TOPIC: Opioid Pain Relievers or Medicines to Treat Opioid Use Disorder: MedWatch Safety Alert - FDA Recommends Health Care Professionals Discuss Naloxone with All Patients when Prescribing.
AUDIENCE: Patient, Health Professional, Pharmacy
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, available at: https://bit.ly/3hzDavc, 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, available at: https://bit.ly/3hx8tXG, 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.
- 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, available at: https://www.usa.gov/state-health, 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.
For more information visit the FDA website at: http://www.fda.gov/Safety/MedWatch/SafetyInformation and http://www.fda.gov/Drugs/DrugSafety.
Benzhydrocodone and acetaminophen may be habit forming, especially with prolonged use. Take benzhydrocodone and acetaminophen exactly as directed. Do not take more of it, take it more often, or take it in a different way than directed by your doctor. While taking benzhydrocodone and acetaminophen, discuss with your health care provider your pain treatment goals, length of treatment, and other ways to manage your pain. Tell your doctor if you or anyone in your family drinks or has ever drunk large amounts of alcohol, uses or has ever used street drugs, uses or has overused prescription medications, or has or have ever had depression or other mental illness. There is a greater risk that you will overuse benzhydrocodone and acetaminophen if you or anyone in your close family has or have ever had any of these conditions. Talk to your health care provider immediately and ask for guidance if you think that you have an opioid addiction or call the U.S. Substance Abuse and Mental Health Services Administration (SAMHSA) National Helpline at 1-800-662-HELP.
Benzhydrocodone and acetaminophen may cause serious or life-threatening breathing problems, especially during the first 24 to 72 hours of your treatment and any time your dose is increased. Your doctor will monitor you carefully during your treatment. Tell your doctor if you have or have ever had slowed breathing or asthma. Your doctor may tell you not to take benzhydrocodone and acetaminophen. Also tell your doctor if you have or have ever had lung disease such as chronic obstructive pulmonary disease (COPD; a group of lung diseases that includes chronic bronchitis and emphysema), a head injury, brain tumor, or any condition that increases the amount of pressure in your brain. The risk that you will develop breathing problems may be higher if you are an older adult or are weakened or malnourished due to disease. If you experience any of the following symptoms, call your doctor immediately or get emergency medical treatment: slowed breathing, long pauses between breaths, or shortness of breath.
Taking certain other medications during your treatment with benzhydrocodone and acetaminophen may increase the risk that you will experience breathing problems or other serious, life threatening breathing problems, sedation, or coma. Tell your doctor if you are taking, plan to take, or plan to stop taking any of the following medications: benzodiazepines such as alprazolam (Xanax), diazepam (Diastat, Valium), estazolam, flurazepam, lorazepam (Ativan), and triazolam (Halcion); carbamazepine (Carbatrol, Tegretol, others); erythromycin (Eryc, E.E,S., others); ketoconazole; other narcotic pain medications; medications for mental illness; muscle relaxants including cyclobenzaprine (Amrix) and metaxalone (Skelaxin); phenytoin (Dilantin, Phenytek); rifampin (Rimactane, in Rifamate, Rifater); ritonavir (Norvir, in Kaletra, Technivie, Viekira Pak); sedatives; sleeping pills; or tranquilizers. Your doctor may need to change the dosages of your medications and will monitor you carefully. If you take benzhydrocodone and acetaminophen with any of these medications and you develop any of the following symptoms, call your doctor immediately or seek emergency medical care: unusual dizziness, lightheadedness, extreme sleepiness, slowed or difficult breathing, or unresponsiveness. Be sure that your caregiver or family members know which symptoms may be serious so they can call the doctor or emergency medical care if you are unable to seek treatment on your own.
Taking too much acetaminophen (found in this combination preparation) can cause liver damage, sometimes serious enough to require liver transplantation or cause death. Be aware that you should not take more than 4,000 mg of acetaminophen per day. You might accidentally take too much acetaminophen if you do not follow the directions on the prescription or package label carefully, or if you take more than one product that contains acetaminophen. If you need to take more than one product that contains acetaminophen, it may be difficult for you to calculate the total amount of acetaminophen you are taking. Ask your doctor or pharmacist to help you. Tell your doctor if you have or have ever had liver disease. Your doctor may tell you not to take benzhydrocodone and acetaminophen.
Drinking alcohol, taking prescription or nonprescription medications that contain alcohol, or using street drugs during your treatment with benzhydrocodone and acetaminophen increases the risk that you will experience serious, life-threatening side effects. Do not drink alcohol, take prescription or nonprescription medications that contain alcohol, or use street drugs during your treatment with benzhydrocodone and acetaminophen.
Do not allow anyone else to take your medication. Benzhydrocodone and acetaminophen may harm or cause death to other people who take your medication, especially children. Keep benzhydrocodone and acetaminophen in a safe place so that no one else can take it accidentally or on purpose. Be especially careful to keep benzhydrocodone and acetaminophen out of the reach of children. Keep track of how many tablets are left so you will know if any medication is missing. Flush any tablets that are outdated or no longer needed down the toilet so that others will not take them.
Tell your doctor if you are pregnant or plan to become pregnant. If you take benzhydrocodone and acetaminophen regularly during your pregnancy, your baby may experience life-threatening withdrawal symptoms after birth. Tell your baby's doctor right away if your baby experiences any of the following symptoms: irritability, hyperactivity, abnormal sleep, high-pitched cry, uncontrollable shaking of a part of the body, vomiting, diarrhea, or failure to gain weight.
Your doctor or pharmacist will give you the manufacturer's patient information sheet (Medication Guide) when you begin treatment with benzhydrocodone and acetaminophen and each time you refill your prescription. Read the information carefully and ask your doctor or pharmacist if you have any questions. You can also visit the Food and Drug Administration (FDA) website (http://www.fda.gov/Drugs/DrugSafety/ucm085729.htm) (or the manufacturer's website) to obtain the Medication Guide.
Talk to your doctor about the risks of taking benzhydrocodone and acetaminophen.
Why is this medication prescribed?
The combination of benzhydrocodone and acetaminophen is used to relieve acute pain (pain that begins suddenly, has a specific cause, and is expected to go away when the cause of the pain is healed) that cannot be relieved by other non-opioid pain medications. Benzhydrocodone is in a class of medications called opiate (narcotic) analgesics. It works by changing the way the brain and nervous system respond to pain. Acetaminophen is in a class of medications called analgesics (pain relievers) and antipyretics (fever reducers). When acetaminophen is used in combination with benzhydrocodone to treat pain, it works by changing the way the body senses pain.
How should this medicine be used?
The combination of benzhydrocodone and acetaminophen comes as a tablet to take by mouth. It is usually taken with or without food every 4 to 6 hours as needed for pain for 2 weeks or less. You should not take more than 12 tablets in 24 hours. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Take benzhydrocodone and acetaminophen exactly as directed.
Do not stop taking benzhydrocodone and acetaminophen without talking to your doctor. If you suddenly stop taking benzhydrocodone and acetaminophen, you may experience withdrawal symptoms such as restlessness, teary eyes, runny nose, yawning, sweating, chills, hair standing on end, muscle pain, widened pupils (black circles in the middle of the eyes), irritability, anxiety, back or joint pain, weakness, stomach cramps, difficulty falling asleep or staying asleep, nausea, loss of appetite, vomiting, diarrhea, fast breathing, or fast heartbeat. Your doctor will probably decrease your dose gradually.
Other uses for this medicine
This medication may be prescribed for other uses; ask your doctor or pharmacist for more information.
What special precautions should I follow?
Before taking benzhydrocodone and acetaminophen,
- tell your doctor and pharmacist if you are allergic to benzhydrocodone, hydrocodone, acetaminophen, any other medications, or any of the ingredients in benzhydrocodone and acetaminophen tablets. Ask your pharmacist or check the Medication Guide for a list of the ingredients.
- tell your doctor and pharmacist what other prescription and nonprescription medications, vitamins, and nutritional supplements you are taking or plan to take. Be sure to mention the medications listed in the IMPORTANT WARNING section and any of the following: antihistamines (found in cold and allergy medications); diuretics ('water pills'); buprenorphine (Butrans, in Suboxone, in Zubsolv, others); butorphanol; medications for irritable bowel disease, Parkinson disease, and urinary problems; linezolid (Zyvox); medications for mental illness and nausea such as chlorpromazine, fluphenazine, prochlorperazine (Compro, Procomp), thioridazine, and trifluoperazine; methylene blue; medications for migraine headaches such as almotriptan (Axert), eletriptan (Relpax), frovatriptan (Frova), naratriptan (Amerge), rizatriptan (Maxalt), sumatriptan (Imitrex, in Treximet), and zolmitriptan (Zomig); mirtazapine (Remeron); nalbuphine; pentazocine (Talwin); 5-HT3 receptor antagonists such as alosetron (Lotronex), granisetron (Sancuso, Sustol), ondansetron (Zofran, Zuplenz), or palonosetron (Aloxi, in Akynzeo); selective serotonin-reuptake inhibitors such as citalopram (Celexa), escitalopram (Lexapro), fluoxetine (Prozac, Sarafem, Selfemra, in Symbyax), fluvoxamine (Luvox), paroxetine (Brisdelle, Paxil, Pexeva), and sertraline (Zoloft); serotonin and norepinephrine reuptake inhibitors such as duloxetine (Cymbalta), desvenlafaxine (Khedezla, Pristiq), levomilnacipran (Fetzima); milnacipran (Savella), and venlafaxine (Effexor); tramadol (Conzip, Ultram, in Ultracet); trazodone; or tricyclic antidepressants ('mood elevators') such as amitriptyline, clomipramine (Anafranil), desipramine (Norpramin), doxepin (Silenor), imipramine (Tofranil, Surmontil), nortriptyline (Pamelor), protriptyline (Vivactil), and trimipramine (Surmontil). Also tell your doctor or pharmacist if you are taking or receiving the following monoamine oxidase (MAO) inhibitors or if you have stopped taking them within the past two weeks: isocarboxazid (Marplan), phenelzine (Nardil), selegiline (Eldepryl, Emsam, Zelapar), or tranylcypromine (Parnate). Many other medications may also interact with benzhydrocodone and acetaminophen, so be sure to tell your doctor about all the medications you are taking, even those that do not appear on this list.
- tell your doctor what herbal products you are taking, especially St. John's wort.
- tell your doctor if you have any of the conditions mentioned in the IMPORTANT WARNING section, a blockage or narrowing of your stomach or intestines, or paralytic ileus (condition in which digested food does not move through the intestines). Your doctor will probably tell you not to take benzhydrocodone and acetaminophen.
- tell your doctor if you have or have ever had seizures, difficulty urinating, or pancreas, gallbladder, thyroid, heart, or kidney disease.
- tell your doctor if you are breastfeeding. If you breastfeed while taking benzhydrocodone and acetaminophen, monitor the breastfed infant carefully for increased sleepiness, trouble breathing, or limpness. If you stop taking benzhydrocodone and acetaminophen, or if you stop breastfeeding the infant, monitor the infant carefully for signs of withdrawal such as restlessness, teary eyes, runny nose, yawning, sweating, chills, or dilated pupils. Call your doctor immediately if the breastfed infant has any of these symptoms.
- you should know that this medication may decrease fertility in men and women. Talk to your doctor about the risks of taking benzhydrocodone and acetaminophen.
- if you are having surgery, including dental surgery, tell the doctor or dentist that you are taking benzhydrocodone and acetaminophen.
- you should know that benzhydrocodone and acetaminophen may make you drowsy, dizzy, or lightheaded. Do not drive a car or operate machinery until you know how this medication affects you.
- you should know that benzhydrocodone and acetaminophen may cause dizziness, lightheadedness, and fainting when you get up too quickly from a lying position. This is more common when you first start taking benzhydrocodone and acetaminophen, or after a dose increase. To avoid this problem, get out of bed slowly, resting your feet on the floor for a few minutes before standing up.
- you should know that benzhydrocodone and acetaminophen may cause constipation. Talk to your doctor about changing your diet or using other medications to prevent or treat constipation while you are taking benzhydrocodone and acetaminophen.
What special dietary instructions should I follow?
Unless your doctor tells you otherwise, continue your normal diet.
What should I do if I forget a dose?
This medication is usually taken as needed. If your doctor has told you to take benzhydrocodone and acetaminophen regularly, take the missed dose as soon as you remember it. However, if it is almost time for the next dose, skip the missed dose and continue your regular dosing schedule. Do not take a double dose to make up for a missed one.
What side effects can this medication cause?
Benzhydrocodone and acetaminophen may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away:
- abdominal swelling or pain
- lack of energy
- feeling faint
- sudden feeling of warmth
Some side effects can be serious. If you experience any of these symptoms or those listed in the IMPORTANT WARNING section, call your doctor immediately or get emergency medical treatment:
- peeling, blistering skin
- sores in your mouth
- swelling of the face, throat, tongue, lips, and eyes
- difficulty swallowing or breathing
- extreme drowsiness
- lightheadedness when changing positions
- agitation, fever, confusion, fast heartbeat, severe muscle stiffness or twitching, loss of coordination
- experiencing more than one of the following symptoms, especially if taking benzhydrocodone and acetaminophone for one month or longer: nausea, vomiting, loss of appetite, extreme tiredness, weakness, dizziness, feeling faint
Benzhydrocodone and acetaminophen may cause other side effects. Call your doctor if you have any unusual problems while taking this medication.
If you experience a serious side effect, you or your doctor may send a report to the Food and Drug Administration's (FDA) MedWatch Adverse Event Reporting program online (http://www.fda.gov/Safety/MedWatch) or by phone (1-800-332-1088).
What should I know about storage and disposal of this medication?
Keep this medication in the container it came in, tightly closed, and out of reach of children. Store it at room temperature and away from excess heat and moisture (not in the bathroom). You must immediately dispose of any medication that is outdated or no longer needed through a medicine take-back program. If you do not have a take-back program nearby or one that you can access promptly, flush any any medication that is outdated or no longer needed down the toilet so that others will not take it. Talk to your pharmacist about the proper disposal of your medication.
It is important to keep all medication out of sight and reach of children as many containers (such as weekly pill minders and those for eye drops, creams, patches, and inhalers) are not child-resistant and young children can open them easily. To protect young children from poisoning, always lock safety caps and immediately place the medication in a safe location – one that is up and away and out of their sight and reach. http://www.upandaway.org
In case of emergency/overdose
In case of overdose, call the poison control helpline at 1-800-222-1222. Information is also available online at https://www.poisonhelp.org/help. If the victim has collapsed, had a seizure, has trouble breathing, or can't be awakened, immediately call emergency services at 911.
While you are taking benzhydrocodone and acetaminophen, you may be told to always have a rescue medication called naloxone available (e.g., home, office). Naloxone is used to reverse the life-threatening effects of an overdose. It works by blocking the effects of opiates to relieve dangerous symptoms caused by high levels of opiates in the blood. You will probably be unable to treat yourself if you experience an opiate overdose. You should make sure that your family members, caregivers, or the people who spend time with you know how to tell if you are experiencing an overdose, how to use naloxone, and what to do until emergency medical help arrives. Your doctor or pharmacist will show you and your family members how to use the medication. Ask your pharmacist for the instructions or visit the manufacturer's website to get the instructions. If someone sees that you are experiencing symptoms of an overdose, he or she should give you your first dose of naloxone, call 911 immediately, and stay with you and watch you closely until emergency medical help arrives. Your symptoms may return within a few minutes after you receive naloxone. If your symptoms return, the person should give you another dose of naloxone. Additional doses may be given every 2 to 3 minutes, if symptoms return before medical help arrives.
Symptoms of overdose may include:
- slowed or stopped breathing
- difficulty breathing
- limp or weak muscles
- cold, clammy skin
- narrowing or widening of the pupils
- slowed heartbeat
- unusual snoring
- feeling unwell
What other information should I know?
Keep all appointments with your doctor.
Before having any laboratory test (especially those that involve methylene blue), tell your doctor and the laboratory personnel that you are taking benzhydrocodone and acetaminophen.
This prescription is not refillable. If you continue to have pain after you finish the benzhydrocodone and acetaminophen, call your doctor.
It is important for you to keep a written list of all of the prescription and nonprescription (over-the-counter) medicines you are taking, as well as any products such as vitamins, minerals, or other dietary supplements. You should bring this list with you each time you visit a doctor or if you are admitted to a hospital. It is also important information to carry with you in case of emergencies.