Tramadol: Uses, Dosage & Side Effects
A prescription opioid analgesic used for moderate to severe pain in adults and adolescents over 12 years
Tramadol is a prescription opioid analgesic used to treat moderate to severe pain in adults and adolescents over 12 years of age. It has a unique dual mechanism of action: weak agonism at mu-opioid receptors combined with inhibition of serotonin and norepinephrine reuptake. While tramadol is considered a weaker opioid compared to morphine or oxycodone, it carries significant risks including dependency, tolerance, serotonin syndrome, seizures, and respiratory depression. It should only be used under medical supervision and for the shortest duration necessary.
Quick Facts: Tramadol
Key Takeaways
- Tramadol is an opioid analgesic used for moderate to severe pain. It works through two mechanisms: weak mu-opioid receptor agonism and inhibition of serotonin and norepinephrine reuptake, providing pain relief through both opioid and non-opioid pathways.
- Dependency, tolerance, and abuse can develop with repeated use. The risk increases with higher doses and longer treatment duration. Tramadol is classified as a controlled substance in many countries.
- Never stop tramadol abruptly after prolonged use. Withdrawal symptoms including anxiety, tremor, sweating, insomnia, and gastrointestinal distress can occur. Always taper gradually under medical supervision.
- Tramadol must not be combined with MAO inhibitors and carries a serious risk of serotonin syndrome when used with antidepressants (SSRIs, SNRIs, tricyclics). Combining with benzodiazepines or alcohol increases the risk of respiratory depression and death.
- The maximum recommended daily dose is 400 mg. Exceeding this significantly increases the risk of seizures. Children under 12 should not take tramadol, and it requires dose adjustment in elderly patients and those with kidney or liver impairment.
What Is Tramadol and What Is It Used For?
Tramadol is a prescription medication belonging to the opioid analgesic class. Developed in Germany in the late 1970s by Grünenthal GmbH, it has been available on the global market since the 1990s and has become one of the most widely prescribed opioid analgesics worldwide. Tramadol is available as a generic drug from numerous manufacturers, including Tramadol Retard Hexal, Tradolan, Tramadol HEXAL, Tramadol STADA, Tramadol Krka, and Tramadol Retard Actavis, among others.
Unlike classical opioids such as morphine or oxycodone, tramadol has a unique dual mechanism of action. Its primary pharmacological effects come from two distinct pathways. First, tramadol and its active metabolite O-desmethyltramadol (M1) bind to mu-opioid receptors in the central nervous system, producing analgesic effects similar to other opioids but with lower affinity. The M1 metabolite has approximately 200 times greater affinity for the mu-opioid receptor than the parent compound and is responsible for a significant portion of the analgesic effect. Second, tramadol inhibits the reuptake of serotonin (5-HT) and norepinephrine in the brain and spinal cord, enhancing descending inhibitory pain pathways. This dual action means tramadol provides pain relief through both opioid and monoaminergic mechanisms, which partly explains its clinical profile that differs from traditional opioids.
Tramadol is metabolized in the liver by the cytochrome P450 enzyme CYP2D6. Genetic variation in this enzyme can significantly affect how individuals respond to tramadol. Approximately 5–10% of the Caucasian population are poor metabolizers, meaning they produce less of the active M1 metabolite and may experience inadequate pain relief. Conversely, ultra-rapid metabolizers (1–2% of the population) convert tramadol to M1 more quickly and may be at higher risk for serious adverse effects including respiratory depression. This pharmacogenetic variability is an important clinical consideration that healthcare providers must take into account.
Tramadol is officially approved for the treatment of moderate to severe pain in adults and adolescents over 12 years of age. Common clinical indications include acute post-operative pain, acute pain following trauma or injury, chronic pain conditions such as osteoarthritis and chronic back pain, and cancer-related pain. It is positioned on step 2 of the World Health Organization (WHO) pain ladder, which recommends weak opioids for moderate pain not adequately controlled by non-opioid analgesics alone. While tramadol may be considered for neuropathic pain, its use in this indication is generally second-line to dedicated neuropathic pain agents such as gabapentin or pregabalin.
Tramadol is available in several pharmaceutical formulations to accommodate different clinical needs. Immediate-release formulations include capsules (typically 50 mg) and film-coated tablets (50 mg) that provide rapid onset pain relief and are suitable for acute pain management. Extended-release (modified-release or depot) tablets are available in strengths of 100 mg, 150 mg, and 200 mg, designed to be taken twice daily for sustained pain control over 12 hours. The extended-release formulation is particularly useful for chronic pain conditions requiring around-the-clock analgesia, as it maintains more stable plasma drug concentrations compared to immediate-release forms.
What Should You Know Before Taking Tramadol?
Contraindications
Tramadol must not be used in certain clinical situations where the risks clearly outweigh any potential benefits. Understanding these absolute contraindications is essential for safe use of this medication. Tramadol is contraindicated if you have a known allergy (hypersensitivity) to tramadol hydrochloride or any of the inactive ingredients in the formulation, as allergic reactions can range from skin rashes and itching to severe anaphylaxis with breathing difficulties, facial swelling, and circulatory collapse.
Tramadol must not be taken during acute intoxication with alcohol, sleeping pills, opiates, or other psychotropic drugs that affect mood or consciousness, as the combination dramatically increases the risk of respiratory depression and central nervous system depression that can be fatal. If you have used monoamine oxidase inhibitors (MAOIs) such as moclobemide, phenelzine, or selegiline within the past 14 days, tramadol is strictly contraindicated due to the risk of life-threatening serotonin syndrome or hypertensive crisis. Additionally, tramadol should not be used if you have epilepsy that is not adequately controlled by medication, as it lowers the seizure threshold and can trigger convulsions. Finally, tramadol must not be used as a substitute treatment for opioid withdrawal, as it is not suitable for managing addiction-related withdrawal symptoms.
Warnings and Precautions
Tramadol is an opioid and carries a recognized risk of dependency, tolerance, and misuse. Repeated use can lead to physical and psychological dependence, and life-threatening overdose is possible. The risk is higher with higher doses, longer treatment duration, and in individuals with a history of substance abuse or psychiatric disorders. Never take more than prescribed, use tramadol for longer than recommended, or take it for purposes other than prescribed.
Before starting tramadol therapy, it is critical to inform your healthcare provider about your complete medical history. Several conditions require special attention, dose adjustments, or additional monitoring:
- History of substance abuse or dependency: Individuals who have previously been dependent on opioids, alcohol, prescription medications, or illicit drugs are at significantly elevated risk of developing tramadol dependency. This includes individuals with a family history of addiction.
- Psychiatric conditions: Depression, anxiety disorders, and personality disorders increase the risk of misuse and dependency. If you are being treated by a psychiatrist or taking medications for mental health conditions, your doctor must be informed.
- Epilepsy or seizure history: Tramadol lowers the seizure threshold and may trigger convulsions, particularly at doses exceeding 400 mg daily. This risk is further increased when tramadol is combined with SSRIs, SNRIs, tricyclic antidepressants, or antipsychotic medications.
- Head injury or increased intracranial pressure: Tramadol can mask symptoms of head injury and may worsen conditions associated with elevated intracranial pressure. It should be used with extreme caution in these patients.
- Impaired consciousness: If you experience episodes of lightheadedness, fainting, or altered awareness, tramadol may exacerbate these symptoms and increase the risk of falls and injury.
- Shock or circulatory failure: Tramadol should not be used in patients experiencing shock, as it can worsen hemodynamic instability.
- Breathing difficulties: Respiratory depression is a serious risk, especially when tramadol is combined with other CNS depressants. Patients with COPD, sleep apnea, or other respiratory conditions must be closely monitored.
- Kidney or liver disease: Both organs play important roles in tramadol metabolism and elimination. Patients with hepatic or renal impairment require dose adjustments and extended dosing intervals to prevent drug accumulation and toxicity.
Tramadol can cause sleep-related breathing disorders including obstructive sleep apnea and sleep-related hypoxemia (low blood oxygen levels during sleep). Symptoms may include breathing pauses during sleep, nighttime awakenings due to shortness of breath, difficulty maintaining sleep, or excessive daytime drowsiness. If you or someone else notices these symptoms, contact your doctor who may consider dose reduction.
CYP2D6 metabolizer status: Tramadol is converted in the liver by the CYP2D6 enzyme to its active metabolite O-desmethyltramadol. Genetic variations in CYP2D6 affect individuals differently: poor metabolizers may not receive adequate pain relief, while ultra-rapid metabolizers are at increased risk of serious adverse effects including slow or shallow breathing, confusion, extreme drowsiness, nausea, and vomiting. If you experience any of these symptoms, stop taking tramadol and seek immediate medical attention.
Adrenal insufficiency: Long-term opioid use, including tramadol, can rarely cause adrenal insufficiency (low cortisol levels). Symptoms include extreme tiredness, loss of appetite, severe abdominal pain, nausea, vomiting, and low blood pressure. If you develop these symptoms, contact your healthcare provider, who will determine if hormone replacement therapy is necessary.
Opioid-induced hyperalgesia: In some patients, tramadol can paradoxically worsen pain or cause new pain. If you notice that your pain increases after taking tramadol, experience increased sensitivity to pain, or develop new pain, do not take additional doses. Contact your doctor to discuss alternative treatment options.
Pregnancy and Breastfeeding
Safety data for tramadol use during pregnancy is limited, and tramadol should generally not be used during pregnancy. Long-term use during pregnancy can lead to neonatal withdrawal syndrome, where the newborn develops symptoms including irritability, excessive crying, tremors, jitteriness, vomiting, diarrhea, and feeding difficulties after birth.
Tramadol is excreted in breast milk. A single dose does not typically require interruption of breastfeeding. However, if repeated doses are necessary, breastfeeding should be discontinued. Based on available human data, tramadol is not believed to significantly affect male or female fertility. Always consult your healthcare provider before using tramadol if you are pregnant, planning to become pregnant, or breastfeeding.
Children and Adolescents
Tramadol is not recommended for children under 12 years of age. It should not be used in children and adolescents with breathing difficulties, as symptoms of tramadol toxicity can be more severe in this population. In adolescents aged 12 and older, tramadol may be used under medical supervision with careful attention to dosing and monitoring for adverse effects. The FDA has issued specific warnings against using tramadol in children under 12 and in adolescents aged 12–18 who are obese or have conditions such as obstructive sleep apnea or severe lung disease.
Driving and Operating Machinery
Tramadol can cause drowsiness, dizziness, and blurred vision, which may impair your ability to react quickly. You should not drive, operate heavy machinery, or engage in activities requiring mental alertness until you know how tramadol affects you. These effects are more pronounced at the start of treatment, when the dose is increased, or when tramadol is combined with alcohol or other CNS depressants.
How Does Tramadol Interact with Other Drugs?
Tramadol interacts with numerous medications through various pharmacological mechanisms. Some interactions are life-threatening and constitute absolute contraindications, while others require dose adjustments, additional monitoring, or careful risk-benefit assessment. Understanding these interactions is essential for safe tramadol use. The table below summarizes the most clinically significant drug interactions.
Major Interactions
| Drug / Drug Class | Risk | Clinical Advice |
|---|---|---|
| MAO inhibitors (moclobemide, phenelzine, selegilin) | Serotonin syndrome, hypertensive crisis | Absolutely contraindicated. Wait at least 14 days after stopping an MAOI before starting tramadol. |
| SSRIs (fluoxetine, sertraline, citalopram) | Serotonin syndrome, increased seizure risk | Use only if no alternatives exist. Monitor closely for agitation, hallucinations, rapid heartbeat, fever, muscle rigidity. |
| SNRIs (venlafaxine, duloxetine) | Serotonin syndrome, increased seizure risk | High risk combination. Careful monitoring required, especially during initiation and dose changes. |
| Tricyclic antidepressants (amitriptyline, nortriptyline) | Serotonin syndrome, increased seizure risk | Avoid if possible. If used together, use the lowest effective doses with close monitoring. |
| Benzodiazepines (diazepam, lorazepam, oxazepam) | Respiratory depression, excessive sedation, coma, death | Use only when no alternative treatment options exist. Limit doses and duration. Monitor breathing closely. |
| Alcohol | Enhanced CNS depression, respiratory depression | Do not consume alcohol during tramadol treatment. Effects of both substances are dangerously amplified. |
| Other opioids (morphine, codeine, buprenorphine) | Reduced analgesic effect, respiratory depression | Buprenorphine, nalbuphine, and pentazocine may reduce tramadol's effectiveness. Avoid combination. |
Moderate Interactions
| Drug / Drug Class | Effect | Clinical Advice |
|---|---|---|
| Carbamazepine | Significantly reduces tramadol effectiveness by increasing metabolism | Combination not recommended. Tramadol pain relief may be substantially shortened or eliminated. |
| Ondansetron | May reduce tramadol analgesic effect | Monitor pain control. Alternative anti-emetics may be preferred. |
| Warfarin (coumarins) | Altered anticoagulant effect; increased bleeding risk | Monitor INR closely when starting, adjusting, or stopping tramadol. Report any unusual bleeding. |
| Gabapentin / Pregabalin | Increased sedation, respiratory depression risk | Use caution. Monitor for excessive drowsiness and breathing difficulties. |
| Antipsychotics | Increased seizure risk | Monitor for seizure activity. Consider alternative pain management. |
This is not an exhaustive list of all possible interactions. Always inform your healthcare provider and pharmacist about all medications you are taking, including over-the-counter drugs, herbal supplements, and vitamins. Particular caution is advised with sedating medications, as the combined sedative effect with tramadol can be dangerous. Inform friends or family members about the signs of excessive sedation and respiratory depression so they can respond appropriately in an emergency.
What Is the Correct Dosage of Tramadol?
Tramadol dosing should be individualized based on the severity of pain, patient response, previous analgesic experience, and risk factors for adverse effects. The fundamental principle of opioid prescribing applies: use the lowest effective dose for the shortest duration necessary. Before starting treatment and at regular intervals during therapy, your doctor should discuss your treatment expectations, duration of use, when to seek medical advice, and when to discontinue treatment.
Adults (Immediate-Release)
Immediate-Release Capsules / Tablets (50 mg)
Starting dose: 50–100 mg every 4–6 hours as needed for pain.
Maximum dose: 400 mg per day (eight 50 mg capsules).
Administration: Swallow whole with water. May be taken with or without food.
Adults (Extended-Release)
Extended-Release Tablets (100 mg, 150 mg, 200 mg)
Starting dose: One 100 mg tablet twice daily (morning and evening).
Dose increase: If pain relief is insufficient, may increase to 150 mg or 200 mg twice daily.
Maximum dose: 400 mg per day (e.g., 200 mg twice daily).
Administration: Swallow whole with water, preferably morning and evening. Do not break, crush, or chew extended-release tablets.
Children and Adolescents
Children Under 12 Years
Tramadol is not recommended for children under 12 years of age.
Adolescents 12–18 Years
Dosing as for adults. Tramadol should not be used in adolescents with breathing difficulties, obesity, or conditions that increase respiratory risk.
Elderly Patients
Patients Over 75 Years
Elimination of tramadol may be slower. Your doctor may recommend extending the interval between doses. No specific dose reduction is required if kidney function is normal, but careful monitoring for sedation and other adverse effects is important.
Kidney and Liver Impairment
Severe Hepatic or Renal Impairment
Patients with severe liver and/or kidney disease should not take tramadol. For mild to moderate impairment, the dosing interval should be extended (e.g., from every 6 hours to every 12 hours). Your doctor will determine the appropriate regimen based on your specific clinical situation. Dialysis patients may require dosing adjustments as tramadol is only partially removed by hemodialysis.
Missed Dose
If you forget to take a dose, take it as soon as you remember unless it is almost time for your next scheduled dose. In that case, skip the missed dose and continue with your regular dosing schedule. Do not take a double dose to compensate for a forgotten one. If you are using tramadol for chronic pain and miss a dose, your pain may return before the next dose is due.
Overdose
If you or someone else has taken too many tramadol tablets, contact emergency services or go to the nearest emergency department immediately. Overdose symptoms include very small (pinpoint) pupils, difficulty breathing or very slow/shallow breathing, unconsciousness or extreme drowsiness, seizures (convulsions), dangerously low blood pressure, nausea and vomiting, and coma. Tramadol overdose can be fatal, especially when combined with alcohol, benzodiazepines, or other CNS depressants.
What Are the Side Effects of Tramadol?
Like all medications, tramadol can cause side effects, although not everyone experiences them. Most side effects are dose-dependent and tend to improve as your body adjusts to the medication. However, some side effects are serious and require immediate medical attention. The following side effect frequency grid organizes adverse effects by how commonly they occur based on clinical trial data and post-marketing surveillance.
Stop taking tramadol and contact emergency services immediately if you experience: difficulty breathing or wheezing, swelling of the face, tongue, or throat, severe skin rash or hives, seizures (convulsions), or signs of anaphylactic shock (sudden circulatory collapse).
Very Common
Affects more than 1 in 10 people
- Dizziness
- Nausea
Common
Affects up to 1 in 10 people
- Headache
- Drowsiness (somnolence)
- Vomiting
- Constipation
- Dry mouth
- Fatigue
- Sweating (hyperhidrosis)
Uncommon
Affects up to 1 in 100 people
- Heart palpitations, rapid heart rate (tachycardia)
- Feeling faint or collapsing (postural hypotension)
- Retching, stomach discomfort, bloating, diarrhea
- Skin reactions: itching (pruritus), rash
Rare
Affects up to 1 in 1,000 people
- Severe allergic reactions (anaphylaxis): breathing difficulties, skin swelling
- Seizures (convulsions)
- Slow heart rate (bradycardia), elevated blood pressure
- Slow or shallow breathing, shortness of breath (dyspnea)
- Appetite changes, abnormal sensations (tingling, numbness), tremor
- Muscle twitching, weakness, uncoordinated movements
- Fainting (syncope), speech difficulties
- Blurred vision, pupil constriction or dilation
- Urinary retention or difficulty urinating
- Hallucinations, confusion, sleep disturbances, anxiety, nightmares
- Mood changes, decreased cognitive function, impaired judgment
- Drug dependence
Very Rare / Frequency Not Known
Affects fewer than 1 in 10,000 people or cannot be estimated
- Vertigo (balance problems)
- Flushing
- Liver enzyme elevations
- Hypoglycemia (low blood sugar)
- Hyponatremia (low sodium levels causing fatigue, confusion, seizures)
- Worsening of asthma
- Hiccups
- Serotonin syndrome: agitation, hallucinations, coma, fever, rapid heartbeat, unstable blood pressure, involuntary muscle jerking, muscle rigidity, gastrointestinal symptoms
- Adrenal insufficiency (with long-term use)
Psychological side effects: Tramadol can cause various psychological effects that vary in intensity and nature depending on the individual and the duration of treatment. These may include mood swings (usually euphoria, sometimes irritability), changes in activity level (usually decreased, sometimes increased), and diminished cognitive function including impaired judgment and decision-making ability.
Withdrawal symptoms: If tramadol treatment is discontinued abruptly after prolonged use, withdrawal symptoms may occur. These can include restlessness, anxiety, nervousness, tremor, sweating, difficulty sleeping, and gastrointestinal disturbances. In rare cases, more severe symptoms may develop including panic attacks, paranoia, hallucinations, altered perception of reality, tinnitus (ringing in the ears), and unusual sensations such as itching, tingling, and numbness. If you experience any withdrawal symptoms, consult your healthcare provider.
How Should You Store Tramadol?
Tramadol is a controlled substance and must be stored securely to prevent access by unauthorized persons, as it can cause serious harm and death in individuals for whom it has not been prescribed. Always keep tramadol in a locked cabinet or secure location, out of sight and reach of children. Accidental ingestion by children can be fatal.
No special storage conditions regarding temperature or humidity are required for tramadol tablets and capsules. Do not use the medication if you notice any discoloration, damage, or signs of deterioration. Always check the expiry date on the blister pack or container before use; the expiry date refers to the last day of the indicated month. Do not flush unused tramadol down the toilet or throw it in household waste. Return any unused or expired medication to your local pharmacy for safe and environmentally responsible disposal.
What Does Tramadol Contain?
The active substance in all tramadol formulations is tramadol hydrochloride. Each dosage form contains a specific amount of the active ingredient as indicated on the packaging. Extended-release tablets are specifically designed with a matrix system that releases the active substance gradually over approximately 12 hours, providing sustained pain relief with twice-daily dosing.
Common inactive ingredients (excipients) found in tramadol formulations include microcrystalline cellulose, hypromellose, colloidal anhydrous silica, and magnesium stearate in the tablet core. Film-coated tablets may also contain hypromellose, lactose monohydrate, talc, macrogol, propylene glycol, titanium dioxide, and various iron oxide coloring agents (E172). Some formulations contain lactose; if you have known lactose intolerance, check with your pharmacist before taking tramadol.
Tramadol is available in numerous generic formulations from various manufacturers worldwide. While the active ingredient is identical across all products, differences in inactive ingredients, coating, and release characteristics may exist. Branded and generic products that have received regulatory approval are considered therapeutically equivalent for clinical purposes. Commonly available brands include Tramadol Retard Hexal, Tradolan Retard, Tramadol HEXAL, Tramadol 2care4, Tramadol STADA, Tradolan, Tramadol Krka, and Tramadol Retard Actavis.
Frequently Asked Questions About Tramadol
Tramadol is used for the treatment of moderate to severe pain in adults and adolescents over 12 years of age. It is commonly prescribed for acute post-operative pain, pain following trauma or injury, chronic pain conditions such as osteoarthritis and back pain, and cancer-related pain. Tramadol belongs to the opioid analgesic class and works through both opioid receptor agonism and inhibition of serotonin and norepinephrine reuptake, providing pain relief through two complementary mechanisms.
Yes, tramadol carries a recognized risk of dependency, tolerance, and addiction. While it is generally considered to have lower abuse potential than stronger opioids like morphine or oxycodone, physical and psychological dependence can develop with repeated use. Risk factors include prolonged use, higher doses, history of substance abuse, and psychiatric conditions. Tramadol is classified as a controlled substance in many countries. Always take tramadol only as prescribed and for the shortest duration necessary.
Combining tramadol with antidepressants, particularly SSRIs (such as fluoxetine, sertraline, citalopram), SNRIs (such as venlafaxine, duloxetine), and tricyclic antidepressants, significantly increases the risk of serotonin syndrome — a potentially life-threatening condition characterized by agitation, hallucinations, rapid heartbeat, fever, muscle rigidity, and loss of coordination. The combination also increases seizure risk. Never start or stop antidepressants while taking tramadol without consulting your doctor.
The most dangerous side effects include seizures (especially at doses exceeding 400 mg daily or in combination with seizure-lowering medications), serotonin syndrome (when combined with serotonergic drugs), severe respiratory depression (particularly with CNS depressants or alcohol), anaphylactic shock, and cardiac arrhythmias. Long-term use can lead to adrenal insufficiency. If you experience difficulty breathing, seizures, loss of consciousness, severe allergic reactions, or high fever with muscle rigidity, seek emergency medical attention immediately.
Abruptly stopping tramadol after prolonged use can trigger withdrawal symptoms including restlessness, anxiety, nervousness, tremor, insomnia, sweating, nausea, diarrhea, and pain. In rare cases, more severe symptoms may occur: panic attacks, paranoia, hallucinations, altered perception of reality, tinnitus (ringing in the ears), and unusual sensory experiences. Tramadol should always be tapered gradually under medical supervision. Your doctor will create a personalized tapering schedule to safely reduce the dose over time.
Tramadol should not be used during pregnancy due to limited safety data. Long-term use during pregnancy can cause neonatal withdrawal syndrome in the newborn, with symptoms including excessive crying, tremors, feeding difficulties, and irritability. Tramadol is excreted in breast milk and should generally be avoided during breastfeeding; if repeated doses are needed, breastfeeding should be discontinued. Always discuss alternative pain management options with your healthcare provider if you are pregnant, planning a pregnancy, or breastfeeding.
References
This article is based on the following peer-reviewed sources and international guidelines. All medical claims are supported by evidence level 1A or higher.
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Medical Review & Editorial Team
This article has been written and reviewed by our medical editorial team, comprising licensed physicians specializing in clinical pharmacology, pain medicine, and addiction medicine. All content follows the GRADE evidence framework and adheres to WHO, EMA, and FDA guidelines.
iMedic Medical Editorial Team — Specialists in Clinical Pharmacology and Pain Medicine
iMedic Medical Review Board — Independent expert panel reviewing all content according to international guidelines
Level 1A — Based on systematic reviews, randomized controlled trials, and international clinical guidelines (WHO, EMA, FDA, NICE, BNF)
— Content reviewed and updated to reflect current prescribing information and safety data