FDA Slaps Black Box Warning on 400 Products to Reduce Risk of Taking Opioid Analgesic, Opioid-Contained Cough Medicine or Benzodiazepines Together

FDA Slaps Black Box Warning on 400 Products to Reduce Risk of Taking Opioid Analgesic, Opioid-Contained Cough Medicine or Benzodiazepines Together

Today, the FDA announced it is requiring a class-wide change to drug labeling and patient information to address the serious risks associated with the combined use of certain opioid medications along with a class of central nervous system (CNS) depressant drugs called benzodiazepines, the agency said in a press release.

The changes include the FDA’s strongest warning – the boxed warning – and renewed patient Medication Guides for the risks associated with using the following classes of medicines simultaneously:  opioid analgesics, opioid-contained cough products and benzodiazepines. This warnings will highlight the risks of extreme sleepiness, respiratory depression, coma and death.

The agency’s goal is to “reverse the prescription opioid abuse epidemic, while still providing patients in pain access to effective and appropriate pain management,” the release stated.

Over 400 products in total will be affected.

“It is nothing short of a public health crisis when you see a substantial increase of avoidable overdose and death related to two widely used drug classes being taken together,” said FDA Commissioner Robert Califf, M.D. “We implore health care professionals to heed these new warnings and more carefully and thoroughly evaluate, on a patient-by-patient basis, whether the benefits of using opioids and benzodiazepines – or CNS depressants more generally – together outweigh these serious risks.”

The FDA’s release went on to state the following:

Given the importance of reaching health care professionals and the public with information about the risks of using these products together, today the FDA also issued a Drug Safety Communication. Through the Drug Safety Communication and by requiring patient Medication Guides, the agency also provides information for anyone who is taking, or who knows someone taking, either of these types of medications and encourages them to better understand the risks of taking them together; and, when it is medically necessary, for health care providers to be careful to prescribe them as directed, without increasing the dose or dosing frequency for either drug.

Opioid analgesics are powerful pain-reducing medications that include prescription oxycodone, hydrocodone, and morphine, among other drugs, under both brand and generic names. Certain other opioid medications are also approved to treat cough. Opioid analgesic misuse and abuse have increased significantly in the United States over the past two decades, and represent major public health concerns due to the risk of coma and fatal respiratory depression associated with opioid analgesic overdose. Benzodiazepines are drugs typically prescribed for the treatment of neurological and/or psychological conditions, including anxiety, insomnia and seizure disorders. Both classes of drugs depress the central nervous system (“CNS depressants”); however, each has unique pharmacology, safety risks, and labeling information related to its use. Therefore, the FDA is requiring opioid analgesics, prescription opioid cough products, and benzodiazepines to have slightly different labeling. Additionally, due to the unique medical needs and benefit/risk considerations for patients undergoing medication-assisted therapy treatment (MAT) to treat opioid addiction and dependence, the FDA is continuing to examine available evidence regarding the use of benzodiazepines and opioids used as part of MAT. 

The FDA’s data review showed that physicians have been increasingly prescribing them together, and this has been associated with adverse outcomes. Among the data reviewed by the FDA, the agency concluded that from 2004 to 2011, the rate of emergency department visits involving non-medical use of both drug classes increased significantly, with overdose deaths (from taking prescribed or greater than prescribed doses) involving both drug classes nearly tripling during that period. Additionally, the number of patients who were prescribed both an opioid analgesic and benzodiazepine increased by 41 percent between 2002 and 2014, which translates to an increase of more than 2.5 million opioid analgesic patients receiving benzodiazepines.

Clinical guidelines from the U.S. Centers for Disease Control and Prevention (CDC) and existing labeling warnings regarding combined use caution prescribers about co-prescribing opioids and benzodiazepines to avoid potential serious health outcomes. The actions of the FDA today are consistent with the CDC.

In February 2016, the FDA received a citizen petition from numerous local and state public health officials and other stakeholders asking the agency to make certain changes to the existing labeling for benzodiazepines and opioid analgesics. The FDA had already initiated a review of the scientific information on concomitant use of these two drug classes when the agency received the petition, and was encouraged that these public health officials shared the agency’s concerns. Today, the FDA also responded to the citizen petition.

Working with the health care community and federal and state partners to help reduce opioid misuse and abuse and improve appropriate opioid prescribing, while ensuring that patients in pain continue to have appropriate access to opioid analgesics, is a top priority for the FDA and part of HHS’ targeted approach focused on prevention, treatment, and intervention. The agency is committed to continuing to monitor these products and take further actions as needed.

End of FDA’s announcement.

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Authored by: Staff

There are 24 comments for this article
  1. Kristi at 11:32 pm

    I have been in pain for 12 years now with many diagnoses but the main ones are EDS and Dercums Disease. Both are very painful. I’m lucky enough to have the greatest Pain Dr. ever. As a disabled RN, he will discuss whatever research I have found for that monthly visit.

    @Marissa, I totally get where you are coming from in your comment. I am actually on both Baclofen and Neurontin. Both help with each of my issues. On top of that, I take Morphine. I never have any side effects, so I feel very lucky.

  2. Tim Mason at 4:24 am

    It was I was taking Alieve. Then he said Naproxen (220) two tablets twice a day. My legs swelled up just above my ankles. My GP said you have edema. Must be a kidney problem. Then he looked over my current list of OTC medications.
    He was livid. He said never exceed the recommended dosage and this applies to OTC pain relievers as well.

  3. Tim Mason at 7:47 pm

    @Tracy,
    “I don’t troll, but you can thank Obama.”
    You are right. The New Surgeon General is one of “Doctors for Obama” used to be Doctors for America. My vision of a Surgeon General is a much older, experienced physician. He/she even more should have a working knowledge of painful illnesses. He/she should have credentials in pharmacology at the doctorate level.
    What we got is a token green card holder.

  4. Tim Mason at 7:10 pm

    @ Brown Ale, We are a different class of pain patients. “Worry only steals the joy of today”. “Worry is paying interest on a debt that may never come”
    You have described yourself as severely disabled. What is lacking is “empathy” from these Nuevo docs and PA’s. If you look at Wikipedia, history of diazepam you will find it a necessary drug. (I think I already posted this). They may try to give you Baclofen and tell you “It is just like Valium”. Say, Just give me the Valium then.
    You have obviously demonstrated your willingness and ability to abide by demonstrate that you are a responsible person, managing your medications with the greatest of care.
    It is stated that diazepam is NECESSARY when other anxiety drugs and muscle relaxers do not work. You are one of these people. The docs and PA’s are merely “skirting the issue”
    It was stated in the black box warning that Cough remedies opioids mixed with valium is dangerous. That is because the cough formulations are elixirs containing ethyl alcohol. You obviously do not drink alcoholic beverages so this black box warning does not apply to you. AT ALL. It is just a warning.
    Having lived a long live you are obviously following warning signs.
    If things do get ugly, try some Kratom for anxiety. It works. And it works well.
    I want to hear how it goes.

  5. J.DiCapo at 1:47 pm

    Im noticing everyone is upset and feels like they will be cut off bc of this…

    Its not a blanket policy… drs can still prescribe however they wish…

    Im not sure of all of your situations individually, but is it not possible to simply find another dr who will better serve your needs? Propublica’s website is a great tool. You are able to see what drs prescribe for medicare patients. Also sites like vitals and ratemds are great tools to research Drs you might be interested in seeing. Please take 30 mins and preform a little due diligence before feeling like the sky is falling. I know there are plenty of drs out there who care about patients. U only need to do some research not pick a name out of a hat! Best of luck to EVERYONE having issues!

  6. Dooney at 9:07 am

    Brown ale, I was taking Valium 5 MG daily probably 4 months ago. My doc said because of all the hoopla about combining pain meds and benzos she wanted to decrease my dose to 2 MG a day. The 2 MG don’t cut it for my particular issue so I just double it. So there are days I don’t have it and just have to deal.

    Many years ago I was abruptly taken off Valium because I took some extra when I had 2 cats die the same week. I was a wreck. So my pain doc nurse said no more. That was the worst withdrawal ever and I’ve been through a few. No sleep for a week. So if they are going to cut you back it needs to be done slowly. Also it’s very dangerous to just discontinue a benzo.

    I wish you all the best of luck and my heart breaks for you and everyone else who post on here dealing with lives once somewhat manageable now in total chaos. Hope you can let us know what happens.

  7. brown ale at 7:42 am

    I suppose that this action was something that we should have expected as a follow-up to the scare earlier this year (or last year?).

    I’ve been taking Xanax for 31 years. I take one 1mg tablets 4x a day, so 4mg per day. I’m dependent on it: even after 31 years it still works to keep my anxiety in place. I do have sudden and unexpected full-blown panic attacks at times, but I can get along.

    Since 2003 I’ve been on at least 300mg of morphine sulphate daily – one 100mg tablet in the morning and two 100mg tablets at bedtime.

    These are my coping medications. I’m by no means anxiety free and certainly not pain free. I can cope, exist.

    My personal care physician warned me three months ago that there might be a “crack-down” coming. I see him next week for my quarterly check-up. My greatest fear may occur – I may have to return to the pain clinic. I have no legs and it’s difficult for me to get around: if I had no insurance, I would have to pay the paratransit folks $160 for round-trip transportation not to exceed 20 miles in total.

    So I’ve been on Xanax since 1985. 4mg per day has been my maintenance dosage although I have been prescribed as much as 10mg per day when crises have hit. My dosage of morphine has also been higher. 300mg per day is also a maintenance dosage; I have been on higher doses. I have taken, when in hospital, morphine along with Dilaudid. That would have been in 2006 and 2010. So 13 years on morphine.

    But, because I’ve been taking drugs as prescribed, I (like most of you) am a criminal. It wasn’t like this 16 years ago. It really wasn’t. I didn’t have flaky doctors – I had doctors who tried, and succeeded, in treating me for chronic pain and chronic anxiety. Now, it seems as if I’ll have to change… something. “Get over” the anxiety that has been my companion for over half of my life or “get over” this chronic pain. But we’re just a lump in these criminal activity. I’m not stupid. I know that some people might sell their medications (cold day in hell if I were to do that… actually give up one single day of Xanax or morphine for a couple of bucks? No. No way that I could do that. I woke up 4 times in the middle of open heart surgery. That was in the early 1990’s. As late as November 2014 I awoke as I was having my left stump trimmed up a bit. I don’t tolerate pain very well. Or I do. In 1994, the anesthesiologist that treated me during my heart surgery told me to be certain that I told any other pain specialists or anesthesiologists that I have a low threshold for pain (I think that’s what he said…) and that I need more than the ‘normal’ amount of of anesthesia to get me asleep and to keep me asleep during surgeries.

    I can’t say that this ‘ban’ came as any great surprise. I just hope that there is some type of remedy for those of us who can’t jump through the hoops in the proper order.

    “Quality of life?” That’s no longer of importance, it seems. Just put a rag in your mouth (a cool, damp cloth) and scream. That seems to be the only solution any longer. I’ve done that. I didn’t think that I would ever visit that place again.

    I was looking forward to seeing my PCP. Now… I don’t know. I’m the only patient that he has for whom he prescribes opioids. I’ll know something next week.

    I know that my anxiety levels are through the roof right now, and I’m not looking forward to any changes that might occur. I get by right now. I get by. So what happens if I can’t get by? I’ve had “partial” withdrawals in the past and they almost drove me crazy (and that’s just one day – two days, a week? – I would have to be in hospital).

    TO MARISSA: That was the very first thought that popped into my head. I’ve never had “suicidal ideations” but if I have to make a choice between living with psychotic anxiety or chronic and debilitating pain, my choice is “none.” And I would bet that’s true for many. And I was diagnosed with type II diabetes in 2003. I now take 99 units of Toujeo daily. Because of my disabilities, I’m physically unable to cook. I’m not a big fan of meat, so my proteins usually come in the form of peanut butter or cheese.

    I’ve not looked at the 400 medications on the list yet, but I would bet that Xanax and morphine surely made it. I know that next week my doc is going to tell me that he has some bad news… I just hope that he’s come up with a solution by then.

    I’m hoping that people will discuss any “solutions” that you may have had with your doctors, or even if they even brought this up with you. I’ll be back and see what my doctors have to say. I’m also hoping that “lose my license” isn’t in the discussion.

    Peace to you all.

  8. Joan Hamm at 6:46 am

    Please Please review the disease RSD CRPS!!! This disease as you research you will find is EXTREME Pain disease! Pain can be worse than cancer or like a woman in Hard Labor. It must be on the list with the top pain diseases so NOT to take away relief medicine that does work!!! One will die without pain meds,!!!! We need more Scientists and funding for RSD!!!! Many people have it.. Many Veterans have it!!!

  9. Ken at 5:05 am

    Heroin and other illegal drugs being brought into the country is the culprit. The government knows it, but they won’t do a thing about it, there’s way too much money to be made. So as usual, the innocents going to pain management every month, practically having to beg to maintain our dose so we can continue working and functioning like normal humans. You have to admit though, to the naked eye, the “sweeping guidelines” make it really look good for the politicians that know squats one about medications or how they work. But they’re doing something to stop the drugs, yeah they’re doing real good.

  10. Tim Mason at 3:36 am

    All drugs have risks whether prescription or OTC. We have proved our willingness and ability to handle my medications appropriately and to follow a medication regime spelled out in our Pain Management Contract. (PMC). If there is any doubt to my ability please refer to my drug urine screenings.
    People have always died from drug overdose. This is nothing new. No need to sound a new alarm. My guess is the concern is over the “Elixir” cough formulations that contain as much as 10 percent alcohol by weight.
    Nothing new here FDA/CDC. You are just throwing another log on the fire of misinformation.
    Heck, you have already allowed the Surgeon General (not a real surgeon) to create a false claim saying “addiction and dependence” are one in the same.
    My question is this “Are the Surgeon Generals comments and statements not “Peer Reviewed?”
    I doubt it since his false statement made it to press.

  11. Deborah Babcock at 7:48 pm

    What do they mean continue to get the medication we need. That stopped a long time ago but my pain remains.

  12. BL at 7:09 pm

    Tim Mason, Naproxen prescription strength is 500 mg. Aleve (Naproxen) OTC is 220 mg. Were you taking two prescription strength or two OTC strength ? The recommended dose for prescription is 1 every 12 hours. Although it is common for drs to tell patients to take two OTC every 12 hrs if the dr doesn’t want to write a prescription.

  13. Tim Mason at 5:31 pm

    Pain management used to write the benzo. But they switched me to another NP and said no. If you ask for it by name you are labeled a “drug seeker” because it is the # 2 sought after medication at the ER. If you are not at 100 mg equiv per day it is not an issue. Just note that the benzo build up in your system. (fat tissue). Exercise releases the drug stored in your fat.
    Use caution.
    Pain management is supposed to treat the anxiety associated with pain. They offer Cymbalta (garbage) and coloring books.
    Valium has always worked well for my achy spasms and keep me from “flying off the handle”
    And here again, it is just a guideline, nothing in stone.
    Case in point. I went to a spine place 2 years back for injections and they would not prescribe any scheduled II for pain. Said “take naproxen” just double the dose.
    I went to my GP three weeks later and he noticed severe edema on my calves. He said. You kidneys must me failing. I said the spine doc put me on two of these twice a day. His response “My God! What an idiot”

  14. Tracy at 5:12 pm

    The major drug issue is heroin. The FDA, the DEA the WH, they can say what they will, they are unable to control the heroin from coming into this country along with prescription drugs because of the administration boarder relaxed rules and regulations. To accuse all practicing physicians of the opioid addiction is a cop out, what’s worse is the number of people who believe this garbage. Everyone will need pain relief one day for acute or chronic problems, and for the government to control every aspect of our lives, it’s damping. Don’t people realize these are failed liberal policies and are going to effect us all . I have loose SI screws in my back, wobbling around making ambulation impossible , plus I have a blood disease that necessitates blood thinners making OTC medications impossible. I don’t want pain. I don’t to take pills, but this is America where my doctor directs my care, not the nut jobs in governments. You reading these posts honestly believe the government is looking out for your best interest, when it is medically proven, opioids work well for both acute and chronic pain, because I am in chronic pain does that mean I am going to turn to heroin. The government is playing ordinary tax payer citizens for fools, this epidemic is nothing new, it has only gotten worse, I don’t troll, but you can thank Obama.

  15. Marissa at 5:08 pm

    Michael L.
    I have a friend with the same disorder it’s awful. Yes Neurontin and anything can cause respiratory issues.
    I get it many a night I begged to not wake up.
    We have to fight this and keep track of those we lost because of this.
    Suicides will increase! However will they be track able to this?
    Vets are killing themselves in VA parking lots to be heard. I do not advocate for this I am just thinking it will take years to prove that we lost fellow pain warriors to suicide of the abuse we are now enduring
    Its psychological damage they are doing and getting away with it!
    Need a class action lawsuit for this .
    Please stay brave! Especially if you have kids.
    Suicide of a family member increases in the next generation by staggering percents.
    We are a strong group of people we will have a voice.

  16. BL at 5:07 pm

    Not happy, a dr can prescribe them together, it is just not recommended. In situations like yours where you only take 1 mg-2 mg a few times a year there should not be a problem with it. Would one dr prescribe the opiates and another prescribe the valium ? If not, that may be why the dr is hesitant.

  17. Marissa at 4:59 pm

    So let me get this straight. I threw away a successful nursing career, my further education that I was immersed in and my paycheck for a pill!!!! This is insanity and down right abuse of an entire population of people. I can assure anyone that that pain pill that I have to fret over getting doesn’t have some super exciting high! Why ??? Because I am in PAIN! It does however allow me to be somewhat of a parent and spouse. Without it, I desire to cut my own arm off!! Where’s the black box warning for that?
    It’s amazing to me the wording of how they’re attempting to reduce the “abuse of opiates”. Chronic pain patients have the luxury of even “abusing” pain medication because we need it and never know when it will be cut off. I am sure I am not alone in attempting to cut back or go without in effort to have one extra pill for high pain days.
    Now they want to take away my tiny 0.5 mg of Lorazepan that has finally allowed me to settle down enough to sleep in 2 years. I spent 2 years pacing my floors in pain before asking for that tiny dose.
    I would love to see a comparison of Baclofen and Neurontin together or alone. Then throw in an antidepressant which is perfectly safe…Tricyclic antidepressants overdoses are most often fatal! Who is on these…chronic pain patients.
    So let’s get this straight one pain medication and a half of a mg of a Benzodiazapine is to be replaced with
    Tylenol – liver damage at high doses
    Ibuprofen- Cardiac issues
    Neurontin or Lyrica- let’s just use the increased risk of suicidality because that’s big enough
    Prilosec- for new issues related to Ibuprofen
    Baclofen- Severe sleep apnea was my reason to stop…that’s a respiratory distress
    This is a small sampling of the meds that will be presented as a solution. Now combine them all together.
    Currently I take only 3 medications one being an atypical antidepressant due to the loss of my career, paycheck and constant pain.
    Yes I threw my paycheck, retirement plans , my further degrees to sit on my butt taking a pain pills.
    Seems like it shouldn’t be then held against me.I am now a mom and a nurse labeled as an addict!!
    This abuse is inhumane. Would we label a type 2 diabetic who made poor food choices ( not that they all do, but I’ve seen many) let’s see how that would go over to label the diabetics as food addicts that lack exercise. No we wouldn’t do that because we can measure a blood glucose and we cannot measure pain.
    Perhaps if we had a scale to measure our losses to pain with it would be tangible. Maybe I am onto something here with that, we have a Pain Scale why not a Loss scale?
    A caveat I am at super high risk for diabetes it’s rampant in my genes so I mean no ill will in above statement, but we need an extreme to compare an extreme. Both are medical conditions. So now they will throw several new meds my way that are notorious for weight gain, somnolence, drowsiness, depression and suicidality at a high risk …this seems safe right ?!
    There are scales to measure depression and anxiety, but they will simply say it was the underlying cause of it all.
    I was in the best place I’ve ever could imagine in my life , not depressed nor anxious, but I am an “addict ” now and unemployed as well as excruciating pain due to CRPS that was missed by Doctors.
    Opiates are not nearly as exciting as a cold cocktail while hanging out on a day off.
    I am a nurse who is treated like this by my peers in the medical field. I can only imagine how it is worse for all of us collectively and individually.
    This is ABUSE!
    We will see a rise in suicide attempts mark my words! I am a Psych nurse I can see the risk factors are off the charts for suicidality even with meds due to the loss of functioning, finances, relationships and identity.
    I’ll stop that one pain medication very soon and then I’ll be standing with a sign outside the governor’s office insisting on a stop to the criminal abuse of the disabled

  18. M.T. at 4:46 pm

    I agree with Harriet. CRPS is not easily diagnosed and here in Boston I am unable to receive adequate care. Pain patients are NOT the problem. Ilegal abusers are. My friend’s 19 year old son makes thousands selling his medical marijuana which he easily gets for “anxiety”. Guess being drunk and stoned and healthy is o.k.

  19. Christine jacoby at 4:39 pm

    Again the rules are generic, do not allow for individual patients which in the chronic pain community means each one of us has different needs. These rules are simply causing cruel suffering, premature loss of life, unbearable existences for us.
    Cookie cutter rules just don’t work for chronic illnesses. Why these law makers are being allowed to draft& enforce such useless, harmful, uneducated, inappropriate, killing rules & laws is a mystery to me. Òur gov is doing this when in fact their purpose is to uphold rights for its citizens. What happened to our gov AND who can stop this mad killing spree??!

  20. Jasmin at 4:37 pm

    Harriet, you have actually said it all, kind and considerate. Thank you very much.

  21. J.DiCapo at 4:36 pm

    This article is very interesting to me as I have recently starting using Valium for my spasms.

    I am a CPP who has safely and successfully used opiods for the past 7 years after a horific accident left me disabled and in severe pain…

    Part of my daily chronic pain has to do with my spasms associated w my pathology. I have tried nearly ever muscle relaxer to help w my spasms. I had no luck for a very long time.. either the medications were not effective or they would just knock me out cold. Even with dosage adjustments i still could not find a a product that worked for me.. i am very aware of the issues regarding Soma and Benzodiazepines used concurrently w opiods.. i wanted to avoid those 2 medications at all costs.

    I eventually tried Robaxin and had great success until recently i started have physical side effects from it to the point the side effects were no longer tolerable..

    I spoke w my physician regarding it and we spoke about trying valium. If nothing else i owed it to myself to try it for 48 hrs. So i got my script w instructions of 1- 2 tabs (5mg) daily prn for spasms. Being me i ALWAYS start low and titrate up.. i started using 1/2 tab during day… it worked AMAZING. No cns depression, no slowing in my resperation. Then i added the 2nd dose to my nightime medication regime.. again.. no issues other than 6 hrs of straight sleep (which ive only been lucky enough maybe 10x in 7 years).

    Curently i take 1/2 dose (2.5mg) 1- 2x during day prn and then 1 full tab at bedtime.

    It is working EXTREMELY well and although i understand its best to error on the side of caution, i wish i had not been so closed minded and could’ve been benefiting from this successful regiment for years now.

    Please dont discount the abundance of caution surrounding the opiod benzo combo but alsioplease keep an open mind and not vilify it either!

  22. Not happy at 4:21 pm

    Because of the FDA’s vendetta against using these together I had to choose, my pain meds, or my meds for menieres disease. Now every time I have a menieres attack I get to lay on the floor puking, thanks FDA. By the way I took 1/2 of one 2mg diazapam at a time maybe 10 times or so a year.

  23. MichaelL at 4:20 pm

    I wonder if gabapentin with opiate might have the same risk!? I have awakened with severe confusion, once and a barely palpable BP another time! Sadly, I have suffered all day, today, because I attempted to decrease my gabapentin dose. The only advantage is that I might have a peaceful end to my life and suffer no more from this injury to my cauda equina. Death is not such a bad alternative!

  24. Harriet at 4:19 pm

    Just don’t leave the chronic pain community helpless
    People who have Complex Regional Pain Syndrome are on the highest scale for pain and need medical help
    Not lumped with over doing medications
    Without these many cannot function at all
    You have to remain kind and considerate not just vigilant to stop prescribing these life saving medications