Xartemis XR FDA Alerts

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

Acetaminophen Prescription Combination Drug Products with more than 325 mg: FDA Statement - Recommendation to Discontinue Prescribing and Dispensing

ISSUE: FDA is recommending health care professionals discontinue prescribing and dispensing prescription combination drug products that contain more than 325 milligrams (mg) of acetaminophen per tablet, capsule or other dosage unit. There are no available data to show that taking more than 325 mg of acetaminophen per dosage unit provides additional benefit that outweighs the added risks for liver injury. Further, limiting the amount of acetaminophen per dosage unit will reduce the risk of severe liver injury from inadvertent acetaminophen overdose, which can lead to liver failure, liver transplant, and death.
 
Cases of severe liver injury with acetaminophen have occurred in patients who:

• took more than the prescribed dose of an acetaminophen-containing product in a 24-hour period;
• took more than one acetaminophen-containing product at the same time; or
• drank alcohol while taking acetaminophen products.

BACKGROUND: In January 2011 FDA asked manufacturers of prescription combination drug products containing acetaminophen to limit the amount of acetaminophen to no more than 325 mg in each tablet or capsule by January 14, 2014. FDA requested this action to protect consumers from the risk of severe liver damage which can result from taking too much acetaminophen. This category of prescription drugs combines acetaminophen with another ingredient intended to treat pain (most often an opioid), and these products are commonly prescribed to consumers for pain, such as pain from acute injuries, post-operative pain, or pain following dental procedures.

Acetaminophen is also widely used as an over-the-counter (OTC) pain and fever medication, and is often combined with other ingredients, such as cough and cold ingredients. FDA will address OTC acetaminophen products in another regulatory action. Many consumers are often unaware that many products (both prescription and OTC) contain acetaminophen, making it easy to accidentally take too much.

More than half of manufacturers have voluntarily complied with the FDA request. However, some prescription combination drug products containing more than 325 mg of acetaminophen per dosage unit remain available. In the near future FDA intends to institute proceedings to withdraw approval of prescription combination drug products containing more than 325 mg of acetaminophen per dosage unit that remain on the market.

RECOMMENDATION: FDA recommends that health care providers consider prescribing combination drug products that contain 325 mg or less of acetaminophen. FDA also recommends that when a pharmacist receives a prescription for a combination product with more than 325 mg of acetaminophen per dosage unit that they contact the prescriber to discuss a product with a lower dose of acetaminophen. A two tablet or two capsule dose may still be prescribed, if appropriate. In that case, the total dose of acetaminophen would be 650 mg (the amount in two 325 mg dosage units). When making individual dosing determinations, health care providers should always consider the amounts of both the acetaminophen and the opioid components in the prescription combination drug product.

Health care providers and pharmacists who have further questions are encouraged to contact the Division of Drug Information at 888.INFO.FDA (888-463-6332) or druginfo@fda.hhs.gov.

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

[01/14/2014 -  FDA Statement - FDA]
[Acetaminophen Information - FDA]

Acetaminophen: Drug Safety Communication - Association with Risk of Serious Skin Reactions

ISSUE: FDA notified healthcare professionals and patients that acetaminophen has been associated with a risk of rare but serious skin reactions. Acetaminophen is a common active ingredient to treat pain and reduce fever; it is included in many prescription and over-the-counter (OTC) products.  These skin reactions, known as Stevens-Johnson Syndrome (SJS), toxic epidermal necrolysis (TEN), and acute generalized exanthematous pustulosis (AGEP), can be fatal. These reactions can occur with first-time use of acetaminophen or at any time while it is being taken.  Other drugs used to treat fever and pain/body aches (e.g., non-steroidal anti-inflammatory drugs, or NSAIDS, such as ibuprofen and naproxen) also carry the risk of causing serious skin reactions, which is already described in the warnings section of their drug labels.

BACKGROUND: This new information resulted from the Agency’s review of the FDA Adverse Event Reporting System (FAERS) database and the medical literature to evaluate cases of serious skin reactions associated with acetaminophen (see Data Summary at link below).  It is difficult to determine how frequently serious skin reactions occur with acetaminophen, due to the widespread use of the drug, differences in usage among individuals (e.g., occasional vs. long-term use), and the long period of time that the drug has been on the market; however it is likely that these events (i.e., SJS, TEN, and AGEP) occur rarely.

RECOMMENDATIONS: Health care professionals should be aware of this rare risk and consider acetaminophen, along with other drugs already known to have such an association, when assessing patients with potentially drug-induced skin reactions. Any patient who develops a skin rash or reaction while using acetaminophen or any other pain reliever/fever reducer should stop the drug and seek medical attention right away.  Anyone who has experienced a serious skin reaction with acetaminophen should not take the drug again and should contact their health care professional to discuss alternative pain relievers/fever reducers.

FDA will require that a warning be added to the labels of prescription drug products containing acetaminophen to address the risk of serious skin reactions. FDA will also request that manufacturers add a warning about serious skin reactions to the product labels of OTC acetaminophen drug products marketed under a new drug application and will encourage manufacturers of drug products marketed under the OTC monograph do the same.

[8/01/2013 - Consumer Update - FDA]

[8/01/2013 - Drug Safety Communication - FDA]

Endocet (Oxycodone / Acetaminophen) Tablets, ( 10mg, 325mg ) : Recall - Some Bottles Contain Different Strength Tablets

ISSUE: Endo Pharmaceuticals  and FDA notified pharmacists and patients of a nationwide consumer level recall of Endocet (oxycodone/acetaminophen, USP) Tablets, 10 mg/325 mg  because some bottles may contain different strength tablets, resulting in  patients taking more than the intended acetaminophen dose. Unintentional administration of tablets with increased acetaminophen content may result in liver toxicity, especially in patients on other acetaminophen containing medications, patients with liver dysfunction, or people who consume more than 3 alcoholic beverages a day.

BACKGROUND: The affected lots were distributed between April 19, 2011 and May 10, 2011 directly to wholesalers who are located in the following states: AL, AZ, CA, CO, NY, OH, ND, PR, IL, KY, NH, NJ, LA, NC, MO, PA, FL and TN. These wholesalers may further distribute to other retailers and wholesalers nationwide. Lot numbers can be found on the side of the manufacturer’s bottle. Tablet descriptions and photographs are provided in the firm's press release.

RECOMMENDATION: Consumers who have the affected product should stop using the product and contact Endo’s agent Stericycle at 1-866-723-2681 for return of the 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

[06/24/2011 - Press Release - Endo Pharmaceuticals]

Acetaminophen Prescription Products Limited to 325 mg Per Dosage Unit: Drug Safety Communication

ISSUE: FDA notified healthcare professionals that it has asked drug manufacturers to limit the strength of acetaminophen in prescription drug products, predominantly combinations of acetaminophen and opioids, to 325 mg per tablet, capsule, or other dosage unit, making these products safer for patients. This action will help to reduce the risk of severe liver injury and allergic reactions associated with acetaminophen. A Boxed Warning highlighting the potential for severe liver injury and a Warning highlighting the potential for allergic reactions (swelling of the face, mouth, and throat, difficulty breathing, itching, or rash) will be added to the label of all prescription drug products that contain acetaminophen.

BACKGROUND: Acetaminophen, one of the most commonly used drugs in the United States, is widely and effectively used in both prescription and over-the-counter (OTC) products to reduce pain and fever. Examples of prescription products that contain acetaminophen include hydrocodone with acetaminophen (Vicodin, Lortab), and oxycodone with acetaminophen (Tylox, Percocet). OTC products containing acetaminophen (e.g., Tylenol) are not affected by this action. Information about the potential for liver injury is already required on the label for OTC products containing acetaminophen. FDA is continuing to evaluate ways to reduce the risk of acetaminophen related liver injury from OTC products. No drug shortages are expected, because the 3-year implementation period should permit adequate time for necessary reformulations.

RECOMMENDATION: Healthcare professionals were reminded to advise patients not to exceed the acetaminophen maximum total daily dose (4 grams/day), and not to drink alcohol while taking acetaminophen-containing medications.

Healthcare professionals were encouraged to inform patients that there is no immediate danger to patients who take these combination pain medications, and patients should continue to take them as directed by their health care provider. The Drug Safety Communication provides additional information for healthcare professionals, information for patients, a data summary and a list of all affected products.

[01/13/2011 - Drug Safety Communication - FDA]
[01/13/2011 - Q&As - FDA]
[01/13/2011 - News Release - FDA]
[01/13/2011 - Consumer Update - FDA]
[01/13/2011 - Prescription Acetaminophen/Opioid Combinations - FDA Video]