Pronunciation: TRAM-a-dol
Generic name: tramadol
Brand names: ConZip, Qdolo, Ultram, Ultram ER
Dosage form: oral tablets, oral capsules, extended-release tablets, extended-release capsules
Drug class: Opioids (narcotic analgesics)

Medically reviewed by Carmen Pope, BPharm. Last updated on May 28, 2024.

What is tramadol?

Tramadol is an opioid agonist that may be used to treat moderate to moderately severe chronic pain in adults.

• Extended-release forms of tramadol may be used in adults who require around-the-clock treatment of their pain for an extended period.

Tramadol is an opioid pain-relieving medicine that also has nonopioid effects. It differs from other opioids in that it is a prodrug and requires metabolism in the body before it is active. Tramadol itself has very little activity at the mu opioid receptor (MOR) but its M1 metabolite (O-desmethyl-tramadol) has an affinity only 10 times less than morphine. Binding to the mu-opioid receptor triggers intracellular events that diminish the transmission of pain signals, which 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). Increases in NE are known to mediate the body's natural pain-relief systems. Some of its pain-relieving effects are due to increased levels of NE that act on alpha2 adrenergic receptors and are completely independent of its effects on opioid receptors.

Brands of tramadol include ConZip, Qdolo, Ultram, and Ultram ER. Generic tramadol is available.

Tramadol was first FDA-approved on March 3, 1995. Originally it was classified as a non-controlled substance but it was reclassified in 2014 to Schedule IV of the Controlled Substances Act with restrictions on its prescribing.

How do genetics affect tramadol?

The opioid effects of tramadol are greatly affected by a person’s genetics, particularly their capacity for tramadol metabolism through a liver enzyme system called cytochrome P450 2D6. 20% of African Americans, 10% of Caucasians, and 2% of Asians have genetic polymorphisms that reduce the activity of this enzyme, which decreases how much tramadol is metabolized. People who are poor metabolizers at CYP 2D6 may find tramadol ineffective.

Individuals 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.

Tramadol side effects

Tramadol may cause serious side effects, some of which may be fatal (see warnings below).

Get emergency medical help if you have signs of an allergic reaction to tramadol (symptoms include hives, difficulty breathing, swelling in your face or throat) or a severe skin reaction (fever, sore throat, burning in your eyes, skin pain, a red or purple skin rash that spreads and causes blistering and peeling).

Common side effects of tramadol affecting 10% of people who take it include nausea, constipation, dry mouth, drowsiness, dizziness, and vomiting.

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.

Call your doctor at once if you have:

• noisy breathing, sighing, shallow breathing, breathing that stops during sleep
• a slow heart rate or weak pulse
• a light-headed feeling, like you might pass out
• seizure (convulsions) or
• low cortisol levels - nausea, vomiting, loss of appetite, dizziness, worsening tiredness or weakness.

Seek medical attention right away if you have symptoms of serotonin syndrome, such as agitation, hallucinations, fever, sweating, shivering, fast heart rate, muscle stiffness, twitching, loss of coordination, nausea, vomiting, or diarrhea.

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 the FDA at 1-800-FDA-1088.

Warnings

Tramadol can slow or stop your breathing and may be habit-forming. MISUSE OF THIS MEDICINE CAN CAUSE ADDICTION, OVERDOSE, OR DEATH, especially in a child or other person using the medicine without a prescription. Keep this medicine where others cannot get to it. Do not take more tramadol than prescribed as an overdosage can be fatal. Selling or giving away this medicine is against the law.

Seizures have been reported in patients taking tramadol. Your risk of seizures is higher if you are taking higher doses than recommended. Seizure risk is also higher in those with a seizure disorder or those taking certain antidepressants or opioid medications.

Tramadol should not be used if you are suicidal or prone to addiction.

You should 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).

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.

Serious allergic reactions, including anaphylaxis, have occurred with tramadol, some of which caused death. People who are allergic to other opioids are at higher risk. Other hypersensitivity reactions include itching, hives, narrowing of the airways, swelling of the face and airways (angioedema), and serious skin reactions such as Stevens-Johnson Syndrome.

Tramadol hydrochloride extended-release capsules/tablets may complicate a healthcare provider’s clinical assessment of an acute abdominal condition. They should also not be used by people with liver or kidney disease.

Taking tramadol during pregnancy may cause life-threatening withdrawal symptoms in the newborn.

Tramadol should not be given to a child younger than 12 years old, or anyone younger than 18 years old who recently had surgery to remove the tonsils or adenoids. Extended-release tramadol (Ultram ER) should not be given to anyone younger than 18 years.

Tramadol may cause drowsiness or affect your ability to drive or perform hazardous tasks. Do not perform these tasks if tramadol causes confusion, mental impairment, or drowsiness.

Before taking this medicine

You should not take tramadol if you are allergic to it, or if you have:

• severe asthma or breathing problems
• a stomach or bowel obstruction (including paralytic ileus)
• if you have recently used alcohol, sedatives, tranquilizers, or narcotic medications or
• if you have used an MAO inhibitor in the past 14 days (such as isocarboxazid, linezolid, methylene blue injection, phenelzine, or tranylcypromine)
• are pregnant or planning a pregnancy
• are breastfeeding.

Tramadol should not be given to a child younger than 12 years old. Ultram ER should not be given to anyone younger than 18 years old. Do not give tramadol to anyone younger than 18 years old who recently had surgery to remove the tonsils or adenoids.

Seizures have occurred in some people taking tramadol. Your seizure risk may be higher if you have ever had:

• a head injury, epilepsy, or other seizure disorder
• drug or alcohol addiction or
• a metabolic disorder.

To make sure tramadol is safe for you, tell your doctor if you have ever had:

• breathing problems, sleep apnea
• liver or kidney disease
• urination problems
• problems with your gallbladder, pancreas, or thyroid
• a stomach disorder or
• mental illness, or suicide attempt.

Pregnancy

If you take tramadol during pregnancy, your baby could be born with life-threatening withdrawal symptoms or seizures and may need medical treatment for several weeks. Fetal death and miscarriage have also been reported. Should not be used in pregnant women unless the benefits outweigh the risks.

Breastfeeding

It is not known if tramadol passes into human milk. Ask a doctor before using tramadol if you are breastfeeding. Tell your doctor if you notice severe drowsiness or slow breathing in the nursing baby.

How should I take tramadol?

Take tramadol exactly as prescribed by your doctor. Never use tramadol in larger amounts, or for longer than prescribed. Tell your doctor if you feel an increased urge to take more of this medicine.

• Swallow the capsule or tablet whole to avoid exposure to a potentially fatal overdose. Do not crush, chew, break, open, or dissolve.
• Never crush or break a tramadol tablet to inhale the powder or mix it into a liquid to inject the drug into your vein. This practice has resulted in death.
• May be taken with or without food.
• Measure the liquid medicine with the supplied syringe or a dose-measuring device (not a kitchen spoon).

You may have withdrawal symptoms if you stop using tramadol suddenly. Ask your doctor before stopping the medicine.

Do not keep leftover tramadol. Just one dose can cause death if someone uses it accidentally or improperly. Ask your pharmacist where to locate a drug take-back disposal program. If there is no take-back program, mix the leftover medicine with cat litter or coffee grounds in a sealed plastic bag and throw the bag in the trash.

Usual adult tramadol dosage

Immediate-release formulations (tablets/capsules/liquid)

• Tramadol 50 mg to 100 mg every 4 to 6 hours as needed. Maximum dose 400 mg/day.
• A lower starting dose of 25 mg once a day, slowly increasing by 25mg every 3 days as needed.

Extended-release capsules/tablets

• Tramadol ER 100 mg once a day.
• Can be increased by 100 mg every 5 days if needed to a maximum dose of 300 mg/day.

What happens if I miss a dose?

Since tramadol is used for pain, you are unlikely to miss a dose. Skip any missed dose if it is almost time for your next dose. Do not use two doses at one time.

What happens if I overdose?

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222. An overdose can be fatal, especially in a child or other person using the medicine without a prescription. Overdose symptoms may include severe drowsiness, pinpoint pupils, slow breathing, or no breathing.

Your doctor may recommend you get naloxone (a medicine to reverse an opioid overdose) and keep it with you at all times. A person caring for you can give naloxone if you stop breathing or don't wake up. Your caregiver must still get emergency medical help and may need to perform CPR (cardiopulmonary resuscitation) on you while waiting for help to arrive.

Anyone can buy naloxone from a pharmacy or local health department. Make sure any person caring for you knows where you keep naloxone and how to use it.

What should I avoid while taking tramadol?

Do not drink alcohol. Dangerous side effects or death could occur.

Avoid driving or hazardous activity until you know how tramadol will affect you. Dizziness or drowsiness can cause falls, accidents, or severe injuries.

What other drugs will affect tramadol?

You may have breathing problems or withdrawal symptoms if you start or stop taking certain other medicines. Tell your doctor if you also use an antibiotic, antifungal medication, heart or blood pressure medication, seizure medication, or medicine to treat HIV or hepatitis C.

Many other drugs can be dangerous when used with tramadol. Tell your doctor if you also use:

• medicine for allergies, asthma, blood pressure, motion sickness, irritable bowel, or overactive bladder
• other opioid medicines
• a benzodiazepine sedative like Valium, Klonopin, or Xanax
• sleep medicine, muscle relaxers, or other drugs that make you drowsy, or
• drugs that affect serotonin, such as antidepressants, stimulants, or medicine for migraines or Parkinson's disease.

This list is not complete. Other drugs may interact with tramadol, including prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible interactions are listed here.

Storage

Store at room temperature away from moisture and heat and out of reach of children. Do not share with others.

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