Tramadol and acetaminophen (Oral route)
TRAM-a-dol hye-droe-KLOR-ide, a-seet-a-MIN-oh-fen
Addiction, Abuse, and MisuseTraMADol hydrochloride/acetaminophen exposes patients and other users to the risks of opioid addiction, abuse, and misuse, which can lead to overdose and death. Assess each patient's risk prior to prescribing traMADol hydrochloride/acetaminophen, and monitor all patients regularly for the development of these behaviors or conditions .Opioid Analgesic Risk Evaluation and Mitigation Strategy (REMS)To ensure that the benefits of opioid analgesics outweigh the risks of addiction, abuse and misuse, the Food and Drug Administration (FDA) has required a REMS for these products. Under the requirements of the REMS, drug companies with approved opioid analgesic products must make REMS-compliant education programs available to healthcare providers. Healthcare providers are strongly encouraged to: complete a REMS-compliant education program, counsel patients and/or their caregivers, with every prescription, on safe use, serious risks, storage, and disposal of these products, emphasize to patients and their caregivers the importance of reading the Medication Guide every time it is provided by their pharmacists, and consider other tools to improve patient, household, and community safety.Life-threatening Respiratory DepressionSerious, life-threatening, or fatal respiratory depression may occur with use of traMADol hydrochloride/acetaminophen. Monitor for respiratory depression, especially during initiation of traMADol hydrochloride/acetaminophen or following a dose increase.Accidental IngestionAccidental ingestion of even one dose of traMADol hydrochloride/acetaminophen, especially by children, can result in a fatal overdose of traMADol.Ultra-Rapid Metabolism of TraMADol and Other Risk Factors for Life-Threatening Respiratory Depression in ChildrenLife-threatening respiratory depression and death have occurred in children who received traMADol. Most of the reported cases occurred following tonsillectomy and/or adenoidectomy, and many of the children had evidence of being an ultra-rapid metabolizer of codeine due to a CYP2D6 polymorphism. TraMADol hydrochloride/acetaminophen tablets are contraindicated in children younger than 12 years of age and in children younger than 18 years of age following tonsillectomy and/or adenoidectomy. Avoid the use of traMADol hydrochloride/acetaminophen tablets in adolescents 12 to 18 years of age who have other risk factors that may increase their sensitivity to the respiratory depressant effects of traMADol.Neonatal Opioid Withdrawal SyndromeProlonged use of traMADol hydrochloride/acetaminophen during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts. If opioid use is required for a prolonged period in a pregnant woman, advise the patient of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available.Interactions with Drugs Affecting Cytochrome P450 IsoenzymesThe effects of concomitant use or discontinuation of CYP3A4 inducers, 3A4 inhibitors, or 2D6 inhibitors with traMADol are complex. Use of CYP3A4 inducers, 3A4 inhibitors, or 2D6 inhibitors with traMADol hydrochloride requires careful consideration of the effects on the parent drug, traMADol, and the active metabolite, M1.HepatotoxicityTraMADol hydrochloride/acetaminophen contains traMADol hydrochloride and acetaminophen. Acetaminophen has been associated with cases of acute liver failure, at times resulting in liver transplant and death. Most of the cases of liver injury are associated with the use of acetaminophen at doses that exceed 4000 mg per day, and often involve more than 1 acetaminophen-containing product.Risks from Concomitant Use with Benzodiazepines or Other CNS DepressantsConcomitant use of opioids with benzodiazepines or other CNS depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death. Reserve concomitant prescribing of traMADol hydrochloride and benzodiazepines or other CNS depressants for use in patients for whom alternative treatment options are inadequate. Limit dosages and durations to the minimum required. Follow patients for signs and symptoms of respiratory depression and sedation .
Uses of This Medicine:
Tramadol and acetaminophen combination is used to relieve acute pain severe enough to require an opioid treatment and when other pain medicines did not work well enough or cannot be tolerated. When used together, the combination provides better pain relief than either medicine used alone. In some cases, you may get relief with lower doses of each medicine.
Tramadol belongs to the group of medicines called opioid analgesics (narcotics). It acts in the central nervous system (CNS) to relieve pain. When tramadol is used for a long time, it may become habit-forming (causing mental or physical dependence). Mental dependence (addiction) is not likely to occur when narcotics are used for this purpose. Physical dependence may lead to side effects when you suddenly stop taking the medicine. Since this medicine is only used for short-term relief of pain, mental and physical dependence will probably not occur.
Acetaminophen is used to relieve pain and reduce fever in patients. It does not become habit-forming when taken for a long time. But acetaminophen may cause other unwanted effects when taken in large doses, including liver damage. Although rare, use of acetaminophen has been reported to lead to liver transplantation and death, usually at high doses and when multiple acetaminophen-containing products have been used.
This medicine is available only under a restricted distribution program called the Opioid Analgesic REMS (Risk Evaluation and Mitigation Strategy) program.
Before Using This Medicine:
In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:
Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.
Appropriate studies have not been performed on the relationship of age to the effects of tramadol and acetaminophen combination in the pediatric population. It should not be used in children younger than 12 years of age. Safety and efficacy have not been established.
This medicine should not be used to relieve pain after surgery removal of tonsils or adenoids in any children. Severe breathing problems and deaths have been reported in some children who received codeine after tonsil or adenoid surgery.
Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of tramadol and acetaminophen combination in the elderly. However, elderly patients are more likely to have age-related liver, kidney, heart, or lung problems which may require caution and an adjustment in the dose for patients receiving tramadol and acetaminophen combination.
Studies in women breastfeeding have demonstrated harmful infant effects. An alternative to this medication should be prescribed or you should stop breastfeeding while using this medicine.
Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking this medicine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.
Using this medicine with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.
- Methylene Blue
Using this medicine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.
- Calcium Oxybate
- Chloral Hydrate
- Eslicarbazepine Acetate
- Gabapentin Enacarbil
- Magnesium Oxybate
- Morphine Sulfate Liposome
- Nitrous Oxide
- Opium Alkaloids
- Peginterferon Alfa-2b
- Pneumococcal 13-Valent Vaccine, Diphtheria Conjugate
- Potassium Oxybate
- Sodium Oxybate
- St John's Wort
- Tolonium Chloride
Using this medicine with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.
Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.
Using this medicine with any of the following is usually not recommended, but may be unavoidable in some cases. If used together, your doctor may change the dose or how often you use this medicine, or give you special instructions about the use of food, alcohol, or tobacco.
- Grapefruit Juice
Using this medicine with any of the following may cause an increased risk of certain side effects but may be unavoidable in some cases. If used together, your doctor may change the dose or how often you use this medicine, or give you special instructions about the use of food, alcohol, or tobacco.
Other medical problems—
The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:
- Adrenal problems or
- Alcohol abuse, or history of or
- Brain tumor or
- Depression, history of or
- Drug dependence, especially narcotic abuse or dependence, or history of or
- Gallstones or
- Head injuries or
- Increased pressure in the head or
- Lung or breathing problems (eg, COPD, hypercapnia, hypoxia, sleep apnea) or
- Mental illness (eg, suicidal ideation), history of or
- Obesity (overweight) or
- Seizures, history of or
- Stomach problems, severe—Use with caution. May increased risk for more side effects.
- Asthma, acute or severe or
- Lung or breathing problems, severe or
- Stomach or bowel blockage (eg, paralytic ileus) or
- Surgery (eg, nasopharyngeal tonsils, tonsils)—Should not be used in patients with these conditions.
- Kidney disease—Use with caution. The effects may be increased because of slower removal of the medicine from the body.
- Liver disease—Use is not recommended in patients with this condition.
Proper Use of This Medicine:
Take this medicine only as directed by your doctor. Do not take more of it, do not take it more often, and do not take it for a longer time than your doctor ordered. This is especially important for elderly patients, who may be more sensitive to the effects of pain medicines. If too much of this medicine is taken for a long time, it may become habit-forming (causing mental or physical dependence) or cause an overdose. Also, large amounts of acetaminophen may cause liver damage if taken for a long time.
It is very important that you understand the rules of the Opioid Analgesic REMS program to prevent addiction, abuse, and misuse of tramadol and acetaminophen combination. This medicine should come with a Medication Guide. Read and follow the instructions carefully. Read it again each time you refill your prescription in case there is new information. Ask your doctor if you have any questions.
Swallow the tablet whole. Do not crush, break, or chew it.
This combination medicine contains acetaminophen (Tylenol®). Carefully check the labels of all other medicines you are using, because they may also contain acetaminophen. It is not safe to use more than 4 grams (4,000 milligrams) of acetaminophen in one day (24 hours), as this may increase the risk for serious liver problems.
The dose of this medicine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.
The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.
- For oral dosage form (tablets):
- For acute pain:
- Adults—2 tablets every 4 to 6 hours as needed for up to 5 days. Do not take more than 8 tablets per day.
- Children 12 years of age and older—Use and dose must be determined by your doctor.
- Children younger than 12 years of age—Should not be used in these patients.
- For acute pain:
If you miss a dose of this medicine, skip the missed dose and go back to your regular dosing schedule. Do not double doses.
Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.
Keep out of the reach of children.
Do not keep outdated medicine or medicine no longer needed.
Ask your healthcare professional how you should dispose of any medicine you do not use.
Drop off any unused narcotic medicine at a drug take-back location right away. If you do not have a drug take-back location near you, flush any unused narcotic medicine down the toilet. Check your local drug store and clinics for take-back locations. You can also check the DEA web site for locations. Here is the link to the FDA safe disposal of medicines website: www.fda.gov/drugs/resourcesforyou/consumers/buyingusingmedicinesafely/ensuringsafeuseofmedicine/safedisposalofmedicines/ucm186187.htm
Precautions While Using This Medicine:
It is very important that your doctor check your or your child's progress at regular visits, especially within the first 24 to 72 hours of treatment, to make sure the medicine is working properly. Blood and urine tests may be needed to check for any unwanted effects.
Do not use this medicine if you are using or have used an MAO inhibitor (MAOI), such as isocarboxazid [Marplan®], linezolid [Zyvox®], phenelzine [Nardil®], selegiline [Eldepryl®], or tranylcypromine [Parnate®] within the past 14 days.
Using this medicine while you are pregnant may cause neonatal withdrawal syndrome in your newborn baby. Check with your doctor right away if your baby has an abnormal sleep pattern, diarrhea, a high-pitched cry, irritability, shakiness or tremors, weight loss, vomiting, or fails to gain weight. Tell your doctor right away if you think you are pregnant or if you plan to become pregnant while using this medicine.
Tramadol is highly metabolized in the body. Some people change tramadol to a stronger product (O-desmethyltramadol) more quickly than others. These individuals are called "ultra-rapid metabolizers of tramadol". Contact your doctor immediately if you experience extreme sleepiness, confusion, or shallow breathing. These symptoms may indicate that you are an "ultra-rapid metabolizer of tramadol." As a result, there is too much O-desmethyltramadol in the body and more side effects of O-desmethyltramadol than usual. Children may be especially sensitive to this effect (eg, serious breathing problems, death). Do not give this medicine to:
- Children younger than 12 years of age.
- Children younger than 18 years of age who have had surgery removal of tonsils or adenoids.
- Children 12 to 18 years of age who have a high risk for breathing problems (eg, obstructive sleep apnea, obesity, lung disease).
If a nursing mother is an ultra-rapid metabolizer of tramadol, it could lead to an overdose in the nursing baby and cause very serious side effects.
For nursing mothers using this medicine
- Talk to your doctor if you have any questions about taking tramadol or about how this medicine may affect your baby.
- Call your doctor if you become extremely tired and have difficulty caring for your baby.
- Your baby should generally nurse every 2 to 3 hours and should not sleep more than 4 hours at a time.
- Check with your doctor, hospital emergency room, or local emergency services (eg, "call 9-1-1") immediately if your baby shows signs of increased sleepiness (more than usual), difficulty breastfeeding, difficulty breathing, or limpness. These may be symptoms of an overdose and need immediate medical attention.
Check with your doctor right away if you or your child have pain or tenderness in the upper stomach, pale stools, dark urine, loss of appetite, nausea, vomiting, or yellow eyes or skin. These could be symptoms of a serious liver problem.
This medicine may cause serious allergic reactions, including anaphylaxis, angioedema, or certain skin conditions (eg, Stevens-Johnson syndrome, toxic epidermal necrolysis). These reactions can be life-threatening and require immediate medical attention. Call your doctor right away if you or your child have a rash, itching, blistering, peeling, or loosening of the skin, fever or chills, cough, red irritated eyes, red skin lesions, often with a purple center, sore throat, sores, ulcers, or white spots in the mouth or on the lips, trouble breathing or swallowing, unusual tiredness or weakness, or any swelling of your hands, face, mouth, or throat while you are using this medicine.
Check the labels of all nonprescription (over-the-counter [OTC]) or prescription medicines you now take. If any contain acetaminophen or tramadol, check with your doctor. Taking them together with this medicine may cause an overdose.
Before having any kind of surgery (including dental surgery) or emergency treatment, tell the doctor or dentist in charge that you or your child are taking this medicine. Serious side effects can occur if your doctor or dentist gives you certain medicines without knowing that you have been taking this medicine.
If you think you or someone else may have taken an overdose of this medicine, get emergency help at once. Your doctor may also give naloxone and other medicines to treat an overdose. Signs of an overdose include: dark urine, difficult or trouble breathing, irregular, fast or slow, or shallow breathing, nausea, vomiting, pain in the upper stomach, pale or blue lips, fingernails, or skin, pinpoint pupils of the eyes, or yellow eyes or skin.
Check with your doctor before using this medicine with alcohol or other medicines that affect the central nervous system (CNS). The use of alcohol or other medicines that affect the CNS with Ultracet® may worsen the side effects of this medicine, such as dizziness, poor concentration, drowsiness, unusual dreams, and trouble with sleeping. Some examples of medicines that affect the CNS are antihistamines or medicine for allergies or colds, sedatives, tranquilizers, or sleeping medicines, medicine for depression, medicine for anxiety, prescription pain medicine or narcotics, medicine for attention deficit and hyperactivity disorder, medicine for seizures or barbiturates, muscle relaxants, or anesthetics, including some dental anesthetics.
This medicine may cause sleep-related breathing problems (eg, sleep apnea, sleep-related hypoxemia). Your doctor may decrease your dose if you have sleep apnea (stop breathing for short periods during sleep) while using this medicine.
This medicine may be habit-forming. If you feel that the medicine is not working as well, do not use more than your prescribed dose. Call your doctor for instructions.
Using narcotics for a long time can cause severe constipation. To prevent this, your doctor may direct you to take laxatives, drink a lot of fluids, or increase the amount of fiber in your diet. Be sure to follow the directions carefully, because continuing constipation can lead to more serious problems.
Check with your doctor right away if you or your child have anxiety, restlessness, a fast heartbeat, fever, sweating, muscle spasms, twitching, nausea, vomiting, diarrhea, or see or hear things that are not there. These may be symptoms of a serious condition called serotonin syndrome. Your risk may be higher if you also take certain other medicines that affect serotonin levels in your body.
This medicine may cause some people to be agitated, irritable, or display other abnormal behaviors. It may also cause some people to have suicidal thoughts and tendencies or to become more depressed. Make sure your doctor knows if you have trouble sleeping, get upset easily, have a big increase in energy, or start to act reckless. Also, tell your doctor if you have any sudden or strong feelings, such as feeling nervous, angry, restless, violent, or scared. Let your doctor know if you or anyone in your family has tried to commit suicide.
This medicine may cause some people to become dizzy, drowsy, or may cause trouble with thinking or controlling body movements, which may lead to falls, fractures or other injuries. Do not drive or do anything else that could be dangerous until you know how this medicine affects you.
This medicine may cause adrenal gland problems. Check with your doctor right away if you have darkening of the skin, diarrhea, dizziness, fainting, loss of appetite, mental depression, nausea, skin rash, unusual tiredness or weakness, or vomiting.
Dizziness, lightheadedness, or fainting may occur, especially when you get up suddenly from a lying or sitting position. Getting up slowly may help. Also, lying down for a while may relieve dizziness or lightheadedness. If this problem continues or gets worse, check with your doctor right away.
Do not change the dose or suddenly stop taking this medicine without first checking with your doctor. Your doctor may want you to gradually reduce the amount you are using before stopping it completely. This may help prevent worsening of your condition and reduce the possibility of withdrawal symptoms, such as anxiety, diarrhea, headache, nausea, shivering, sweating, tremors, or trouble sleeping.
Analgesics may cause dryness of the mouth. For temporary relief, use sugarless candy or gum, melted bits of ice in your mouth, or a saliva substitute. However, if dry mouth continues for more than 2 weeks, check with your dentist. Continuing dryness of the mouth may increase the chance of dental disease, including tooth decay, gum disease, and fungus infections.
Using too much of this medicine may cause infertility (unable to have children). Talk with your doctor before using this medicine if you plan to have children.
Do not take other medicines unless they have been discussed with your doctor. This includes prescription or nonprescription (over-the-counter [OTC]) medicines and herbal or vitamin supplements.
Side Effects of This Medicine:
- Burning, itching, and redness of the skin
- chest pain or tightness
- difficulty with swallowing
- fast heartbeat
- puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue
- skin rash, hives, or itching skin
- trouble breathing
- unusual tiredness or weakness
- Incidence not known
- bigger, dilated, or enlarged pupils
- blistering, peeling, or loosening of the skin
- confusion as to time, place, or person
- constricted, pinpoint, or small pupils
- darkening of the skin
- holding false beliefs that cannot be changed by fact
- increased sensitivity of the eyes to light
- irregular or slow heart rate
- joint or muscle pain
- large, hive-like swelling on the face, eyelids, lips, tongue, throat, hands, legs, feet, or genitals
- loss of appetite
- noisy breathing
- overactive reflexes
- poor coordination
- red skin lesions, often with a purple center
- red, irritated eyes
- sore throat
- sores, ulcers, or white spots in the mouth or on the lips
- talking or acting with excitement you cannot control
- trembling or shaking
- unusual excitement, nervousness, or restlessness
- Symptoms of overdose
- Black, tarry stools
- dark urine
- dizziness, faintness, or lightheadedness when getting up suddenly from a lying or sitting position
- drowsiness to profound coma
- irregular, fast or slow, or shallow breathing
- loss of appetite
- mood or other mental changes
- pale or blue lips, fingernails, or skin
- seeing, hearing, or feeling things that are not there
- stomach pain
- trouble sleeping
- unpleasant breath odor
- unusual drowsiness, dullness, tiredness, weakness, or feeling of sluggishness
- vomiting of blood
- yellow eyes or skin
- Less common
- bloated or feeling of fullness
- dry mouth
- excess air or gas in the stomach or bowels
- false or unusual sense of well-being
- feeling of warmth
- increase in bowel movements
- increased sweating
- loose stools
- loss of strength or energy
- muscle pain or weakness
- numbness or tingling of the hands, legs, and feet
- painful or difficult urination
- redness of the face, neck, arms, and occasionally the upper chest
- sleepiness or unusual drowsiness
- soft stools
- stomach discomfort
- weight loss
- Abnormal thinking
- blurred vision
- change in vision
- clumsiness, unsteadiness, trembling, or problems with muscle control or coordination
- cold sweats
- continuing ringing, buzzing, or unexplained noise in the ears
- decrease in the frequency or amount of urination
- decreased awareness or responsiveness
- decreased interest in sexual intercourse
- delusions of persecution, mistrust, suspiciousness, or combativeness
- difficulty in passing urine (dribbling)
- false or unusual sense of well-being
- feeling of constant movement of self or surroundings
- feeling unusually cold
- headache, severe or continuing
- increased muscle tone
- involuntary muscle contractions
- loss of memory
- loss of sense of reality
- loss of sexual ability, desire, drive, or performance
- migraine headache
- morbid dreaming
- pounding in the ears
- problems with memory
- quick to react or overreact emotionally
- rapidly changing moods
- sensation of spinning
- severe stomach pain
- shakiness and unsteady walk
- vomiting of blood or material that looks like coffee grounds
Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.
Check with your doctor immediately if any of the following side effects occur:
Get emergency help immediately if any of the following symptoms of overdose occur:
Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:
Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.
Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.
Last Updated: 6/10/2021