact SCA Pharmaceuticals at 877-550-5059, between the hours of 8:00 am and 5:00 pm (Central Standard Time), Monday thru Friday. Consumers should contact their physician or healthcare provider if they have experienced any problems that may be related to taking or using this drug product.

Healthcare professionals and patients are encouraged to report adverse events or side effects related to the use of these products to the FDA's MedWatch Safety Information and Adverse Event Reporting Program:

• Complete and submit the report Online: www.accessdata.fda.gov/scripts/medwatch/index.cfm
• Download form or call 1-800-332-1088 to request a reporting form, then complete and return to the address on the pre-addressed form, or submit by fax to 1-800-FDA-0178.

[10/20/2017 - Recall Notice - SCA Pharmaceuticals]

Compounded Drugs Stored in Becton-Dickinson (BD) 3 ml and 5 ml Syringes: FDA Warning - Do Not Use

ISSUE: FDA is alerting health care professionals not to administer to patients compounded or repackaged drugs that have been stored in 3 milliliter (ml) and 5ml syringes manufactured by Becton-Dickinson (BD) unless there is no suitable alternative available. Preliminary information indicates that drugs stored in these syringes may lose potency over a period of time due to a possible interaction with the rubber stopper in the syringe.

If you have been using products packaged in these syringes, be aware that using a substitute product may require a dosage adjustment in case the patient has been receiving a subpotent product, or adverse consequences could occur.

BD’s 10ml, 20ml and 30ml syringes may also contain the same rubber stopper. The company is alerting their customers not to use these syringes as a closed container system for compounded and repackaged drugs.

BACKGROUND: FDA has cleared these syringes as medical devices for general purpose fluid aspiration and injection only.  These syringes were not cleared for use as a closed container storage system for drug products, and the suitability of these syringes for that purpose has not been established.  This issue may extend to other general use syringes made by other manufacturers that were not cleared for the purpose of closed-container storage usage. FDA has received several reports of compounded and repackaged drugs, such as fentanyl, morphine, methadone and atropine, losing potency when stored in BD 3ml and 5ml general purpose syringes. It is possible that this chemical reaction may affect other compounded and repackaged drugs stored in syringes not FDA cleared for closed-container storage.

RECOMMENDATION: Hospital and pharmacy staff should check supply stocks and remove drug products that were filled by pharmacies or outsourcing facilities and stored in general purpose BD 3ml and 5ml syringes.  These syringes are marked with the BD logo at the base of the syringe. At this time, FDA does not have information on how long drugs can be stored in these syringes before degrading. There is no information to suggest that there is a problem with potency or drug degradation when medication is administered promptly after the syringes are filled.

This warning does not extend to products approved by FDA for marketing as pre-filled syringes, because as part of the approval process, FDA has determined that these products have been shown to maintain stability in the syringe container through the expiration date on the product.

The FDA is continuing to investigate this issue and will provide more information when it is available.

Healthcare professionals and patients are encouraged to report adverse events or side effects related to the use of these products to the FDA's MedWatch Safety Information and Adverse Event Reporting Program:

• Complete and submit the report Online: www.accessdata.fda.gov/scripts/medwatch/index.cfm
• Download form or call 1-800-332-1088 to request a reporting form, then complete and return to the address on the pre-addressed form, or submit by fax to 1-800-FDA-0178

[08/18/2015 - Warning - FDA]
 

Fentanyl Transdermal System: Recall - Potential for Active Ingredient to Release Faster Than Specified

[Posted 10/22/2010]

UPDATED 11/05/2010. Consumers encouraged to return any product in their possession from the October 2010 recall.

ISSUE: FDA notified healthcare professionals and patients that laboratory testing identified a patch that released its active ingredient faster than the approved specification. An accelerated release of Fentanyl can lead to adverse events for at-risk patients, including excessive sedation, respiratory depression, hypoventilation (slow breathing), and apnea (temporary suspension of breathing). 

BACKGROUND: Fentanyl Transdermal System is indicated for the management of persistent, moderate to severe chronic pain that requires continuous, around-the-clock opioid administration for an extended period of time and cannot be managed by other means such as non-steroidal analgesics, opioid combination products, or immediate release opioids. The product is manufactured for Actavis by Corium International in the United States.

RECOMMENDATION: Wholesalers and retailers are being asked to return the product they have on hand or in stock. See the Press Release for recalled product lots. The Control/Lot number appears on the bottom of the product box and on the black and white side of each individual patch packaging, in the lower left corner.
 
Healthcare professionals and patients are encouraged to report adverse events or side effects related to the use of these products to the FDA's MedWatch Safety Information and Adverse Event Reporting Program:

• Complete and submit the report Online: www.accessdata.fda.gov/scripts/medwatch/index.cfm
• Download form or call 1-800-332-1088 to request a reporting form, then complete and return to the address on the pre-addressed form, or submit by fax to 1-800-FDA-0178

[11/04/2010 - Press Release - Actavis, Inc.]
[10/21/2010 - Press Release - Actavis, Inc.]

Fentanyl Transdermal System: Recall - Potential for Active Ingredient to Release Faster Than Specified

ISSUE: FDA notified healthcare professionals and patients that laboratory testing identified a patch that released its active ingredient faster than the approved specification. An accelerated release of Fentanyl can lead to adverse events for at-risk patients, including excessive sedation, respiratory depression, hypoventilation (slow breathing), and apnea (temporary suspension of breathing). 

BACKGROUND: Fentanyl Transdermal System is indicated for the management of persistent, moderate to severe chronic pain that requires continuous, around-the-clock opioid administration for an extended period of time and cannot be managed by other means such as non-steroidal analgesics, opioid combination products, or immediate release opioids. The product is manufactured for Actavis by Corium International in the United States.

RECOMMENDATION: Wholesalers and retailers are being asked to return the product they have on hand or in stock. See the Press Release for recalled product lots. The Control/Lot number appears on the bottom of the product box and on the black and white side of each individual patch packaging, in the lower left corner.
 
Healthcare professionals and patients are encouraged to report adverse events or side effects related to the use of these products to the FDA's MedWatch Safety Information and Adverse Event Reporting Program:

• Complete and submit the report Online: www.accessdata.fda.gov/scripts/medwatch/index.cfm
• Download form or call 1-800-332-1088 to request a reporting form, then complete and return to the address on the pre-addressed form, or submit by fax to 1-800-FDA-0178

[10/21/2010 - Press Release - Actavis Inc.]

Fentanyl Transdermal System CII Patches

Fentanyl transdermal system CII Patches

Duragesic 25 mcg/hr (fentanyl transdermal system) CII Pain Patches

Fentanyl Transdermal System (marketed as Duragesic and generics)

Fentanyl Transdermal (Skin) Patch

Injectable drugs prepared by Urgent Care Pharmacy