Applies to acetaminophen / tramadol: oral tablet.
Warning
Oral route (Tablet)
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.
Serious side effects
Along with its needed effects, acetaminophen / tramadol 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 while taking acetaminophen / tramadol:
Rare
- Burning, itching, and redness of the skin
- chest pain or tightness
- cough
- difficulty with swallowing
- dizziness
- fast heartbeat
- puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue
- seizures
- skin rash, hives, or itching skin
- trouble breathing
- unusual tiredness or weakness
- vomiting
Incidence not known
- Agitation
- anxiety
- bigger, dilated, or enlarged pupils
- blistering, peeling, or loosening of the skin
- blurred vision
- chills
- cold sweats
- coma
- confusion
- confusion as to time, place, or person
- constricted, pinpoint, or small pupils
- cool, pale skin
- darkening of the skin
- decreased urine output
- depression
- diarrhea
- fainting
- fever
- hallucinations
- headache
- holding false beliefs that cannot be changed by fact
- increased hunger
- increased sensitivity of the eyes to light
- increased thirst
- 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
- muscle cramps
- nausea
- nervousness
- nightmares
- noisy breathing
- overactive reflexes
- poor coordination
- red skin lesions, often with a purple center
- red, irritated eyes
- shakiness
- shivering
- slurred speech
- sore throat
- sores, ulcers, or white spots in the mouth or on the lips
- sweating
- swelling of the face, ankles, or hands
- talking or acting with excitement you cannot control
- trembling or shaking
- twitching
- unusual excitement, nervousness, or restlessness
Get emergency help immediately if any of the following symptoms of overdose occur while taking acetaminophen / tramadol:
Symptoms of overdose
- Black, tarry stools
- dark urine
- depression
- disorientation
- dizziness, faintness, or lightheadedness when getting up suddenly from a lying or sitting position
- drowsiness to profound coma
- fever
- headache
- irregular, fast or slow, or shallow breathing
- lightheadedness
- loss of appetite
- mood or other mental changes
- nausea
- 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
Other side effects
Some side effects of acetaminophen / tramadol 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:
Less common
- Anxiety
- belching
- bloated or feeling of fullness
- constipation
- dry mouth
- excess air or gas in the stomach or bowels
- false or unusual sense of well-being
- feeling of warmth
- heartburn
- increase in bowel movements
- increased sweating
- indigestion
- loose stools
- loss of strength or energy
- muscle 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
Rare
- 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
- crying
- 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
- shivering
- vomiting of blood or material that looks like coffee grounds
For Healthcare Professionals
Applies to acetaminophen / tramadol: oral tablet.
General
The most common adverse reactions include nausea, somnolence, and dizziness.[Ref]
Hepatic
Acetaminophen-Tramadol
Uncommon (0.1% to 1%): Increased transaminases, abnormal hepatic function
Acetaminophen:
Frequency not reported: Acute liver failure
Tramadol:
Frequency not reported: Hepatitis, liver failure[Ref]
Psychiatric
A psychic reaction with symptoms of nervousness, anxiety, agitation, tremor, spasticity, euphoria, emotional lability, and hallucinations has been reported with tramadol use. During clinical trials, tolerance development was mild and the reports of a withdrawal syndrome were rare. Symptoms of a withdrawal syndrome have included: panic attacks, severe anxiety, hallucinations, paresthesias, tinnitus and unusual CNS symptoms (i.e. confusion, delusions, personalization, derealization, and paranoia).[Ref]
Acetaminophen-Tramadol
Very common (10% or more): Insomnia
Common (1% to 10%): Altered mood (anxiety, nervousness, euphoric mood), sleep disorders
Uncommon (0.1% to 1%): Depression, hallucinations, nightmares, amnesia
Rare (less than 0.1%): Delirium, dependency
Frequency not reported: Depersonalization, paranoia
Postmarketing reports: Abuse
Tramadol:
Frequency not reported: Psychic reactions including mood changes, withdrawal symptoms[Ref]
Gastrointestinal
Acetaminophen-Tramadol
Very common (10% or more): Nausea (up to 18%), constipation (up to 11%)
Common (1% to 10%): Vomiting, dyspepsia, dry mouth, diarrhea, abdominal pain, flatulence
Uncommon (0.1% to 1%): Dysphagia, melena, tongue edema
Tramadol
Frequency not reported: Gastrointestinal bleeding[Ref]
Nervous system
Acetaminophen-Tramadol
Very common (10% or more): Dizziness (up to 15%), Somnolence (up to 12%), headache (up to 11%),
Common (1% to 10%): Tremor, confusion, paresthesia, hypoesthesia
Uncommon (0.1% to 1%): Migraine, hypertonia, stupor, involuntary muscle contractions
Rare (less than 0.1%): Seizures, ataxia, speech disorders
Tramadol:
Frequency not reported: Serotonin syndrome[Ref]
Dermatologic
Common (1% to 10%): Sweating, pruritus, rash
Uncommon (0.11% to 1%): dermal reactions such as rash and urticaria[Ref]
Genitourinary
Uncommon (0.1% to 1%): Albuminuria, micturition disorders (dysuria and urinary retention)
Frequency not reported: Impotence[Ref]
Cardiovascular
Acetaminophen-Tramadol:
Uncommon: Hypertension, palpitations, tachycardia, arrhythmia
Less than 1%: Aggravated hypertension, hypotension, chest pain
Tramadol:
Frequency not reported: Postural hypotension, bradycardia, syncope, vasodilation, myocardial ischemia
Postmarketing reports: QT prolongation/torsade de pointes[Ref]
Postmarketing reports of QT prolongation and/or torsade de pointes have been received for tramadol-containing products. In many cases, patients were taking another drug associated with QT prolongation, had risk factors for QT prolongation such as hypokalemia, or in the overdose setting.[Ref]
Hypersensitivity
Acetaminophen:
Frequency not reported: Allergic reactions (primarily skin rash)
Tramadol:
Rare (less than 0.1%): Anaphylaxis, allergic reactions such as dyspnea, bronchospasm, wheezing, urticarial and Stevens-Johnson syndrome/TENS[Ref]
Respiratory
Acetaminophen-Tramadol:
Uncommon (0.1% to 1%): Dyspnea
Tramadol:
Frequency not reported: Asthma aggravated[Ref]
Other
Common (1% to 10%): Asthenia, fatigue, hot flushes
Uncommon (0.1% to 1%): Tinnitus, shivers[Ref]
Hematologic
Acetaminophen-Tramadol
Frequency not reported: Anemia
Acetaminophen:
Frequency not reported: Blood dyscrasias including thrombocytopenia and agranulocytosis[Ref]
Ocular
Uncommon (0.1% to 1%): Abnormal vision
Rare (less than 0.1%): Blurred vision, mydriasis, miosis[Ref]
Metabolic
Severe hyponatremia and/or SIADH have been reported, most often in females over 65 years old, and within the first week of therapy.[Ref]
Common (1% to 10%): Anorexia
Frequency not reported: Hypoglycemia, decreased weight
Postmarketing reports: Hyponatremia[Ref]
Endocrine
Common (1% to 10%): Prostatic disorder
Opioids:
Postmarketing reports: Adrenal insufficiency; androgen deficiency[Ref]
