AUDIENCE: Family Practice, Psychiatry, Pain Management, Nursing, Endocrinology
ISSUE: FDA is warning about several safety issues with the entire class of opioid pain medicines. See the http://www.fda.gov/Drugs/DrugSafety/ucm489676.htm for a complete listing. These safety risks are potentially harmful interactions with numerous other medications, problems with the adrenal glands, and decreased sex hormone levels. We are requiring changes to the labels of all opioid drugs to warn about these risks.
BACKGROUND: Opioids are powerful prescription medicines that can help manage pain when other treatments and medicines are not able to provide enough pain relief (see List of Opioid Medicines in the http://www.fda.gov/Drugs/DrugSafety/ucm489676.htm). However, opioids also carry serious risks, including of misuse and abuse, addiction, overdose, and death.
Prescription opioids are divided into two main categories – immediate-release (IR) products, usually intended for use every 4 to 6 hours; and extended release/long acting (ER/LA) products, intended to be taken once or twice a day, depending on the individual product and patient.
See the http://www.fda.gov/Drugs/DrugSafety/ucm489676.htm for additional information, including a listing of opioids, serotonergic medicines, and a data summary.
Health care professionals should discontinue opioid treatment and/or use of the other medicine if serotonin syndrome is suspected.
Health care professionals should perform diagnostic testing if adrenal insufficiency is suspected. If diagnosed, treat with corticosteroids and wean the patient off of the opioid, if appropriate. If the opioid can be discontinued, follow-up assessment of adrenal function should be performed to determine if treatment with corticosteroids can be discontinued.
Decreased sex hormone levels:
Health care professionals should conduct laboratory evaluation in patients presenting with such signs or symptoms.
For more information visit the FDA website at: http://www.fda.gov/Safety/MedWatch/SafetyInformation and http://www.fda.gov/Drugs/DrugSafety.
AUDIENCE: Health Professionals
ISSUE: FDA is investigating the use of the pain medicine tramadol in children aged 17 years and younger, because of the rare but serious risk of slowed or difficult breathing. This risk may be increased in children treated with tramadol for pain after surgery to remove their tonsils and/or adenoids. FDA is evaluating all available information and will communicate final conclusions and recommendations to the public when the review is complete.
Tramadol is not FDA-approved for use in children; however, data show it is being used "off-label" in the pediatric population. Health care professionals should be aware of this and consider prescribing alternative FDA-approved pain medicines for children.
BACKGROUND: In the body, tramadol is converted in the liver to the active form of the opioid, called O-desmethyltramadol. Some people have genetic variations that cause tramadol to be converted to the active form of the opioid faster and more completely than usual. These people, called ultra-rapid metabolizers, are more likely to have higher-than-normal amounts of the active form of the opioid in their blood after taking tramadol, which can result in breathing difficulty that may lead to death. Recently, a 5-year-old child in France experienced severely slowed and difficult breathing requiring emergency intervention and hospitalization after taking a single prescribed dose of tramadol oral solution for pain relief following surgery to remove his tonsils and adenoids. The child was later found to be an ultra-rapid metabolizer and had high levels of O-desmethyltramadol in his body.
RECOMMENDATION: Parents and caregivers of children taking tramadol who notice any signs of slow or shallow breathing, difficult or noisy breathing, confusion, or unusual sleepiness should stop tramadol and seek medical attention immediately by taking their child to the emergency room or calling 911. Parents and caregivers should talk with their child's health care professional if they have any questions or concerns about tramadol or other pain medicines their child is taking.
For more information visit the FDA website at: http://www.fda.gov/Safety/MedWatch/SafetyInformation and http://www.fda.gov/Drugs/DrugSafety.
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, an extended-release (long-acting) capsule, and an orally disintegrating tablet (tablet that dissolves quickly in the mouth) to take by mouth. The regular tablet and orally disintegrating tablets are usually taken with or without food every 4-6 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.
Swallow the extended-release tablets and extended-release capsules whole; do not split, chew, or crush them.
To take the orally disintegrating tablets, peel back the foil to remove a tablet from the blister pack. Do not try to push the tablet through the foil. Place the tablet in your mouth and it will dissolve in a few seconds. You may take the tablet with or without water. Do not chew, break, or split the tablet.
Tramadol can be habit-forming. Do not take a larger dose, take it more often, or take it for a longer period of time than prescribed by your doctor.
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 or other opiate pain or cough medications any other medications, or any of the ingredients in tramadol tablets, extended-release tablets, extended-release capsules, or orally disintegrating tablets. Ask your pharmacist 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 any of the following: anticoagulants ('blood thinners') such as warfarin (Coumadin); certain antifungal medications such as ketoconazole (Nizoral); digoxin (Lanoxin); erythromycin (E.E.S., E-Mycin, Erythrocin); linezolid (Zyvox); lithium (Lithobid); medications for anxiety, mental illness, nausea, and pain; certain medications for migraine headaches such as almotriptan (Axert), eletriptan (Relpax), frovatriptan (Frova), naratriptan (Amerge), rizatriptan (Maxalt), sumatriptan (Imitrex), and zolmitriptan (Zomig); medications for seizures, such as carbamazepine (Equetro, Tegretol); monoamine oxidase (MAO) inhibitors, including isocarboxazid (Marplan), phenelzine (Nardil), selegiline (Eldepryl, Emsam, Zelapar), and tranylcypromine (Parnate); muscle relaxants such as cyclobenzaprine (Flexeril); promethazine (Phenergan); quinidine; rifampin (Rifadin, Rifamate, Rimactane, others); sedatives; sleeping pills; selective serotonin reuptake inhibitors (SSRIs) such as citalopram (Celexa), fluoxetine (Prozac, Sarafem), fluvoxamine (Luvox), paroxetine (Paxil, Pexeva), and sertraline (Zoloft); serotonin norepinephrine reuptake inhibitors (SNRIs) such as desvenlafaxine (Pristiq), duloxetine (Cymbalta), and venlafaxine (Effexor); tranquilizers; and tricyclic antidepressants such as amitriptyline, amoxapine, clomipramine (Anafranil), desipramine (Norpramin), doxepin (Silenor), imipramine (Tofranil), nortriptyline (Aventyl, 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.
- tell your doctor if you have or have ever had slowed breathing, lung disease, or asthma. Your doctor may tell you not to take tramadol.
- tell your doctor if you have or have ever had seizures; an infection in your brain or spine; a head injury, a brain tumor, a stroke, or any other condition that caused high pressure inside your skull; depression; thoughts about harming or killing yourself or planning or trying to do so; mental illness; or kidney or liver disease. Also tell your doctor if you drink or have ever drunk large amounts of alcohol, use or have ever used street drugs, or have overused prescription medications.
- tell your doctor if you are pregnant, plan to become pregnant, or are breast-feeding. If you become pregnant while taking tramadol, call your doctor.
- 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 drinking alcohol or using street drugs during your treatment with tramadol increases the risk that you will experience serious, life-threatening side effects. Talk to your doctor about the risks of drinking alcohol or using street drugs during your treatment.
- 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.
What special dietary instructions should I follow?
Talk to your doctor about drinking grapefruit juice while you are taking this medication.
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
- loss of appetite
- dry mouth
Some side effects can be serious. If you experience any of these symptoms, 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
- hallucinations (seeing things or hearing voices that do not exist)
- loss of consciousness
- lack of coordination
- fast heartbeat
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). Keep tramadol in a safe place so that no one else can take it accidentally or on purpose. Keep track of how many tablets or capsules are left so you will know if any are missing Throw away any medication that is outdated or no longer needed. Talk to your pharmacist about the proper disposal of your medication.
In case of emergency/overdose
In case of overdose, call your local poison control center at 1-800-222-1222. If the victim has collapsed or is not breathing, call local emergency services at 911.
Symptoms of overdose may include:
- 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.
Do not let anyone else take your medication. Ask your pharmacist any questions you have about refilling your prescription.
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.
- Rybix® ODT
- Ultram® ER
Brand names of combination products
- Ultracet® (containing Acetaminophen, Tramadol)
¶ This branded product is no longer on the market. Generic alternatives may be available.