Tramadol: 7 things you should know

Medically reviewed by Carmen Pope, BPharm. Last updated on May 30, 2024.

1. How it works

• Tramadol is a man-made (synthetic), pain-relieving medicine with opioid and non-opioid pain-relieving effects. It may be used for the treatment of moderate-to-severe pain.
• Tramadol itself has very little activity at the mu opioid receptor (MOR) but its M1 metabolite (O-desmethyl-tramadol) binds to the mu-opioid receptor and triggers intracellular events that diminish the transmission of pain signals. This blunts the emotional response to pain, providing pain relief. The nonopioid effects of tramadol are due to its ability to block the reuptake of monoamines, such as norepinephrine (NE) and serotonin (5HT) resulting in increases in NE that help mediate the body's natural pain-relieving systems.
• Tramadol is an opioid that belongs to the group of medicines known as narcotic analgesics.

2. Upsides

• Tramadol may be used for the treatment of moderate-to-severe pain such as that caused by cancer, osteoarthritis, and other musculoskeletal diseases. Tramadol is often prescribed after surgery.
• Tramadol may also be effective for nerve-related pain because of its nonopioid pain-relieving effects.
• May be less likely than other narcotic analgesics to cause respiratory depression.
• Available as immediate-release conventional tablets, an oral solution (Qdolo), and extended-release capsules or tablets. Available as a fixed combination tablet with acetaminophen.
• May be taken with or without food.
• Generic tramadol is available.

3. Downsides

If you are between the ages of 18 and 60, take no other medication or have no other medical conditions, side effects you are more likely to experience include:

• A headache, nausea, dizziness, constipation, vomiting, joint pains, dry mouth, sweating, and itchy skin are commonly reported side effects.
• Sedation, which may affect a person's ability to drive or operate machinery, or perform hazardous tasks is also commonly reported. Alcohol may enhance this effect.
• May cause dependence, addiction, and slowed breathing. Tramadol may be misused and sought after by drug abusers. Tolerance may develop to its effect.
• Seizures have been reported with tramadol use. The risk is increased in people taking certain types of antidepressants (such as SSRIs, SNRIs, TCAs, MAO inhibitors), other opioids, antipsychotics, other drugs that reduce the seizure threshold, with a pre-existing seizure disorder, head trauma, excessive alcohol use, or with a metabolic disorder predisposing to an increased risk of seizures.
• Do not take tramadol if you are also using alcohol, drugs with sedative properties, or other narcotic medications; dangerous or fatal side effects, such as slowed breathing, can occur.
• Seniors over the age of 65 years may be more sensitive to the side effects of tramadol. Tramadol should be initiated cautiously, and extended-release tramadol is best avoided.
• May not be suitable for some people including those with a history of depression or prone to addiction. Tramadol may increase the risk of suicidal thoughts or behaviors.
• Tramadol may not be appropriate for people at risk for respiratory depression, head trauma, increased intracranial pressure, or acute abdominal disease.
• The dosage of tramadol may require adjusting for liver or kidney disease.
• Withdrawal symptoms (such as anxiety, sweating, insomnia, nausea, diarrhea, pain, and piloerection [bristling of hairs]) have been reported when tramadol has been abruptly stopped after being taken for a long time. The dosage of tramadol should always be tapered off slowly on discontinuation.
• Tramadol may interact with several other drugs including antidepressants, antipsychotics, St John's Wort, bupropion, triptans, or other drugs that are metabolized by CYP 2D6 or CYP3A4 hepatic enzymes.
• The metabolism of tramadol may be slowed by people who are poor metabolizers at CYP 2D6. While concentrations of tramadol may be higher in these people, concentrations of the active metabolite of tramadol may be lower, resulting in insufficient pain relief. People who are CYP2D6 ultra-rapid metabolizers (about 3% of the population) are at risk of life-threatening or fatal breathing side effects from tramadol (respiratory depression) even at regular dosages because they convert tramadol into its active metabolite more rapidly than other people. These people should not use tramadol.
• Interaction or overdosage may cause serotonin syndrome (symptoms include mental status changes [such as agitation, hallucinations, coma, delirium]), fast heart rate, dizziness, flushing, muscle tremor or rigidity, and stomach symptoms (including nausea, vomiting, and diarrhea).
• Rarely, anaphylaxis (a potentially fatal allergic reaction) has occurred with tramadol use, usually following the initial dose. Itchy skin, a rash, difficulty breathing, and other allergy-type symptoms may be more common. Do not use in people with a history of an allergic reaction to codeine or another opioid.
• Tramadol is not FDA-approved for use in children under the age of 12 (immediate-release capsules) or 18 (extended-release capsules).

Note: In general, seniors or children, people with certain medical conditions (such as liver or kidney problems, heart disease, diabetes, seizures) or people who take other medications are more at risk of developing a wider range of side effects. View complete list of side effects

4. Bottom Line

• Tramadol is a strong opioid pain relieving medication that may be used to treat moderate to severe general and nerve-related pain. Tramadol may be habit-forming and misuse can cause addiction, overdose, or death. Its use may be limited by side effects such as nausea, constipation, and sedation. Pain-relieving effects or side effects may be altered in some people due to genetic variation at CYP 2D6 or drug interactions. 

5. Tips

• Tramadol may be taken with or without food.
• The long-acting formulation must be swallowed whole; do not crush or chew as you may receive a dangerous or fatal dose. Extended-release tramadol capsules are intended to be taken only once a day. Do not increase the dosage of tramadol unless your doctor has advised you to do so.
• Do not take tramadol if you have severe breathing problems, a head injury or increased pressure inside your skull, a blockage in your stomach or intestines, or if you have recently used alcohol, sedatives, tranquilizers, narcotic medication, or an MAO inhibitor (isocarboxazid, linezolid, methylene blue injection, phenelzine, rasagiline, selegiline, tranylcypromine, and others).
• May make you sleepy and affect your ability to drive or operate machinery. Refrain from driving or potentially hazardous tasks until you are sure tramadol is not having this effect.
• Tramadol can slow or stop your breathing, and death may occur. A person caring for you should give naloxone and seek emergency medical attention if you have slow breathing with long pauses, blue-colored lips, or if you find it hard to wake up. Serious breathing problems may be more likely in older adults and people who are debilitated or have wasting syndrome or chronic breathing disorders.
• Tramadol may be habit-forming. Misuse can cause addiction, overdose, or death, especially in a child or other person using the medicine without a prescription. Do not take more tramadol than prescribed as an overdosage can be fatal. Selling or giving away this medicine is against the law. Keep your medicine in a safe, private storage area, out of view of any person that may illegally misuse it. Keep out of reach of children and pets.
• Fatal side effects can occur if you use this medicine with alcohol, or with other drugs that cause drowsiness or slow your breathing. People taking extended-release forms of tramadol should not consume alcohol-containing beverages at the same time. Alcohol is also not advised with immediate-release forms of tramadol.
• Can cause nausea. Taking an antiemetic (anti-sickness medicine) with tramadol can counteract this effect. Starting treatment with low doses or taking it with food may also help to lessen nausea.
• If you have been taking tramadol for long periods, do not stop it suddenly. Your doctor will advise you on the best way to taper down the dosage over several weeks.
• Tell a doctor immediately if you experience an allergic reaction to tramadol, excessive sweating, feel agitated or confused, develop a fever or diarrhea, find it difficult to control your limbs, or notice spasmodic jerky contractions of your muscles.
• Do not use if pregnant or breastfeeding unless specifically recommended by your doctor.

6. Response and effectiveness

• Peak levels of immediate-release tramadol are reached approximately two hours after oral administration. Peak levels of extended-release tramadol capsules occur within 10 to 12 hours. There is a lot of variability in the way people respond to tramadol - some people may require higher or lower dosages than others for the same level of pain relief.
• Starting at the lowest possible dose and increasing the dose slowly may lessen side effects like nausea, dizziness, and headache.
• When stopping treatment with tramadol, it's best to slowly discontinue the medicine to avoid withdrawal symptoms. Your doctor will give you a schedule.

7. Interactions

Medicines that interact with tramadol may either decrease its effect, affect how long it works, increase side effects, or have less of an effect when taken with tramadol. An interaction between two medications does not always mean that you must stop taking one of the medications; however, sometimes it does. Speak to your doctor about how drug interactions should be managed.

Common medications that may interact with tramadol include:

• anticoagulants (blood thinners), such as warfarin, or other drugs that have blood-thinning effects such as aspirin or NSAIDs
• anticonvulsants, such as carbamazepine, phenytoin, phenobarbital, or primidone
• antidepressants, such as tricyclic antidepressants (eg, amitriptyline), monoamine oxidase inhibitors (eg, isocarboxazid, phenelzine, and tranylcypromine), or SSRIs (eg, fluoxetine, sertraline)
• antipsychotics (such as butyrophenones, phenothiazines, or thioxanthenes) and atypical antipsychotics (eg, olanzapine, quetiapine, ziprasidone)
• any medication that may cause drowsiness, such as benzodiazepines (eg, diazepam, lorazepam), first-generation antihistamines (such as doxylamine or promethazine), metoclopramide, or opioids (such as codeine, morphine)
• diuretics, such as furosemide
• heart medications, such as digoxin
• medications that are metabolized by the same enzymes such as bupropion, erythromycin, fluoxetine, ketoconazole, paroxetine, quinidine, or ritonavir
• migraine medications, such as almotriptan, eletriptan, or sumatriptan
• muscle relaxants, such as cyclobenzaprine
• other medications that affect serotonin, such as amphetamines, fentanyl, lithium, triptans (eg, almotriptan, eletriptan, or sumatriptan), or St. John's Wort
• others, such as quinidine, or rifampin.

Avoid drinking alcohol or taking illegal or recreational drugs while taking tramadol.

Note that this list is not all-inclusive and includes only common medications that may interact with tramadol. You should refer to the prescribing information for tramadol for a complete list of interactions.

References

• Tramadol ER. Revised 01/2024. Sun Pharmaceutical Industries, Inc. https://www.drugs.com/pro/tramadol-er.html
• Tramadol Tablets Prescribing Information. Updated 03/2024. Rising Pharma Holdings, Inc. https://www.drugs.com/pro/tramadol-tablets.html

Further information

Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use Tramadol only for the indication prescribed.

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

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