tramadol/acetaminophen

Action and Spectrum

Actions and Spectrum: 

tramadol/acetaminophen is a combination medication that contains two active ingredients: tramadol and acetaminophen. 

tramadol is a centrally-acting opioid analgesic that works by binding to the mu-opioid receptors in the brain and spinal cord. This binding reduces the perception of pain and increases pain tolerance. tramadol also inhibits the reuptake of serotonin and norepinephrine neurotransmitters, which can enhance its analgesic effects. 

On the other hand, acetaminophen is a non-opioid pain reliever and fever reducer that works by blocking the production of prostaglandins, which are substances responsible for causing pain and inflammation in the body. 

The combination of tramadol and acetaminophen provides a dual mechanism of action that can effectively manage moderate to severe pain. tramadol/acetaminophen is indicated to relieve acute pain, such as postoperative pain, and chronic pain conditions, such as osteoarthritis. 

Drug Interaction

Adverse Reaction

Frequency defined 

1-10% 

Anxiety 

Dry mouth 

Dyspepsia 

Asthenia 

Rash 

Abdominal pain 

Diarrhea 

Insomnia 

Tremor 

Somnolence 

Headache 

Flatulence 

Vomiting 

Confusion 

Fatigue 

Hot flushes 

Pruritus 

Nausea 

Euphoria 

Dizziness 

Nervousness 

Constipation 

Sweating 

<1% 

Hypertension 

Depersonalization 

Micturition disorder 

Aggravated hypertension 

Convulsions 

Amnesia 

Abnormal vision 

Ataxia 

Paresthesias 

Tinnitus 

Emotional lability 

Hypotension 

Syncope 

Involuntary muscle contractions 

Aggravated migraine 

Tongue edema 

Weight decrease 

Chest pain 

Dysphagia 

Melena 

Albuminuria 

Arrhythmia 

Palpitation 

Stupor 

Withdrawal syndrome 

Abnormal hepatic function 

Anemia 

Tachycardia 

Urinary retention 

Hallucination 

Depression 

Vertigo 

Oliguria 

Paroniria 

Dyspnea 

Impotence 

Drug abuse 

Rigors 

Migraine 

Frequency not defined 

Cognitive dysfunction 

Hyponatremia 

Difficulty concentrating 

Hypoglycemia 

Depression 

Gastrointestinal bleeding 

Black Box Warning

Black Box Warning: 

The black box warning for tramadol/acetaminophen states that the medication carries a risk of addiction, abuse, and misuse, which can lead to overdose and death. It also warns that tramadol, one of the active ingredients in the combination medication, can cause respiratory depression and death, especially when taken in high doses or combination with other central nervous system depressants, such as alcohol, benzodiazepines, or other opioids. 

The warning advises healthcare professionals to use caution when prescribing tramadol/acetaminophen to patients with a history of substance abuse or addiction and to closely monitor patients for signs of respiratory depression and other adverse effects. It also advises patients to take the medication exactly as prescribed and seek medical attention immediately if they experience difficulty breathing excessive drowsiness, or other overdose symptoms. 

Contraindication / Caution

Contraindication/Caution: 

Contraindication 

tramadol/acetaminophen has several contraindications in which the medication should not be used. These include: 

Hypersensitivity: tramadol/acetaminophen should not be used in patients with a known hypersensitivity to tramadol, acetaminophen, or other ingredients in the medication. 

Severe respiratory depression: tramadol/acetaminophen should not be used in patients with severe respiratory depression or acute or severe bronchial asthma. 

Paralytic ileus: tramadol/acetaminophen should not be used in patients with paralytic ileus, a condition in which the bowel is paralyzed and unable to move food or waste through the intestines. 

Concurrent use of monoamine oxidase inhibitors (MAOIs): tramadol/acetaminophen should not be used in patients taking or taking MAOIs within the past 14 days, as this can increase the risk of serotonin syndrome, a potentially life-threatening condition. 

Seizure disorders: tramadol/acetaminophen should be used with caution in patients with a history of seizure disorders or at risk for seizures, as tramadol can lower the seizure threshold. 

Pregnancy and breastfeeding: tramadol/acetaminophen should be used cautiously in pregnant and breastfeeding women, as it can pass into breast milk and potentially harm a nursing infant. 

Caution 

tramadol/acetaminophen should be used with caution in certain situations. These include: 

Respiratory depression: tramadol/acetaminophen can cause respiratory depression, especially in patients with respiratory disorders or those taking other medications that depress the respiratory system. Patients should be monitored for signs like respiratory depression, and the medication should be used cautiously in patients with compromised respiratory function. 

Liver disease: acetaminophen, one of the active ingredients in tramadol/acetaminophen, is metabolized by the liver. Patients with liver disease, including cirrhosis or hepatitis, may be at increased risk of acetaminophen toxicity and should be monitored closely while taking this medication. 

Renal impairment: tramadol is eliminated from the body primarily by the kidneys. Patients with impaired renal function may experience slower drug elimination, leading to a higher risk of side effects. Dose adjustments may be necessary for patients with renal impairment. 

Elderly patients: Elderly patients may be more sensitive to the effects of tramadol/acetaminophen and may be at increased risk of adverse effects such as confusion, dizziness, and falls. 

Interactions with other medications: tramadol/acetaminophen can interact with other medications, such as benzodiazepines, antidepressants, and antipsychotics, increasing the risk of respiratory depression and other side effects. Patients should talk to their physician about all medications before starting tramadol/acetaminophen. 

Abuse potential: tramadol, one of the active ingredients in tramadol/acetaminophen, has a high potential for abuse and dependence.  

Pregnancy / Lactation

Pregnancy consideration:  

AU TGA pregnancy category: C
US FDA pregnancy category: Not assigned 

Lactation:   

Excreted into human milk: Yes  

Breastfeeding warnings:  

Pregnancy category: 

• Category A: well-controlled and Satisfactory studies do not show risk to the fetus in the first/later trimester.        
• Category B: there was no evidence of risk to the fetus in animal studies, and there were not enough studies on pregnant women        
• Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.       
• Category D: adequate data with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits.        
• Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women.        
• Category N: There is no data available for the drug under this category 

Pharmacology

Pharmacology: 

tramadol/acetaminophen is a combination medication containing two active ingredients, tramadol, and acetaminophen, which work together to relieve pain. 

tramadol is a centrally acting synthetic opioid analgesic that binds to mu-opioid receptors in the brain and spinal cord, inhibiting the transmission of pain signals. tramadol also increases neurotransmitters in the brain, including serotonin and norepinephrine, which can contribute to its analgesic effects. 

acetaminophen, also known as paracetamol, is a non-opioid analgesic that works by blocking the production of prostaglandins, chemicals in the body that cause pain and inflammation. acetaminophen is also thought to work by reducing the sensitivity of pain receptors in the body. 

When taken together, combining tramadol and acetaminophen can provide more effective pain relief than either medication alone. The onset of pain relief is relatively rapid, with peak effects occurring within 1-2 hours of ingestion. 

Pharmacodynamics: 

Mechanism of action: tramadol is a synthetic opioid not derived from opiates. It acts as a centrally-acting analgesic and may bind to the mu-opioid receptors, but its mechanism of action is not fully understood. 

acetaminophen works by inhibiting the synthesis of PG (prostaglandins), which are chemical mediators responsible for pain and fever. It acts on the hypothalamus to produce antipyresis (reduction of fever) and analgesia (reduction of pain). 

Pharmacokinetics: 

Absorption 

After administration, the drug has a bioavailability of 75%. The peak plasma time, or when the drug reaches its highest concentration in the bloodstream, is 2-3 hours after administration. 

Distribution 

The drug has a volume of distribution (VD) of 2.6-2.9 L/kg, which means that it is distributed throughout the body and tends to accumulate in specific tissues. The drug is also 20% protein-bound. 

Metabolism 

tramadol undergoes significant liver metabolism, where CYP2D6 breaks it down into its active metabolite, O-desmethyl tramadol (M1), which has a much higher affinity for opioid receptors than tramadol itself. Individuals who are poor metabolizers of CYP2D6 have been observed to have a 20% increase in tramadol levels and a 40% decrease in O-desmethyl tramadol (M1). In contrast, acetaminophen undergoes conjugation with glucuronide and sulfate. 

Elimination and Excretion 

tramadol has a half-life of 5-7 hours and is primarily eliminated through renal excretion. On the other hand, acetaminophen has a shorter half-life of 2-4 hours, and less than 9% of it is excreted unchanged in urine. 

Adminstartion

Administration: 

Oral administration 

tramadol/acetaminophen is typically administered orally in tablets or capsules. The drug should be taken exactly as prescribed by the healthcare provider. 

The dosage of tramadol/acetaminophen will depend on several factors, including the patient’s age, weight, medical condition, and other medications they may be taking. The healthcare provider will determine each patient’s appropriate dosage and dosing schedule. 

It’s important to take tramadol/acetaminophen with a full glass of water and to take it with food or milk if it upsets the stomach. Patients should not crush, break, or chew tablets or capsules, as this can alter the release of the medication. 

Patients should not exceed the recommended dosage of tramadol/acetaminophen, as this can increase the risk of side effects, including liver damage and overdose.  

If a dose is missed, it is recommended to take it as soon as possible. However, if the next scheduled dose is missed, it should be skipped and the following dose should be taken at the appropriate time. It is important to avoid taking a double dose of the medication to compensate for the missed dose.

Patients must report any side effects or concerns to their healthcare provider while taking tramadol/acetaminophen. Patients should also talk to their healthcare provider if they take other medications, including over-the-counter medications and supplements, before starting tramadol/acetaminophen. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: tramadol/acetaminophen 

Pronounced: [ a-SEET-a-MIN-o-fen-and-TRAM-a-dol ] 

Why do we use tramadol/acetaminophen? 

tramadol/acetaminophen is a combination medication that relieves moderate to moderately severe pain. The medications contains two active ingredients, tramadol, and acetaminophen, which work together to relieve pain. 

tramadol is an opioid pain reliever that works by binding to opioid receptors in the brain and blocking the transmission of pain signals. acetaminophen is a non-opioid pain reliever that works by blocking the production of certain chemicals in the body that cause pain and inflammation. 

tramadol/acetaminophen is used to treat a variety of painful conditions, including: 

Post-operative pain 

Dental pain 

Arthritis pain 

Back pain 

Neuralgia (nerve pain) 

Fibromyalgia 

tramadol/acetaminophen is typically used as a short-term treatment for pain and is not recommended for long-term use. The medication should be used exactly as the healthcare provider prescribes, and patients should not exceed the recommended dosage or duration of use.