Acetaminophen and tramadol

Name: Acetaminophen and tramadol

What brand names are available for tramadol and acetaminophen?

Ultracet

Acetaminophen and tramadol side effects

Get emergency medical help if you have signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Like other narcotic medicines, tramadol can slow your breathing. Death may occur if breathing becomes too weak.

In rare cases, acetaminophen may cause a severe skin reaction that can be fatal. This could occur even if you have taken acetaminophen in the past and had no reaction. Stop taking this medicine and call your doctor right away if you have skin redness or a rash that spreads and causes blistering and peeling.

A person caring for you should seek emergency medical attention if you have slow breathing with long pauses, blue colored lips, or if you are hard to wake up.

Stop using this medicine and call your doctor at once if you have:

  • noisy breathing, sighing, shallow breathing;

  • a slow heart rate or weak pulse;

  • a light-headed feeling, like you might pass out;

  • seizure (convulsions);

  • chest pain;

  • sexual problems, loss of interest in sex;

  • low cortisol levels-- nausea, vomiting, loss of appetite, dizziness, worsening tiredness or weakness;

  • liver problems--upper stomach pain, loss of appetite, dark urine, jaundice (yellowing of the skin or eyes); or

  • high levels of serotonin in the body--agitation, hallucinations, fever, fast heart rate, overactive reflexes, nausea, vomiting, diarrhea, loss of coordination, fainting.

Serious side effects may be more likely in older adults and those who are overweight, malnourished, or debilitated.

Long-term use of opioid medication may affect fertility (ability to have children) in men or women. It is not known whether opioid effects on fertility are permanent.

Common side effects may include:

  • dizziness, drowsiness, tired feeling;

  • stomach pain, nausea, loss of appetite;

  • diarrhea, constipation; or

  • sweating.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Consumer Information Use and Disclaimer

  • If your symptoms or health problems do not get better or if they become worse, call your doctor.
  • Do not share your drugs with others and do not take anyone else's drugs.
  • Keep a list of all your drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your doctor.
  • Talk with the doctor before starting any new drug, including prescription or OTC, natural products, or vitamins.
  • This medicine comes with an extra patient fact sheet called a Medication Guide. Read it with care. Read it again each time acetaminophen and tramadol is refilled. If you have any questions about this medicine, please talk with the doctor, pharmacist, or other health care provider.
  • If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

This information should not be used to decide whether or not to take acetaminophen and tramadol or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to acetaminophen and tramadol. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.

Review Date: October 4, 2017

Pharmacology

Acetaminophen: Inhibits the synthesis of prostaglandins in the central nervous system and peripherally blocks pain impulse generation; produces antipyresis from inhibition of hypothalamic heat-regulating center

Tramadol: Binds to μ-opiate receptors in the CNS causing inhibition of ascending pain pathways, altering the perception of and response to pain; also inhibits the reuptake of norepinephrine and serotonin, which also modifies the ascending pain pathway

Dosing Hepatic Impairment

Use is not recommended (acetaminophen and tramadol undergo extensive hepatic metabolism).

Adverse Reactions

Also see individual agents.

1% to 10%:

Central nervous system: Drowsiness (6%), dizziness (3%), insomnia (2%), anxiety, confusion, euphoria, fatigue, headache, nervousness

Dermatologic: Diaphoresis (4%), pruritus (2%), skin rash

Endocrine & metabolic: Hot flash

Gastrointestinal: Constipation (6%), anorexia (3%), diarrhea (3%), nausea (3%), xerostomia (2%), abdominal pain, dyspepsia, flatulence, vomiting

Genitourinary: Prostatic disease (2%)

Neuromuscular & skeletal: Tremor, weakness

<1% (Limited to important or life-threatening): Amnesia, cardiac arrhythmia, depersonalization, drug abuse, dysphagia, dyspnea, emotional lability, hallucination, hypertension, hypertonia, hypotension, impotence, migraine, muscle spasm, nightmares, oliguria, rigors, stupor, syncope, tongue edema, urinary retention, withdrawal syndrome (with abrupt discontinuation; includes anxiety, diarrhea, hallucination [rare], nausea, pain, piloerection, rigors, sweating, and tremor; uncommon discontinuation symptoms may include severe anxiety, panic attacks, or paresthesia)

Warnings/Precautions

Concerns related to adverse effects:

• Anaphylactoid reactions: Serious anaphylactoid reactions (including rare fatalities) often following initial dosing have been reported. Pruritus, hives, bronchospasm, angioedema, toxic epidermal necrolysis (TEN), and Stevens-Johnson syndrome have also been reported with use. Previous anaphylactoid reactions to opioids may increase risks for similar reactions to tramadol. If anaphylaxis or other hypersensitivity occurs, discontinue permanently; do not rechallenge.

• CNS depression: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving).

• Hepatotoxicity: [US Boxed Warning]: 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 >4 g/day, and often involve more than 1 acetaminophen-containing product. Risk is increased with alcohol use, preexisting liver disease, and intake of more than one source of acetaminophen-containing medications. Chronic daily dosing in adults has also resulted in liver damage in some patients.

• Hypotension: May cause severe hypotension (including orthostatic hypotension and syncope); use with caution in patients with hypovolemia, cardiovascular disease (including acute MI), or drugs which may exaggerate hypotensive effects (including phenothiazines or general anesthetics). Monitor for symptoms of hypotension following initiation or dose titration. Avoid use in patients with circulatory shock.

• Respiratory depression: [US Boxed Warning]: Serious, life-threatening, or fatal respiratory depression may occur. Monitor closely for respiratory depression, especially during initiation or dose increase. Carbon dioxide retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids.

• Seizures: Even when taken within the recommended dosage seizures may occur; risk is increased in patients receiving serotonin reuptake inhibitors (SSRIs or anorectics), other opioids, tricyclic antidepressants or other cyclic compounds (including cyclobenzaprine, promethazine), neuroleptics, MAO inhibitors, drugs which may lower seizure threshold, or drugs which impair metabolism of tramadol (ie, CYP2D6 and 3A4 inhibitors). Patients with a history of seizures, or with a risk of seizures (head trauma, metabolic disorders, CNS infection, malignancy, or during alcohol/drug withdrawal) are also at increased risk.

• Serotonin syndrome: May occur with concomitant use of serotonergic agents (eg, SSRIs, SNRIs, triptans, TCAs), lithium, St John’s wort, agents that impair metabolism of serotonin (eg, MAO inhibitors), or agents that impair metabolism of tramadol (eg, CYP2D6 and 3A4 inhibitors). Monitor patients for serotonin syndrome such as mental status changes (eg, agitation, hallucinations, coma); autonomic instability (eg, tachycardia, labile blood pressure, hyperthermia); neuromuscular changes (eg, hyperreflexia, incoordination); and/or GI symptoms (eg, nausea, vomiting, diarrhea).

• Skin reactions: Rarely, acetaminophen may cause serious and potentially fatal skin reactions such as acute generalized exanthematous pustulosis, Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN). Discontinue treatment if severe skin reactions develop.

Disease-related concerns:

• Abdominal conditions: May obscure diagnosis or clinical course of patients with acute abdominal conditions.

• Adrenocortical insufficiency: Use with caution in patients with adrenal insufficiency, including Addison disease.

• Biliary tract impairment: Use caution in patients with biliary tract dysfunction or acute pancreatitis; opioids may cause spasm of the sphincter of Oddi.

• CNS depression/coma: Avoid use in patients with impaired consciousness or coma as these patients are susceptible to intracranial effects of CO2 retention.

• Delirium tremens: Use with caution in patients with delirium tremens.

• G6PD deficiency: Use with caution in patients with known G6PD deficiency.

• Head trauma: Use with extreme caution in patients with head injury, intracranial lesions, or elevated intracranial pressure (ICP); exaggerated elevation of ICP may occur.

• Hepatic impairment: Use is not recommended; acetaminophen and tramadol undergo extensive hepatic metabolism.

• Obesity: Use with caution in patients who are morbidly obese.

• Prostatic hyperplasia/urinary stricture: Use with caution in patients with prostatic hyperplasia and/or urinary stricture.

• Psychosis: Use with caution in patients with toxic psychosis.

• Renal impairment: Use with caution in patients with renal impairment.

• Respiratory disease: Use with caution and monitor for respiratory depression in patients with significant chronic obstructive pulmonary disease or cor pulmonale, and those with a substantially decreased respiratory reserve, hypoxia, hypercapnia, or preexisting respiratory depression, particularly when initiating and titrating therapy; critical respiratory depression may occur, even at therapeutic dosages. Consider the use of alternative nonopioid analgesics in these patients.

• Suicide risk: Avoid use in patients who are suicidal; use with caution in patients taking tranquilizers and/or antidepressants, or those with an emotional disturbance including depression. Consider the use of alternative nonopioid analgesics in these patients.

• Thyroid dysfunction: Use with caution in patients with thyroid dysfunction.

Concurrent drug therapy issues:

• Benzodiazepines or other CNS depressants: [US Boxed Warning]: Concomitant 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/acetaminophen and benzodiazepines or other CNS depressants for use in patients for whom alternative treatment options are inadequate. Limit dosage and durations to the minimum required and follow patients for signs and symptoms of respiratory depression and sedation.

• CYP P450 interactions: [US Boxed Warning]: The effects of concomitant use or discontinuation of cytochrome P450 3A4 inducers, 3A4 inhibitors, or 2D6 inhibitors with tramadol are complex. Use of cytochrome P450 3A4 inducers, 3A4 inhibitors, or 2D6 inhibitors with tramadol/acetaminophen requires careful consideration of the effects on the parent drug, tramadol, and the active metabolite, M1.

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information

Special populations:

• Cachectic or debilitated patients: Use with caution in cachectic or debilitated patients; there is a greater potential for critical respiratory depression, even at therapeutic dosages. Consider the use of alternative nonopioid analgesics in these patients.

• Elderly: Use with caution in the elderly; may be more sensitive to adverse effects. Clearance may be reduced in older adults (with or without renal impairment) resulting in a narrow therapeutic window and increasing the risk for respiratory depression or overdose (Dowell [CDC 2016]). Consider the use of alternative nonopioid analgesics in these patients.

• Neonates: Neonatal withdrawal syndrome: [US Boxed Warning]: Prolonged use of opioids during pregnancy can cause neonatal withdrawal syndrome, which may be life-threatening if not recognized and treated 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. Signs and symptoms include irritability, hyperactivity and abnormal sleep pattern, high pitched cry, tremor, vomiting, diarrhea and failure to gain weight. Onset, duration and severity depend on the drug used, duration of use, maternal dose, and rate of drug elimination by the newborn.

Other warnings/precautions:

• Abuse/misuse/diversion: [US Boxed Warning]: Use exposes patients and other users to the risks of addiction, abuse, and misuse, potentially leading to overdose and death. Assess each patient’s risk prior to prescribing; monitor all patients regularly for development of these behaviors or conditions. Use with caution in patients with a history of drug abuse or acute alcoholism; potential for drug dependency exists. Other factors associated with increased risk for misuse include younger age, concomitant depression (major), and psychotropic medication use.

• Accidental ingestion: [US Boxed Warning]: Accidental ingestion of even one dose, especially in children, can result in a fatal overdose of tramadol.

• Dosage limit: Limit acetaminophen dose from all sources (prescription and OTC) to <4 g/day.

• Optimal regimen: An opioid-containing analgesic regimen should be tailored to each patient's needs and based upon the type of pain being treated, the route of administration, degree of tolerance for opioids (naive versus chronic user), age, weight, and medical condition. The optimal analgesic dose varies widely among patients; doses should be titrated to pain relief/prevention.

• Surgery: Opioids decrease bowel motility; monitor for decrease bowel motility in postop patients receiving opioids. Use with caution in the perioperative setting; individualize treatment when transitioning from parenteral to oral analgesics.

• Withdrawal: Tolerance or drug dependence may result from extended use (withdrawal symptoms have been reported); abrupt discontinuation should be avoided. Tapering of dose at the time of discontinuation limits the risk of withdrawal symptoms.

Renal Dose Adjustments

Severe renal impairment (CrCl less than 30 mL/min): Maximum dose: 2 tablets orally every 12 hours

Liver Dose Adjustments

Use is not recommended

Dose Adjustments

Severe renal impairment (CrCl less than 30 mL/min): Maximum dose: 2 tablets orally every 12 hours

Other Comments

Administration advice:
-May be taken with or without food

General:
-Seizures and/serotonin syndrome may occur when used concomitantly with serotonergic agents (SSRIs, SNRIs, and triptans) or with drugs that significantly reduce the metabolic clearance of tramadol.
-Taking this drug in excessive doses, either alone or in combination with other CNS depressants, including alcohol, is a major cause of drug-related deaths.
-This drug should not be used for longer than therapeutically necessary; evaluate continued use at regular intervals.

Monitoring:
-Monitor for respiratory depression, especially with therapy initiation and with dose increases
-Monitor regularly for the development of addiction, abuse, and misuse
-Consider monitoring renal function in elderly patients

Patient advice:
-Patients should understand that taking this medication exposes them to the risk of addiction.
-Patients should be instructed not to exceed the recommended dose or take this product with any other product that contains acetaminophen without first speaking with their healthcare provider; if a patient takes more than 4000 mg of acetaminophen in a day, they should be instructed to seek medical advice, even if they feel fine.
-Patients should be instructed to speak with their healthcare provider regarding all concomitant medications including starting or stopping any products while taking this drug.
-Patients should avoid alcohol while taking this product.
-Patients should understand the risks of life-threatening respiratory depression, and be informed as to when this risk is greatest.
-This drug may cause drowsiness, dizziness, or impair thinking or motor skills; patients should avoid driving or operating machinery until adverse effects are determined.
-Advise patient to speak to physician or health care professional if pregnant, intend to become pregnant, or are breastfeeding.
-Women of child bearing potential should understand that prolonged use during pregnancy can result in neonatal opioid withdrawal syndrome and that prompt recognition and treatment will be necessary.

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