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.
Tramadol may be habit forming, especially with prolonged use. Take tramadol 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 tramadol, 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, or has overused prescription medications, or if you have or have ever had depression or another mental illness. There is a greater risk that you will overuse tramadol if you have 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.
Tramadol 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 will probably tell you not to take tramadol. Also tell your doctor if you have or have ever had lung disease such as chronic obstructive pulmonary disease (COPD; a group of diseases that affect the lungs and airways), a head injury 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 weak 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.
When tramadol was used in children, serious and life-threatening breathing problems such as slow or difficulty breathing and deaths were reported. Tramadol should never be used to treat pain in children younger than 12 years of age or to relieve pain after surgery to remove the tonsils and/or adenoids in children younger than 18 years of age. Tramadol should also not be used in used in children 12 to 18 years of age who are obese or who have a neuromuscular disease (disease that affects the nerves that control voluntary muscles), a lung disease, or obstructive sleep apnea (condition in which the airway becomes blocked or narrow and breathing stops for short periods during sleep) as these conditions may increase their risk of breathing problems.
Taking certain other medications during your treatment with tramadol 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 or plan to take any of the following medications: amiodarone (Nexterone, Pacerone); certain antifungal medications including itraconazole (Onmel, Sporanox), ketoconazole (Nizoral), and voriconazole (Vfend); benzodiazepines such as alprazolam (Xanax), diazepam (Diastat, Valium), estazolam, flurazepam, lorazepam (Ativan), and triazolam (Halcion); carbamazepine (Carbatrol, Epitol, Equetro, Tegretol, Teril); erythromycin (Erytab, Erythrocin); certain medications for human immunodeficiency virus (HIV) including indinavir (Crixivan), nelfinavir (Viracept), and ritonavir (Norvir, in Kaletra); medications for mental illness, nausea, or pain; muscle relaxants; phenytoin (Dilantin, Phenytek); quinidine (in Nuedexta); rifampin (Rifadin, Rimactane, in Rifamate); sedatives; sleeping pills; or tranquilizers. Your doctor may need to change the dosages of your medications and will monitor you carefully. If you take tramadol 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.
Drinking alcohol, taking prescription or nonprescription medications that contain alcohol, or using street drugs during your treatment with tramadol increases the risk that you will experience these serious, life-threatening side effects. Do not drink alcohol, take prescription or nonprescription medications that contain alcohol, or use street drugs during your treatment.
Tell your doctor if you are pregnant or plan to become pregnant. If you take tramadol 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.
If you are taking the tramadol extended-release tablet or capsule, swallow them whole; do not chew, break, divide, crush, or dissolve them. Swallow each tablet right after you put it in your mouth. If you swallow broken, chewed, crushed, or dissolved extended-release preparations, you may receive too much tramadol at once instead and this may cause serious problems, including overdose and death.
Do not allow anyone else to take your medication. Tramadol may harm or cause death to other people who take your medication, especially children.
Your doctor or pharmacist will give you the manufacturer's patient information sheet (Medication Guide) when you begin treatment with tramadol 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.
Why is this medication prescribed?
Tramadol is used to relieve moderate to moderately severe pain. Tramadol extended-release tablets and capsules are only used by people who are expected to need medication to relieve pain around-the-clock. Tramadol is in a class of medications called opiate (narcotic) analgesics. It works by changing the way the brain and nervous system respond to pain.
How should this medicine be used?
Tramadol comes as a tablet, an extended-release (long-acting) tablet, and an extended-release (long-acting) capsule to take by mouth. The regular tablet is taken usually with or without food every 4 to 6 hours as needed. The extended-release tablet and extended-release capsule should be taken once a day. Take the extended-release tablet and the extended-release capsule at about the same time of day every day. If you are taking the extended-release capsule, you may take it with or without food. If you are taking the extended-release tablet, you should either always take it with food or always take it without food. Take tramadol exactly as directed. Do not take more medication as a single dose or take more doses per day than prescribed by your doctor. Taking more tramadol than prescribed by your doctor or in a way that is not recommended may cause serious side effects or death.
Your doctor may start you on a low dose of tramadol and gradually increase the amount of medication you take, not more often than every 3 days if you are taking the regular tablets or orally disintegrating tablets or every 5 days if you are taking the extended-release tablets or extended-release capsules.
Do not stop taking tramadol without talking to your doctor. Your doctor will probably decrease your dose gradually. If you suddenly stop taking tramadol, you may experience withdrawal symptoms such as nervousness; panic; sweating; difficulty falling asleep or staying asleep; runny nose, sneezing, or cough; pain; hair standing on end; chills; nausea; uncontrollable shaking of a part of your body; diarrhea; or rarely, hallucinations (seeing things or hearing voices that do not exist).
Other uses for this medicine
This medication is sometimes prescribed for other uses; ask your doctor or pharmacist for more information.
What special precautions should I follow?
Before taking tramadol,
- tell your doctor and pharmacist if you are allergic to tramadol, other opiate pain medications, any other medications, or any of the ingredients in tramadol tablets, extended-release tablets, or extended-release capsules. Ask your pharmacist for a list of the ingredients.
- 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 2 weeks: isocarboxazid (Marplan), linezolid (Zyvox), methylene blue, phenelzine (Nardil), selegiline (Eldepryl, Emsam, Zelapar), or tranylcypromine (Parnate). Your doctor will probably tell you not to take tramadol if you are taking one or more of these medications, or have taken them within the past 2 weeks.
- 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 any of the following: anticoagulants ('blood thinners') such as warfarin (Coumadin, Jantoven); bupropion (Aplenzin, Wellbutrin, Zyban); cyclobenzaprine (Amrix); dextromethorphan (found in many cough medications; in Nuedexta); digoxin (Lanoxin); diuretics ('water pills'); lithium (Lithobid); certain 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); promethazine; 5-HT3 receptor antagonists such as alosetron (Lotronex), dolasetron (Anzemet), granisetron (Kytril), ondansetron (Zofran, Zuplenz), or palonosetron (Aloxi); selective serotonin reuptake inhibitors (SSRIs) such as citalopram (Celexa), fluoxetine (Prozac, Sarafem, Selfemra), fluvoxamine (Luvox), paroxetine (Paxil, Pexeva), and sertraline (Zoloft); serotonin norepinephrine reuptake inhibitors (SNRIs) such as desvenlafaxine (Pristiq, Khedezla), duloxetine (Cymbalta), milnacipran (Savella), and venlafaxine (Effexor); trazodone (Oleptro); and tricyclic antidepressants such as amitriptyline, amoxapine, clomipramine (Anafranil), desipramine (Norpramin), doxepin (Silenor, Zonalon), imipramine (Tofranil), nortriptyline (Pamelor), protriptyline (Vivactil), and trimipramine (Surmontil). Many other medications may also interact with tramadol, so be sure to tell your doctor about all the medications you are taking, even those that do not appear on this list. Your doctor may need to change the doses of your medications or monitor you carefully for side effects.
- tell your doctor what herbal products you are taking, especially St. John's wort and tryptophan.
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 may tell you not to take tramadol if you have any of these conditions.
- tell your doctor if you have or have ever had seizures; an infection in your brain or spine; difficulty urinating; thoughts about harming or killing yourself or planning or trying to do so; or kidney or liver disease.
- tell your doctor if you are breastfeeding. You should not breastfeed while taking tramadol. Tramadol can cause shallow breathing, difficulty or noisy breathing, confusion, more than usual sleepiness, trouble breastfeeding, or limpness in breastfed infants.
- you should know that this medication may decrease fertility in men and women. Talk to your doctor about the risks of taking tramadol.
- if you are having surgery, including dental surgery, tell the doctor or dentist that you are taking tramadol.
- you should know that this medication may make you drowsy and may affect your coordination. Do not drive a car or operate machinery until you know how this medication affects you.
- you should know that tramadol may cause dizziness, lightheadedness, and fainting when you get up from a lying position. To avoid this, get out of bed slowly, resting your feet on the floor for a few minutes before standing up.
- if you have phenylketonuria (PKU; an inherited condition in which a special diet must be followed to prevent mental retardation, you should know that the orally disintegrating tablets contain aspartame, a source of phenylalanine.
- you should know that tramadol may cause constipation. Talk to your doctor about changing your diet and using other medications to treat or prevent constipation.
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?
If your doctor has told you to take tramadol 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?
Tramadol may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away:
- difficulty falling asleep or staying asleep
- uncontrollable shaking of a part of the body
- muscle tightness
- changes in mood
- heartburn or indigestion
- dry mouth
Some side effects can be serious. If you experience any of these symptoms or those mentioned in the IMPORTANT WARNING section, call your doctor immediately or get emergency medical treatment:
- difficulty swallowing or breathing
- swelling of the eyes, face, throat, tongue, lips, hands, feet, ankles, or lower legs
- agitation, hallucinations (seeing things or hearing voices that do not exist), fever, sweating, confusion, fast heartbeat, shivering, severe muscle stiffness or twitching, loss of coordination, nausea, vomiting, or diarrhea
- nausea, vomiting, loss of appetite, weakness, or dizziness
- inability to get or keep an erection
- irregular menstruation
- decreased sexual desire
- changes in heartbeat
- loss of consciousness
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).
Tramadol may cause other side effects. Tell your doctor if you have any unusual problems while you are taking this medication.
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).
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
Unneeded medications should be disposed of in special ways to ensure that pets, children, and other people cannot consume them. However, you should not flush this medication down the toilet. Instead, the best way to dispose of your medication is through a medicine take-back program. Talk to your pharmacist or contact your local garbage/recycling department to learn about take-back programs in your community. See the FDA's Safe Disposal of Medicines website (http://goo.gl/c4Rm4p) for more information if you do not have access to a take-back program.
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 taking tramadol, 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 the following:
- decreased size of the pupil (the black circle in the center of the eye)
- difficulty breathing
- extreme drowsiness
- coma (loss of consciousness for a period of time)
- slowed heartbeat
- muscle weakness
- cold, clammy skin
What other information should I know?
Keep all appointments with your doctor and laboratory. Your doctor may order certain lab tests to check your body's response to tramadol.
Before having any laboratory test (especially those that involve methylene blue), tell your doctor and the laboratory personnel that you are taking tramadol.
Do not let anyone else take your medication. Tramadol is a controlled substance. Prescriptions may be refilled only a limited number of times; ask your pharmacist if you have any questions.
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.
Brand names of combination products
- Ultracet® (containing Acetaminophen, Tramadol)
¶ This branded product is no longer on the market. Generic alternatives may be available.